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27 February2015

COMPANY NEWS 2 RivalstoRemicade reach Cipla gains ground in 2 North Africa via JVs Actavis intends to adopt Allergan name 3 Te va plans to set up abiologicals facility 4 major European markets Wockhardt resolves faults at US factory 5 Sawai sees turnoverrise 6 faster than profit ivals to the Remicade (infliximab) monoclonal antibody marketed by Janssen and Aurobindo venturetotarget PCV vaccines 7 RMerck arenow available throughout Europe after Celltrion and Hospira seized on Growth in US helps Zydus to advance 8 expiries of paediatric extensions to supplementary protection certificates (SPCs) during Lannett turns gaze to Western Europe 9 February to enter the market (see pages 24 and 28). Russia and Ukraine hit Richter’sresults 10 On 25 February,Celltrion announced launches of its Remsima biosimilar through partners such as Kern Pharma and Mundipharma (see page 26) in Austria, Belgium, Denmark, France, Protopic rival peps Perrigo’sturnover 11 Germanyand Greece, as well as in Italy,Luxembourg, the Netherlands, Spain, Sweden and the To wa cuts its costs to improvemargins 12 UK. The treatment for autoimmune diseases wasnow available in 31 countries, the firm noted. Siegfried sorts out FDAHameln letter 13 Hospira has launched its Inflectra (infliximab) biosimilar monoclonal antibody in Glenmark growsits sales as profits slide 14 several European markets, includingAustria, Denmark, France, Germany, Greece, Italy, Luxembourg, the Netherlands, Spain and Sweden. “Inflectra is nowavailable in 24 European MARKET NEWS 15 countries,”noted the injectables specialist, which already markets infliximab in Central and Eastern Europe, as well as in some smaller Western European markets. FDAreopens debate on label change rule15 In September 2013, the European Commission authorised Remsima and Inflectra for treating France must address declining sales trend 16 inflammatory conditions including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Canada will require 17 adult and paediatric Crohn’sdisease, adult and paediatric ulcerative colitis and plaque psoriasis. shortage notification Global Remicade turnoverahead by 2.9% to US$6.87 billion last year reported by Janssen’s Input is invited over US interchangeability 19 parent group, Johnson &Johnson, included US$1.64 billion in non-US International markets. OGD sets target forANDAaction dates 20 On 17 March, the US Food and Drug Administration’s(FDA’s) Arthritis Advisory Committee will hold apublic meeting to discuss abiologics license application (BLA) that PRODUCT NEWS 21 has been submitted by Celltrion for its CT-P13 proposed rivaltoRemicade. US patent 6,284,471 protecting Remicade until September 2018 has just been rejected Lupin enlists Celon forAmerican Advair 21 upon re-examination by the US Patent and Trademark Office (USPTO). The ‘471 patent – which covers assays using anti-tumournecrosis factor (TNF) antibodies – was one of three Mylan must wait for 22 esomeprazole in US patents for which Celltrion sought adeclaratory judgement of non-infringement last year. However, the twoparties settled the litigation on confidential terms. G Hospira and Pfenex develop ranibizumab 23 Lupin wins appeal on US Trizivir patent 24 Pregabalin dispute will persist in the UK25 Spain’sKern Pharma 26 introduces infliximab Pfizer pays US$17bn for Hospira Momenta is open to abatacept options 27 fizer has agreed to pay around US$17 billion, including assumed debt, to acquire Norwayenjoys steep infliximab price cut 29 Pinjectables specialist Hospira. The US$90-per-share deal has been approvedunanimously by both firms’ boards and is scheduled to close during the second half of this year,subject to FEATURES 32 antitrust clearance and approvalbyHospira’sshareholders. The agreement – which represents a39% premium on Hospira’sclosing price on 4February,and around four-times Hospira’s Pfizer eyes twotop spots 32 annual sales – includes aUS$500 million break-up fee. with Hospira acquisition “Hospira’sbusiness aligns well with our newcommercial structure and is an excellent strategic fitfor our Global Established Pharmaceutical (GEP) business, which will benefit REGULARS from asignificantly enhanced product portfolio in growing markets,”commented Pfizer’s chairman and chief executive officer,Ian Read. Pipeline Watch – Remicade 28 “The expanded portfolio of sterile injectablepharmaceuticals, composed of Hospira’s Events – Our regular listing 30 broad generic sterileinjectables product line, including acute-care and oncology injectables, Price Watch UK – UK pricing trends 31 with anumber of differentiated presentations, as well as its biosimilars portfolio, combined with GEP’sbranded sterile injectables, including anti-infectives, anti-inflammatories and People – Bayer’sBrandicourt 34 leads SanofiasCEO cytotoxics, will create aleading global sterile injectables business,”Pfizer maintained. G Fordetails of the deal, turntopage 32. Gen 27-02-15 Pgs.2-14_Layout 1 25/02/2015 18:33 Page 2

COMPANY NEWS

STRATEGICALLIANCES/THIRD-QUARTER RESULTS Ciplagains ground in North Africa via JVs

ipla has broadened its presence in North Africa by agreeing to Third-quarter sales* Change Proportion Cestablish joint ventures with the company’sexisting partners in (Rs millions) (%) of total (%) Algeria and Morocco. Through its UK subsidiary,Cipla EU, the Indian firm will hold a Formulations 12,750 -6.2 46 40% stakeinaventure it is creating with its Algerian partner,Biopharm, APIs 1,510 -4.4 5 and a60% stakeinasimilar scheme it is establishing with Cooper Exports 14,260 -6.1 52 Pharma and The Pharmaceutical Institute, Cipla’sallies in Morocco. India 11,990+14.2 43 Both ventures –which are subject to certainregulatory approvals – will be used as avehicle to market Cipla’srespiratory franchise in Other 1,410 –5 the respective countries, and will include the companies supplying Cipla 27,650 +6.5 100 funds to build local manufacturing facilities. The Indian firm is expected to contribute US$6 million of atotal US$15 million in *rounded to nearest Rs10 million Algeria, while it will pour up to US$15 million into its scheme in Figure1:Breakdown of Cipla’s net sales in its financial third quarter ended 31 Morocco, where Cipla will also promote its neurology drugs. December 2014 (Source –Cipla) Meanwhile, Cipla has agreed to acquire for Rs960 million (US$15.4million) a60% stakeinprivately-owned Indian firm Jay to Teva,following the Israeli group’srecent nod for the first US Precision Pharma, an existing supplier of Cipla’srespiratory devices. generic rivaltoAstraZeneca’sNexium blockbuster (Generics bulletin, Jay Precision –which boasts amanufacturing facility in Vasai, 6February 2015, page 17). Maharashtra –had sales of around Rs300 million in its financial year Elsewhere, Cipla’sin-licensing agreement with Teva in South ended 31 March 2014. Slated to close by the end of next month, the Africa though its local Cipla Medpro affiliate for access to “65 new transaction wasaimed at “integrating the value chain and will serve molecules” (Generics bulletin,17October 2014, page 6) has received as aplatform for the development of next-generation respiratory clearance from the country’sCompetition Commission. The Indian devices”, Cipla said. firm has also just been awarded aUS$189 million share in aGlobal Fund antiretroviral tender (see page 27). Indian sales increased by 14% Meanwhile, the founder of the Serum Institute of India, Cyrus In Cipla’sfinancial third quarter ended 31 December 2014, Poonwalla, has revealed that the companyand Cipla had held initial domestic sales rising by 14.2% to Rs12.0 billion helped overcome merger talks following their agreement covering paediatric vaccines single-digit turnoverslips from exports of active pharmaceutical in Europe that wasstruck late last year (Generics bulletin,5 ingredients (APIs) and finished-dose formulations as the Indian December 2014, page 6). “We[Serum Institute] could nevergoup companyimprovedits sales by 6.5% to Rs27.7 billion (see Figure 1). for sale,”hesaid, “but we could merge with acompany, for example However, the Indian firm’sexport sales could soon be bolstered Cipla…there is asmall chance that could happen.” after Cipla announced that it had “gone live”inNorth America,and “Wefirst have to see if the initial partnership bears fruit,” had subsequently introduced its first ‘own-label’ productsinthe region Poonwalla added. “If it movesinthe right direction, maybe we will including doxycycline, meloxicam, topiramate and valaciclovir. takeittothe next stage.” Moreover, Cipla has revealed that it will be supplying esomeprazole Amarginal increase in Cipla’sexpenses wasoffset by the firm’s active pharmaceutical ingredient (API) and finished-dose formulation 6.5% sales rise, as its pre-tax profit rose by 8.3% to Rs4.28 billion. G

27 February2015 Issue 226 Individual subscriptions Te rms &Conditions: These can be viewedinfull at www.Generics-bulletin.com/subscribe. Editor: Aidan Fry An annual subscription comprises: ■ 20 Generics bulletin newsletters; No partofthis publication maybe copied, reproduced, Deputy Editor: David Wallace ■ AND at least 46 weekly News@Genericsbulletin stored in aretrieval system, distributed or transmitted Assistant Editor: Liudmila Kotko electronic newsflashes containing the week’stop by anymeans, including electronic,mechanical, news stories (currentlydelivered by email). photocopying or recording, without the prior written Business Reporter: Dean Rudge permission of the publisher,orunder the terms and Production Controller: Debi Minal Choice of formats conditions of aGlobal Site Licence or of alicence Production Editor: Jenna Meredith The 20 Generics bulletin newsletters are available: issued by the Copyright Licensing Agency (CLA) in ■ EITHER as the digital Generics bulletin-i for London, UK, or rights bodies in other countries that Director of Subscriptions: ValDavis online access by desktop,and tablet and smartphone. have reciprocal agreements with the CLA. Awards Manager: Natalie Cornwell Mobile devices can have Apple or Android Neither maythis publication be exported, distributed Managing Director: Mike Rice operating systems. or circulated by anymeans without the prior written ■ OR in traditional hard-copyprint format, permission of the publisher. While due care has been taken to ensure the accuracy Editorial enquiries: GENERICS bulletin, delivered by airmail. of information contained in this publication, the 4Poplar Road, Dorridge,Solihull, Corporate and multiple subscriptions publisher makes no claim that it is free of errorand West Midlands B93 8DB, UK. Global Site Licences are available to companies. disclaims anyliability whatsoeverfor anydecisions or Website: www.Generics-bulletin.com These provide in-house electronic access forstaff to actions taken as aresult of its contents. Te l: +44 (0)1564 777550 Fax: +44 (0)1564 777524 Generics bulletin and News@Genericsbulletin. ©OTC Publications Ltd.All rights reserved. E-mail: [email protected] Please ask foraquotation. Generics bulletin® is registered as atrademark in Advertising enquiries: the European Community. Discounted multiple subscriptions are available to As above,[email protected] ISSN 1742-0784. Generics bulletin-i at the same location. SUBSCRIPTIONS Companyregistered in England No 2765878. Subscription rates are published at Subscription enquiries: Printed by Warwick Printing CompanyLimited, www.Generics-bulletin.com/subscribe. Contact [email protected] Leamington Spa CV31 1QD, UK.

2 GENERICS bulletin 27 February2015 Gen 27-02-15 Pgs.2-14_Layout 1 25/02/2015 18:33 Page 3

COMPANY NEWS

BUSINESS STRATEGY/ANNUAL RESULTS BUSINESS STRATEGY/ANNUAL RESULTS Clarisrejects talk Actavis intends to of injectables sale adopt Allergan name

laris Lifesciences has quashed media speculation that it is ctavis plans to adopt the Allerganname for its corporate identity Cconsidering selling its generic sterile injectables business, Aand branded portfolio once it completes its US$66 billion takeover Claris Injectables. of the ophthalmics specialist in the next fewweeks. However, the Responding to an article that appeared in India’s Economic Times group will retain the Actavis name “for select geographic regions and newspaper on 12 February,Claris announced in adisclosure to the product portfolios”. The change in corporate name is subject to Bombay Stock Exchange (BSE): “Atpresent we are not negotiating shareholder approval. the sale of astakeinthe injectables business, and the board of “By adopting the Allerganname for the corporation, we will directorsofthe companyhas neither considered nor taken any ensure that our corporate identity reflects the dramatic evolution of decision in this regard.” our company,”explained president and chief executive officer Brent According to the Times’article, as manyasseven companies Saunders. “For more than 65 years, the Allerganname has represented –Cipla, Dr Reddy’s, Lupin, Pfizer,Sandoz, Sun and Zydus Cadila – innovation in branded pharmaceuticals.” had shown some levelofinterest in acquiring Claris Injectables for “The Actavis name has represented our global commitment to around Rs25-30 billion (US$402-US$482 million), with several leadership in generic, branded generic and OTCpharmaceuticals and having submitted initial bids. to increased access to more affordable prescription medicine,”he Operating three manufacturing facilities that have been approved continued. “Retaining the Actavis name reflects this heritage, as well by various regulatory authorities–including from the US, UK and as the considerable equity of the Actavis name with our customers Australia –atasite in Ahmedabad, India, Claris Injectables offers in keymarkets around the world.” awide portfolio of injectables across multiple delivery systems. The Actavis –which has recently unveiled its senior management operation –which Claris created last year by transferring its specialty team following the Allergandeal (see page 35) –increased its turnover injectables business to asubsidiary –also spans product development, regulatory affairs and sales and marketing units. Business Annual sales Change Operating Claris Injectables forms the bulk of Claris’ operations, after the segment (US$ millions) (%) margin (%) Indian group sold an 80% stakeinits infusion business in India and North American Generics 4,174 +6.6 – other emerging markets to Japanese players Otsuka and Mitsui two years ago (Generics bulletin,9August 2013, page 10). International 2,574 +2.8 – The Indian group said its injectables sales grewby“approximately” Generics/International 6,747 +5.1 32.0 62% to Rs4.06 billion last year.Including acontribution made by the North American Brands 4,631 +335.9 20.0 Indian firm’sminority stakeinits infusion business, group turnover ANDADistribution 1,684 +40.7 4.7 reached Rs7.14billion. Emerging markets accounted for half of that total, the US 23%, and other regulated markets the remaining 27%. Actavis 13,062 +50.5 –* Having filed nine abbreviated newdrug applications (ANDAs) *operating loss of US$1.27 billion includes US$4.43 billion during 2014, the injectables unit ended the year with 13 of its 37 of expenses not attributed to business segments filings approved, and 24 pending review. The unit –which generated earnings before interest, tax, depreciation and amortisation (EBITDA) Figure1:Breakdown of Cipla’s net sales in its financial third quarter ended 31 December 2014 (Source –Cipla) of Rs1.49 billion last year –plans to file 18 ANDAs this year,in line with its target “to have atotal of 100 ANDAs in the US within last year by 50.5% to US$13.1 billion due to afull-year contribution the next three years”. G from Warner Chilcott and consolidating Forest from 1July 2014. International sales outside of North America grewby2.8% to US$2.57 billion, due to aUS$123 million input from Forest’snon- US brands and acontribution from Warner Chilcott that almost trebled INVESTIGATIONS to US$181 million. Those factors were offset in part by aUS$237 Teva reports likely corruption million decrease from the Western European commercial operations that the group divested to Aurobindo on 1April last year.Atthe same eva has identified, following avoluntary global investigation time, Actavis closed its acquisition of Thai generics specialist Silom Tinto its business practices, potential issues in “Russia, certain (Generics bulletin,18April 2014, page 3). Eastern European countries, certain Latin American countries and “In our North American Generics business, strong results were other countries”that “likely constitute” violation of the US Foreign drivenbycontinued performance of our generic versions of Lidoderm Corrupt Practices Act (FCPA). (lidocaine)and Concerta (methylphenidate),and fourth-quarter launches “In connection with our investigation, we have also become of generic versions of Intuniv(guanfacine) and Celebrex(celecoxib),” aware that affiliates in certain countries provided to local authorities Saunders stated. Sales rose by 6.6% to US$4.17 billion (see Figure 1). inaccurate or altered information relating to marketing or promotional North American Brands turnoverreached US$4.63 billion, while practices,”the Israeligroup admitted. higher prices and volumes pushed up revenues by the group’sUS Noting that its investigation wasexpected to continue at least until Anda Distribution business by 40.7% to US$1.68 billion. the end of the year,Teva stressed that it had “brought and continue Acquisition-related charges –including aUS$190 million to bring these issues to the attention of the Securities and Exchange goodwill write-offonthe Pharmatech drug-delivery business that Commission (SEC) and the US Department of Justice (DoJ)”. Any Actavis has agreed to sell to investment firm TPG –caused the group fines or disgorged profits could be “material”, it acknowledged. G to post aUS$1.27 billion operating loss. G

27 February2015 GENERICS bulletin 3 Gen 27-02-15 Pgs.2-14_Layout 1 25/02/2015 18:33 Page 4

COMPANY NEWS

BUSINESS STRATEGY/ANNUAL RESULTS Teva planstoset up abiologicals facility

eva is developing aplan to establish a“significant” biologics Annual sales Change Proportion Tproduction facility,according to its chief executive officer,Erez (US$ millions) (%) of total (%) Vigodman. “That is one gapwehave. And we will overtime also craft aplan to deal with go-to-market capability.Wemight then pursue a US 4,418 +6 22 partner to accelerate the pace of execution,”hetold investors. Europe 3,148 -6 16 Operations chief Carlo De Notaristefani noted that the group’s Rest of the World 2,248 -5 11 current mammalian and microbial manufacturing capacity was“at a Generic Medicines 9,814 -1 48 small scale”. “Weneed to expand that, and we are currentlyassessing Copaxone/CNS 5,575 +1 28 the best location to do this,”herevealed. Oncology 1,180 +17 6 Commenting on Teva’s biosimilars strategy,Generics head Siggi Olafsson admitted he would “love to have more” candidates in the Respiratory 957 -1 5 biosimilars second wave,comprising mainly monoclonal antibodies. Women’sHealth 504 -1 2 The first wave of growth hormones, epoetins and filgrastims were Others344 -5 2 generating annual sales of US$200-US$300 million for Teva,henoted. Specialty Medicines 8,560 +2 42 “Weneed alittle bit bigger pipeline in wave twotobeareal OTC/Other 1,898 -6 9 player in the 2020-2021 timeframe,”Olafsson recognised. “Weare looking for the right assets and partner to be areal player in the Teva 20,272 ±0 100 market in five to six years.” Options included acquisitions, joint ventures and co-development Figure1:Breakdown by business segment of Teva Pharmacetical Industries’ sales in 2014 (Source –Teva) deals, he explained. While more than 100 companies claimed to have usable second-waveprojects, he said Teva had limited that selection profitable business as well as market dynamics in certain countries to “probably five to 10 companies that really have strong assets”. including Germany, France and Spain”. Teva’s combination of generics and specialty brands expertise Olafsson said Teva’s team in Germanywas “doing extremely wasakey commercial advantage, Olafsson maintained. “Wedonot well”. While local Generics sales were down by 13% last year on expect anyinterchangeability,atleast in the first fewyears,”hesaid. “lower participation in the tender market and increasing pressure As an example of Teva’s ability to market biologics, he cited the firm’s on prices in the retail generics segment”, the team had successfully Granix (tbo-filgrastim) brand –authorised as astandalone biologic – launched several respiratory brands. French Generics sales fell by 12% in the US, which had captured more than a15% market share. amid “increasing competition” and revised rules on pharmacydiscounts. Olafsson said Teva wasalso expanding its presence in generic “Wereally do not want to go too much into the tender business in injectables, especially in long-acting formulations. Having tackled Spain,”Olafsson added. The firm said a13% Generics slide in Spain manufacturing issues in recent years, the companywas “re-entering was“due mainly to the impact of the implementation of new the market” in the US, he said, with recent launches such as commercial policies, and the increasing scope of the tendering system enoxaparin and linezolid set to push up US injectables turnoverfrom in the Andalucía region, in which we chose not to participate”. “just overUS$100 million” in 2014 to at least US$300 million this Olafsson said “the UK did very well”, seizing on local supply year (Generics bulletin,16January 2015, page 29). Teva’s global shortages to raise local sales by 1%. And “improvements in our supply injectables turnoverwas around US$500-US$700 million he added. management” helped Italian sales to growby12%, while turnover Noting Pfizer’sUS$17 billion planned takeoverofHospira, in Switzerland rose by 4% on higher volumes drivenbyrecent launches. Olafsson said Teva intended to be aniche US injectables player. Areported 5% Generics decline to US$2.25 billion in the group’s “Weare not competing on the big-volume antibiotics and oncology Rest of the World region equated to 4% local-currency growth. In products,”hesaid. Rather,headded, Teva wasfocusing on hard-to- Russia, a14% slide translated to a3%local-currencygain as higher makeinjectablessuch as aversion of Luitpold’sVenofer (iron sucrose). sales of branded generics outweighed lower revenues from government A6%sales rise to US$4.42 billion in US Generics sales last tenders. Canadian sales rose by 5%, or by 12% in local-currency year failed to compensate fully for declines in Teva’s Europe and terms, aided by reversing apricing reserve. But “quality and supply Rest of the World regions as its global Generics turnoverdipped by issues”, as well as price cuts imposed in April 2014, cut turnoverin 1% to US$9.81 billion (see Figure 1). In local currencies, global Japan by atenth, or by 3% in the local currency. sales –including sales of active pharmaceutical ingredients(APIs) Higher sales in the US and Canada, as well as better margins to third parties that stalled at US$724 million –edged up by 1%. on third-party API sales, boosted Teva’s Generics gross margin by Exclusive or first-to-market launches of generic Xeloda 2.1 percentage points to 43.3%. Research and development costs (capecitabine) and Lovaza (omega-3 ethyl esters) contributed to the rose by 5% to US$517 million, butsales and marketing expenses US gains, as did introducingarivaltoEvista (raloxifene). Launching fell by 18% to US$1.58 billion, due in part to lower royalty payments injectable carboplatin and enoxaparin, as well as celecoxib capsules on US sales of generic Pulmicort (budesonide). A29% gain to US$2.15 and buprenorphine/naloxone sublingual tablets helped to maintain billion in the Generics segment’soperating profit –excluding fourth-quarter US Generics sales at US$1.18 billion. But declines unallocatedcorporate expenses –improvedthe segment’soperating of 16% in Europe and of 12% in the Rest of the World –due in part margin by 5.1 points to 21.9%. to exchange-rate shifts –reduced global Generics turnoverby8% The Israeli group’soverall performance followed asimilar trend. to US$2.47 billion in the fourth quarter. Operating profit more than doubled to US$3.95 billion following a Full-year Generics sales in Teva’s 36 European countries –the prior-year charge to settle damages for the firm’sat-risk US launch European Union, Norway,Switzerland, Albania and the countries of pantoprazole.But turnoverstagnated at US$20.3 billion, as of the former Yugoslavia –fell by 6% to US$3.15 billion. Teva said Copaxone (glatiramer acetate)accounted for almost half of Specialty the 7% local-currencydecrease was“mainly due to our focus on Medicines sales ahead by 2% to US$8.56 billion. G

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COMPANY NEWS

MANUFACTURING MANUFACTURING/THIRD-QUARTER RESULTS FDA warns Apotex Wockhardt resolves over Indian facility faults at US factory

ailing to ensure laboratory records include complete data, to ockhardt says it has “resolved all issues” at its Morton Grove Fexercise appropriate controls overcomputer systems and to Wfacility in Illinois, US, which last year led the US Food and establish and followappropriate written procedures are among the Drug Administration (FDA) to issue the Indian firm with ‘Form “serious current good manufacturing practice (cGMP) violations” 483’ observations for deficienciesrelated to quality controls and listed in awarning letter that the US Food and Drug Administration procedures (Generics bulletin,5September 2014, page 4). (FDA) has issued to the ApotexResearch Private Limited (ARPL) “Our responses to the [Form] 483…have been found satisfactory finished-dose facility in Bommasandra near Bangalore, India. by the FDAand operations continue as normal,”the Indian firm’s “The FDA’sconcern pertains to the practiceofdisregarding managing director,Murtaza Khorakiwala, told investors. “We failing results, conducting trial injections and retesting products [appointed] anew leadership in quality function [six months ago], without anyinvestigation,”the letter states. “Weare also concerned and then we had aone-on-one meeting with the FDA,”herevealed. that you do not have documentation to support your decision to retest “[The agency] wanted some more clarification, buttheyvery clearly samples of lots that had initially failed to meet specifications, and indicated that theyintend to takenofurther action.” you allowed manufacturing activities to occur without the oversight The firm’sMorton Grove facility has increased in importance of your quality unit.” to Wockhardt since the FDAbarred US imports from its Indian Noting that some of the deficiencies found during an inspection Chikalthana and Waluj plants in 2013 (Generics bulletin,6December of the ARPL site conducted in June and July last year were repeat 2013, page 3). However, Khorakiwala revealed, Wockhardt had observations from a2010 warning letter,the FDAtells Apotexto invited the FDAtobegin inspections of all its facilities. This provide “a comprehensive evaluation of the extent of the inaccuracy included Wockhardt’snewest facility in Shendra, India, from where of recorded and reported data” along with arisk assessment of the the companyhas filed the “majority” of its abbreviated newdrug effects of the observed failures and amanagement strategy for global applications (ANDAs) overthe past twoyears. corrective and preventive action plans. Meanwhile, the UK’sMedicines and Healthcare products “The inspection of your facility documented multiple incidents Regulatory Agency(MHRA) has allowed Wockhardt to begin of performing ‘trial’testing of samples, disregarding test results importing products from Chikalthana to the UK again after it removed and reporting only those results from additional tests conducted,” astatement of non-compliance from the site. the letter states. In particular,itaccuses the firm of using only “the The agencyhad only just extended that statement of non-compliance most favourable result” from impurity testing, while quality-control to coverall drugs manufactured at Chikalthana (Generics bulletin, personnel “createdunauthorised folders on laboratory 6February 2015, page 2), having twoyears ago issued the facility computerised systems with appropriate oversight”. with arestricted good manufacturing practice (GMP) certificate, to “ARPL’s inability to prevent and detect poor recordkeeping avoid market shortages, following observations of critical practices raises serious concerns regarding the quality system in place deficiencies(Generics bulletin,18October 2013, page 6). at the time of the inspection,”objects the FDA. In its financial third quarter ended 31 December 2014, aUK Pointing out that it had notified the firm of the agency’sconcern sales boom offset depleted turnoverinthe US caused by those about trial injections during aJanuary 2014 inspection of the manufacturing issues as Wockhardt’ssales rose by 12% to Rs13.8 ApotexPharmachem bulk-drugs unit at Bommasandra, the FDA billion (US$223 million).UKturnovermore than doubled –increasing states: “Our findings during this inspection suggest that corrective by 141% to Rs6.30 billion –while sales in the US tumbled by 48% actions were not implemented globally.” As aresult of that inspection, to Rs2.82 billion (see Figure 1). the FDAissued awarning letter to ApotexPharmachem midway That UK turnoversurge also comfortably offset sales dips of through last year (Generics bulletin,11July 2014, page 2), followed 16% to Rs330 million and 37% to Rs390 million in France and Ireland by an import alert. In response, Health Canada asked Apotexto respectively.But Wockhardt’sturnoverinIndia and Emerging Markets quarantine products made at the ARPL plant (Generics bulletin,3 rose by almost afifth to Rs3.86 billion, as the Indian firm launched October 2014, page 3). sevenproducts in its domestic market during the quarter. At that time, Apotexinsisted it was“absolutely confident in the Despite ramping up research and development spending by more safety and effectiveness of all our products throughout the entirety than afifth to Rs1.19 billion, Wockhardt’spre-tax profit improved of our manufacturing and testing processes,regardless of where it by 29% to Rs4.08 billion. G wasmanufactured”. Meanwhile, the FDAhas also issued awarning letter to Micro Region Third-quarter sales Change Proportion Labs’ facility in Verna, India, following an inspection in May 2014. (Rs millions*) (%) of total (%) The cGMP deficiencies listed include: failure to ensure that laboratory records include complete data derivedfrom necessary Europe 7,140 +92 52 testing; failure to exercise appropriate controls overcomputer India/Emerging 3,860 +18 28 systems; and failure to record or justify deviations from required laboratory-control mechanisms. US 2,820 -48 20 As in the Apotexwarning letter,the FDAtook issue with Wockhardt 13,820 +12 100 unauthorised‘trial’ high performance liquid chromatography(HPLC) injections prior to injections used in reported test results. The agency *rounded to the nearest Rs10 million also pulled up the Indian companyfor filing field alert reports of Figure1:Breakdown by region of Wockhardt’s sales in its financial third quarter failed impurity results almost amonth late. G ended 31 December 2014 (Source –Wockhardt)

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COMPANY NEWS

THIRD-QUARTER RESULTS NINE-MONTHRESULTS Sun’s sales stall on Sawai sees turnover constraintsinsupply rise faster than profit

un Pharma blamed “temporarysupply constraintsarising from overnment initiativestoincrease the use of generics were Sremediation efforts” for its net sales stalling at Rs42.8billion Gcredited by SawaiPharmaceutical as the primary driverfor its (US$688 million) in the Indian group’sfinancial third quarter ended sales increasing by 18.0% to ¥80.2 billion (US$669 million) in the 31 December 2014. The company–which is awaiting Indian court first nine months of its financial year ending 31 March 2015. But clearance to complete its US$4 billion takeoverofRanbaxy –posted during that period, the Japanese firm’soperating profit grewbyjust a9%fall in pre-tax profit to Rs18.5 billion. 2.4% to ¥17.4 billion, giving it an operating margin 3.3 percentage Managing director Dilip Shanghvi said he expected supplies from points lower at 21.7%. the firm’sformulations facility in Halol, India, to improve as Sun Recent price revisions –mandated by Japan’sNational Health implemented corrective actions to deficiencies identified during an Insurance (NHI) system –and “growing sales of low-priced products” inspection by the US Food and Drug Administration (FDA) in explained the disparity between the growth in sales and operating September last year (Generics bulletin,5December 2014, page 3). profit, Sawaisaid. Volumes had increased by 26.9%, the company “Wehavegiven adetailed response, and we are meeting all the dates observed, compared to the 18.0% value rise. that we shared with the FDA,”hetold investors. Cardiovascular drugs enjoyed asales rise of just under afifth Shanghvi blamed “temporary supply constraints at Halol, the loss to ¥24.5 billion, or around 30% of Sawai’sturnover. The category of exclusivity for generic Prandin (repaglinide) and asignificant accounted for aquarter of Sawai’ssales by volume, as the number decline in doxycycline sales” for US Formulations turnoversliding of units sold advanced by athird. Meanwhile, volume rises of 42.5% by 4.4% to Rs25.6 billion. The local-currencydecline was5%to for blood productsand 59.3% for respiratory drugs translated to value US$413 million, even though the group’sTaro affiliate –inwhich rises of 34.8% to ¥9.13 billion and 46.6% to ¥2.27 billion respectively. Sun holds a69% stake–posted an 11.3% sales rise to US$238 million, Sawaienvisages annual sales ahead by 18.0% to ¥106 billion and despite “a volume decrease across all markets”. an operating profit that will growbyatenth to ¥21.0 billion. G “Temporary supply constraints arising from remediation efforts” also contributed to Formulations turnoverinSun’sRest of the World region tumbling by 14.7% to Rs4.44billion (see Figure 1). And MERGERS&ACQUISITIONS/ANNUAL RESULTS excluding Taro’snon-US sales, turnoverinthe region plunged by 29%. But the US and Rest of the World declines were cancelled out by Valeant aims to acquireSalix the Indian group improving branded generics turnoverinits domestic market by 21.4% to Rs11.5 billion, aided by 15 product launches since aleant has agreed to buySalix Pharmaceuticals in deal that values Vthe US gastrointestinal specialist at US$14.5 billion. The US$158- Third-quarter sales Change Proportion per-share cash transaction is scheduledtoclose during the second (Rs millions) (%) of total (%) quarter of this year. “The growing gastrointestinal market has attractive fundamentals, US 25,602 -4.4 60 and Salix has aportfolio of terrific products that are outpacing the India 11,500+21.4 27 market in terms of volume growth, [as well as] apromising near-term Rest of the World 4,444 -14.7 10 pipeline of innovative products,”commented Valeant’schairman and Formulations 41,546+0.2 97 chief executive officer,Michael Pearson. Bulk Drugs 1,811 +4.0 4 Meanwhile, Valeant has just closed aUS$400 million deal to buy Other/eliminations -562 –-1 several assets of bankruptProvenge (sipuleucel-T) provider Dendreon. Last year,afull-year contribution from its Bausch &Lomb Sun Pharma 42,795 -0.2 100 acquisition lifted Valeant’sgroup turnoverby43% to US$8.26 billion. The firm said this equated to 13% ‘same-store’ organic growth. Figure1:Breakdown by region and business of Sun Pharma’s gross sales in its financial third quarter ended 31 December 2014 (Source –Sun Pharma) On the same basis, the group’sEmerging Markets sales rose by 8%. As Figure 1shows, the reported increase was42% to US$2.10 April 2014. Bulk Drugs sales to third parties rose by 4.0% to Rs1.81 billion, as turnoverinthe firm’sAsia/Africa region more than doubled. billion as Sun stepped up internal vertical integration for keyproducts. “Wecontinued to see strong organic growth in several emerging markets Supply constraints and increased compliance costs at Halol, as such as China, the Middle East and Russia,”Pearson stated. G well as integration planning ahead of the planned closure of the Ranbaxy deal by the end of March, contributed to a3%slide to Annual sales Change Proportion Rs19.1 billion in group earnings before interest, tax, depreciation (US$ millions) (%) of total (%) and amortisation (EBITDA). Developed markets 6,167 +44 75 Sun’sresearch and development spending reached Rs3.89 billion, Europe/Middle East 1,087 +34 13 or just over9%ofsales, as the firm made “significant investments” in clinical development of tildrakizumab, apsoriasis monoclonal Asia/Africa 574 +110 7 antibody recently licensed from Merck &Co. Latin America 435 +11 5 Having submitted 19 abbreviated newdrug applications(ANDAs) Emerging markets 2,096 +42 25 between April and December2014 –and received14approvals – Valeant 8,264 +43 100 Sun ended the quarter with 358 approvedANDAs and 131 pending FDAfinal clearance, including 11 tentative approvals. G Figure1:Breakdown of Valeant’s sales in 2014 (Source –Valeant)

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COMPANY NEWS

MERGERS&ACQUISITIONS BUSINESS STRATEGY/THIRD-QUARTER RESULTS Julphar buys stake in Aurobindo ventureto Bangladeshipartner target PCV vaccines

ulphar has establishedadirect presence in Bangladesh by acquiring a urobindo Pharma plans to set up ajoint venture with Tergene Jmajority stakeinits local partner,RAK Pharmaceuticals, for US$9.5 ABiotech, an Indian companythat is developing apneumococcal million. The twofirms, the group based in the United Arab Emirates conjugate vaccine (PCV). “Aurobindo will hold amajority stakein (UAE) pointed out, had held a“long-term strategic alliance” that the joint venture and will fund the product development in aphased covered atechnology-transfer and marketing deal for several products. manner spanning three years,”the Indian firm stated, adding that “RAK is arelatively young, fresh companywith solid the commercially-available PCV had “limited competition and a infrastructure, growth rates and ahealthypipeline,”commented global branded market of more than US$5 billion”. Julphar’schief executive officer,Ayman Sahli. The deal, he said, “It will takearound three years for us to get the development would help the firm to serve160 million people and aBangladeshi completed and the facility up and running,”noted Aurobindo’s pharma market valued at around US$1.3 billion. managing director NGovindarajan. “Initially our focus will be on “The stable investment outlook and the growing healthcare needs tender markets.”“This is an area that is much tougher than typical of alarge, mostly underserved population makeBangladesh an development projects,”hecommented, highlighting limited competition. attactive market for investors,”Sahli added. “Healthcare plays a Stronger Formulationssales, driveninpart by having acquired major role in the expanding economy of Bangladesh, and with this Actavis’ commercial operations in Western Europe, enabled Aurobindo comes aclear need for increased manufacturing.” to raise its group turnoverby47.9% to Rs31.7 billion (US$513 million) Asubsidiary of RAK Ceramics, RAK Pharma operates in its financial third quarter ended 31 December 2014. Formulations production facilities 42 kilometres north of Dhaka, Bangladesh, on turnoverahead by 76.2% to Rs25.3 billion more than offset a9.4% acomplexthat includes aseparate unit for cephalosporin antibiotics fall to Rs6.74 billion in sales of active pharmaceutical ingredients in tablet, capsule and dry-syrup forms. Having started marketing (APIs) due to lower semi-synthetic and non-betalactam revenues. operations in mid-2009, the companyhas built up abroad portfolio Incorporating the former Actavis operationshad strengthened of more than 100 branded generics that in 2013 generated aturnover of US$5.7 million, representing growth of 24%. Business Third-quarter sales Change Proportion Having in 2012 invested US$150 million in amanufacturing segment (Rs millions) (%) of total (%) facility in the UAEdedicated to producing rawmaterials for insulins and biosimilars, Julphar in 2013 launched its first international US 12,012 +29.0 38 finished-dose facility in Ethiopia with local partner Medtech,“initiating Europe 8,609 +470.9 27 aglobal expansion strategy to increase manufacturing capabilities Rest of world 1,338 ±0.0 4 across its major markets”. Antiretrovirals 3,338 +51.5 11 Formulations 25,297+76.2 80 “Weare in the early stages of expanding our manufacturing capabilities in Ethiopia,”the group’sdirector of Sub-Saharan Active Ingredients 6,744 -9.4 21 Africa, Steve Gravenor,told Generics bulletin.“We plan to build a Eliminations/Others -379 –-1 newfill-and-finish facility which will produce insulin, using our own active pharmaceutical ingredient (API) manufactured in the UAE.” Aurobindo 31,662 +47.9 100 “Our short-term aim is to expand our manufacturing base in Ethiopia, to supply domestic and eventually export markets. Further Figure1:Breakdown by business segment of Aurobindo Pharma’s sales in its financial third quarter ended 31 December 2014 (Source –Aurobindo) abroad, Julphar is exploring partnerships with local players from private and government sectors,”Gravenor explained, adding that Aurobindo’spresence in Germany, the Netherlands, Portugal and this strategy fitted well with the African Union Commission’s Spain, Govindarajan pointed out, while providing access to Belgium, Pharmaceutical Manufacturing Plan (PMP) to expand and improve France and Italy.“The revenue and profit numbers for the integrated the quality and scale of pharmaceutical production in the continent. European operations have been in line with our expectations,” he stated. Meanwhile, Julphar –which achievedaturnoverofAED1.4 Aurobindo’sEuropean Formulationssales showed an almost billion (US$381 million) last year –isconstructing afacility in Jeddah, six-fold rise to Rs8.61 billion, accounting for more than aquarter Saudi Arabia, with local partner Cigalah Group. G of group turnover. Another 38% came from US Formulations turnover rising by 29.0% to Rs12.0billion (see Figure 1) on market-share IN BRIEF gains and “opportunistic price increases”. The firm’sAuroMedics US injectables unit –which has 45 files STADA ARZNEIMITTEL said impairment charges of just over pending approval–contributed sales ahead by 71% to US$18 million. C100 million (US$113 million) relatedtoits businesses in the Having incorporated its US$133 million purchase of nutraceuticals Commonwealth of Independent States (CIS) and EasternEurope companyNatrol from 4December,Aurobindo intends to expand almost halved its 2014 net profit to C64.6 million, according to the business –which has annual sales of around US$100 million – preliminary annual results. Currencyeffects added afurther C20.7 beyond the US (Generics bulletin,5December 2014, page 5). million burden. The German group expects to report annual group Formulations sales in the Rest of the World region stalled at turnoverahead by 3% to C2.06 billion, equivalent to a1%rise once Rs1.34 billion as the companyswitched focus in South Africa from adjusted for acquisitions and currencyshifts. And this year,Stada tenders to the private market. Antiretroviral Formulations turnover anticipates lower profits from Russia due to devaluation of the rouble climbed by 51.5% to Rs3.34 billion as the firm won“notable tenders”. and “increased risks in connection with consumer mood”. G Higher raw-material and operating expenses caused the Indian group’spre-tax profit to slip by 2.0% to Rs5.39billion. G

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COMPANY NEWS

SECOND-QUARTERRESULTS THIRD-QUARTER RESULTS Pack pushes Aceto Growth in US helps to single-digit rise Zydus to advance

uman Health sales rising by almost two-fifths to US$55.4 million SFormulations turnoverthat increasedby41.8%, coupled with Hhelped Aceto to increase its group sales by 6.2% to US$124 Usales growth of more than afifth in its Emerging Markets million in its financial second quarter ended 31 December 2014. region, helped Zydus Cadila to report group sales ahead by 17.4% Higher selling, general and administrative expenses caused aslight to Rs22.0 billion (US$353 million) in its financial third quarter drop in pre-tax profit to US$10.5 million. ended 31 December 2014. However, chief executive officer Sal Guccione commented, With sales of Rs8.96 billion, US Formulations accounted for Human Health turnover–which wasdrivenbyAceto’sacquisition just overtwo-fifths of the Indian group’sturnover, while Emerging of Pack Pharmaceuticals last year (Generics bulletin,4April 2014, Markets added 5% with Rs1.01 billion. During the quarter,the companyfiled five abbreviated newdrug applications (ANDAs), Business Second-quarter sales Change Gross taking its total US submissions to 255. segment (US$ millions) (%) margin (%) Meanwhile, in India –where Zydus recently became “the first Human Health 55.4 +39.2 29.5 companyanywhere in the world” to launch biosimilar adalimumab after introducing its Exemptia rivaltoAbbVie’sHumira blockbuster Performance Chemicals 35.8 -8.8 18.9 (Generics bulletin,16January 2015, page 17) –sales rose by Pharmaceutical Ingredients 32.6 -13.1 21.3 more than atenth to Rs8.46 billion, comfortably compensating for Aceto 123.8 +6.2 24.3 double-digit sales dips in Europe and Latin America to Rs847 million and Rs610 million respectively (see Figure 1). Figure1:Breakdown by business segment of Aceto’s sales and gross margin in Zydus –which halted operations in Japan ayear ago (Generics the financial second quarter ended 31 December 2014 (Source –Aceto) bulletin,3February 2014, page 3) –increased its turnoverthrough page 3) –had been stung by aUS$12.5 million impact from price- joint ventures and alliancesbyafifth to Rs1.22 billion as active protection adjustmentsassociated with increases. “The benefit of [this] pharmaceutical ingredient (API) sales stalled at Rs734 million. should be realised later this fiscal year and in future periods,”henoted. The group’spre-tax profit rose by more than half to Rs3.75 Those improvedHuman Health sales marginally overcame billion, aided by lower finance costs, as Zydus increasedits research Pharmaceutical Ingredients and Performance Chemicals dips (see and development investment by 52.7% to Rs1.88 billion. G Figure 1), the former of which Guccione attributed to lower sales of an undisclosed “high-margin” active pharmaceutical ingredient (API). Third-quarter sales Change Proportion While the Aceto head insisted he wasconfident that Aceto’s (Rs millions) (%) of total (%) pipeline of 52 abbreviated newdrug applications (ANDAs) –of India 8,464 +10.5 39 which 24 had been pending US Food and Drug Administration (FDA) approvalfor more than twoyears –would further drive sales, he US 8,959 +41.8 41 acknowledged the industry was“seeing slowness” in FDAapprovals. Europe 847 -28.6 4 Potential launches this year include paricalcitol soft-gel capsules Latin America 610 -11.3 3 bought from Parlast year as part of aUS$8.2 million deal (Generics Emerging Markets 1,013 +22.5 5 bulletin,19September 2014, page 17). G APIs 734 +0.4 3 Animal Health/others136 -16.5 1 Exports 12,298 +22.3 56

MANUFACTURING/ANNUAL RESULTS Joint ventures 1,217 +20.2 6 Biocad plans monoclonal site Zydus Cadila 21,979 +17.4 100 Figure1:Breakdown by business and region of Zydus Cadila’s gross sales in its ussia’sBiocad plans to invest more than RUB3.0 billion (US$48 financial third quarter ended 31 December 2014 (Source –Zydus Cadila) Rmillion) into constructing araw-materials plant for monoclonal antibodies next to its existing operations in Saint Petersburg, Russia. The companyhas started designing the project and expects commercial DIVESTMENTS production to begin by 2018. According to the company’sfounder and chief executive,Dmitriy Kabi divests its compounder Morozov, the facility will help to meet “unforeseen demand” for the firm’smonoclonal antibodies,especially for rituximab, for which resenius Kabi has divested its German intravenous oncology Biocad wonasupply contract worth of RUB5.98 billion in arecent Fcompounding business, CFL, for an undisclosed sum. The purchaser Russian government tender (Generics bulletin,3November 2014, is NewCo Pharma, acompounding companyfounded by pharmacist page 19). He said the newplant would mainly produce oncology Michael Schill. and autoimmune monoclonal antibodies. Despite having sold Oberursel-based CFL, which generated a Meanwhile, last year,Biocad almost trebled its turnoverto turnoverof C77 million (US$88 million) last year through anetwork RUB8.5 billion. With three upcoming oncologylaunches –including of centres spread through Germany, Kabi plans to remain active in bortezomib, bevacizumab and empegfilgrastim (Generics bulletin, the compoundingbusiness. “In Germany,”the firm stated, “the focus 16 January 2015, page 22) –the Russian companyexpects to raise will be on parenteral nutrition products, an area that offers attractive its turnoverby30% to around RUB11.0 billion this year. G growth opportunities.” G

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COMPANY NEWS

ANNUAL RESULTS BUSINESS STRATEGY/SECOND-QUARTERRESULTS Brazil bouncesfor Lannett turns gaze Generics at Sanofi to WesternEurope

recovery in its Brazilian business enabled Sanofi’sGenerics unit annett remains interested in globalising through acquisitions, Ato report sales that increased by 11.1% as reported, and by 16.2% Land is focused on opportunities in Western Europe, according to at constant exchange rates, to C1.81 billion (US$2.06 billion) last year. chief executive officer Arthur Bedrosian. Excluding Brazil, the unit suffered a2.8% constant-currencydecline. Speaking to investors as Lannett reported sales ahead by 70.5% IncludingBrazil, Generics sales in Emerging Markets advanced to US$115 million in its financial second quarter ended 31 December by 38.8% on aconstant-currencybasis to C1.11 billion. That gain 2014, Bedrosian revealed that Lannett had conducted due-diligence more than outweighed sales slides of 4.3% to C533 in Western Europe evaluations of twocompanies, one of which wasan“attractive company” and 31.3% to C123 million in the US, as Generics turnoverinSanofi’s that would be a“good candidate” for atax-favourable inversion move. Rest of the World region climbed by 27.8% to C43 million. But ultimately,Bedrosian insisted, an accretive transaction was The Generics unit’s“very satisfactory recovery in Brazil” came Lannett’spriority as the companysought to close its first transaction. against a2013 performance in which “challengesinBrazil” –resulting Lannett recently enlisted the global expertise and acquisitions from loading trade channels with “significantly and inappropriately experience of Teva’s Americas Technical Operations head, Michael in excess of volumes needed to satisfy sell-out demand” –caused Bogda, appointing him as companypresident in lieu of Bedrosian global Generics turnovertofall by 11.9% to C1.63 billion (Generics (Generics bulletin,16January 2015, page 30). bulletin,14February 2014, page 2). Investors did not quiz Bedrosian on the federal investigation Brazilianturnoverupby22% to C71 million in the fourth surrounding Lannett in relation to the company’spricing practices, quarter of last year contributed to a4.5% constant-currencyGenerics for which it wasrecently served with agrand jury subpoena seeking gain in Emerging Markets to C291 million. But Sanofi’stotal fourth- corporate documents (Generics bulletin,16January 2015, page 4). quarter sales of Generics fell by 0.6% –and by 2.3% as reported – As Figure 1shows, those price increasescaused sales in several to C467 million, reflecting declines of 7.7% to C133 million in of Lannett’stherapeutic categories to soar ahead, including anear Western Europe and of 25.7% to C29 million in the US. The Rest fifteen-fold increase in turnoverfrom the company’sgallstone of the World region added C14 million. treatments, while the US firm’sbiggest sellers –its thyroid-deficiency Overall annual group sales in Brazil that rose by just overa treatments such as levothyroxine –rose by 69.7% to US$44.5 million. third –orby6.9% excluding generics –to C1.38 billion contributed In total, price increases added US$50.9million to Lannett’ssales, to Sanofi’stotal Emerging Markets turnoverup9.3% at constant comfortably outstripping aUS$3.4 million hit from reduced volumes. exchange rates to C11.3 billion. “Newinitiativesare underway to During its financial second quarter,the US firm receivedfinal further expand our footprint in these markets,”stated chairman and approvalfor ageneric version of Oak Pharmaceuticals’ Cosopt interim chief executive officer Serge Weinberg, pledging to “dedicate (dorzolamide/timolol) 2%/0.5% ophthalmic solution (Generics additional resources to leverage our leadership position”. Emerging bulletin,16January 2015, page 20), although Bedrosian conceded Markets made up athird of group turnoverthat rose by 2.5% as that sales were expected to be “modest” as Lannett wasalate entrant to reported, and by 4.9% in constant currencies, to C33.8 billion. G market. The US firm currently has 20 abbreviated newdrug applications (ANDAs) pendingUSapproval, five of which contain paragraph IV patent challenges, including generic Thalomid (thalidomide) that is the subject of litigation versus Celgene. MANUFACTURING With research and development and other operating expenses only slightly higher than in the prior-year quarter,Lannett’s FDA okays Polpharma plants operating profit soared by 162% to US$66.5 million. G rivately-owned Polpharma has told Generics bulletin that its active Ppharmaceutical ingredient (API) manufacturing facilities in January this year passed aUSFood and Drug Administration (FDA) inspection Second-quarter sales Change Proportion with no Form 483 observations. The Polish firm noted that this was (US$ millions) (%) of total (%) the fourth time in 11 years the FDAhad reported no manufacturing Thyroid deficiency44.5 +69.7 39 deficiencies at its API plants, following previous inspections in Cardiovascular 18.3 +8.3 16 2004, 2009 and 2012. The group –which claims to be “among the top-20 generic drug Gallstone 16.7 +1372.7 15 manufacturers in the world, and asignificant European producer of Pain management 7.6 +11.4 7 APIs” –has sevenmanufacturing plants and six research and Migraine 6.9 +195.4 6 development centres in Poland, Russia and Kazakhstan. Glaucoma 5.5 +272.2 5 Polpharma’sChimfarm subsidiary in Kazakhstanhas just opened Antibiotic 3.3 -22.8 3 an injectables unit at its facility in Shymkent as part of the Gout 3.0 +48.8 3 company’s“major investment project” aimed at expanding its production capacities. The unit –which should produce over100 million ampoules Obesity 1.0 +12.9 1 in its first year of production–has an annual capacity of filling 300 Other 7.9 +52.0 7 million injectable ampoules, 2million bags and 2million vials. Lannett 114.8 +70.5 100 Chimfarm –which is investing around US$100 million in the project –has also started modernising its production lines for solid-dose Figure1:Breakdown by therapeutic categoryofLannett’s sales in its financial forms and antibiotic powder filling. G second quarter ended 31 December 2014 (Source –Lannett)

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COMPANY NEWS

ANNUAL RESULTS IN BRIEF PARPHARMACEUTICAL expects to record a turnoverofUS$1.31 Russia and Ukraine billion for 2014. Generic Entocort EC (budesonide) should contribute US$143 million to that total, with rivals to Wellbutrin XL (bupropion) and Rythmol SR (propafenone) adding US$84 million and US$76 million respectively.Sales of generic versions of Kapvay (clonidine), hit Richter’s results Lamictal XR (lamotrigine) and Toprol XL (metoprolol) are each set to top US$40 million, according to preliminary figures. The ouble-digit sales declines in Russia and Ukraine caused Gedeon US generics specialist anticipates 2014 research and development DRichter’sPharmaceutical turnovertodecline by 3.9% to C988 spending of US$116 million, with agross profit of US$474 million million (US$1.13 billion) last year.Including the Hungarian group’s and earnings before interest, tax, depreciation and amortisation loss-making Wholesale and Retail business, which operates mainly (EBITDA) of US$183 million. in Romania, group turnoverfell by 3.4% to C1.15 billion. Pharmaceutical sales in Russia tumbled by 18.6% to C274 PHARMASYNTEZ –which claims to be the Russia’slargest million, although the local-currencyslide wasamore modest 3.7%. manufacturer of tuberculosis drugs –is acquiring aproduction While wholesaler destocking had depleted local turnover, Richter plant located in Tyumen, Russia, from local firm YugraFarm to enjoyed “good sales performances” from oral contraceptives, Diroton produce its domestic infusion solutions, as well as hormone therapies. (lisinopril), Mydocalm (tolperisone), and Panangin (asparaginates). The Russian companyintends to invest RUB1.7 billion (US$27 The firm blamed “more strict receivables control and voluntary million) overthe next twoyears in modernising the facility,which shipment restrictions” amid the local political and economic upheaval its says will comply with international good manufacturing practice for its turnoverinUkraine plummeting by 23.0% to C55.0 million. (GMP) standards and employ250 staff. That fall wasoffset in part by sales in other Commonwealth of CO-OPERATIVE PHARMACY –the UK’sthird-largest pharmacy Annual sales Change Proportion chain with 780 stores – is to be renamed as Well following its (C millions) (%) of total (%) takeoverbyBestway Group in a£620 million (US$955 million) deal last year (Generics bulletin,8August 2014, page 10). Bestway Russia/CIS 407.3 -15.1 36 plans to invest £200 million overthe next five years in expanding European Union* 321.2 +2.5 28 the business, with the goal of lifting the chain’sannual turnover Hungary 103.5 +1.3 10 from £750 million to £1.0 billion by 2019. US 52.1 +9.5 4 China 44.1 +25.6 4 DIVI’S LABORATORIES intends to invest around Rs5.0 billion Latin America 18.8 +66.4 2 (US$81.0million) in setting up athird manufacturing facility in Rest of World 41.4 +5.3 4 India. The Indian bulk-drugs producer has asked the regional Pharmaceutical 988.4 -3.9 86 government of Andhra Pradesh to allot land near Kakinada.Inits Wholesale &Retail 179.5 -0.5 16 financial third quarter ended 31 December 2014, Divi’sincreased its turnoverby15% to Rs7.91 billion, butits pre-tax profit edged Eliminations/Other -22.2 –-2 up by just 2% to Rs2.78 billion. Gedeon Richter 1,145.7 -3.4 100 AMNEAL has appointed GE Capital to act as its agent for a US$250 *excluding Hungary million loan.“The proceeds from this financing will be used to Figure1:Breakdown of Gedeon Richter’s sales in 2014 (Source –Gedeon Richter) fund capital expansion related to manufacturing and adistribution to existing shareholders,”GECapital said. Independent States (CIS) members rising by 9.0% to C78.5 million. Total sales in the region fell by 15.1% to C407 million (see Figure 1). INDOCO REMEDIES reported net sales ahead by 13% to Rs2.13 Pharmaceutical turnoverinthe European Union (EU), excluding billion (US$34.2 million) in the three months ended 31 December Hungary,advanced by 2.5% to C321 million. This came despite a 2014. The Indian firm’sdomestic turnovergrewby7%toRs1.30 13.5% drop to C64.1 million in Poland amid wholesaler destocking billion, while its sales outside of India expanded by 23% to and amild flu season hitting sales of Groprinosin (inosine pranobex). Rs833 million. Lower finance costs helped Indoco to improve its Sales in Romania fell by 11.1% to C28.8 million even after the pre-tax profit by 56% to Rs282 million. fourth-quarter introduction of Coltowan(ezetimibe), while turnover in the Czech Republic was8.8% lower at C24.8 million. FARMAK said it remained market leader in Ukraine,despite the In Western Europe, stronger sales of Esmya (ulipristal acetate) group’sturnoverfalling by atenth to US$122 million last year. helped to push up Pharmaceutical turnoverby2.9% to C66.5 million Citing data from market researcher SMD, the companyclaimed it in Germany, by around two-fifths to C18.0 million in France, and ranked first by value in Ukraine, ahead of Novartis and Menarini. by about 70% to C13.9 million in the UK. Spanish sales doubled to C14.8 million on the “good performance of Esmya”. JB CHEMICALS &PHARMACEUTICALS increased its net sales The Hungarian group said its reported 1.3% sales rise to C104 by atenth to Rs2.57 billion (US$41.3 million) in its financial third million in its domestic market equated to alocal-currencyadvance quarter ended 31 December 2014. That growth wasaided by starting of 5.4% as the firm launched Ossica (ibandronate), Panagin Forte sales and distribution activities in Russia and the Commonwealth (asparaginates) and zoledronic acid towards the end of last year. of Independent States (CIS) last year through awholly-owned In the US, turnoverincreasedby9.5% to C52.1 million “from subsidiary.Indian formulations sales increasedby11% to Rs950 alow base” on higher sales of finished-dose finasteride and the Plan million, while formulations exports grewby9%toRs1.29 billion. BOne Step (levonorgestrel)emergencycontraceptive. But active pharmaceutical ingredient (API) turnoverslipped Lower gross margins and alack of milestone payments cut the slightly to Rs258 million. G group’soperating profit by 18.9% to C127 million. G

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COMPANY NEWS

MANUFACTURING/ANNUAL RESULTS SECOND-QUARTERRESULTS Cambrex is growing Protopic rival peps Iowa bulk-drugs site Perrigo’s turnover

ncreased demand for its active pharmaceutical ingredient (API) ecent launches such an authorised generic of Astellas’ Protopic Icontract-manufacturing services has led Cambrextobegin expansion R(tacrolimus)0.03% and 0.1% ointments and “increased volumes” work at its US production facility in Charles City,Iowa. pushed up Perrigo’sPrescription Pharmaceuticals sales by 12% to Noting that this wasthe second such expansion in less than three US$277 million in the US firm’sfinancial second quarter ended 27 years at its Charles City complex, the US companysaid it expected December 2014. The Prescription business accounted for overaquarter to invest US$45-US$50 million building an additional current good of group turnoverthat advanced by 9% to US$1.07 billion, largely due manufacturing practice (cGMP) production unit and related infrastructure to US$54 million of new-product sales and aUS$79 million increase alongside existing operations. in royalties from Biogen Idec’ssales of Tysabri (natalizumab). Slated for completion early next year,the newplant, which will Double-digit Prescription sales growth helped to offset lower be capable of handling potent APIs, will allowCambrexto“quickly Consumer Healthcareand Nutritionals sales, while turnoverfrom and efficiently further expand cGMP capacity,asfuture growth Perrigo’sActive Pharmaceutical Ingredient (API) segment stalled requires”. It will add 70 cubic metres of reactor capacity as well as at US$30.0 million (see Figure 1). 4,200 sq mofwarehouse space. Expansion work has also begun at the The Protopic authorised generic launch (Generics bulletin,5 US firm’ssites in Karlskoga, Sweden, and Milan, Italy,revealed Steven December 2014, page 27) contributed to the Prescription segment Klosk, Cambrex’ president and chief executive officer. generating US$33 million of sales from newproducts. Those gains Last year,strong demand for its exclusive and controlled-substance comfortably offset aUS$14 million hit from discontinuing products. products pushed Cambrex’ group turnoverahead by 17.7% to US$375 Having also introduced aUSrivaltoMallinckrodt’sPennsaid million. But increased research and development spending and a (diclofenac sodium) 1.5% topical solution in December last year,Perrigo pension-settlement charge lowered the US firm’soperating margin in January introduced an alternative to AbbVie’sAndrogel (testosterone) by 1.6 percentage points to 14.0%. Cambrexisforecasting sales 1.0% gel and arivaltoGalderma’sClobex(clobetasol propionate) 0.05% growth of 16-20% this year. G spray with 180-day generic market exclusivity (Generics bulletin, 6February 2015, page 20). And the firm has just receivedUSFood and Drug Administration (FDA) approvalfor the first generic of Novartis’ Transderm Scop (scopolamine) extended-release transdermal film. MANUFACTURING/ANNUAL RESULTS The Prescription segment improvedits second-quarter gross margin by 1.8 percentage points to 54.0%, but“higher investments Podravka invests in plant in both clinical research and development and in growing the specialty pharmaceuticals salesforce” following adeal for Lumara’swomen’s odravka is building a23,000 sq msolid-dose, semi-solids and health portfolio contributed to its operating margin dipping by just Pliquids facility in Croatia to ease capacity constraints and develop overapoint to 39.6%. Perrigo’sgroup operating margin improvedby value-added generics such as effervescent tablets, sprays, patches and more than eight percentage points to 17.2% following prior-year charges medicated chewing gum. The Croatian firm said its utilisation of linked to acquiring Elan and Tysabri. its current granulation and compression capacity wasat89%, while In its current financial year ending in June 2015, Perrigo expects semi-solids and liquids lines were working on Saturdays. Construction to generate at least US$235 million from sales of newly-launched of the C51.4 million (US$58.5 million) project –including agovernment products. Among the firm’spipeline is an OTCstore-brand version incentive worth up to C20.0 million –isdue to start in March, with of Sanofi’sNasacort Allergy 24HR (triamcinolone) nasal spray that amanufacturing licence targetted by the end of March 2017. it plans to launch through atie-up with Teva in time for the next US Podravka’sPharmaceuticals turnoverfell by 1.3% to CrK840 allergy season. Perrigo is also pushing into gummy vitamins through million (US$124 million) last year,equivalent to a1.9% increase at arecently struck alliance with Ferrara Candy. constant exchange rates. By the end of March, Perrigo expects to close a C3.6 billion In its home market, an estimated CrK57.2million hit from from (US$4.1 billion) deal for Belgium’sOmega Pharma that it agreed in reimbursement cuts imposed by the Croatian Health Insurance Fund November last year (Generics bulletin,14November 2014, page 3). G in May 2013 and February 2014 wiped out 7.0% volume growth as sales fell by 10.4% to CrK396 million despite launches via its Belupo Business Second-quarter sales Change Operating unit including Eminens SR (ropinirole) sustained-release tablets and segment (US$ millions) (%) margin (%) Viner Mint (sildenafil) chewable tablets. Consumer Healthcare530 -1 14.1 Gains in Bosnia &Herzegovina contributed to double-digit growth Prescription Pharma 277 +12 39.6 to CrK225 million in the firm’sSouth-East Europe region. But a16.1% Nutritionals 131 -7 5.5 constant-currencyrise in Eastern Europe became areported 1.6% drop Specialty Sciences 87 +1.070 11.0 to CrK162 million due to the devaluation of the Russian rouble. Growth of more than athird to CrK49.5 million in Central API 30 ±0 24.7 Europe came from dermatology products, entering the Polish market Other 18 -4 6.4 and high single-digit growth in the Czech Republic. Perrigo 1,072 +9 17.2* Pharmaceuticals sales accounted for just under aquarter of the Croatian food and beverages group’sturnoverthat fell by 3.4% to *includes US$25.4 million of unallocated expenses CrK3.50 billion. But aPharma operating profit down by 31.6% to Figure1:Breakdown by business segment of Perrigo’s sales and operating margin CrK80.2 million wasstill more than half of the group total. G in its financial second quarter ended 27 December 2014 (Source –Perrigo)

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COMPANY NEWS

THIRD-QUARTER RESULTS NINE-MONTHRESULTS Lupin grows despite Towa cuts its costs regulatoryhold-ups to improve margins

upin overcame delays in obtainingregulatory approvals to post utting manufacturing costs helped Japan’sTowatoimprove its Lgroup turnoverahead by 5% to Rs31.4 billion (US$506 million) Cprofit margins in the first nine months of its financial year ending in its financial third quarter ended 31 December 2014. Double-digit 31 March 2015, despite price cuts mandated by the country’sNational advances in Europe and India pushed up Formulations sales by 7% Health Insurance (NHI) system. to Rs28.7 billion, more than countering a7%slide to Rs2.76 billion As Towa’s sales for the period rose by 17.3% to ¥53.1 billion in active pharmaceutical ingredient (API) turnoveronsteep declines (US$443 million), the firm’scosts of goods rose by 15.5% to ¥25.8 in the US and Europe. billion, while selling, general and administrative expenses increased Lower raw-material costs and a4%reduction in research and by just 12.9% to ¥18.7 billion. This gave Towa an operating profit development spending helped to boost the debt-free Indian group’s 34.8% higher at ¥8.61 billion, and an operating margin that jumped pre-tax profit by 16% to Rs8.53 billion. by 2.1 percentage points to 16.2%. “The company’scontinued focus on improving operational Improvedprofitability came despite a17.8% increase in research efficiencies has led to sustained margins and profit growth, and development costs to ¥4.66 billion –ofaforecastedtotal of notwithstanding regulatory delays that have resulted in pressures ¥6.5 billion for the full financial year –asaresult of Towa investing on the top line,”remarked managing director Nilesh Gupta. in its development pipeline. Products launched in 2014, including Three abbreviated newdrug application(ANDA) submissions orodispersible valsartan, contributed ¥1.4 billion to sales, while and three approvals during the quarter left approvedjust overhalf those introduced in 2013 –such as orodispersible pitavastatin – –108 –ofthe 203 ANDAs the firm has filed with the US Food and accounted for ¥3.7 billion, or around 7% of sales. In light of the latest figures, Towa has revised its full-yearforecast Third-quarter sales Change Proportion to reflect its improvedprofitability.The firm expects to generate an (Rs millions) (%) of total (%) operating profit of ¥10.0 billion –compared to its previous estimate US 14,043 +4 45 of ¥7.80 billion –onprojected full-year sales that remain unchanged India 7,438 +14 24 at ¥72.0 billion. This will give Towa an operating margin of 13.9%, Japan 3,422 -8 11 rather than the 10.8% originally forecast. G South Africa 1,070 +9 3 Europe 805 +15 2 Rest of World 1,913 +35 6 ANNUAL RESULTS Formulations 28,691+791 APIs 2,758 -7 9 Off-patentdrugs assist Orion Lupin 31,449 +5 100 rion says its generics are now“accounting for agreater proportion Oof total sales” as several of its brands come under generic Figure1:Breakdown by region and business of Lupin’s sales in its financial third competition. The Finnish group reported a0.8% increase in group quarter ended 31 December 2014 (Source –Lupin) turnoverto C1.02 billion (US$1.15 billion) last year. Drug Administration (FDA). The Indian companybelievesithas to “Competition in Finland, the most important generics market for date made 30 first-to-file opportunities –targeting US$13.7 billion Orion, remains intense in 2015. However, product launches continue in annual brand sales –ofwhich half are exclusive opportunities. to support Orion’sposition as market leader,” the firm stated. Pointing out that it had received“no [Form] 483 observations Last year,sales by Orion’sSpecialty Products off-patent,generics, in the past five FDAaudits”, Lupin said it wasmarket leader for 30 OTCand biosimilars division increasedby11% to C427 million. That of the 74 US generics it marketed as of 31 December 2014. Eight US rise wasdriveninpart by sales of generic entacapone more than doubling product launches since April 2014 helped to lift US Formulations to C26 million, as the rest of the division’sportfolio showed 7% growth. sales by 4% to Rs14.0 billion, equivalent to a1%local-currencyrise. In Finland,the division posted a9%sales increase to C256 million, European turnoverclimbed by 15% to Rs805 million as Lupin while in Scandinavia turnoveradvanced by 21% to C50 million. But “sawrobust growth across all businesses”. The Indian group achieved the depreciation of the Russian rouble caused sales in Eastern Europe a14% sales rise to Rs7.44 billion in its domestic market through and Russia to stall at C56 million. growth in chronic conditions. In Japan –where Lupin claims to be the eighth-largest generics Infliximab sales reached C6million player –turnoverfell by 8% to Rs3.42 billion as reported, butincreased Orion said the division had derivedsales of C6million from by 4% in local-currencyterms. The Kyowasolid-dose business marketing the Remsima (infliximab) biosimilar in Finland, Scandinavia registered a9%turnoverrise on “good matured-products growth”, but and the Baltic States through an agreement with South Korea’s the Irom subsidiary’ssales slipped by 1% as the injectables specialist Celltrion. In Norway,Orion is offering discounts of up to 72% undertook “cost-rationalisation initiatives to enhance profitability”. compared to the reference brand, Remicade (see page 29). Adverse currencyshifts halved the 19% local-currencygrowth Weaker sales of akey product reduced by atenth to C57 million produced by Lupin’sPharma Dynamics affiliate in South Africa to a turnoverbyOrion’sFermion active pharmaceutical ingredients(APIs) reported 9% turnovergain to Rs1.07 billion. Formulations sales up by division. Proprietary Products sales fell by 4.4% to C373 million, due more than athird to Rs1.91 billion in the Rest of the World region in part to generic competition to Stalevo (carbidopa/levodopa/ included the first full quarter after Lupin bought Mexican ophthalmics entacapone) in Germany, while Animal Health, Diagnostics and firm Laboratorios Grin (Generics bulletin,4April 2014, page 3). G other operations contributed C158 million. G

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COMPANY NEWS

FIRST-QUARTERRESULTS MANUFACTURING Oxycodone bulks up Siegfried sorts out Mallinckrodt’s sales FDA Hameln letter

uadrupling sales of its bulk and finished-dose oxycodone helped he US Food and Drug Administration (FDA) has rescinded a QMallinckrodt to increase its Specialty Generics turnoverby13.7% Twarning letter that the agencyissued in 2012 against aHameln to US$284 million in the US firm’sfinancial first quarter ended 26 Pharma sterile injectables facility in Germanythat has just been December 2014. Of that total, US$234 million wasgenerated in the acquired by Swiss group Siegfried. US, US$23.7 million in Europe, the Middle East and Africa (EMEA), In abrief close-out letter,the agencysaid corrective actions and US$26.7 million in other markets. undertaken at the factory in Hamelin, Germany, appeared to have The oxycodonegains following “strategic pricing initiatives” addressed the violations listed in the warning letter from December more than made up for the blowofMallinckrodt’srivals to Janssen’s 2012. That letter –which resulted from an inspection conducted in June Concerta (methylphenidate) extended-release tablets –along with 2012 –highlighted issues with stafftraining and systems for monitoring Kudco’sgeneric versions –losing their AB-rating for therapeutic environmental conditions (Generics bulletin,1February 2013, page 6). equivalence to the brand last year (Generics bulletin,5December “Following revocation of the warning letter,the path has been 2014, page 23). The firm’smethylphenidate sales fell by 13.7% to cleared for the Hameln Pharma facility to be immediately and fully US$48.6 million (see Figure 1). integrated into Siegfried’sworldwide compliance system,”stated Mark Trudeau, Mallinckrodt’spresident and chief executive the Swiss group, which bought the German injectables contract officer,said the firm planned to keep methylphenidate on the market manufacturer towards the end of last year (Generics bulletin,5 as aBX-rated product –indicating insufficient data to determine December 2014, page 1). therapeutic equivalence –for the “foreseeable future”. “Clearly,asa BX-rated product, it’sgoing to be at alower revenue rate [in 2015] German authorities cleared facility than it wasin2014,”Trudeau commented,reiterating that Mallinckrodt Pointing out that one of its US customers could nowresume imports believed“very strongly”that the product wassafe and effective. of products made at the Hameln site, Siegfried said German regulatory The companyhad acted quickly to launch aline of hydrocodone authorities had recently renewed Hameln’sgood manufacturing Schedule II combination products following reclassification of the practice (GMP) certificate. controlled substance, he pointed out. At the time the SFr60 million (US$63 million) deal for Hameln Meanwhile, Trudeau said that Mallinckrodt was“aggressively wasannounced, aspokesperson for Siegfried told Generics bulletin pursuing” anumber of acquisitions, based on the firm’sstrong cash the Swiss firm wasconfident that the FDAwould soon lift the warning flowand operational capability. letter following arecent re-inspection. G The bulk of Mallinckrodt’s60.4% group turnoverrise to US$866 million came from Specialty Brands sales rising by more than six times to US$374 million as the US firm added US$338 million through INVESTIGATIONS incorporating the Ofirmev(acetaminophen) and Acthar (corticotropin) injectables that it purchased in March and August last year respectively. This dwarfed aturnoverslide of almost atenth to US$199 Impax investigated for delays million in Mallinckrodt’sMedical Imaging segment, which the US atent settlement agreements reached by Impax for three US brands – firm attributed to restructuringinitiativesand adverse exchange rates. PShire’sAdderall XR (amphetamine salts), Endo’sOpana ER Even with aUS$126 million intangible amortisation charge linked (oxymorphone) and Pfizer’sEffexor XR (venlafaxine) –are being largely to the Acthar deal, Mallinckrodt’soperating profit jumped by investigated by Alaska’sattorney-general to determine whether they 74.3% to US$127 million. Oxycodone pushed up the SpecialtyGenerics violated state lawbyunlawfully delaying generic entry in Alaska. segment’soperating margin by almost apercentage point to 49.4%. G The US firm said it intended to cooperate with the investigation, and would produce documents and information in response to the First-quarter sales Change Operating civil investigative demands it had receivedfor each product. “Tothe (US$ millions) (%) margin (%) knowledge of the company,”commented Impax, “no proceedings Specialty Brands 373.6 +526.8 39.7 have been initiatedatthis time.” G Methylphenidate ER 48.6 -13.7 – Oxycodone 47.0 +305.2 – THIRD-QUARTER RESULTS Hydrocodone 34.0 +13.0 – Other controlled substances 111.9 -6.9 – Alembic advances in India Other generics 42.7 +34.7 – 12% increase in Indian Formulations sales waslargely responsible Specialty Generics 284.2 +13.7 49.4 Afor Alembic Pharmaceuticals increasing its turnoverby6%to Medical Imaging 199.3 -8.8 8.7 Rs5.15 billion (US$82.8 million) in its financial third quarter ended Other 9.2 -24.0 – 31 December 2014. With sales of Rs2.83 billion, Indian Formulations accountedfor Mallinckrodt 866.3 +60.4 14.7* 55% of the group total as International Formulations turnoverfell by *includes US$179 million of unallocated corporate expenses 4% to Rs1.47 billion. Active pharmaceutical ingredient (API) sales rose Figure1:Breakdown of Mallinckrodt’s sales in its financial first quarter ended by 7% to Rs813 million, while export incentivesadded Rs36.5 million. 26 December 2014 (Source –Mallinckrodt) The group’spre-tax profit edged up by 1% to Rs900 million. G

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COMPANY NEWS

THIRD-QUARTER RESULTS IN BRIEF DSM said “solid growth and operational improvements at its Yushu, Glenmark grows its China, intermediates plant” helped to push up turnover by its DSM Sinochem affiliate by 8% to C399 million (US$452 million) last year. sales as profits slide LUPIN said its manufacturing facility at Pithampur near Indore, India, had receivedsix ‘Form 483’ observations following an audit by the US Food and Drug Administration (FDA) in January ouble-digit sales growth in India and Europe, coupled with this year.“Since then, the Indore facility has receivedone DturnoverinLatin America more than doubling, helped Glenmark abbreviated newdrug application(ANDA) approvaland twosite- overcome asales tumble of almost athird in its Rest of the World transfer approvals,”the Indian group noted, adding that its LBC business as the Indian company’sgroup turnoverincreased by 6.2% bioresearch centre in Pune, India, had passed an FDAinspection to Rs17.0 billion (US$273 million) in its financial third quarter without anyobservations. Lupin has just secured US approvalfor ended 31 December 2014. bimatoprost 0.03% ophthalmic solution from the Indore facility. But aramp up in material costs and purchase of stock-in-trade caused Glenmark’spre-tax profit to tumble by 31.4% to Rs1.51billion. NATCO PHARMA reported consolidated turnoverdownby4% In the firm’sRest of the World segment, sales fell by 31.3% to to Rs1.95 billion (US$31.4 million) in its financial third quarter Rs2.07 billion, due in part to currencydepreciation throughout the ended 31 December 2014. An exceptional charge of Rs151 million business. However, Glenn Saldanha, the Indian firm’schairman and for settling alegal case contributed to the Indian firm’spre-tax managing director,revealed that the companyhad been boosted in profit halving to Rs191 million. Russia by arecent approvalfor generic Seretide (fluticasone/salmeterol), and wasalso anticipating afurther “twoorthree large approvals”. JEAN COUTU said sales by its Pro Doc generics operation advanced “Wehaveapositive viewofRussia, it is very profitable and our by 6% to C$50.7 million (US$42.0 million) in its financial third respiratory portfolio is doing very well,”Saldanha told investors, adding quarter ended 29 November 2014. The Pro Doc rise helped to push that the companywould not look to capitalise in the country with price up the Canadian retailing group’sturnoverby3%toC$737 million. increases and would instead adopt a“wait and watch approach”. As Figure 1shows, Glenmark’ssales in the US slid by 2.7% to DISHMAN said athree-day inspection by the US Food and Drug Rs5.07 billion. Saldanha blamed aslowdown in US generic approvals Administration (FDA) –initially planned to last five days –confirmed –evidenced by Glenmark receiving just one US Food and Drug that its site in Veenendaal, the Netherlands, complied with current Administration (FDA) approvalduring the quarter,for rivals to good manufacturing practice (cGMP) standards.The plant AstraZeneca’sPrilosec (omeprazole) 10mg, 20mg and 40mg delayed- specialises in making vitamin Danalogues. Three-quarters of the release capsules –and channel consolidation for that turnoverfall. Indian group’sturnoverthat movedahead ahead by 23% to Rs3.86 But, Saldanha insisted, the company’sfortunes in the US would billion (US$62.0 million) in the three months ended 31 December turn as product approvals accelerated, beginning in Glenmark’scurrent 2014 came from contract researchand manufacturing services, with the other quarter derivedfrom other activities such as sales Region Third-quarter sales Change Proportion of bulk drugs and intermediates. (Rs millions) (%) of total (%) STRIDES ARCOLAB reported sales that stalled at Rs3.26 US 5,072 -2.7 30 billion (US$52.5million) in its financial third quarter ended 31 India 4,331 +13.6 25 December 2014, during which it filed four products with the US Latin America 2,344 +105.8 14 Food and Drug Administration (FDA) and receivedapprovalfor Rest of world 2,071 -31.3 12 calcitriol soft-gel capsules. The Indian firm’sInstitutionalbusiness Europe 1,730 +27.3 10 accounted for Rs1.28 billion of that total, emerging markets APIs 1,465 -1.0 9 Rs1.01 billion and regulated markets Rs966 million. Glenmark 17,013 +6.2 100 VERTEX has completed construction of amanufacturing facility Figure1:Breakdown by business segment and region of Glenmark Pharmaceuticals’ in Saint Petersburg, Russia, following aRUB1.8 billion (US$27.1 sales in its financial third quarter ended 31 December 2014 (Source –Glenmark) million) investment. Intended to comply with international good manufacturing practice (GMP) standards, the plant will have an financial quarter.The firm also had “a couple of sure launches”, annual capacity of around 70 million packs, covering tablets, capsules, including generic desmopressin,according to Glenmark’sUShead, ointments, creams, and sprays. The firm expects to start production, Robert Matsuk. including for contract-manufacturing customers, in the third quarter The Indian firm’sdomestic sales rose by 13.6% to Rs4.33 billion, of this year. as Glenmark improvedits market share for cardiovascular and respiratory disease treatments, anti-infectivesand diabetes drugs. AJANTAPHARMA is qualifying an oral solid-dose facility in However, these gains were partially offset by losing share for Dahej, India, and expects to produce regulatory-filing batches within gynaecology and dermatology drugs. the next fewmonths. In its financial third quarter ended 31 December Elsewhere, Latin American sales continued to soar,more than 2014, the Indian formulations specialist increasedits turnoverby doubling to Rs2.34 billion, thanks to surges in Mexico and Venezuela. 21% to Rs3.63 billion (US$58.4 million).Ajanta’sdomestic sales “We’ve launched arespiratory product in Brazil, butstill continue to rose by 35% to Rs1.32billion, while its turnoverinemerging markets struggle for product approvals in the country,” Glenmark revealed. grewby15% to Rs2.23 million, comprising Rs1.10 billion from Meanwhile, despite sales growing by more than aquarter to Africa, Rs1.09 billion from Asia and Rs40 million from Latin Rs1.73 billion in Europe, Glenmark said it had struggled in Romania America. In the US, the firm has 23 abbreviated newdrug applications due to the “challenging business environment”. However, this was (ANDAs) pendingapproval. G comfortably offset by strong growth in the UK, Germanyand Poland. G

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MARKET NEWS

INTELLECTUAL PROPERTY REGULATORY AFFAIRS Australiacan allow FDA reopens debate compulsorylicensing on labelchange rule

enerics manufacturers can nowapply to Australia’sFederal Court urther comments on aproposed rule to change requirementsfor Gto obtain compulsory licences that will allowthem to produce Fgeneric labelling are being solicitedbythe US Food and Drug patented drugs for export to developing countries facing health crises. Administration (FDA) both in writing and at apublic meeting. The country’sIntellectual Property Laws Amendment Act 2015 passed On 27 March, the agencyplans to hold ameeting at its White by the country’sSenate on 9February permits the court to determine Oak campus in Maryland to “listen to comments on the proposed appropriate remuneration for the patent holder. rule” –which would require generics firms to update safety information Aspecific section of the amendments dealing with compulsory using the same ‘changes being effected’ (CBE) process as originators licences for patented pharmaceuticals sets out the conditions that must –aswell as alternativestothe proposal that wasfirst made in late be met. The court may order acompulsory licence “if the proposed 2013 (Generics bulletin, 15November 2013, page 1). Attendees must use of the pharmaceutical product is to address apublic health issue register by 20 March, while comments can be made until 27 April. in the eligible importing country”, either in anational emergencyor “Stakeholders may present or comment on the proposed rule “by the public non-commercial use of the product”. or anyalternative proposals intended to improve communication of Noting that such an order may be amended or revokedbythe court, important newly-acquired drug safety information to healthcare the amendments also state that the patentee “must be paid an agreed professionals and the public,”the FDAsaid. The meeting comes in amount of remuneration, or an amount of remuneration determined responsetorequests from the US Generic Pharmaceutical Association by the court”. (GPhA) and brand industry association PhRMA. This “adequate remuneration” decided by the court would take The GPhA has repeatedly voiced its opposition to the proposed into account “the economic value to the eligible importing country of rule, citing concerns that it could lead to multiple labels, causing the use of the patented pharmaceutical invention”. confusion. The association last year threatened legalaction if the FDA If the compulsory licensing order is granted on the basis of a released an unchanged final rule as originallyscheduled in December “public non-commercial use of the product”, the applicant must first (Generics bulletin,3October 2014, page 9). The FDAsubsequently give the patentee anotice seeking an authorisation to exploit the deferredits decision, having received“agreat deal of public input patented invention for non-commercial use. Furthermore, the applicant from various stakeholders during the comment period” (Generics must have within 30 days of this notice tried without success to obtain bulletin,5December 2014, page 15). G such an authorisation “on reasonable terms and conditions”. Applicants and importing countries must also take“reasonable measures” to prevent pharmaceuticals that are exported from Australia REGULATORY AFFAIRS under such alicence from being used “for apurpose other than the purpose of addressing the public health problem”. EU clarifies SPC importlaw Separately, the amendments include abroader section on compulsory licensing in general that allows the Federal Court to grant irms that imported medicines into aEuropean Union (EU) member alicence in Australia “if the reasonable requirements of the public Fstate in which the product enjoyed supplementary protection are not being met with respect to apatented invention”. certificate (SPC) protection from acountry that only became an EU Despite pharmaceuticals being governed by the separate specific member state in 2004 –and in which similar SPC protection wasnot compulsory licensing measures, the general section notes, this “does available –can rely on the EU’s‘specific mechanism’ to justify the not prevent acompulsory licence from being ordered under this part import, provided that the SPC holder did not oppose it during the in relation to such an invention”. G mechanism’sone-month waiting period, the Court of Justice of the EU (CJEU) has ruled (Generics bulletin,3November 2014, page 14). The case involved Sigma and Pharma XL importing Merck, Sharp REGULATORY AFFAIRS and Dohme’sSingulair (montelukast) from Poland and repackaging it for the UK market in 2010. While an SPC in the UK –which Quebec lifts substitution bar expired on 24 February 2014 –existed based on European patent EP0,480,717, similar protection wasnot available in Poland. anadian province Quebec expects to save around C$40 million Under the ‘specific mechanism’, patent or SPC holders can give C(US$32 million) annually by removing doctors’ ability to mark notification of their intent to oppose parties from importing aproduct prescriptions as non-substitutable, according to provincial health from the Czech Republic, Estonia, Latvia, Lithuania, Hungary,Poland, minister Gaétan Barrette. From 24 April, pharmacists will be able Slovenia or Slovakia into astate where the product is protected. G to substitute ageneric even when the prescription is marked “do not substitute”, Barrette announced, although for valid prescriptions IN BRIEF issued before this date the direction not to substitute would be honoured by pharmacists until 1June. BIO –the US Biotechnology Industry Organization –has claimed that Exceptions to the rule included ‘class seven’ medicines–agroup a proposed patent-reform bill would “undermine the ability of of drugs for which treatment needed to be monitored very closely or legitimate patent owners to commercialise their inventions and enforce which required very precise dosing –such as immunosuppressants, their patent rights against infringers”. US Representative Bob Goodlatte Barretteexplained. Substitution will also still be able to be blocked in insisted that the Innovation Act would help “curb abusive patent cases such as patient allergies to inactive ingredients –such as sugars litigation” based on “weak or poorly-granted patents”. G or colourants –that were present in generics butnot in the brand. G

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MARKET NEWS

MARKET RESEARCH IN BRIEF CGPA –the Canadian Generic Pharmaceutical Association –has France must address welcomed savings that will be generated through a healthcare ‘action plan’ set out by the government of Ontario, Canada. However, the association insisted that higher usage of generics wasessential to unlock greater savings in the Canadian province. “If Ontario’s declining sales trend utilisation of generic drugs increasedtothe same levels as in the US,”the association said, stating that generics were dispensed “rapid reaction” is needed to address declining turnoverand to fill 86% of US prescriptions, “it would save the province’s A“stagnant” volumes in France’sgenerics market, according to healthcaresystem more than C$2.6 billion (US$2.1 billion) in local industry association Gemme. Generics sales fell by 4% to the first year alone.” C3.30 billion (US$3.74 million) in 2014, Gemme said, citing data from local market researcher GERS, while volumes improvedby ROMANIA’s mandatory pharmaceutical clawback rising to more just 2% to 800 million units. than 25% in the last quarter of 2014 is “unsustainable” and will GERS’ figures indicated that generics enjoyed an 18% value be “catastrophic for both patients and generic manufacturers”, share of France’sreimbursable pharmaceutical market, and ashare according to local generics industry association APMGR. Noting of almost athird by volume. that the 25.23% clawback was“the highest levelcalculated to date”, Moreover, Gemme pointed out, if aconstant ‘perimeter’ of APMGR’spresident, Dragos Damian, said the rise –from 20.92% products wasapplied –excluding from the comparison newlaunches in the third quarter of 2014 –did “not correlate in anyway to internal in 2014 –value sales would have fallen by 8% to C3.16 billion last companydata on growth in drug consumption”. The clawback had year, while volumes would have declined by 2% to 769 million already forced generics firms to cut 300 jobs and reduce production units. “Market progress is only being supported by newlaunches,” by atenth in 2014, APMGR noted, appealing to Romania’s the association observed. government to intervene in the clawback calculation. Insisting that the “worrying” decline demonstrated the “absolute necessity” to overhaul France’sprescribing structure, Gemme also SPAIN must introduce a national policy framework to encourage noted that the fall in value wasdue to “massive price cuts applied the uptakeofbiosimilars, local generics industry association Aeseg in 2014”, which had wiped around C220 million offgenerics turnover. has told aconference including representativesfrom the country’s This “blind” policyofprice cuts wasputting at risk continuity of congress and senate. Aeseg’sdirector-general Ángel Luis Rodríguez supply, the association warned. de la Cuerda said specific rules recognising the special characteristics Gemme’spresident, Pascal Brière, noted that using generic of biosimilars were needed, rather than relying on the existing medicines had savedFrance around C2billion in 2014. But “if generic reference-pricing system for small-molecule generics. medicines were used in the same proportions as in Germanyand the UK”, he noted, “these savings could be doubled”. SOUTH AFRICA will allowamaximum increase of 7.50% in the Meanwhile, areport by market researcher GlobalData has country’sSingle Exit Price (SEP), the uniform price for each forecasted that France’soverall pharmaceutical market will achieve product that manufacturersmust offer to all private customers. acompound annual growth rate (CAGR) of just 0.7% from 2014 to Companies have until 13 March to submit revised prices. The 2020, “restricted by an increasing focus on generic drugs”. increase –which follows a5.82% rise last year (Generics bulletin, While France had been a“relatively late entrant to the generics 14 February 2014, page 9) –does not apply to products introduced market”, GlobalData said, the researcher expected generics volumes after 23 December 2014. to “shift closer to levels seen in the rest of Europe”, restricting overall growth for pharmaceuticals. G AUSTRALIA must address “significant market barriers” to the regulation and reimbursement of biosimilars, according to the country’sGeneric Medicines Industry Association (GMiA). Market entry barriers –also including obstacles to prescribing and dispensing REGULATORY AFFAIRS biosimilars –need “urgent attention”, the GMiA said, recommending “the implementation of aclear and predictable market access US looks for biologics savings pathway, with uptakedrivers, for biosimilars”. educing data exclusivity for branded biologics from 12 years to Rsevenand prohibiting additional exclusivity periods for such drugs RUSSIA’s Civic Chamber has urged the country’sMinistry of for “minor changes in product formulations” would save the US around Health to launch an information campaign to advise the public of US$16 billion over10years, according to proposals set out in the domestically-produced generic alternativestobranded medicines. country’s2016 budget. Other measuresaimed at lowering costs for The Civic Chamber claimed that large pharmaceutical firms based the Medicaid insurance programme –including collecting additional outside Russia were providing financial incentivesfor doctors and rebates for generics with prices that growfaster than inflation, and pharmacists to prescribe and dispense originator products at the excluding authorised generics from average manufacturer price same time as “unreasonable” price increases were being applied calculations –would save afurther US$6.3 billion, the document states. to certain brands. Local brand biologics association the Biotechnology Industry Organization (BIO) said reducing data exclusivity would “jeopardise QATAR’s Supreme Council of Health (SCH) has cut the prices of the careful, overwhelmingly bipartisan balance established in the law 457 generics by an average of 28.5% as part of ascheme to unify to reduce costs, expand access, and encourage continued innovation”. import prices for Gulf Cooperation Council countries. Noting that Meanwhile, the US Food and Drug Administration (FDA) said the drugs included cardiovascular, endocrine, musculoskeletal, it had requested an overall budget of US$4.9 billion, which FDA dermatological and gastrointestinal treatments, the SCH said some CommissionerMargaret Hamburgsaid “accurately reflects the medicines had prices cut by as much as four-fifths. Afurther wave challenges FDAfaces in aglobal regulatory environment, which is of price cuts will be implemented in the second half of this year. G becoming increasingly complexand scientifically demanding”. G

16 GENERICS bulletin 27 February2015 Gen 27-02-15 Pgs.15-19_Layout 1 25/02/2015 18:34 Page 4

MARKET NEWS

REGULATORY AFFAIRS MARKET RESEARCH FDA unveils plans to Canadawill require codify rules on stays shortage notification

educing unnecessary litigation and accelerating approvals of anada will require manufacturers to publicly report drug Rabbreviated newdrug applications (ANDAs) and hybrid 505(b)(2) Cshortages “for Canadians to better plan for their health and applications are among the stated goals of aproposed rule the US Food safety”, according to draft regulations set out by the country’s and Drug Administration (FDA) has released for public comment government. “By providing advanced warning of upcomingshortages, until 7May.Having for the past decade implemented the 2003 Canadians will be able to better proactively work with their healthcare Medicare Modernization Act (MMA) directly from the statute, the professionals to find alternativeoptions,”said Health Canada. FDAnow plans to amend its regulations to codify parts of the act Companies failing to comply will face fines and penalties. covering 30-month stays on approvaland other matters not related to The “mandatory reporting system” would see “timely, 180-day generic market exclusivity. comprehensive and reliable information on actual and anticipated Among the proposed measures are: tackling originators including drug shortages” made available on an independent third-party website, overly broad use codes for patents listed in the FDA’sOrange Book; Health Canada said. “While this newwebsite and the regulations treating original and reissued patents as a‘single bundle’ of patent are being developed, manufacturers are expected to voluntarily rights; and clarifying the agency’spractices on patent informationthat post information on all shortages on the industry-run website.” is submitted late. The FDAisalso proposing to accept paragraph IV “Toreflect and encourage industry accountability,apublic certifications to newly-listed patents only from the first working day notification register has been launched on Health Canada’swebsite after the patent is published in the Orange Book. that lists all the manufacturers that fail to voluntarily post their Also included in the proposals are plans to revise the content that shortages,”the agencysaid. Federal health minister Rona Ambrose must be included in notices of paragraph IV certifications. The FDA said this would help to “name and shame” manufacturerswho fail also plans to “clarify and augment the patent certification requirements to provide voluntary notice. for amendmentsand supplements to 505(b)(2) applications and ANDAs Jim Keon, president of the Canadian Generic Pharmaceutical to ensure that changes to the drug product that could be protected by Association (CGPA), said the association’smembers were currently patent are accompaniedbyanew patent certification”. reporting shortagesonthe voluntary website “and will comply with any Another rule involves requiring 505(b)(2) applicants to identify newrequirements”. The CGPAand its members had “taken an active apharmaceutically equivalent product if one is already approved. This leadership role” to lessen the impact of drug shortages, Keon insisted. is “to help ensure that the 505(b)(2) pathway is not used to circumvent As well as working with the Canadian government and other the statutory patent certification obligations that would have applied stakeholders through the multi-stakeholder steering committee on if the product wasnot ineligible for approvalinanANDA”. drug shortages (MSSC), the CGPAnoted that it had also developed The FDAalso intends to “codify current practice” by clarifying aspecific protocol for generics firms to notify and communicate drug that 30-month stays of approvalfor ANDAs or 505(b)(2) applications shortages. “CGPAwill continue to work with other stakeholders to begin on “the later of the date of receipt of notice of paragraph IV address the root causes of drug shortages,”the association stated. certification by anyowner of the listed patent or by the newdrug Voicing support for the government proposals, Canadian brand application (NDA) holder who is an exclusive licensee”. industry association Rx&D said it was“committed to working with The FDAsaid the rule’sannual costs of US$91,400 would be officials to ensure the smooth implementation of amandatory reporting outweighed by benefits of around US$194,300. The agencyhas also system”. Noting that its members were already committed to voluntarily “identified, butisunable to quantify, impacts from proposed changes to reporting shortages publicly –evenif“the same cannot be said for submitted patent information and the implementation of an administrative some companies outside of our association” –Rx&D claimed that consequence for ANDAapplicants who fail to provide notice of a “in general, four out of five drug shortages are associatedwith paragraph IV certification within the timeframe required”. G generic pharmaceutical companies”. G

REGULATORY AFFAIRS REGULATORY AFFAIRS Ukraine urges asingle agency West Africa seeksalignment roposals to set up asingle medicines agencyfor drug control and nsuring “rapid access to safe and effective medicines of good Pregistration in Ukraine have been released for public consultation Equality for the treatment of priority diseases” is the goal of a by the country’sMinistry of Health as part of efforts to “harmonise medicines registration harmonisation project that has been launched the country’smedicines regulations to European standards”. in West Africa. Led by the NewPartnership for Africa’sDevelopment At present, procedures for drug licensing, registration, import, (NEPAD) –an“African Union strategic framework” –through its safety and quality control, as well as inspection are controlled by technical working group on medicines policyand regulatory reforms, separate state authorities including the Ministry of Health and the the initiative also includes other African regulatory bodies as well country’sService for Medicines. This, the Ministry of Health says, as the World Health Organization (WHO) and United Nations (UN). results in unnecessary duplication. “Most countries that have policies in place have not developed Citing countries that have already such agencies in place, including their implementation plans,”the NEPAD pointed out. “This creates the Czech Republic, France, the UK and the US, the Ministry of Health agap in the execution of the existing policies and in turn affects local believesthat implementing a“one-stop-shop” for all types of licences medicines regulation.”Acommon action plan for the entire West and permits will benefit the industry. G Africa region is envisaged. G

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MARKET NEWS

REGULATORY AFFAIRS REGULATORY AFFAIRS Russia couldrequire Input is invited over new round of tests US interchangeability

anufacturers of generics that are registered in Russia before 1 nterestedparties have until 6April to comment on whether the MJuly 2015 may have to rerun trials demonstrating that their Iinformation the US Food and Drug Administration (FDA) intends versions can be considered as interchangeable with equivalent brands, to collect in biosimilar applications and supplements to support according to draft legislation on approvalprocedures for determining interchangeability are necessary and “will have practicalutility”. interchangeability between medicines that have been developed by The agencyalso wants to hear about ways to “enhance the quality, the country’sMinistry of Health. However, herbal and homeopathic utility and clarity” of some information while minimising the burden products, as well as medicines that have been marketed for more than on respondents. Based on its experience to date, the FDAexpects 20 years, are exempt from the requirement. to receive five biosimilarapplications per year, each requiring the The draft –which has been releasedfor public consultation until applicant to spend 860 hours compiling the necessary information. 13 April –issplit into five sections covering general provisions; But each notification of apatent dispute will takejust twohours. interchangeability criteria; procedures for determining interchangeability Meanwhile, five FDAdraft guidances covering the 2012 Generic of first-time registered medicines;medicines registered before 1July; Drug User Fee Amendments (GDUFA) are nowopen for comment and procedures for verifying interchangeability.Ifpassed, it will until early March after the agencyreopened the docket in response complement other bioequivalence legislation that is expected to come to requests for additional time. into force on 1July (Generics bulletin,5December 2014, page 15). Having first been issued by the FDAlast year before afull-day Meanwhile, Nikolai Gerasimenko, deputy chairman of the Russian public hearing on 17 September (Generics bulletin,5September 2014, parliament’shealth committee, has urged the country to reviewimport page 16), the five guidance documents cover: the content and format duties on pharmaceutical substances and certain medicines to help of abbreviated newdrug applications (ANDAs); refusal to receive bolster the domestic pharmaceutical industry as part of Russia’s“Pharma for lack of proper justification of impurity limits; amendmentsand 2020 strategy”. During aparliamentary debate, Gerasimenkoproposed easily correctable deficiencies; prior-approvalsupplements; and temporarily to introduce areduced or zero rate of customs duties on controlled correspondence related to generic-drug development. G imported substances and vital drugs until more favourable conditions for local manufacturing were met. “According to the Pharma 2020 strategy, 90% of pharmaceuticals PRICING&REIMBURSEMENT should be produced locally by 2018”, Gerasimenkonoted. “However, 90% of Russian drugs are made using imported components”. Moreover, plans for setting up production facilities for active substances BGMA urges new approach in Russia had not been laid out yet, he emphasised. eviews of payment and reimbursement mechanisms are needed At the same time, Russia’sdeputy prime minister,Igor Shuvalov, Rin the UK to “delivermaximum value and sustain the market” has proposed setting up apilot project by 2018 to help reduce medicines for generics and biosimilars, according to the British Generic costs by introducing aregulatory framework for parallel imports of Manufacturers Association (BGMA). “Newthinking is needed if medicines into the country. patients are to benefit from the more complexmedicines that generic However, local manufacturers opposed to the scheme have warned manufacturers are increasingly producing,”said BGMA director that the Russian pharmacopeia is “very different” to that of Europe, general Warwick Smith. insisting that further regulatory harmonisation is needed. Moreover, “The traditional generic market in the UK has been enormously theyhaveraised concerns overlabels, packaging and instructions successful, saving the National Health Service (NHS) billions of pounds appearing in aforeign language. G annually,” Smith observed. “But we are also seeing the development of ever more complexmedicines which will revolutionise patient outcomes.”These included biological drugs, Smith said, as well as REGULATORY AFFAIRS “greater incremental innovation” in areas such as delivery systems, Swiss not affected by GVK combinations or patient-care packages. G

one of the medicinesthat have been called into question in the PATENT LITIGATION NEuropean Union (EU) overbioequivalence studies conductedby GVK Biosciences are currently on the Swiss market, according to Lillykeeps up Canada attack local medicines agencySwissmedic. After the European Medicines Agency(EMA) recommended the li Lilly is maintaining its pursuit of damages from the Canadian European Commission to suspend hundredsofmarketing authorisations Egovernment under the North American Free Trade Agreement in the EU based on concerns raised following an inspection of GVK (NAFTA) for “illegal” decisions to invalidate brand patents, despite a (Generics bulletin,6February 2015, page 17), Swissmedic said it had counter-filing from the government backing the decisions. “Nothing confirmed through “comprehensive analysis” that no corresponding in their filing changes our strongly-held belief that Canada’simproper preparations were available in Switzerland. invalidation of our patents under its unique and burdensome ‘promise’ However, Swissmedic observed, “three preparations with export utility is inconsistent with Canada’sNAFTAobligations,”the firm authorisationswere identified”. These authorisations–granted for said. Action wasinitiated in 2013 overdecisions to invalidate patents products intended exclusively for export –would nowbe“reviewed protecting Lilly’sStrattera (atomoxetine) and Zyprexa (olanzapine) in detail”, the regulator stated. G brands (Generics bulletin,6September 2013, page 23). G

27 February2015 GENERICS bulletin 19 Gen 27-02-15 Pgs.20-29_Layout 1 26/02/2015 08:52 Page 2

GPHA ANNUAL MEETING

REGULATORY AFFAIRS REGULATORY AFFAIRS CDER pledges araft OGD sets targets for of ‘radical changes’ ANDA actiondates

ajor changes on quality –moving away from punishing round 1,000 target action dates (TADs) –internal deadlines for Mmanufacturing deficiencies to incentivising industry to adapt a Athe US Food and Drug Administration (FDA) to act on pending culture of quality –are underway at the US Food and Drug abbreviated newdrug applications (ANDAs) –are to be assigned by Administration (FDA), according to the director of the agency’s the end of March this year.“The TADs will be March to September Center for Drug Evaluation and Research (CDER), Janet Woodcock. 2015,”stated Kathleen Uhl, who wasrecently made the permanent Woodcock told delegates to the Annual Meeting of the US Generic director of the FDA’sOffice of Generic Drugs (OGD). Pharmaceutical Association (GPhA) in Miami, US, this month that Delivering the keynote address at the 2015 Annual Meeting of CDER planned to “radically change the waywedothings on regulating the US Generic Pharmaceutical Association (GPhA) in Miami, US, quality”. The goal of initiativessuch as setting up an Office of Uhl described assigning TADs and notifying applicants as “a work Pharmaceutical Quality (OPQ), coordinating inspections more in progress”, as the agencyfinalised plans on howtocommunicate effectively and implementing aharmonised information-technology its plans to industry. platform was, she said, to incentivise industry to makehigh-quality Such TADs, Uhl stressed, applied only to ANDAs, and not to drugs “without extensive regulatory oversight”. prior-approvalsupplements (PASs). Setting such target dates wasnot Bringing together around 1,000 staffinthe OPQ would, Woodcock required by the Generic Drug User Fee Act (GDUFA), she explained, insisted, give CDER “one quality voice” for generics and brands, and adding that the agencywould regard an action as afinal or tentative help the agencymove away from “giving out tickets” to performing approval, or as acomplete response letter. surveillance of quality based on metrics and site inspections. AProgram AlignmentGroup (PAG)was ensuring that CDER was Target dates for pre-year-3 ANDAs improving coordination between reviewers and field inspectors within Uhl said OGD’sgoal wastoassign TADs for all ANDAs submitted the FDA’sOffice of Regulatory Affairs (ORA), Woodcock noted. And before the third year of GDUFAstarted on 1October 2014, after an information-technologyplatform wascollating in asingle repository which the agencyistoreviewand act on 60% of original ANDA information on registered facilities, field reports and inspection history. submissions within 15 months from the submission date. However, “Wewelcome the agency’sfocus on quality,including its work she said, assigning TADs would occur gradually “and with caveats” to enhance inspection protocol,”stated the GPhA’s president and to enable the OGD to “manage inventory and synchronise review chief executive officer,Ralph Neas. Applauding the FDA’s“strides work”, as well as to align reviewand inspection activities. towards process improvements and structural evolution”, Neas expressed While TADs would be based on “workload-management factors”, optimism that the agencywould start to clear abacklog of around the agencywould makeexceptions for large, first-time generics, Uhl 4,000 abbreviated newdrug applications (ANDAs) awaiting approval. G clarified. Forthese drugs, it would aim to assign TADs that corresponded with the patent expiry dates or the earliest possible date IN BRIEF that the FDAcould approve each ANDA. Several months before the TADs for such major first-time generics, the agencywould aim to GPhA –the US Generic Pharmaceutical Association –will soon ask provide “launch planning updates”, Uhl revealed, although this its members to vote on proposed changes to its bylaws that would remained “a work in progress”. enable the association to create abiosimilars division.Acknowledging Acknowledging that TADwas “a made-up term” not found in that several originators, either alone or through alliances with legislation, Uhl said the agencywould implement target dates without generics players, were developing biosimilars, GPhA chairman guidance or amanual of policies and procedures (MAPP). One fixed Craig Wheeler said the division would have aseparate budget and date assigned to each ANDAcould not be exchanged for another board. The division’schair would sit on the full GPhA board, which TAD, she added, not least because such dates were in part dictated by would ensure that the division acted consistentlywithin the the OGD’sworkload. “Wemay miss aTAD if we can get an ANDA association’sbroader goals and vision. to approvalinashort amount of time,”she stated. Acknowledging that the OGD had abacklog of around 3,300 GLOBAL GENERICS SALES are approaching US$200 billion ANDAs pending action –plus another 700 that were with industry annually,according to IMS Health’sDoug Long. In the 12 months awaiting responses –Uhl admitted that the agencyneeded to “move ended September 2014, turnovergrewby10% to just overUS$195 the freight”. At the same time, she pointed out, GDUFAhad imposed billion. Volume growth was5%toalmost 1.02 trillion standard units. fixedtargets to act on applications currently being submitted. “The US and ‘pharmerging’ markets generate most of the generics During the first twoyears of GDUFAended October 2014 –which value sales. The volume growth rate is declining,”Long observed. had seen 2,441 ANDAs filed, more than the agencyhad expected – OGD had movedtoWhite Oak, restructured into a‘super office’ and EXPRESS SCRIPTS is the winner of the GPhA’s inaugural set up an integrated information-technology platform, Uhl explained. Outstanding Partner Recognition.Handing the award to Express Having exceeded Congressional targets by hiring 952 staffunder Scripts’ vice-president of government affairs, Jonah Houts, GPhA GDUFAasof19November 2014, the agencywas “in agood place” president and chief executive officer Ralph Neas described the to meet its commitments, she maintained. Enhanced information- pharmacybenefits manager as “one of the staunchest and most technology systems in place from 1October 2014 were helping the effective allies” the association had. Noting that Express Scripts OGD to coordinate reviews, correspondence, inspections and user fees. handled more than 1million prescriptionseach day,Neas praised the “Your patience, feedback and input during GDUFAimplementation companyfor sponsoring research on biosimilars’ savings potential. G is greatly appreciated,”Uhl told delegates. “Werecognise that this has been difficult, disruptive and painful.” G

20 GENERICS bulletin 27 February2015 Gen 27-02-15 Pgs.20-29_Layout 1 26/02/2015 08:52 Page 3

PRODUCT NEWS

BIOLOGICALDRUGS RESPIRATORY DRUGS Apotex has filgrastim Lupin enlists Celon accepted in the US for American Advair

potexsays it has become the first companytohavetwo biosimilar upin has struck an agreement with Polish firm Celon Pharma to Afilgrastim applications under active reviewbythe US Food and Ljointly develop ageneric version of GlaxoSmithKline’sUS$7 billion Drug Administration (FDA) after the Canadian firm’sGrastofil Advair Diskus (fluticasone/salmeterol) dry-powder inhaler in the US, (filgrastim) biosimilar version of Amgen’sNeupogen brand was Canada, Mexico and “other keymarkets”. accepted for filing by the agency. This follows quickly on from the Under the agreement, Celon will supply the respiratory-disease FDAaccepting Apotex’ filing for biosimilar pegfilgrastim –equivalent treatment to Lupin, which will, in turn, hold marketing rights. No to the US originator’sUS$3 billion Neulasta blockbuster –late last financial terms were disclosed. year (Generics bulletin,16January 2015, page 15). Vinita Gupta, Lupin’schief executive officer,maintained that Grastofil wasdeveloped through a2008 North Americanand Celon’s“experience in the development and manufacturing of European partnership with India’sIntas Pharmaceuticals that wasayear fluticasone/salmeterol dry-powder inhalers in Europe”, coupled with later extended to coverpegfilgrastim (Generics bulletin,13February the Indian firm’s“expertise in inhalation-product development and 2009, page 17). Intas provides the active substance from its plant in commercialisation in the US and other markets”, would accelerate Moraiya, India. the process of bringing generic Advair Diskus to global markets. Around 18 months ago, Apotexsecured apan-European centralised Around ayear ago, the Indian firm hired Maurice Chagnaud, marketing authorisation for Grastofil, and subsequently licensed the formerly head of Teva’s businesses in central and eastern Europe, to biosimilartoStada (Generics bulletin,1November 2013, page 14). further its respiratory franchise in the role of presidentofEuropean Noting that it would, likeits pegfilgrastim candidate, market operations and head of inhalation strategy (Generics bulletin,7March Grastofil in the US through its ApoBiologix business, the Canadian 2014, page 31). Lupin then appointed Theresa Stevens, who gained firm said US sales of Neupogen reached approximately US$1 billion experience in the respiratory arena during anine-year stint with last year,according to SymphonyHealth Solutions. Novartis, as chief corporate development officer (Generics bulletin, Sandoz’ US biosimilar filgrastim candidate –filed with the FDA 2May 2014, page 27). last year (Generics bulletin,8August 2014, page 1) –has received Last year,Mylan said it expected to imminentlycommence backing from the agency’sOncologic Drugs Advisory Committee. G Phase III clinical trials for the first US generic rivaltoAdvair (Generics bulletin,3October 2014, page 19), having acquired the global rights to develop and market ageneric version of the product from Pfizer three years earlier. The US generics player plans to file an abbreviated newdrug application (ANDA) for Advair in the third quarter of this year and introduce the first AB-rated, substitutable generic in 2016. Meanwhile, Lupin has allied with US-based respiratory specialist InspiRX to launch in the US the “all new” InspiraChamber anti-static valved holding chamber (VHC) device. Under the agreement, the Indian companywill gain the exclusive US rights to promote, distribute and market the product, which is said to provide amore effective delivery for asthma medicines, particularly for young children and the elderly. G

REGULATORY AFFAIRS GPhA responds over REMS larity is needed overUSFood and Drug Administration (FDA) Cdraft guidance aimed at helping applicants to obtain samples of brands governed by arisk evaluation and mitigation strategy (REMS), according to the US Generic Pharmaceutical Association (GPhA). Commenting on the recent draft guidance –which describes how firms can obtain aletter from the FDAstating that bioequivalence study protocols contain safety protections comparable to reference listed drug (RLD) protections (Generics bulletin,16January 2015, page 9) – the GPhA said it wasconcerned that brand companies may still “use this guidance as another tool to denyorfurther delay providing RLD samples”. The agencyshould thereforespecify that an FDAapprovalletter is not alegal requirement for abrand companytosupply samples, the GPhA suggested. The association also recommended a30-day clock be applied to FDAreviews of bioequivalence study protocols to help applicants “plan their development activities”. G

27 February2015 GENERICS bulletin 21 Gen 27-02-15 Pgs.20-29_Layout 1 26/02/2015 08:52 Page 4

PRODUCT NEWS

GASTROINTESTINAL DRUGS IN BRIEF PAR has receivedatentative US Food and Drug Administration Mylan must wait for (FDA) nod for ageneric rivaltoTakeda’s Colcrys (colchicine) 0.6mg tablets. The Japanese originator recently lost its bid to have an injunction placed on Hikma to prevent the Jordanian firm from launching its 505(b)(2) hybrid colchicine 0.6mg capsules (Generics esomeprazole in US bulletin,6February 2015, page 20), and subsequently licensed an authorised generic of Colcrys to Prasco. ylan has been awarded atentative approvalfor its US rivals to MAstraZeneca’sNexium (esomeprazole) blockbuster,but will EUROFARMA has struck adeal with Melinta Therapeutics in have to wait until paediatric exclusivities associated with two US Brazil to market delafloxacin,“an investigational fluoroquinolone”. patents expire later this year to receive final clearancefrom the US Under the terms of the agreement, Eurofarma will be responsible Food and Drug Administration (FDA). for obtainingregulatory approvalinBrazil and will be able to According to aletter addressed to Mylan’ssenior manager of market, sell and distribute the drug for treating acute bacterial skin regulatory affairs, Shane Shupe, the US firm’sesomeprazole 20mg and skin-structure infections. Melinta will receive acombined and 40mg delayed-release capsules are “safe and effective for use as upfront cash and equity payment of US$15 million, as well as recommended in the submitted labelling”, warranting atentative nod. milestone and royalty payments. But until paediatricexclusivities attached to US patents 5,690,960 and 5,714,504 expire –on25May 2015 and 3August 2015 ACTAVIS has sent aparagraph IV notification to Orexo and respectively –the FDAwill not grant Mylan final approval. Galena Biopharma for generic rivals to the originators’ Abstral Nexium is also protected by eight other US patents, but, Mylan (fentanyl)0.1mg, 0.2mg, 0.3mg, 0.4mg, 0.6mg and 0.8mg sublingual told the FDA, no litigation wasbrought in responsetothe company’s tablets. Three US patents, all of which expire on 24 September 2019 paragraph IV patent challenges to sevenofthem within the 45-day and belong to newdrug application(NDA) holder Galena, shield windowthat would have triggered a30-month stay on approval. An the analgesic. Orexo said it was“working closely with our partner eighth US patent covers acarved-out indication. Galena to reviewthe details of this notice letter”. Teva recently became the first companytoreceive final approval for generic esomeprazole capsules after the FDAstripped Ranbaxy CIPLA says it has been awarded its first tender in Germanyfor the of its tentative approval(Generics bulletin,14November 2014, Indian firm’s salmeterol/fluticasone 25µg/125µg and 25µg/250µg page 20) and, later,the Indian firm’sright to 180-day generic pressurisedmetered-dose inhalers (pMDIs), which it markets in market exclusivity (Generics bulletin,6February 2015, page 17). the country under the Serroflo brand name. Having launched in Siggi Olafsson, head of Teva’s global generics business, told Germanylast year,Cipla also in 2014 rolled out the treatment for investors that the firm would introduce its rivaltoNexium this month asthma and chronic obstructive pulmonary disease (COPD) in into abrand market valued at almost US$2 billion. The launch, he Sweden, Slovakia, the Czech Republic and Croatia under various explained, had been held up by AstraZeneca having changed the fantasy names (Generics bulletin,19September 2014, page 21). original’slabel just before Teva got its approval, requiring Teva to re-label its version. “There are quite afew applications pending at GEDEON RICHTER has agreed to loan US$5 million to US-based the FDA. Of those, quite afew are on 30-month stays,”henoted. women’shealthcare specialist Evestra to help advance its pipeline India’sCipla says it is supplying Teva with both the esomeprazole of innovative products into clinical stages. active pharmaceutical ingredient and the formulation (see page 2). G BERLIN CHEMIE,asubsidiary of Italianfirm Menarini, intends to invest around C10 million (US$11 million) in constructing a BIOLOGICALDRUGS distribution unit next to its existing pharmaceutical facility in the Kalugaregion of Russia. An 80,000 sq munit –which is to comply Actavis drops rFSH project with international good distribution practice (GDP) standards –will eventually form a“single logistic-production complex” with the ctavis has terminated development of its recombinant follicle- firm’ssolid dose facility that wasopened twoyears ago. Astimulating hormone (rFSH) “as part of portfolio rationalisation”. The firm had licensed the female-infertility treatment from Itero in SANDOZ has launched US rivals to Boehringer Ingelheim’s 2010 (Generics bulletin,6August 2010, page 19). Micardis (telmisartan)20mg, 40mg and 80mg tablets. Six other Through an alliance with Amgen, Actavis is developing four generics players –Actavis, Alembic, Glenmark, Mylan, Torrent and biosimilars. Their ABP980 and ABP215 alternativestoHerceptin Zydus Cadila –hold approvedabbreviated newdrug applications (trastuzumab) and Avastin (bevacizumab) are currently in Phase III (ANDAs) for the antihypertensive brand, which had sales of clinical trials, while an ABP798 rivaltoRituxan (rituximab) is “clinical around US$174 million last year,according to IMS Health data. ready”. The firms are at the process-development stage for biosimilar Erbitux (cetuximab) with their ABP494 project. Actavis is also FARMAK has expanded its range of nasal products by launching independently developing acell line for afifth, undisclosed biosimilar.G phenylephrine 10ml nasal drops in Ukraine. Containing 2.5mg phenylephrine as well as 0.25mg dimetindene,the product –which is indicated for treating allergic rhinitis, nasal congestion and otitis –ismarketed under the brand name Milt. KIDNEYDISEASE DRUGS SANOFI has sued four companies –Actavis, Apotex, Breckenridge Teva launches UK sevelamer and Mylan’sOnco Therapies –inaNew Jerseydistrict court over eva says it is “among the first” to launch arivaltoSanofi’sRenvela paragraph IV challenges to US patents protecting the originator’s T(sevelamer) 800mg tablets in the UK following patent expiry.The Jevtana (cabazitaxel)prostate-cancer drug. G kidney-disease treatment is available in 180-countpacks. G

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PRODUCT NEWS

ONCOLOGY DRUGS BIOLOGICALDRUGS Canadarefuses abar Hospira and Pfenex on Teva’s bortezomib develop ranibizumab

anada’sFederal Court of Appeal has rejected Janssen’sappeal ospira and Pfenexhavestruck adeal to develop abiosimilar rival Cagainst alower court’sruling not to bar Teva from obtaininga Hto Genentech’sLucentis (ranibizumab) that the twofirms will Notice of Compliance (NOC), or marketing authorisation, for “commercialise for worldwide sales”. bortezomib3.5mg vials. “Asking acourt to prohibit an NOC after Under the terms of the deal, Pfenexwill receive an upfront payment it has issued is likeasking someone to close the barn door after the of US$51 million once the collaboration receivesantitrust approval. horses have escaped,”the panel of three judges stated. Over the following five years, the firm will be eligible to receive “a Noting that Teva had obtained an NOC for ageneric rival to combination of development and sales-based milestone payments up Janssen’sVelcade in December last year,the appeals judges rejected to an additional US$291 million”, as well as a“tiered double-digit the originator’sargument that the Comprehensive Economic and Trade royalty on net sales of the product”. Agreement (CETA) between Canada and the European Union (EU) Noting that Lucentis had global sales of around US$4 billion in guaranteed it “equivalent and effective rights of appeal”. CETA, the 2014, Hospira said it would share Phase III equivalence clinical-trial judges pointed out, wasnot yet part of Canadian lawbecause it had costs with Pfenex, while Hospira would be responsible for not been implemented by statute. manufacturing and selling the product worldwide. An executive Anyconflict arising from Teva having recentlyfiled an abbreviated steering committee comprised of equal representation from the two newdrug submission (ANDS) covering anew route of administration firms will govern the collaboration, which includes an option for future for bortezomib would have to be addressed by aseparate legal alliances on other products. action, the judges added. G Pfenex’ ranibizumab candidate, ‘PF582’, is currently undergoing Phase Ib/IIa safety and tolerability trials, with secondary objectives that include comparative pharmacokinetic and pharmacodynamic evaluations to help demonstrate biosimilarity to Lucentis. ONCOLOGY DRUGS The ophthalmic biosimilar would “expand Hospira’sbiosimilars pipeline to include anew therapeutic area”, observed the firm’schief Mylan sued over US Nexavar scientific officer,Sumant Ramachandra.Bertrand Liang, Pfenex’ chief ylan has been sued in aUSdistrict court by Bayer and its partner executive officer,said the deal “further validates the product- MOnyx Pharmaceuticals for submitting an abbreviated newdrug development strength and capability of Pfenexaswecontinue to application (ANDA) containing aparagraph IV patent challenge for advance our pipeline”. G generic versions of the originators’ Nexavar(sorafenib) 200mg tablets. Six US patents are listed against Nexavarinthe US Food and Drug Administration’s(FDA’s) Orange Book, the latest of which BIOLOGICALDRUGS expires on 24 December 2027.

Expects 180-day exclusivity US courtsets filgrastim date As the first companytofile an ANDAcontaining aparagraph IV Californiadistrict court has set 2March as the date on which it certification, Mylan expects to be eligible for 180-day generic market Awill hear Amgen’smotion for apreliminary injunction to prevent exclusivity for the kidney-cancer treatment, which had US sales of Sandoz from marketing arivaltoits Neupogen (filgrastim) original around US$48 million in the 12 months ended 31 December 2014, in the US. Amgen alleges that Sandoz has failed to followstatutory according to IMS data. Mylan is partnering with Natco on sorafenib. G requirements for handlingpatent disputes, butthe biosimilarapplicant insists it can elect not to disclose details of its application and manufacturing practice. Last month, an advisory committee ANTIRETROVIRALDRUGS recommendedthat the US Food and Drug Administration (FDA) approve Sandoz’ Zarxio (filgrastim) biosimilar with all the same Patent Pool adds raltegravir indications as Neupogen. G erck, Sharp and Dohme (MSD) has agreed adeal with the MMedicines Patent Pool that will allowgenerics firms to “develop, WEIGHT-LOSSTREATMENTS/ANALGESICS manufacture and sell low-cost paediatric versions of raltegravir in countries with the highest burden of disease, where 98% of children with HIV in the developing world live”. TWiUStakes two from Teva GregPerry,the Patent Pool’sexecutive director,said the group Wi Pharmaceuticals has announced that its US rivals to Megace ES was“pleased to have MSD on board as anew private-sector partner T(megestrol) 625mg/5ml and Lidoderm (lidocaine) 5% patches will working with us on paediatric programmes”. The World Health be marketed by the Taiwanese company’sUSsubsidiary,rather than Organization (WHO) recommends raltegravir as acomponent of Teva as originally planned, following an agreement with Teva. paediatric third-line treatment. “TWihas assembled asales and distribution team in the US and “Raltegravir adds to our arsenal of paediatric licences in plans to launch several productsinthe US under TWi’slabel this year,” supporting better options for children in low- and middle-income the firm revealed. This meant that TWiwould be able to “enjoyall countries,”Perry said, “and can benefit the most neglected sub- the profits derivedfrom the products”, said TWi’spresident, Calvin segment: infants and toddlers less than three years of age.” G Chen. “This is consistent with the company’sstrategy.” G

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PRODUCT NEWS

BIOLOGICALDRUGS ANTIRETROVIRALS Celltrion and Hospira Lupin winsanappeal gear up for infliximab on US Trizivir patent

elltrion and Hospira prepared to launch their Remsima and district-court victory wonbyLupin overaUSpatent protecting CInflectra biosimilar rivals to Janssen’sRemicade (infliximab) in ATrizivir (abacavir/lamivudine/zidovudine) until March 2016 Europe by unveiling their latest data and research at the 10th annual has been upheld without comment by apanel of three US Court of congress of the European Crohn’sand Colitis Organisation (ECCO). Appeals judges. South Korea’sCelltrion –which launched Remsima in several Lupin had at the end of 2013 convinced aDelaware district court European markets through local partners on 25 February (see page 26) that its generic version of Trizivir did not infringe Viiv Healthcare’s –revealed astudy suggesting that its Remsima monoclonal antibody US patent 6,417,191. The same court found that the ‘191 patent was could reduce the cost of treating Crohn’sdisease in France, Italy and not invalid. Teva had already admitted that its ANDAfor arival to the UK by up to C336 million (US$380 million) overfiveyears. “These Epzicom (abacavir/lamivudine) infringed the patent (Generics cost savings could help improve patient access to life-changing bulletin,10January 2014, page 19). treatments,”the companyargued. Delaware District Judge Richard Andrews ruled that Lupin’suse Presenting the study as aposter in Barcelona, Spain, Celltrion of the abacavir sulfate salt put its generic outside the scope of akey said three pricing scenarios produced savings between 2015 and 2019 tablet formulation claim in the ‘191 patent that covered pure or ‘free across the three countries ranging from C76 million to C336 million. base’ abacavir.“The patentee differentiated between the pure, or free This calculation wasbased on discounts of 10%, 20% and 30% to base, form of abacavir and the salt form in the claims themselves, the originator brand, which wasassumed to maintain the same price undermining the argument that the salt form is intrinsically following the entry of biosimilar competition. encompassed by the free base of pure form,”Andrews stated. “Market-uptakegrowth wasalso varied in each of the scenarios Teva had stipulatedtoinfringement under the Delaware court’s at 20%, 30%, and 40%, respectively.The market share wasassumed to claim construction. The Israeli firm, along with Lupin, failed in its be 25% in the first year in all scenarios,” Celltrion noted, adding that obviousness attack on the ‘191 patent. G it had calculated the number of patients eligible for infliximab treatment based on the prevalence of Crohn’sdisease, total population and annual population growth in France, Italy and the UK. MULTIPLE SCLEROSISDRUGS Furthermore, the South Korean companypresented six posters on clinical experience with biosimilarinfliximabduring the ECCO BioIntegrator sued on Gilenya congress. These covered 332 patients, includingchildren, with inflammatory bowel disease (IBD). “The safety and efficacy of ovartis has filed asuit against Russia’sBioIntegrator in aMoscow biosimilarinfliximabinrheumatoid arthritis and ankylosing spondylitis Narbitration court, following the firm securing aRussian registration have previously been demonstrated in twopivotal clinical trials, Planetas for its Nescler (fingolimod) generic rivaltothe originator’s Gilenya and Planetra,”the companypointed out. 0.5mg capsules in November last year. The Switzerland-based originator demanded that the registration Three infusions reduce disease activity for the multiple-sclerosis drug be deemed invalid as it “has reasonable During asatellite symposium session, Jørgen Jahnsen, Professor of grounds to suspect” that the Russian companyhad infringed six-year Gastroenterology at the University of Oslo in Norway,presented data exclusivity for Gilenya –which wasregistered in Russia on 17 evidence of areduction in disease activity at week 14 in 74 IBD August 2010 –while establishing bioequivalence between the twodrugs. patients following three infusions of biosimilarinfliximab. Meanwhile, BioIntegrator has responded by claiming that it had Celltrion’spresident, StanleyHong, said the data presented at “all legalgrounds”for registering Nescler,the bioequivalence of which the ECCO congress supported the decision made by the European had been proventhough comparative pre-clinical and clinical trials. Medicines Agency(EMA) to approve Remsima and Inflectrafor The Russian companyalso said that its registration wasfiled before treating IBD based on extrapolating data from the Planetas and such legislation on data protection came into force in Russia. Moreover, Planetra rheumatology trials. “Weare conducting prospective it added, fingolimod “has neverbeen patented in Russia”. observational and registry trials as part of pharmacovigilance in the At Novartis’ request, the court has ordered the Russian Ministry European Union (EU) and South Korea to monitor the safety of of Health to present the Nescler dossier at ahearing on 11 March. G biosimilar infliximab,”henoted. Hospira highlighted aposter presented during the same congress by Hungarian clinicians that detailed interim results from anationwide BIOLOGICALDRUGS observational cohort startedafter biosimilar infliximab entered the Hungarian market in May 2014. “For the first 90 patients –57with Oncobiologics meets endpoints Crohn’sdisease and 33 with ulcerative colitis –treated with Inflectra,” Hospira observed, “reductions compared with baseline were seen in ncobiologics says its ONS-3010 potential biosimilarrival to validated measures of disease activity after both twoand six weeks OAbbVie’sHumira (adalimumab) “met the primary endpoints in of treatment.” its first clinical study”. Athree-arm, single-dose pharmacokinetic “Results showacomparable response in patients treatedwith study in healthyvolunteers that wasconducted in Leiden, the Inflectra to that expected with the reference product, Remicade,”Hospira Netherlands, produced endpoints that “met the bioequivalencycriteria stressed, adding that the independent Hungarian study would continue of geometricmean ratios within a90% confidence interval of 80%- to enrol patients whom it would followfor 108 weeks for those with 125%”. An exploratory ex vivo pharmacodynamic study “showed Crohn’sdisease and for 54 weeks for those with ulcerative colitis. G encouraging results”, the US developer said. G

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PRODUCT NEWS

RESPIRATORY DRUGS EPILEPSY DRUGS Actavis has to halt Pregabalin dispute budesonide in the US willpersistinthe UK

ctavis has been forced to halt distribution of its generic rival to UK legalbattle between Actavis and Pfizer overapregabalin AAstraZeneca’sPulmicort Respules (budesonide) inhalation Amethod-of-use patent is set to continue after Justice Richard Arnold suspension in the US. The Court of Appeals has issued atemporary refused Actavis’ motion for summary judgementand for Pfizer’s injunction preventing further distribution of the paediatricrespiratory infringement allegation to be struck out. Arnold also allowed Pfizer drug pending ahearing on the originator’sappeal against aNew Jersey to amend its infringement stance to plead acase of subjective intention, district court’sfinding that AstraZeneca’sUSpatent 7,524,834 was even though the disclosure that the originator waslikely to seek from invalid due to obviousness. Actavis could “amount to afishing expedition”. “The temporary injunction does not address product shipped prior Arnold –who recently refused to grant Pfizer an interim to its issuance,”Actavis pointed out. On 13 February,immediately upon injunction preventing Actavis from offering its Lecaent (pregabalin) the NewJerseycourt’sobviousness ruling, Actavis had announced its branded generic for indications not covered by Pfizer’spain method- launch of the 0.25mg and 0.5mg vials for which it had held final of-use patent (Generics bulletin,6February 2015, page 22) –was approvalfor two-and-a-half years, buthad been unable to market due not convinced that Pfizer had presented “reasonablegrounds”for to an injunction obtained by AstraZeneca. The NewJerseyruling Actavis having subjective intention to infringe. But he could be wrong lifted the previous injunction. in “a developing area of the law”, so facts should be established at trial. In April 2013, the NewJerseycourt had found that generic “The issue is one which is likely to be suitable for consideration defendants Actavis, Apotexand Sandoz did not infringe the ‘834 patent, not merely by the Court of Appeal, butalso by the Supreme Court,” while AstraZeneca’sUSpatent 6,598,603was invalid (Generics bulletin, Arnold commented. 5April 2013, page 12). But afew months later,the US Court of Appeals Actavis has just launched Lecaent in eight strengths with list reversed and remanded the non-infringement finding on the ‘834 prices of £57.96 (US$89.82) for 56 capsules, and £86.94 for 84. patent, which expires on 11 May 2019, including asix-month paediatric Addressing arecent finding by Hague Court of Appeal that Sun extension (Generics bulletin,15November 2013, page 19). Pharma had infringed asecond medical-use patent protecting Novartis Ruling in light of the Court of Appeals’ construction of the term Aclasta (zoledronic acid) brand (Generics bulletin,6February 2015, ‘micronised powder composition’, NewJerseyDistrict Judge Renée page 22), Arnold noted that the Dutch court had held that Sun “had Marie Bumb said prior art rendered the ‘834 patent invalid. “Evidence the requisite knowledge” that supplying its version via atender was clearly and convincingly demonstrates that aperson of skill in the likely to infringe indirectly Novartis’ osteoporosis method-of-use art would have had areasonable expectation of successfully preparing patent. “The court took into account the fact that Sun had not taken the claimed sterile budesonide compositions using four of the five steps which it could have taken,”headded. conventional sterilisation techniques,”she decided, ordering atrial to Arnold agreed with Actavis that Pfizer had ignored the steps the be held to determine damages. AstraZeneca immediately appealed. generics firm had, and would, taketoavoid its Bulgarian-made Lecaent Actavis and Sandoz currently hold US approvals for generic capsules from being prescribed for the patented pain indication. In versions of the paediatric asthma remedy,asdoes Teva,which has anycase, he said, Pfizer had not alleged intent on the part of Actavis, marketed ageneric since late 2009 under the terms of apatent-litigation merely that third-party infringement was“aforeseeableconsequence” settlement reached between the Israeli firm and AstraZeneca the of having carved out the patented indication from the generic’slabel. previous year (Generics bulletin,5December 2008, page 19). “Actavis contends that these allegations ignore the fact that the non- AstraZeneca reported US Pulmicort sales down by 6% to US$211 pain market is very substantial,”Arnold remarked, adding that Pfizer million last year.Actavis said combined brand and generic sales of accepted that Consilient Health had avoided infringement by carving budesonide suspension totalled around US$1.1 billion in the year out the patented indication from labelling for its Rewisca pregabalin ended June 2014. capsules. Dr Reddy’shas adopted asimilar approach for the Alzain Meanwhile, Actavis has agreed to sell the rights to its US branded branded generic for which it has just secured UK approval. G respiratory business to AstraZeneca for an initial US$600 million plus “lowsingle-digit royalties above acertain revenue threshold”. Actavis insisted the transaction would “have no impact” on its commitment BIOLOGICALDRUGS to developing generic respiratory drugs. Actavis will sell the US and Canadian development and commercial rights to Tudorza Pressair(aclidinium bromide) and Biocad rivals Russian Avastin Daliresp (roflumilast) treatments for chronic obstructive pulmonary iocad expects to launch its Russian rivaltoRoche’sAvastin disease (COPD), along similar rights to its investigational ‘LAS40464’ B(bevacizumab) monoclonal antibody in the second half of 2015, aclidinium/formoterol combination that is approvedinthe European having recentlysubmitted its registration dossier for the drug to the Union (EU) under the Duaklir Genuair name. country’sMinistry of Health. The Russian companyclaims that its The deal includes AstraZeneca paying Actavis –which gained metastatic-cancer treatment –inwhich the firm has invested the respiratory franchise through its US$28 billion deal for Forest US$10 million –isthe first domestic bevacizumab and “does not Laboratories last year (Generics bulletin,7March 2014, page 1) – differ in efficacyand safety compared to the original drug”. an additional US$100 million, linked to Actavis agreeing to amend Pointing out that the Russian government and patients spent a existing collaborations between the twocompanies. total of RUB3.2 billion (US$48 million) on imported branded Actavis said selling the respiratory brands would allowittofocus bevacizumab last year,Biocad’svice-president, Roman Ivanov, on core therapeuticareas, pay offdebt and “invest in further expansion anticipated that with its “significantly cheaper” alternative,the firm through business development”. G would “fully meet patients’ demand” for the drug. G

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PRODUCT NEWS

ANALGESICS/ATTENTIONDEFICIT HYPERACTIVITY DISORDER DRUGS BIOLOGICALDRUGS Mayne pays US$16m Spain’s KernPharma to control two in US introduces infliximab

ayne Pharma has agreed to pay up to US$15.7 million in total ern Pharma says it has become the first Spanish company to Mto takefull control of twoUSgenerics –methamphetamine Kmarket abiosimilar monoclonal antibody by introducing infliximab tablets and triple-dose combination butalbital/acetaminophen/caffeine in mid-February through alocal alliance with South Korea’sCelltrion (BAC)capsules –that the Australianfirm currently markets Healthcare. The Spanish firm is distributing the Remsima anti- through local partnerships. Methamphetamine is distributed by Mylan, inflammatory agent through its newly-created Kern Pharma Biologics while Libertas Pharma markets the BACcombination. biosimilars unit (Generics bulletin,6February 2015, page 18). While both products are currently marketed under aprofit-sharing To ensure full traceability,Remsima features an adhesive label scheme, Mayne will through the deal acquire “full ownership” of both on the vial, as well as a2Ddata matrix on cartons and 100mg vials generics, including manufacture, distribution and sales control. The that details the batch number and expiration date. agreement for methamphetamine is due to close on 5March, while “This launch marks the first in along list of biosimilarproducts the BACdeal is expected to followbyJune. Mayne plans to bring and, therefore, the start of adevelopment project which is one of the methamphetamine distribution in-house from April. most important and strategic branches of the companyinthe coming Pointing out that the market for both products was“attractive with years,”stated Kern’sdirector,Raúl Díaz-Varela. “The goal is to expand limited generic competition”, Mayne said the twoproducts –for which our biosimilars portfolio through Celltrion,”hesaid, adding that the companyisUSmarket leader –were expected to add around this formed part of agrowth and diversification strategy of offering US$3.5 million annually to its earnings before interest, tax, depreciation added-value products. and amortisation (EBITDA). Kern cited data from Spain’sgenerics industry association, Aeseg, Meanwhile, Mayne has agreed to buythe US rights to the Doryx suggesting biosimilars could generate savings of C1.50 billion (US$1.70 (doxycycline) acne treatment brand and “related assets” from Actavis billion) by 2020 (Generics bulletin,21March 2014, page 13). for US$50 million. Celltrion has held acentralised European authorisation for The transaction is set to close by the end of February,but Actavis – Remsima since September 2013, butpaediatric extensions to which had gained the rights to the Doryx brand through its acquisition supplementary protection certificates (SPCs) protecting the reference of Mayne’sDoryx partner,Warner Chilcott, in 2013 –will continue brand, Janssen/MSD’sRemicade, have only just expired in many of to distribute Doryx 75mg, 100mg and 150mg delayed-release tablets Europe’slargest markets. in the US for atransition period lasting until 2May this year. To support the implementation of Doryx, Mayne has announced Network of alliances in Europe plans to establish adedicated US Specialty Brands division that The deal with Kern in Spain forms part of anetwork of national will include 66 sales representatives. G and regional alliances that the South Korean firm has struck for Remsima in Europe. In the Nordic region, Orion already markets the drug (see pages 12 and 29), while Hungary’sEgis holds rights in central and eastern Europe, including the Commonwealth of BIOLOGICALDRUGS Independent States (CIS). Under the terms of adeal reached last year (Generics bulletin,5September 2014, page 22), Mundipharma Mabion eyes Latin rituximab secured rights to market the biosimilar upon SPC expiry in Belgium, olish firm Mabion says it has filed aregistration dossier for its Germany, Italy,Luxembourgand the Netherlands, as well as in the PrivaltoRoche’sMabThera (rituximab) monoclonal antibody in UK, where an SPC extension ran until 24 February. G Argentina. At present, the firm has submitted pre-clinical analysis and studies for its MabionCD20 version of the cancer and rheumatoid- arthritis treatment to the country’sMinistry of Health while it completes MULTIPLE SCLEROSISDRUGS Phase III clinical trials. The companysaid it intended –incollaboration with its Argentine partner LKM –toseek further marketing Eight are sued on US Ampyra authorisations for the drug in other Latin American countries, including Bolivia, Chile, Colombia, Ecuador,Paraguay,Uruguay and Venezuela.G ight generics firms have been sued by Acorda Therapeutics for Efiling paragraph IV patent challenges for generic versions of the originator’sAmpyra (dalfampridine) 10mg extended-release tablets. Acorda’saction has triggered 30-month stays of final US OPHTHALMIC DRUGS Food and Drug Administration (FDA) approvalfor the multiple sclerosis treatment, which had sales of US$366 million last year. Lupingets US bimatoprost nod Five US patents currently protect Ampyra, the latest of which upin has receivedfinal US Food and Drug Administration (FDA) expires on 26 May 2027. Actavis waslast year sued by Acorda for Lapprovalfor its generic version of Allergan’sLumigan (bimatoprost) sending the originator aparagraph IV patent challenge for generic 0.03% ophthalmic solution which the US originator discontinued in versions of Ampyra (Generics bulletin,5September 2014, page 23). 2012. The Indian firm says it intends to introduce the treatment for Meanwhile, Acorda said it would oppose an inter partes review elevated intraocular pressure in patients with open angle glaucoma or (IPR) petition ahedge fund had recently filed with the US Patent and ocular hypertension in the US “shortly”.Generics players Apotexand Trademark Office (USPTO) that challenges one of Ampyra’sfive US Sandoz currently hold tentative US nods for bimatoprost 0.03% patents. The 30-month stay on the infringement lawsuits against the ophthalmic solution. G eight ANDAfilers would not be impacted by the IPR, Acorda noted. G

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PRODUCT NEWS

IN BRIEF BIOLOGICALDRUGS ACTAVIS intends shortly to launch rivals to Reckitt Benckiser’s Subutex (buprenorphine)2mg and 8mg sublingual tablets following Momenta is open to final US Food and Drug Administration (FDA) approval. The treatment for opioid dependence –which sawits first rivalfrom Roxane in 2009 (Generics bulletin,30October 2009, page 17) and has since been joined by generic versions offered by Teva’s Barr options on abatacept and Akorn’sHi-Tech Pharmacal –had branded sales of around US$108 million last year,according to IMS Health data. Twoyears omenta Pharmaceuticals plans to open negotiations with potential ago, Actavis, along with Amneal, launched the sublingual tablet Mpartners for its M834 biosimilarrivaltoBristol Myers-Squibb’s formulation of Reckitt’sbuprenorphine/naloxone combination, Orencia (abatacept), as well as for six undisclosed early-stage biosimilar Suboxone (Generics bulletin,8March 2013, page 16). candidates, after Baxter chose to limit the twofirms’ collaboration to an alternative to Humira (adalimumab). INTAS says its Accofil (filgrastim)biosimilar rivaltoAmgen’s On 14 February,Baxter’sright to select three biological originals Neupogen original has won“twoprestigioustenders”, in the to target for biosimilar development expired without being exercised. Netherlands and the UK. Having recently rolled out Accofil pre-filled Acouple of days later,Baxter told Momenta it wasterminating syringes in twostrengths –30MU/0.5ml and 48MU/0.5ml –through collaboration on abatacept for automimmune and inflammatory diseases itsAccord Healthcare subsidiary (Generics bulletin,6February 2015, such as rheumatoid arthritis under adeal struck three years ago page 23), Intas said at the time that the biosimilarwould initially (Generics bulletin,13January 2012, page 23). be available in the Netherlands, followed by the UK and Poland. Follows Baxter pipeline review ENDO and its partner BioDelivery Sciences International (BDSI) Noting that Baxter had been undertaking restructuring and a have had their newdrug application(NDA) for Belbuca pipeline review, Momenta’spresident and chief executive officer, (buprenorphine)buccal film accepted for filing by the US Food Craig Wheeler,stated: “Our collaboration with Baxter on M923, and Drug Administration (FDA). Having been awarded astandard biosimilarHumira, remains strong, and we look forward to discussions reviewbythe agency, the treatment for severe pain will, Endo in 2015 with potential newpartners for M834, abiosimilar version expects, be reviewed by the agencybyOctober this year. of Orencia, and our additional biosimilarprogrammes.” Wheeler said Momenta –which had cash and marketable STRIDES ARCOLAB has reached an agreement with Gilead Sciences securities totalling US$192 million at the end of last year –would for alicence to the originator’sinvestigational tenofovir alafenamide prefer to strikedeals across aportfolio of biosimilars, rather than reach (TAF), both “as asingle-agent product and in combination with agreements for individual molecules, as it would simplify investments other drugs”, in 112 countries. The agreement also provides for a in areas such as manufacturing. technology transfer from Gilead to enable the production of “low- “There is avery attractive partnering environment out there,” he cost versions” of the antiretroviral, pending US Food and Drug insisted, adding that Pfizer’sprospective takeoverofHospira (see cover) Administration (FDA) approvalofthe product. “raises the stakes for people who want to compete in this game”. “Orencia is acomplexinfusion protein which plays to our strength, MYLAN has receivedUSFood and Drug Administration (FDA) and as of nowthere are fewcompetitorsinthe hunt,”Wheeler said. approvalfor its memantine 5mg and 10mg tablets. The nod makes “Weare conducting the necessary pre-clinical and process-development it the first generic to be listed by the FDAasarivaltothe Namenda work to advance to the clinic in 2016.” brand marketed by Actavis’ Forest Laboratories. Baxter wasaiming to enrol around 300 healthyvolunteers across three sites in the UK for asingle-dose pharmacokinetic study for the RUSSIAN manufacturers will produce 12 pharmaceutical substances M923 adalimumab candidate, Wheeler said. With an interim safety including caspofungin, deferasirox and lenalidomide by 2016 as part analysis for alarger patient study planned, Baxter wastargeting of the country’sPharma 2020 strategy aimed at developing domestic regulatory submissions from 2017. G alternativestoimported brands. In total, the Russian government is providing RUB4.45 billion (US$67.3 million) to support the domestic pharma companies in producing atotal of 22 pharmaceutical ANTICOAGULANTS substances, including 10 that had previously been announced. Aspen adds an anticoagulant OHIO attorneygeneral MikeDeWine has written to Amphastar’s chief executive officer,Jack Zhang, requesting rebates for certain spen has further bolstered its anticoagulants portfolio by agreeing consumers –including police departments–following “dramatic” Ato acquire the rights to Novartis’ Mono-Embolex(certoparin price increases for the US firm’sgeneric naloxone that is used to sodium) injectable for US$142 million. The transaction is subject to treat narcotics overdose. Pointing to an agreement reached with New German competition authorities’ approval. York attorneygeneral Eric Schneiderman that allows for aUS$6.00 As aheparin-based anticoagulant, Aspen pointed out, Mono- rebate for naloxone distributors, DeWine said a“similar agreement” Embolexwas in the same therapeutic category as its Arixtra would makea“tremendous difference” in Ohio. (fondaparinux) and Fraxiparine(nadroparin) injectables that it bought from GlaxoSmithKline for £700 million (US$1.08billion) twoyears CIPLA has wonaUS$189 million share of aGlobal Fund ago (Generics bulletin,28June 2013, page 5). But the brand offered antiretroviral tender.The contract –which runs from the start of the advantage of weight-independent dosing. this year until the end of 2017 –covers supplies that will begin in The South African group noted the drug –which had sales of the near future. The Indian firm said the deal “offers us agreat C68 million (US$77.9million) in 2013 –was currently only marketed opportunity to makeHIV and AIDS treatment accessible to more in Austria, Germanyand Switzerland. However, Aspen insisted that than 140 countries”. G this “presented an opportunity”for the firm to launch the Mono- Embolexbrand in other countries. G

27 February2015 GENERICS bulletin 27 Gen 27-02-15 Pgs.20-29_Layout 1 26/02/2015 08:52 Page 10

PIPELINE WATCH Remicade expiries openoptions in Europe ebruary brought the expiry of six-month paediatric extensions to and data exclusivity durations. In several countries, SPCs linked to Fsupplementary protection certificates (SPCs) for Janssen’s other patents have been granted six-month paediatricextensions, but blockbuster monoclonal antibody Remicade (infliximab) in some of all SPCs have expired in Norway and Switzerland. Europe’slargest markets, including France, Germanyand the UK (see The European Medicines Agency(EMA) recently accepted for Figure 1). Hospira seized immediately on the end of SPCs linked to reviewanapplication for biosimilaretanercept submitted by Samsung European patent EP0,610,201 to launch in several countries its Bioepis (Generics bulletin,6February 2015, page 18). biosimilarinfliximab, Inflectra, that it developed with South Korea’s In terms of data exclusivity (see Figure 2), January brought the Celltrion (see front page). end of 10 years of data and market exclusivity for Roche’sAvastin January and February also brought initial SPC expiries for Amgen’s (bevacizumab). An eight-year data exclusivity period for Novartis’ Enbrel (etanercept). These SPCs were linked to European patents Lucentis (ranibizumab) has also just ended, to be followed by atwo- EP0,464,533 and EP0,471,701. “The Portuguese equivalent of ‘533 year market exclusivity period. Ark notes that both molecules share has been extended by asix-month paediatric extension until August acommon patent family that forms the basis of SPCs running until 2015,”notes Ark Patent Intelligence, which monitors patent, SPC December 2019 for bevacizumab and January 2022 for ranibizumab.G

SPC expiries in January/February Data exclusivity expiries in January/February INN Country INN Country/Region January January Etanercept Ireland, Sweden, Switzerland, UK Amlodipine/Valsartan European Union** Gadobutrol Belgium, Greece, Hungary,Sweden Bevacizumab European Union Levosimendan Austria, Greece, Italy,Luxembourg, Sweden Bortezomib Switzerland Certolizumab pegol Australia Palifermin Austria, Belgium, Denmark, France, Germany, Italy,Luxembourg, Netherlands, Spain, Deslorelin Belgium, France, Germany, Italy,Luxembourg, Sweden, Switzerland, UK Netherlands, Sweden, UK Eculizumab Canada* Sevelamer Austria, Belgium, Denmark, France, Germany, Fampridine US Greece, Ireland, Italy,Luxembourg, Liraglutide US Netherlands, Portugal, Spain, Sweden, UK Metformin/Linagliptin US Trastuzumab Greece PemetrexedSwitzerland February Ranibizumab European Union** Corifollitropin alfaAustria, Belgium, Denmark, France, Germany, Trilostane Canada* Italy,Luxembourg, Netherlands, Spain, February Sweden, UK Clodronic acid Switzerland Desogestrel Portugal Darunavir European Union** Drospirenone/EE Sweden Degarelix Australia Efavirenz Czech Republic Desvenlafaxine Canada* Emtricitabine/Tenofovir European Union Emtricitabine Slovenia Eplerenone Canada* Etanercept Austria, Belgium, Denmark, France, Germany, Lisdexamfetamine Canada* Greece, Italy,Luxembourg, Netherlands, Nitisinone European Union Norway,Spain Rasagiline European Union Fluticasone/Salmeterol Cyprus Romiplostim Canada* Infliximab Austria*, Belgium*,Denmark*, France*, Treprostinil European Union Germany*, Italy*, Luxembourg*, Netherlands*, Velaglucerase alfa US Spain*, Sweden*, UK* Ziconotide European Union Nesiritide Switzerland *This will be followed by ano-marketing period of twoyears during which anotice of compliance will not be granted to ageneric manufacturer.Inaddition, afurther six months Paliperidone Portugal data protection will be added to the 8-year term for studies of desvenlafaxine, eculizumab, Rizatriptan Czech Republic eplerenone, lisdexamfetamine, romiplostim and trilostane in paediatric populations. ** This will be followed by ano-marketing period of twoyears during which ageneric *indicates expiry of paediatric extension to the SPC may not enter the market in the European Union.

Figure 1: Molecules for which supplementaryprotection certificates (SPCs) expire in Figure 2: Molecules for which data exclusivity expires in key markets during key markets during Januaryand February2015 (Source –Ark Patent Intelligence) Januaryand February2015 (Source –Ark Patent Intelligence)

This monthly update of keypatent, SPC and data exclusivity data is extracted from Ark Patent Intelligence Expiry Database. Covering 50 countries and over1,600 INNs, Ark Expiry Database contains watertight data teamed with the ultimate in generic launch analysis. Forfurther information, visit www.arkpatentintelligence.com, or contact: Europe: +44 870 879 0081. North America: +1 704 665 1986. Or e-mail: [email protected].

28 GENERICS bulletin 27 February2015 Gen 27-02-15 Pgs.20-29_Layout 1 26/02/2015 08:52 Page 11

PRODUCT NEWS

HEPATITIS CDRUGS BIOLOGICALDRUGS Doctors challenge Norway enjoys steep EU sofosbuvir patent infliximab price cut

edical charity Doctors of the World has filed an opposition against orway will be able to procure abiosimilar version of infliximab MaEuropean patent protecting Gilead’sSovaldi (sofosbuvir) Nat a72% discount to the existing brand price, according to the hepatitis Ctreatment. The opposition against the EP2,203,462 patent results of atender announced by local procurement organisation LIS. submitted to the European Patent Office (EPO) puts forward several Orion offered Remsima at a72% discount to the current price for grounds of objection, including lack of novelty and inventive step. Remicade, and a69% discount to the lowest price offer made by “This is the first time anymedical organisation has challenged Merck, Sharp and Dohme for the brand version as part of the tender. adrug patent in Europe,”the charity claimed. Citing “the exorbitant LIS said Orion had offered Remsima for treating rheumatoid price” of £33,000 (US$50,735) per course of treatment with Sovaldi arthritis at acost of NOK26,011 (US$3,418) per patient for acourse in the UK –and asimilar price in France –the charity said “generic of treatment, compared to an offer of NOK41,244 for Hospira’sInflectra versions of sofosbuvir can be producedfor as little as £66”. Within the and NOK83,438 for Remicade. European Union (EU), it added, 7.3-8.8 million people were estimated to be infected with hepatitis C, but“several hundred thousand Saves NOK57,000 per patient individuals” were being denied access due to the price. Choosing Remsima overRemicade would thereforesave The ‘462 patent, Doctors of the World alleged, was“clearly aimed NOK57,427 per patient, LIS pointed out (see Figure 1). at reserving an unexplored field of research, instead of protecting Fortreating ankylosing spondylitis, Crohn’ssyndrome, psoriasis, factual results of successful research”. psoriatic arthritis and ulcerativecolitis, the procurement cost of On 20 February,Mylan, Polpharma and Teva each filed oppositions Remsima wasNOK43,352, compared to NOK68,740 for Inflectra and to the ‘462 patent with the EPO. G NOK139,063 for Remicade. This would save NOK95,711 per patient.G

139,063 ONCOLOGY DRUGS  140 Remsima  130 
 120 Remicade 95,711 Eagle strikes deal with Teva  
 savings 110 agle Pharmaceuticals has licensed its EP-3102 rapid-infusion 100 90 83,438 Ealternative to Treanda (bendamustine) to the injectable oncology  80  57,427 brand’sowner,Teva,inadeal worth up to US$120 million. Treanda 70 60 savings had sales of US$767 million last year,Teva reported (see page 4).  43,352 Under the exclusive US licence, Teva will waiveits orphan-drug 50 NOK (thousands) 40 26,011 exclusivities for chronic lymphocytic leukaemia (CLL) and non-Hodgkin 30 lymphoma (NHL) to accelerate EP-3102’smarket entry.Eagle –which 20 has just submitted anew drug application (NDA) and requested priority 10 0 reviewbythe US Food and Drug Administration (FDA) –believes Rheumatoid arthritis Ulcerative colitis its ready-to-dilute, rapid-infusion 50ml formulation may qualify for   seven-year orphan exclusivities for both CLL and NHL. Figure 1: Price offers submitted to LIS for acourse of treatment of Orion’s Teva will pay Eagle an initial US$30 million, and up to US$90 Remsima and MSD’s Remicade infliximabs for treating rheumatoid arthritis and ulcerative colitis (Source –LIS) million in additional milestone payments. Moreover, the US firm will receive unspecified double-digit royalties on future sales by Teva. The Israeli firm will be responsible for promotingand distributing EP-3102 –which wasrecently found by aclinical trial to be OPHTHALMIC DRUGS bioequivalent to the original, butable to be administered more quickly (Generics bulletin,16January 2015, page 8) –while the US company Xalatan rivals aid compliance will be in charge of regulatory approvals, conducting post-approval laucoma patients are more likely to adhere to their medication clinical studies and initial supply to Teva. Gwhen switched from abrand to ageneric drug, according to a Eagle already holds tentative FDAapprovalfor a505(b)(2) hybrid study of 8,427 patients published online by Ophthalmology,the NDAfor a100mg/4ml liquid formulation of Treanda (Generics bulletin, journal of the American Academy of Ophthalmology. 1November 2013, page 17). But Teva’s orphan-drug exclusivity blocks Researchersfrom the University of Michigan examined data taken approvalfor that formulation until September this year.Eagle is also from patients taking aprostaglandin analogue(PGA) –such as one of several defendants in acase overTeva’s US Treanda patent latanoprost, bimatoprost or travoprost –18months before and after 8,791,270 that will be heard by aDelaware district court. Litigation the first US generic PGA wasintroduced, Pfizer’sXalatan overUSpatent 8,445,524 wasdismissed. (latanoprost), four years ago (Generics bulletin,8April 2011, page 22). Meanwhile, Teva has begun shipping US generic rivals to Sanofi’s Adherence in patients who switched from Lumigan (bimatoprost) Lovenox (enoxaparin) and Pfizer’sZyvox (linezolid) injectables. to generic latanoprost improvedonaverage from 47% of the time to The Israeli firm –which has partneredwith Chemi to develop and 61% of the time, while for Travatan (travoprost) that figure increased manufacture enoxaparin –had been waiting to launch its Lovenox from 43% to 54%. Researchers speculatedthat the lower cost of the rivals since receiving final US Food and Drug Administration (FDA) generic wasthe “primaryreason” for improvedcompliance. approvalfor the anticoagulant in sevenstrengths last year (Generics “Individuals’ out-of-pocket costs for glaucoma medications can bulletin,11July 2014, page 24). G exceed US$100 per month,”the study noted. G

27 February2015 GENERICS bulletin 29 Gen 27-02-15 Pgs.30 Events_Layout 1 25/02/2015 18:35 Page 2

EVENTS

MARCH focusing on the improvement of generics from firms includingAmgen and Sanofi. quality and transition from imitation to Contact:DIA. 4-5 March innovation. WCGF will provide Tel: +41 61 225 5151. ■ World Generic Medicines communication and exhibition platforms E-mail: [email protected]. Congress Europe 2015 for chemical drug professionals in China Website: www.diaeurope.org. and abroad and promote international Madrid,Spain cooperation and interaction. 20-21 April Topics covered at this two-day conference Contact: Violet Chang. ■ 3rdAnnual Biosimilars & will include growth strategies, pricing, Tel: +86 21 51869310. Biobetters Congress biosimilars, legalissues and market trends. E-mail: [email protected]. Contact:Health Network Communications. Register onlineatwww.wcgenericsforum.com. London, UK Tel: +44 207 092 1210. This event will address topics including E-mail: customerservices@healthnetwork market access and strategies. Presentations 23-24 March communications.com. will provide information on emerging Website: www.healthnetworkcommunications.com. ■ EU Biosimilar Registration markets as well as global commercialisation and Marketing Requirements strategies. The development of biosimilars 9-10 March London, UK and biobetters will be the focus of day two. ■ EuroPLX 57 An interactive two-day training course Contact:OxfordGlobal. Cascais, Portugal that will look at practical solutions on Tel: +44 1865 248455. howtogain regulatory approvalthrough E-mail: [email protected]. This meeting provides aforum for business- Website: www.oxfordglobal.co.uk. development decision makers to discuss and fast, compliant registration applications. Contact:Informa UK. negotiate agreements, in-licensing, marketing 23-24 April and distribution of patented medicines, Tel: +44 20 7017 7481. E-mail: [email protected]. generics, biosimilars, OTCproducts, ■ 13th EGA International Website: www.pti-global.co.uk. medical devices and food supplements. BiosimilarsConference London, UK Contact:Raucon. 26-27 March Tel: +49 6221 426296 0. This meeting is organised by the EGA E-mail: [email protected]. ■ 11th EGA Legal and will covertopics including industry Website: www.europlx.com. Affairs Forum developments and regulatory issues for Brussels,Belgium the biosimilars industry. 18-20 March This is atwo-day event organised by Contact:Lucia Romagnoli, GPAConferences. ■ 2nd World-China the European Generic medicines Tel: +44 7562 876 873. Association (EGA) which will look at E-mail: [email protected]. BiosimilarsForum Register onlineatwww.egagenerics.comor Wuhan, China issues including litigation, regulatory www.egaevents.org. “World-China Biosimilars Forum (WCBF)” is matters and patent settlements. an international conference which is claimed Contact:Lucia Romagnoli, GPAConferences. to be the only event in China to provide a Tel: +44 7562 876 873. MAY E-mail: [email protected]. platform of technical exchange and strategic Register onlineatwww.egagenerics.comor 27-28 May2015 collaboration for Chinese biosimilar players www.egaevents.org. and regulators and global leading biopharmas. ■ World Biosimilar Contact:Ray Fu. Congress USA Tel: +86 21 51869310. APRIL SanDiego,USA E-mail: [email protected]. Topics looked at during this two-day 13-15 April Register onlineatwww.wcbiosimilarsforum.com. conference will include biosimilar ■ DIA 27th Annual development and regulation, clinical 24-26 March EuroMeeting studies, reimbursement and legalstrategies. ■ World-China Generics Forum Paris,France Contact:Terrapinn. Shanghai,China Issues to be covered at this three-day event Tel: +1 212 379 6322. “World-China Generics Forum (WCGF)” include innovation, clinical trials legislation E-mail: [email protected]. calls for high-quality and high-end generics, and medical devices. There will be speakers Website: www.terrapinn.com.

16-19 September JUNE ■ 18th IGPAAnnual Conference 8, 9-10 June Toronto, Canada ■ 6th European This three-day event is being organised by the Canadian Generic Pharmaceutical Association. It is the annual joint meeting of the Canadian, European, GMP Conference Japanese, Jordanian, South African and US generics industry associations, the CGPA, Heidelberg, Germany EGA, JAPM, JGA, NAPM and GPhA. Pharmaceutical executiveshavethe opportunity to This two-day conference will discuss takepart in conference workshops, and listen to industry experts discuss current issues current and planned changes to the good regarding the international pharmaceutical sector during afull schedule of plenary manufacturing practice (GMP) regulation. sessions. There are also opportunities to network. Contact:Concept Heidelberg. Contact:Julie Ta m, CGPA.Tel:+1416 223 2333. Tel: +496221 84 44 34. E-mail: [email protected] Website: www.igpa2015toronto.com. E-mail: [email protected]. Website: www.gmp-conference.org.

30 GENERICS bulletin 27 February2015 Gen 27-02-15 Pg.31 Pricewatch_Layout 1 25/02/2015 18:40 Page 3

PRICE WATCH ...... UK Escitalopram discounts settle quickly

nJune of last year,wenoted that escitalopram had started life as Escitalopram 5mg Escitalopram 5mg Cipralex5mg Cipralex5mg I Trade Average Drug Tariff Trade Average Parallel Import acommodity generic, and contrastedits dramatic price fall at 30 launch with that of generic citalopram more than adecade earlier (Generics bulletin,20June 2014, page 25). Citalopramhad been 25 introduced in the UK at the start of 2002 with prices offering a10% 20 discount to the Cipramil brand. More than twoyears later,the average trade price of citalopram wasstill more than 50% of the brand price. 15 Price (£) Launch prices for citalopram’ssuccessor –effectively on Monday, 10 2June 2014 –offered a90% discount to Lundbeck’sCipralexbrand. Actavis and Teva both launched immediately upon expiry of the brand’s 5 supplementary protection certificate on 31 May. 0 Looking back overthe six months that escitalopram has been 4 v1 Jul 14 Jan 15 Jun 14 Oct 14 Sep 14 Apr 14 Dec 14 No Aug 14

on the market, it is clear that little has changed in the generic’sprice, May 14 butalot has happened to pharmacists’ dispensing margins. The Figure1:Average trade, Drug Tariff, Brand and Parallel Importprices for 28-tablet average prices at generic launch offered to independent pharmacists packs of escitalopram 5mg since generic launch (Source –WaveData) and dispensing doctors were £0.88 (US$1.36) for the 5mg strength, Escitalopram 20mg Escitalopram 20mg Cipralex20mg Cipralex20mg £1.18 for 10mg and £2.00 for 20mg. This compared with £8.97, £14.91 Drug Tariff 30 Trade Average Trade Average Parallel Import and £25.20 for the equivalent Cipralexstrengths, or between 90% and 92% discount to the brand price. 25 Average trade prices for the twolower strengths were just £0.04 or £0.02 lower last month than theyhad been the previous June. The 20 price of the 20mg strength, however, had dropped to £1.76, which 15 represented a93% discount to the brand equivalent. 10 Meanwhile, the Drug Tariffofpharmacyreimbursement prices Price (£) had changed in October 2014 from category C–the Cipralextrade 5 price –tocategory M, which is based on actual generic trade prices in the marketplace. The result wasasdramatic as the price fall on Day 0 4

1and had the same effect on pharmacists’ dispensing margins. For v1 Jul 14 Jan 15 Jun 14 Oct 14 Sep 14 Apr 14 Dec 14 No Aug 14 four months theyhad enjoyed margins of 90% or more on average, May 14 butthese were suddenly reduced to 44% for the 5mg strength (see Figure2:Average trade, Drug Tariff, Brand and Parallel Importprices for 28-tablet Figure 1) and as lowas33% for 20mg (see Figure 2). packs of escitalopram 20mg since generic launch (Source –WaveData)

Today,pharmacists’ dispensing margins are even tighter,having Escitalopram 5mg Cipralex5mg Parallel Import Cipralex5mg fallen on average to 30% for the highest 20mg strength, 33% for 100 the 10mg strength and 39% for the 5mg presentation. In terms of trade marketing activity,escitalopram got offtoa 80 slowstart. Despite the large discounts on offer,WaveData only recorded 10 price offers in the first full month on the market of 60 escitalopram 5mg from generics manufacturers and wholesalers to independent pharmacists and dispensing doctors (see Figure 3). 40 Similarly,there were only 14 for the 20mg strength (see Figure 4). 20 In subsequent months, however, the activity has been fairly Number of price offers consistent, peaking in July –the second full month after launch – 0

with about 70 price offers, and settling to about 60 more recently. 4 v1 Jul 14 Jan 15

This measure of competitive activity compares with monthly scores Jun 14 Oct 14 Sep 14 Apr 14 Dec 14 No Aug 14 of over100 price offers for the most active ‘fast movers’, such as May 14 Figure3:Price offers for 28-tablet packs of escitalopram 5mg made each month omeprazole,lansoprazole and simvastatin. by generics suppliers to independent pharmacists (Source –WaveData) Although the average prices of escitalopram changed little over the six months, some suppliers questioned whether the Day 1price Escitalopram 20mg Cipralex20mg Parallel Import Cipralex20mg discount had been too steep. There were shallowprice peaks in July 100 when the competition started to get heated, with average prices of £1.08 for the 5mg strength, £1.66 for 10mg and £2.82 for 20mg. G rs 80 offe 60 WANT MORE LIKE THIS? rice Long-term product price trends or other price analyses are available. of p 40 ber Please specify the product and period of time you would liketo 20 investigate and email your request to [email protected]. Num 0

■ Forfurther information see www.bppi.co.uk. 4

Alternatively,contact Charles Joynson at v1 Jul 14 Jan 15 Jun 14 Oct 14 Sep 14 Apr 14 Dec 14 No Aug 14 WaveData Limited, UK. Tel: +44 (0)1702 425125. May 14 E-mail: [email protected]. Figure4:Price offers for 28-tablet packs of escitalopram 20mg made each month by generics suppliers to independent pharmacists (Source –WaveData)

27 February2015 GENERICS bulletin 31 Gen 27-02-15 Pgs.32-33_Layout 1 25/02/2015 18:36 Page 2

BUSINESS STRATEGY Pfizer eyestwo top spots with Hospiraacquisition

Pfizer expects its mid aclimate in which mergers and acquisitions of which are to be delivered in the first year after involving generics firms are not uncommon, closing, which is expected in the second half of this US$17 billion deal APfizer’sdeal to acquire Hospira still stands out year.More than half the savings are to come from to acquireHospira for its sheer scale. And the originator’sgoal with the selling and administrative expenses, with most of the US$17 billion deal is similarly broad: to become a remainder derivedfrom cost of goods. will makethe leading global player in the two“large and growing Last year,Hospira’sSpecialty Injectables categories” of generic injectables and biosimilars. Pharmaceuticals business generated sales that grewby combined companya Acquiring Hospira will let Pfizer “vault into a atenth to US$3.04 billion (see Figure 1). The Devices market leader in both leadership position in the large and growing off-patent business advanced by almost the same proportion sterile injectables marketplace”, aglobal market that to US$840 million, while other pharma contributed generic injectables the brand companysaid would be worth around US$70 US$589 million. Total sales that rose by 11.5% to billion in 2020. The market’scompound annual growth US$4.46 billion generated an operating margin that and in the burgeoning rate (CAGR) of 10% overthe next five years would rose by 10 percentage points to 10.4%. biosimilars arena. be drivenbygrowth in China and the US, as well as Price increases and higher volumes in the US emerging markets, Pfizer stated. helped to push up overall sales in the Americas region David Wallace reports. Meanwhile, the deal would also allowPfizer to by 13.5% to US$3.61 billion, or four-fifths of Hospira’s “advance its goal to be among the world’smost pre- total (see Figure 2). This rise came despite generic eminent biosimilars providers”, taking aleading role competition to the firm’sPrecedex(dexmedetomidine) in amarket that the firm said would growtobeworth brand and “continued price erosion” for docetaxel. US$20 billion in 2020, as global development, regulatory In Hospira’sEurope, the Middle East and Africa and intellectual-property pathways became clearer. (EMEA) region, increased volumes for biosimilars – Combining the twocompanies reinforced the including Nivestim (filgrastim), Inflectra (infliximab) growth strategy of Pfizer’sGlobal Established Pharma and Retacrit (epoetin zeta) –were partly offset by (GEP) unit “to build abroad portfolio of biosimilars continued pricing pressure on antibiotics and cancer in Pfizer’stherapeutic areas of strength through the drugs, resulting in areported sales increase for addition of Hospira’sportfolio that includes several injectables of just 0.8% to US$336 million. However, marketed biosimilars,”the originator stated. overall turnoverinthe region waslifted by the Devices John Young, who heads Pfizer’sGEP business, said and contract-manufacturing units, rising by 4.6% to Pfizer would use its global scale and commercial US$532 million. network to takethe overall portfolio that Hospira Meanwhile, in the Asia-Pacific region higher marketed mainly in the US and Europe into emerging volumes of Precedexand “strong sales of docetaxel” markets in regions such as Asia-Pacific –including in Japan across the region helped to drive a1.1% China –and Latin America. increase in injectables sales to US$266 million. In total, Hospira’s“broadest portfolio in the industry” Asia-Pacific sales rose by 2.6% to US$327 million, or would complement the ability to develop niche generic just over7%of Hospira’soverall turnover. injectables that Pfizer had gained through last year’s In 2014, Pfizer’ssales dropped by 4% to US$49.6 US$360 million takeoverof Innopharma (Generics billion as turnoverfrom the originator’sGEP unit slid bulletin,8August 2014, page 3), Young said. He by 9% to US$25.1 billion. This wasinpart due to also highlighted the considerablecapacity and lower increased global competition on Lipitor (atorvastatin) costs offered by Hospira’ssteriles facility in Vizag, that cut worldwide brand sales by 11% to US$2.06 India, that is awaiting approvalfrom the US Food billion, as well as generic rivals to Celebrex(celecoxib) and Drug Administration (FDA). launching in the US late in 2014, which wiped atenth Pfizer anticipates the transaction delivering off local sales of the brand at US$1.74 billion. US$800 million of annual cost savings by 2018, half Pfizer’schairman and chief executive officer,Ian Read, stressed that Pfizer intended to retain Hospira’s Annual sales Reported Constant-currency Devices business –which generates almost afifth of (US$ millions) change (%) change (%) the firm’stotal sales (see Figure 3) –aspart of GEP. The Hospira transaction would not, Read added, Americas 2,433 +12.5 +13.2 affect the timing of adecision on whether to split Pfizer EMEA 336 +0.8 +0.7 into twobusinesses –with one covering mature products Asia-Pacific 266 +1.1 +5.8 and the other innovative and pipeline drugs (Generics Specialty Injectables 3,035 +10.0 +11.0 bulletin,14November 2014, page 10) –once the Devices 840 +9.1 +10.8 originator had amassed three years of financial data at the end of 2016. Other Pharma 589 +24.4 +24.3 Outlining Pfizer’scurrent sterile injectables Hospira 4,464 +11.5 +12.5 capabilities, Read noted that the firm currently had “a branded portfolio of 73 products across multiple Figure1:Breakdown by product type and region of Hospira’s sales in 2014 (Source –Hospira) therapeutic areas, primarily resulting from historic

32 GENERICS bulletin 27 February2015 Gen 27-02-15 Pgs.32-33_Layout 1 25/02/2015 18:36 Page 3

BUSINESS STRATEGY

acquisitions”. These included anaesthetics, anti- APAC Americas infectives, and oncology drugs. US$327m,+2.6% US$3,605m, +13.5%

“The addition of Hospira will greatly expand our EMEA capabilities through the addition of their top-tier and US$532m, +4.6% broad portfolio of organically-grownsterile injectables, including acute care and oncology injectables,”Read insisted, highlighting Hospira’sfocus on first-to-market opportunities. He also cited an “untapped demand for generic sterile injectablesinthe projectedmedium- term in anumber of markets”. Hospira’scurrent generics pipeline comprises 65 compounds, mostly in the areas of oncology,anti- infectives, anaesthesia and analgesia. In emerging markets, Read observed, Pfizer’s Figure2:Breakdown by region of Hospira’s sales that increased “strong brand equity across these geographies” would by 11.5% to US$4.46 billion in 2014 (Source –Hospira)

allowPfizer to extend the reach of Hospira’sbroad Specialty Injectables portfolio into territories “where Pfizer has an extensive US$3,035m, +10.0% OtherPharma footprint and strong capabilities”. US$589m,+24.4% In particular,suggested GEP president Young, China –where Pfizer says it has “a much larger and growing business” compared to Hospira, with a“very large commercial footprint” –was ripe with “opportunities for future growth” and synergies. Meanwhile, Young observed that “the addition of Hospira comes at akey point in the growth and development of the biosimilars segment”, with the Devices firm offering Pfizer “a robust in-line portfolio of US$840m, +9.1% biosimilars and expanded capabilities to capitalise on growth opportunities”. Figure3:Breakdown by business of Hospira’s sales that increased Hospira has just rolled out its Inflectra in 24 by 11.5% to US$4.46 billion in 2014 (Source –Hospira) European countries (see front page), while it also has exclusive rights to the Celltrion-developed infliximab supplied by Hospira regarding corrective actions. in the US and Canada and certain other territories. Although FDAapprovalfor Vizag wasstill pending, Arecent US filing for Hospira’sRetacrit biosimilar Young acknowledged, “immediate approvalwas not an rivaltotwo epoetin alfa-based brands –Amgen’s essential component of value creation in this transaction”. Epogen and Janssen’sProcrit (Generics bulletin,6 Hospira is also currently in the process of February 2015, page 19) –has nowbeen accepted by responding to the FDAoverdeficiencies at its plant in the US Food and Drug Administration (FDA). The Irungattukottai, India. Following Form 483 observations firm is also developing filgrastim and pegfilgrastim. reported at the facility at the end of 2013, the FDA And Hospira has also agreed to develop a recently performed afollow-up inspection, resulting trastuzumab candidate through afurther collaboration in further observations. The firm has also recently with Celltrion, and ranibizumab through adeal with responded to FDAobservations regarding its plant in Pfenex(see page 23). Mulgrave,Australia (Generics bulletin,17October “The addition of Read described discussions Pfizer would hold with 2014, page 5). Hospira’sbiosimilars partner,Celltrion, and potential Having recently announced that it would be closing Hospiracomes at akey overlap in biosimilar development programmes as its facility in Clayton, North Carolina, in the second point in the growth and “not amajor issue for the transaction”. half of 2015 (Generics bulletin,6February 2015, page Pfizer is currently enrolling for or conducting 5), Hospira said this would result in total charges of development of the Phase III trials for rivals to Herceptin (trastuzumab), around US$45 million, including aUS$21.9 million Rituxan (rituximab) and Remicade (infliximab). It has impairment charge in the Americas segment for 2014. biosimilarssegment” just completed aPhase Itrial for aversion of Avastin However, the firm’sRockyMount facility –also (bevacizumab) and plans later this year to launch a in North Carolina –was upgraded by the FDAto Phase III trial, while aPhase Itrial for Humira ‘voluntary action indicated’status ayear ago, and no (adalimumab) is underway. Form 483 observations were issued after the agency’s Turning to the subject of Hospira’spast quality latest inspection in June. and regulatory issues, Pfizer said it was“comfortable Despite these ongoing regulatory and compliance that the issues raised by the regulators have been issues, Pfizer said it was“comfortable with the addressed or are being properly addressed”. transaction” based on areviewithad completed of At the Vizag injectables plant in India that had Hospira’s“keysites”. been highlighted by Young as “an important component “Wesee the addition of Hospira as providing us for future growth and cost reduction when it comes with adurable growth opportunity,” Read concluded, on line”, Hospira expects to begin commercial “drivenbytheir broad portfolios of sterile injectables production “during the first half of 2015”. In early and biosimilars, technical manufacturing capabilities, 2014, the plant received10‘Form 483’ observations and our ability to growthe portfolio with our commercial from the FDAafter apre-approvalinspection, and capabilities, global scale, scientific expertise and world- the agencyisstill reviewing additional information class development skills.” G

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APPOINTMENTS IN BRIEF INVENT FARMA,the Icelandic companythat in 2005 acquired Bayer’s Brandicourt Spanish generics and bulk-drugs suppliers Lesvi and Inke Laboratories, has appointed Ervin Veszprémi as its chief executive officer.He previously headed Spanish active pharmaceutical leads Sanofi as CEO ingredient (API) specialist Medichem. CUSTOPHARM –the generic injectables drug-services firm based in anofihas named Olivier Brandicourt –currently chairmanof Carlsbad, California–has recruited former Bedford Laboratories SBayer HealthCare’s board –asits chief executive officer. general manager Bill Larkins to serve aschief executive officer after Brandicourt, who joined Bayer in 2013 having previously led it wasbankrolled by US investor Water Street Healthcare Partners. Pfizer’sEmerging Markets and Established Products business units, Larkins led Bedford, the generic injectables business owned by will take the reins at Sanofifrom 2April. Until that time, Sanofi’s Boehringer Ingelheim’sUSBen Venue subsidiary –that wasrecently chairman, Serge Weinberg, will remain in temporary charge. bought by Jordanian firm Hikma in adeal worth up to US$300 million Sanofihas lacked apermanent head since late October,when (Generics bulletin,6June 2014, page 3) –from April 2012 to Chris Viehbacher wasousted after six years at the helm following a December last year.Larkins has previously worked as adirector for fall-out with the board (Generics bulletin,3November 2014, page 1).G Sandoz, Pfizer affiliate Wyeth and Teva subsidiary Barr.

APMGR –Romania’sgenerics industry association –has re-elected Dragos Damian,chief executive officer of Ranbaxy’sTerapia RESIGNATIONS Ranbaxy Romania subsidiary,asits chairman and president for a Frost resignsfrom Teva board further term. Damian has served as the association’spresident since it wasestablished six years ago. Meanwhile, APMGR has also elected ormer Teva chairman Phillip Frost has givenupall responsibility Krka’s Amelia Tataru and Sandoz’ Cezar Zaharia to its board Fwith the companyafter resigning from the Israeli firm’sboard. of directors. Along with Damian, the pair join aboard consisting Having announced his intention to retire as chairman midway of Zentiva’s Simona Cocos and Teva’s Artur Banaszak. through last year after four years in the role (Generics bulletin,11 July 2014, page 31), Frost wasreplaced by Yitzhak Peterburg in MCKESSON has appointed Bansi Nagji as its head of corporate December (Generics bulletin,5December 2014, page 34). Frost had strategy and business development. Nagji replaces Brian Tyler –who joined Teva as vice-chairman in 2006 following the Israeli firm’s has taken up the role of president of McKesson’sNorth American US$7.4 billion acquisition of Ivax. G Pharmaceutical Distribution and Services unit –and will in his new role report directly to the US wholesaler’schairman and chief executive officer, John Hammergren.

INDUSTRY ASSOCIATIONS BOEHRINGER INGELHEIM has named Ivan Blanarik as director of global biosimilardevelopment, based at the group’s GPhA elects Wheeleraschair headquartersinIngelheim. PavolDobrotskiy will take current he US Generic Pharmaceutical Association has re-elected responsibilities from Blanarik when he becomes Boehringer’s TMomenta’spresident and chief executive officer, Craig Wheeler, Russian general director and head of sales and marketing of as its chairman. Joining Wheeler on the GPhA’s board are Teva’s prescription medicines from 1March. Debra Barrett,Perrigo’s Doug Boothe,Ranbaxy’s Chuck Caprariello and Fresenius Kabi’s John Ducker,aswell as Jeff Glazer from PERRIGO has appointed JonMichael Pardo as human resources Heritage, Peter Goldschmidt from Sandoz and Marcy Macdonald manager for the firm’stopical drugs facility in Bronx, NewYork. from Impax. Mylan’s Marcie McClintic Coates,Lupin’s Paul He will be responsible for employee and labour relations as well McGarty,Amneal’s Chirag Patel and Par’s Tony Pera also sit on as “strategic and operational roles” for Perrigo’sNew York and the board, as do Julie Reed from Hospira, Joseph Renner from NewJerseysites. G Zydus and Jeff Watson from Apotex. G

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RESHUFFLES RESIGNATIONS Actavis reveals its FDA Commissioner local generics heads Hamburg stepsdown

ctavis has unveiled the regional presidents and corresponding SFood and Drug Administration (FDA) commissioner Acountry managers that will lead its generics division once it UMargaret Hamburg has announced that she will step down at completes its US$66 billion merger with Allergan(Generics bulletin, the end of March after nearly six years in the role. Following her 5December 2014, page 3). resignation, the FDA’schief scientist, Stephen Ostroff,will pick up Of six regional presidents, five will report to president of Hamburg’sresponsibilities on an acting basis while the agencyseeks International Generics, Lars Ramneborn.The only exception will apermanent replacement. be Jean-Guy Goulet,head of generics in Canada and Latin America, Having being appointed commissioner in May 2009 following who will report directly to incoming president of Generics and Global nomination by US President Barack Obama (Generics bulletin,1 Operations, Robert Stewart,anew role created by Actavis that sees June 2009, page 27), Hamburg, 59, has overseen the implementation Stewart replacing David Buchen as head of Actavis’ generics arm. of reforms including the introduction of the Generic Drug User Fee Only one Allerganemployee, Camilla Hartvig,will oversee an Amendments (GDUFA) in 2012. She has also overseen the progress Actavis generics region within the proposed combination. She will of aUSbiosimilar pathway,which has resulted in Sandoz’ filgrastim balance her role as head of generics for Actavis’ Nordics region with candidate recently receiving arecommendation for approval. those as country manager for Denmark, and oversee ateam consisting Applauding the “significant progress” the FDAhad made under of Christian Jonsson in Finland, Thordis Olafsdottir in Iceland, Hamburg, the US Generic Pharmaceutical Association (GPhA) said she Fredrik Juserius in Norway and Carl-Johan Lye in Sweden. had been a“tireless advocate for patient safety” and a“leader in efforts Actavis’ Central and Eastern Europe generics business –consisting to assure that FDAdecisions are guided by scientific principles”. of the Baltic States, the Czech Republic, Hungary and Slovenia, Poland Meanwhile, Robert Califf,vice-chancellor of clinical and and Slovakia –will be led by Josef Valenta.Respectively,those translational research at Duke University,will join the FDAin“late country managers will be GiedreBieliauskaité, Jana Bánhidalová, February” as Deputy Commissioner for Medicinal Products and Gyorgy Varadi, Izabela Zimmermann and Milan Cernek. Tobacco. Califf, the FDAnoted, would in his newrole provide “executive The company’sSouth Eastern Europe unit, which will fall under leadership” to the FDA’sCenter for Drug Evaluation and Research the remit of Peter Bergquist,will consist of Iliya Pashov in Bulgaria, (CDER) and Center for Biologics Evaluation and Research (CBER). G Makis Economou in Greece, Dan Ivan in Romania and Pavle Marjanovic in Actavis’ Serbia and Adria segment. Meanwhile, Grigoriy Chudakov will lead Actavis’ generics business in Russia, Ukraine and the Commonwealth of Independent States (CIS) and will supervise Alena Vitorskaya in Belarus, Murat Nigmatov in Kazakhstan, Volodymyr Mitin in Ukraine and Moldova and Gairat Gulyamov in the Caucasus and Central Asia segment. Chudakov will also serve ascountry manager for Russia. Finally, Sara Vincent will head Actavis’ UK and Ireland unit, along with serving as country manager in the UK. Tony Hynds will oversee Actavis’ operations in Ireland.

Follows Boyer and Swanton appointments These pending appointments come soon after Actavis announced senior leadership positions within the proposed combination with Allergan, including the appointments of Andy Boyer as head of US generics and Wayne Swanton as head of global generics operations (Generics bulletin,16January 2015, page 31). President and chief executive officer Brent Saunders and executive chairman Paul Bisaro will keep their respective roles following the close of the transaction. Meanwhile, Actavis has announced that four directors will resign from its board as part of the company’splans to simultaneously accommodate twoAllergandirectors as stipulated under the merger agreement, and reduce the size of its board from 14 to 12 members as decided in arecent board meeting. Announcing that Tamar Howson, John King, Jiri Michal and Andrew Turner would be leaving its board either upon the close of the transaction or Actavis’ 2015 annual general meeting, the company insisted the resignationswere “not the result of anydisagreement with Actavis on anymatter relating to its operations, policies or practices”. The selection of the Allergandirectors was“ongoing”, noted Actavis, which has not yet allocated arole for the US originator’s chief executive officer, David Pyott,within the proposed combination. G

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