Gen 13-3-15 Pg.1_Gen 18/11/05 Pg. 1 11/03/2015 17:44 Page 1

13 March 2015

COMPANY NEWS 2 FDA approves Zarxio with Te va agrees to sell US Sellersville plant 2 Sun gets opiates as Ranbaxy deal nears 3 IGI expands during ‘transformative’ year 4 a‘placeholder’ INN name Endo gets US$1.6bn by 5 selling AMS units Mylan makes movesinrespiratoryarena 6 Impax holds back on plans forbiosimilars 7 andoz on 6March secured US Food and Drug Administration (FDA) approvalfor Sits Zarxio biosimilar rivaltoAmgen’sNeupogen (filgrastim). But the agency has Aspen almost ready for 8 assigned the first biosimilar it has approveda“placeholder non-proprietary name” of trading in Japan ‘filgrastim-sndz’ while it works on draft guidance on naming forbiological drugs. Kabi cuts its costs to 10 “The provision of aplaceholder non-proprietary name for this product should not be viewed save C40m ayear as reflective of the agency’sdecision on acomprehensive naming policyfor biosimilarand other biological products,”the FDAinsisted. “While the FDAhas not yet issued draft guidance on how MARKET NEWS 11 current and future biological products marketed in the US should be named, the agencyintends to do so in the near future.” EGA hails ‘landmark’ on 11 Departing from the currently accepted international non-proprietary name (INN) system counterfeit drugs “could disrupt the ability to track and dispense these medicines, risking provider confusion and GPhA praises bill to protect 13 patient safety”, the US Generic Pharmaceutical Association (GPhA) warned. Urging the FDA GDUFAfees to issue draft naming guidance for comment, the US BiotechnologyIndustry Organization US advances drivegrowth 14 (BIO) said it was“unfortunate that the lack of publicly available naming guidance resulted in global market in the FDA’sassignment of a‘placeholder’name for the approvedbiosimilar”. Following the unanimous advice of its Oncology Drugs Advisory Committee (ODAC) PRODUCT NEWS 15 givenearlier this year (Generics bulletin,16January 2015, page 1), the FDAapprovedZarxio for the same indications as Neupogen, includingfor patients undergoing chemotherapyorwith Germanyupholds its 15 severe chronic neutropenia. However, it did not classify the biosimilar as interchangeable. ruling on quetiapine Among the package of analytical, non-clinical and clinical data submitted by Sandoz wasa Infliximab meeting is postponed by FDA 16 head-to-head ‘Pioneer’ study showing similar reductions in the duration of severe neutropenia Ranbaxy fails in case over 17 and the mean time to absolute neutrophil-countrecovery between Zarxio and Neupogen. US exclusivities “Filgrastim has provenclinical value in treating patients at increased risk of neutropenia, First US Tarka rivals claimed 18 butitisunderused in the US for avariety of reasons, including price,”commented Georgetown by Glenmark University oncology specialist Louis Weiner.Answering questions posed by the FDA’sODAC panel, Sandoz’ Mark McCamish said the firm had learnt from launchingOmnitrope (somatropin) Courtorders NHS to protect 19 Pfizer patent at almost a50% discount, thereby cutting margins for specialtypharmacies. “By pricing it that low, theyhad ahuge disincentive,” he admitted. US Atelvia patents aredeclared invalid 21 ACalifornia court hearing in Sandoz’ legaldispute with Amgen is set for 13 March. G FEATURES 24

Sovaldi recasts US specialty 24 as generic price rises hold French firms must declarerebates As the US pharma market grows at double- rench generics manufacturers, wholesalers and distributors must declare annually details of digit rates, the generics sector is keeping Fanyrebates, discounts or other “financial and commercial advantages” offered to pharmacies pace, according to the latest IMS Health for all reimbursable generic medicines, under legislation that has just been published in the data. Aidan Fry reports. country’s Journal Officiel.Adeclaration must be made to France’seconomic committee for healthcare products (CEPS) before 1March each year. REGULARS Last year,France set aceiling for discounts and rebates of 40% of ageneric’spre-tax ex-factory price (Generics bulletin,19September 2014, page 10). Paragraph IV Watch – Ella 20 Each declaration must include pre-tax sales figures for each product; the number of packs Events – Our regular listing 22 sold; and the total value of anyrebates, discounts or other financial and commercial advantages Price Watch UK – UK pricing trends 23 “of anynature” –including services–attributed to each product. If services rendered to People – Ruepp takes the lead 27 pharmacies cannot be attributed to aspecific product, the value allocated to each will be at Germany’sAristo calculated on apro-rata basis according to sales figures. Firms that do not comply with the obligation will face financial penalties. G Gen 13-3-15 Pgs. 2-10_Layout 1 11/03/2015 17:45 Page 2

COMPANY NEWS

MANUFACTURING MANUFACTURING FDA finds faults at Teva agreestosell Hospira’s Vizag site US Sellersvilleplant

ospira’sinjectablesmanufacturing facility in Vizag, India, that eva has agreed to sell its US manufacturing facility in Sellersville, His gearing up for commercial production has received14‘Form TPennsylvania –including “all buildings, land and equipment” 483’ observations from the US Food and Drug Administration (FDA) located at the 19,100 sq msite –and an associatedbasket of 25 following arecent inspection. generic products to US player G&W Laboratories for an undisclosed Commenting on the FDA’sinspection –which took place between sum. The Israeli group had twoyears ago announced plans to close 16 and 25 February –Hospira said it intended to “respond fully and down the plant (Generics bulletin,17May 2013, page 5). in atimely manner to the observations contained in the Form 483”. Slated to close by the end of April, the transaction also includes “There can be no assurance that the FDAwill be satisfied with the G&W gaining the exclusive US rights to sell up to twoadditional company’sresponse,”Hospira stated. Teva products –which the Israeli firm will continuetomanufacture In March last year,the FDAissued Hospira with aForm 483 at its facility in Zagreb, Croatia –under its ownlabel. containing 10 observations following apre-approvalinspection at Under the agreement, G&W will manufacture the portfolio of the plant. The US firm then receivedaletter from the FDArequesting more than 50 generics made at the site, which includes oral solids, additional information regarding Hospira’splans to address those liquids, creams and ointments, and supply them to Teva until the Israeli deficiencies, after the agencytook issue with twoofthe firm’scorrective firm has transferred production to one of its other sites. actions (Generics bulletin,8August 2014, page 5). Moreover, the US firm has agreed to retain all staffemployed At arecent investor day discussing Pfizer’sUS$17 billion at the Sellersville site. agreement to acquire Hospira, the US originator’sGlobal Established “The acquisition of the Sellersville facility and products Product (GEP) head, John Young, insisted that “immediate approval” strengthens our long-term relationship with Teva,” commented for Vizag “was not an essential component of value creation in this Aaron Greenblatt, G&W’schief commercial officer,“and fits with transaction” (Generics bulletin,27February 2015, page 33). our strategy of acquiring platformsfrom which we can growthe Having broken ground at the site four years ago, Hospira, prior business and expand our product and dosage offering.”Last year the to the FDA’slatest action, said it expected to commence operations firm also purchaseda13,000 sq mplant in Lincolnton, North at Vizag “during the first half of 2015”. G Carolina, from Actavis. G

2 GENERICS bulletin 13 March 2015 Gen 13-3-15 Pgs. 2-10_Layout 1 11/03/2015 17:45 Page 3

COMPANY NEWS

MERGERS&ACQUISITIONS/FIRST-HALF RESULTS MERGERS&ACQUISITIONS Bidvest makesabid Sun gets opiates as to buy all of Adcock Ranbaxy deal nears

idvest has offered around ZAR5.75 billion (US$503 million) to un Pharma is looking to strengthen its analgesicsportfolio by Bacquire the 65.5% of Adcock Ingram that it does not already own. Sagreeing to acquire for an undisclosed sum GlaxoSmithKline’s The conglomerate is offering ZAR52.00 per share, which it says (GSK’s) opiates business in Australia. Meanwhile, the Indian company represents apremium of 13% to the South African firm’saverage share is awaiting awritten version of an oral order handed down on 9March price of ZAR46.03 in the 30 days ended 20 February 2015. Adcock’s by the High Court of Punjab and Haryana, India, clearing Sun’s closing share price on 20 February wasZAR50.00. proposed US$4 billion takeoverofRanbaxy. “Making this proposed offer will remove the uncertainty The Australian opiates transaction –which is subject to certain surrounding Bidvest’sintention to acquire the remaining Adcock regulatory conditions, and is expected to close by August this year – ordinary shares that it does not already own,”stated the conglomerate, includes manufacturing sites in Latrobe, Tasmania, and Port Fairy, which has for months been pondering amove to gain “full strategic and Victoria, along with the UK-based originator’sportfolio of poppy-derived managerial influence” (Generics bulletin,5September 2014, page 3). rawmaterials and related inventory.Moreover, under the agreement, As part of the move,black economic empowerment (BEE) entities Sun will retain all employees from both manufacturing facilities. Blue Falcon and Bophelo Trust have agreed to sell 2.57 million Adcock Iftach Seri, executive vice-president of Sun’sactive pharmaceutical shares to Bidvest for ZAR52.00 each. The BEE deal covers around ingredient (API) business, said the deal was“part of our strategy towards 13% of Adcock’sshare capital. building our portfolio of opiates and accessing strong capabilities “Bidvest continues to believe that the potential for the investment in this segment”. The Indian firm forayed into controlledsubstances in Adcock remains positive in the medium term,”the conglomerate in 2005 when it acquired the Hungarian operations and finished-dose told investors. “Significant effort has been undertaken by Adcock manufacturing facility of Alkaloida, as well as the controlled-substance management to reorganise and restructure the business and these manufacturing assets of Able Laboratories. Three years later,Sun broadened its footprint by buying US-based narcotic raw-materials Region First-half sales Change Operating importer and producer,Chattem Chemicals (Generics bulletin,5 (ZAR millions) (%) margin (%) December 2008, page 3). G Prescription 881 -7 6.6 OTC699 +16 20.2 MANUFACTURING Hospital 558 +6 0.2 Consumer 304 -12 12.6 Southern Africa 2,441 ±0 9.8 Wockhardt allays Waluj fears Rest of Africa 129 +2 3.5 ockhardt says arecent US Food and Drug Administration (FDA) Winspection of its manufacturing facility in Waluj, India, raised India 136 +15 –* “no serious observations which would have bearing on the performance Eliminations/others 10 ––** or operations of the company”. Responding to an article that appeared in India’s Financial Adcock Ingram 2,717 +1 7.4 Chronicle newspaper entitled “US FDAraises concern overWockhardt’s *operating loss of ZAR25.8 million ** non-trading expenses of ZAR17.0 million plant”, the Indian firm told the Bombay Stock Exchange(BSE) it had no “important information or announcements to be shared” on Figure1:Breakdown by region of Adcock Ingram’s sales and operating margin in the six months ended 31 December 2014 (Source –Adcock Ingram) issues at its Waluj facility,which has been banned from importing product to the US since receiving an import alert midway through corrective measures and actions have resulted in amore energised 2013 (Generics bulletin,7June 2013, page 5). workplace within all of its operating divisions.” In atelevision interview, Wockhardt’schairman, Habil Khorakiwala, Having “significantly overpaid” for its stake, Bidvest has already said the firm would respond to several minor observations overthe written down the value of its Adcock investment by ZAR1 billion. next three to four months. G In the six months ended 31 December 2014, advances by its Southern African OTCbusiness and its Indian operations helped Adcock to edge up group turnoverby1%toZAR2.72 billion despite “lower MANUFACTURING volumes in the antiretroviral and tender businesses” (see Figure 1). Lower finance and non-trading expenses improvedAdcock’spre-tax Infarmed clears Nectar site profit by 44% to ZAR193 million. G ectar Lifesciences says it has “touched yet another significant IN BRIEF Nmilestone” after its Indian cephalosporin active pharmaceutical ingredient (API) plant in Dera Bassi, Punjab, receivedaEuropean DR REDDY’S has revealed that US state attorneys-general from current good manufacturing practice (cGMP) approvalfrom Portugal’s Californiaand Texas have asked the firm for information on pricing. Infarmed agency. Last year,Infarmed granted cGMP approvaltothe The California subpoenaseeks “records and documents relating to Indian firm’scephalosporin API plant in Baddi, Himachal Pradesh, the pricing of 15 products”, while acivil investigative demand in India (Generics bulletin,20June 2014, page 8). Texas requests information dating back to 1January 1995. G The Dera Bassi approval, Nectar noted, would be recognised and accepted by “all European Union (EU) health authorities.” G

13 March 2015 GENERICS bulletin 3 Gen 13-3-15 Pgs. 2-10_Layout 1 11/03/2015 17:45 Page 4

COMPANY NEWS

BUSINESS STRATEGY/ANNUAL RESULTS ANNUAL RESULTS Siegfried will buy to IGI expands during securecritical mass ‘transformative’ year

iegfried intends to followupits purchase of German injectables ales of its own-label products soaring by 168% to US$19.8 million Sproducer Hameln Pharma with further acquisitions, as the Swiss Shelped IGI Laboratories to increase its group turnoverby85% group strivestoreach the SFr500-SFr600 million (US$502-US$603 to US$33.7 million last year.The US firm’shead, Jason Grenfell- million) turnoveritbelievesconstitutes “critical mass” in the contract Gardner,said 2014 had been a“remarkable year of transformation development and manufacturing arena. and growth” for the company. “Our industry is in the midst of aconsolidation process. Siegfried Acquiring 17 injectables and asuppository product from aims to be, and will be, an active participant in this process,”insisted AstraZeneca in September,followed by twoophthalmics and the rights chief executive officer Rudolf Hanko, adding that he planned to reach to three previously-marketed injectables from Valeant soon after the SFr500-SFr600 million target within twoyears. (Generics bulletin,17October 2014, page 18), allowed IGI to lay the The SFr52.3 million purchase of Hameln added large-scale steriles foundation for its topicals, injectables,complexgenerics and capacity to the more niche, small-scale AMP operation in Irvine, ophthalmics –or‘TICO’ –strategy to diversify its roster beyond topicals into niche generics (Generics bulletin,3November 2014, page 7). Region Annual sales Change Proportion Ayear ago, the US firm receivedits first abbreviated newdrug (SFr millions) (%) of total (%) application (ANDA) approval, for lidocaine 4% solution (Generics Drug Substances 234.4 -14.5 74 bulletin,21March 2014, page 4). In 2014, the US firm filed 11 Drug Products 80.9 -19.7 26 ANDAs, taking its total pending US Food and Drug Administration (FDA) approvalto22. And, Grenfell-Gardner noted, IGI planned to Siegfried 315.3 -15.9 100 file “at least 20 more” ANDAs this year. “Weare currently waiting for the FDAtocome out with the Figure1:Siegfried’s sales in 2014 (Source –Siegfried) details of target action dates for those things that are on file,” California,that Siegfried acquired in 2012. The US Food and Drug Grenfell-Gardner observed. Administration (FDA) recently lifted awarning letter against Hameln’s Having closed aUS$125 million bond offering to institutional facility in Germany(Generics bulletin,27February 2015, page 13). buyers in December (Generics bulletin,16January 2015, page 6), Siegfried anticipates an FDAinspection of its recently constructed IGI has accrued alittle under US$159 million in cash and cash bulk-drugs plant in Nantong, China, during the second half of this equivalents as of 31 December 2014, compared to US$2.10 million year.Commercial operations in Nantong will start later this year. the previous year.Noting that IGI had looked at manufacturing facilities Last year,the Swiss group suffered a15.9% sales slide to SFr315 both in the US and abroad to help bring its injectables portfolio to million (see Figure 1). Turnoverfrom Drug Substances fell by 14.5% market, Grenfell-Gardner said “current asset valuations made many to SFr234 million, due largely to the cancellation of alarge exclusive- potential transactions, frankly,bad deals from our perspective”. synthesis order,aswell as a3%dip in sales of controlled substances. An operating profit of US$3.91 million in 2014 –compared to Finished-dose Drug Products sales declined by afifth to SFr80.9 aUS$0.08 million operating loss the previous year –meant that IGI million on lower supplies of candesartan. Siegfried’soperating had returned to profitabilityfor the first time “since 1997”, pointed profit decreasedby16.7% to SFr34.0 million. G out chief financial officer Jennifer Collins. G

13 March 2015 Issue 227 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.

4 GENERICS bulletin 13 March 2015 Gen 13-3-15 Pgs. 2-10_Layout 1 11/03/2015 17:45 Page 5

COMPANY NEWS

RESULTSFORECAST/ANNUAL RESULTS BUSINESS STRATEGY/ANNUAL RESULTS Akornanticipates a Endo gets US$1.6bn rise to near US$1bn by selling AMS units

ull-year contributions from acquisitions closed in 2014, coupled ndo has agreed to sell the men’shealth and prostate health units Fwith launching anumber of generics from abbreviated newdrug Eof its AmericanMedical Systems (AMS) urology business to applications (ANDAs) approvedlast year,will help Akorn approach Boston Scientific for US$1.6 billion in cash, along with aUS$50 US$1 billion in sales in 2015, the US firm believes. million milestone payment based on sales in 2016. The twobusinesses Targetting turnoverofUS$960-US$980 million this year,the had combined sales of US$395 million last year,Endo reported. US-based ophthalmics and sterile injectables specialist will be bolstered Slated to close in the third quarter of this year,the transaction by both its US$640 million move for fellowUSniche generics player does not include the women’shealth segment of AMS. However, Hi-Tech Pharmacal, which closed in mid-April last year (Generics Endo, which paid US$2.9 billion for AMS around three years ago bulletin,2May 2014, page 3), and its subsequent US$440 million (Generics bulletin,22April 2011, page 4), said it was“evaluating acquisition of privately-owned VersaPharm, which closed in August. strategic alternatives” for women’shealth. Those transactions together added more than 70 newproducts to Closing deals for US-based generics players Boca Pharmacaland the US firm’sroster,with the latter deal diversifying Akorn’sportfolio Dava Pharmaceuticals last year,inFebruary and August respectively, by taking the companyinto the US dermatology arena (Generics helped Endo’sUSGenerics sales to advance by 56% to US$1.14 billion. bulletin,16May 2014, page 1). The US firm’sdeal for Dava,which closed quickly following Endo’s The US firm also expects to begin shipping nine products this year US$615 million agreement midway through last year (Generics bulletin, from the 14 “unique”ANDAapprovals it receivedin2014 butdid 11 July 2014, page 3), added US$47 million to Endo’sturnover, while not launch. Of those approvals, Akorn noted it had already introduced an almost full-year contribution from Boca added US$102 million. bromfenac 0.09% ophthalmic drops, tobramycin300mg/5ml inhalation Moreover, sales of Endo’sauthorised generic of its Lidoderm solution and gatifloxacin 0.5% ophthalmic drops, as well as atropine (lidocaine)patch that the US firm introduced in May following 1% ophthalmic solution and adenosine 3mg/ml injectable. competition from Actavis totalled US$176 million. The US firm – Moreover, in early October,Akorn agreed to acquire certain US which said that Generics sales grewby15% excluding these effects rights to Sunovion’sXopenex(levalbuterol) inhalation solution –also launched rivals to Roche’sValcyte (valganciclovir) after the US (Generics bulletin,17October 2014, page 19), adding to the generic Food and Drug Administration (FDA) rescinded an approvalfor fluticasonenasal sprays it had picked up through the Hi-Tech deal. Ranbaxy’sversion (Generics bulletin,5December 2014, page 27). In 2014, Endo established afootprint overseas by acquiring Plans 35-40 ANDAs per year Canada’sPaladin Labs and its Litha Healthcare affiliate in South Africa, Raj Rai, Akorn’schief executive officer,said the firm wasaiming and later Mexican generics player Somar (Generics bulletin,16May to file 30 ANDAs in 2015 –for ophthalmics,injectables, nasal sprays 2014, page 3). Together,these operations added US$270 million to and topicals –leading to a“run-rate to consistently submit 35-40 Endo’ssales, helping to overcome US Brands sales tumbling by 30% filings per year”. Rai noted that Akorn currently had 87 ANDAs to US$969 million to push group turnoverupbyatenth to US$2.88 pending approval. billion (see Figure 1). Endo at the start of February also bought for Having last year queried howthe FDAplanned to tackle its US$40.1 million the 29.7% stakeinLitha it did not already own. backlog of generic filings (Generics bulletin,5December 2014, Endo recently bolstered its US Brands business by completing page 6), the Akorn head said that newstaffand resources that the its acquisition of men’shealthcare and orthopaedics specialist agencyhad added in the meantime offered “a glimmer of hope that Auxilium for US$2.6 billion. Moreover, Endo and partner BioDelivery we will start to get more products approved”. Sciences International (BDSI) have just had their newdrug application The US firm early in February introduced generic rivals to (NDA) for Belbuca (buprenorphine) buccal film accepted for filing AbbVie’sMarinol (dronabinol) capsules, and expects by June to have by the FDA(Generics bulletin,27February 2015, page 27). launched phenylephrine ophthalmic solution that wasapprovedas In spite of Endo’sgroup turnoverrise, significant litigation anew drug application (NDA) in January. expenses –coupled with the firm’scost of goods rising by more than Meanwhile, Rai said that Akorn was“taking all the right steps athird to US$1.40 billion –saw Endo’soperating loss increase from toward FDAreadiness” at the cluster of sterile-injectable manufacturing US$426 million to US$897 million last year. G facilities in Paonta Sahib, India, that it bought from KilitchDrugs four years ago (Generics bulletin,14October 2011, page 5). “Weare Business Annual sales Change Porportion of focused on filing newmarketing authorisationsout of Akorn India unit (US$ millions) (%) total (%) in less regulated markets,”Rai commented, pointing out that the site had “over30authorisations pending in overadozen countries”. Pain and controlled substances 602 +91 21 Rai also insisted that the US firm had “some cash in our war Other solid doses 449 +32 16 chest to do some decent-sized acquisitions”. “Weare not concerned Other liquids and semi-solids 89 +18 3 about [the company’sdebt],”hesaid. US Generics 1,141 +56 40 Closing the twotransactions helped Akorn’sprescription US Brands 969 -30 34 pharmaceuticals turnovertoalmost double –rising by 97% –to Devices 497 +1 17 US$552 million last year.With the US firm’sconsumer health sales improving by athird to US$50 million, group turnoverincreased by International 270 –9 89% to US$602 million. Despite ramping up research and development Endo 2,877 +10 100 costs in 2014 by almost half to US$29.2 million, Akorn’soperating profit rose by 20% to US$106 million. G Figure1:Breakdown by business unit of Endo’s sales in 2014 (Source –Endo)

13 March 2015 GENERICS bulletin 5 Gen 13-3-15 Pgs. 2-10_Layout 1 11/03/2015 17:45 Page 6

COMPANY NEWS

BUSINESS STRATEGY/ANNUAL RESULTS Mylan makes moves in respiratoryarena

ylan expects to launch European generics of Seretide (fluticasone/ Annual sales Reported Constant-currency Msalmeterol) and Flixotide (fluticasone) pressured metered-dose (US$ millions) change (%) change (%) inhalers (pMDIs) during 2015. And at the end of this year,itexpects to file for an interchangeable version of Advair Diskus (fluticasone/ North America 3,361 +12 +12 salmeterol) with the US Food and Drug Administration (FDA). Europe 1,477 +3 +3 Almost ayear ago, Mylan struck aglobal licensing deal with Rest of world 1,621 +13 +18 UK-based developer Prosonix for pMDI versions of GlaxoSmithKline’s Generics 6,459 +10 +11 Flixotide/Flovent respiratory brand (Generics bulletin,2May 2014, Specialty 1,187 +21 +21 page 13). RajivMalik, Mylan’spresident, said closing the acquisition of Abbott’sestablished products business on 27 February had given Other 73 +39 – Mylan the sales infrastructure in Europe to market products through Mylan 7,720 +12 +13 generic, tender or brand-drivenmodels. Phase III clinical trials for generic Advair were “progressing well” Figure1:Breakdown by business of Mylan’s sales in 2014 (Source –Mylan) as Mylan aimed to bring the first AB-rated substitutable generic to the US market, Malik said. “Weexpect to launch after maybe 12 to and brand promotion, helped to push up European Generics turnover 15 months [from filing],”headded, noting that Phase III trials would by 3% to US$1.48 billion. Mylan benefitted from stronger volumes start this year for the TD-4208 nebulised chronic obstructive pulmonary and local-currencysales rises in France, Italy and UK. “Asaresult disease (COPD) candidate that the firm had licensed from Theravance. of tenders, our business in Germanyhas grown,”itadded. TwoPhase III trials are underway for arivaltoSanofi’sLantus Generics sales in Mylan’sRest of the World region grewby13% (insulin glargine) brand –one for type-1 diabetes over52weeks, and as reported, and by 18% on aconstant-currencybasis, to US$1.62 the second in type-2 diabetes over24weeks –with top-line data due billion. The group’sIndian operation capitalised on strong demand for during the second half of next year.“We continue to pursue the antiretrovirals from customers such as the Global Fund and the South opportunity to have one of the first interchangeable insulin analogues African government, while productlaunches increased local-currency to Lantus,”Malik stated, adding that Mylan and its partner,Biocon, sales in Japan, where Mylan has agenerics alliance with Pfizer. were investing in an insulins production site in Malaysia. Specialty sales climbed by 21% to US$1.19 billion as the EpiPen Along with India’sBiocon, Mylan has nowsubmitted dossiers (epinephrine) became the group’sfirst US$1 billion blockbuster. for its trastuzumab biosimilar in 15 countries,having launched the Investing in respiratory and biosimilar programmes drove up drug in India under the Hertraz brand name. Mylan plans to have Mylan’sresearch and development spending by 15% to US$582 three biosimilar monoclonal antibodies in Phase III trials this year. million. Nevertheless, the group improvedits operating profit by 19% Acquiring the Agila injectables business from India’sStrides to US$1.35 billion, as an exceptional US$80.0 million compensation Arcolab at the end of 2013 helped Mylan to raise its group turnover for revenues lost due to supply disruptions from former Strides’ by 12% to US$7.72 billion last year,aided by aUS$593 million injectables sites outweighed alitigation-settlement charge that included contribution from acquisitions and newproducts. Global Generics US$21.7 million for resolving adispute with the European Commission. sales advanced by atenth to US$6.46 billion (see Figure 1), including This year,Mylan expects to increase its group turnoverby28% a12% rise to US$1.82 billion in the fourth quarter (see Figure 2). as reported –and by athird at constant exchange rates –toUS$9.6 Newproducts and acquisitions added US$480 million to North billion to US$10.1 billion. That growth is expected to come solely American generics sales ahead by 12%, or by US$355 million, to from the group’sGenerics business, which should expand by 38% on a US$3.36 billion in 2014. During the year,Mylan –which paid Aspen constant-currencybasis, boosted by US$1.5-US$1.8 billion for the US$300 million for US rights to the Arixtra (fondaparinux) acquisitions of the Abbott operations from 27 February as well as of the anticoagulant (Generics bulletin,19September 2014, page 19) – Famy Care women’shealth portfolio after Mylan closes aUS$800 secured 43 final and four tentative abbreviated newdrug application million deal in the second half of this year (Generics bulletin,6February (ANDA) approvals, including for six first-to-file opportunities. The 2015, page 1). No other acquisitions are included in the guidance. firm said this left 283 ANDAs pending approval, of which 44 were Mylan’sGenerics outlook also assumes that the firm will launch first-to-file patent challenges. asubstitutableAB-rated rivaltoTeva’s Copaxone (glatiramer acetate) “Regaining some market share” in France, aided by advertising multiple-sclerosis brand in the second half of 2015. Malik believed that the US Federal Court of Appeals would uphold its earlier invalidity Fourth-quarter sales Reported Constant-currency ruling on aCopaxone patent expiring in September 2015, having been (US$ millions) change (%) change (%) ordered to reconsider its ruling by the US Supreme Court. Specialty sales are set to stall this year as Mylan is anticipating North America 1,001 +17 +18 generic competition to EpiPen during the second half of this year. Europe 373 -1 +8 Chief executive officer Heather Bresch said closing the Abbott Rest of world 441 +13 +18 transaction had givenMylan “evenmore financial firepower”, as well Generics 1,815 +12 +16 as amore favourable tax position through redomiciling in the Netherlands, from which to pursue business-development opportunities. Specialty 243 +38 +38 “You can expect us to aggressively pursue additional acquisition Other 25 +70 – opportunitiesthat makefinancial and strategic sense for the company. Mylan 2,083 +15 +18 We could announce another material transaction before the end of this year,” Bresch told investors, adding that the group waslooking Figure2:Breakdown by business of Mylan’s sales in the fourth quarter of 2014 at abroad range of generics and brands targets that could expand (Source –Mylan) its portfolio or geographic reach. G

6 GENERICS bulletin 13 March 2015 Gen 13-3-15 Pgs. 2-10_Layout 1 11/03/2015 17:45 Page 7

COMPANY NEWS

ANNUAL RESULTS BUSINESS STRATEGY/ANNUAL RESULTS Krka’s sales decline Impax holds back on after currency shifts plans for biosimilars

round C100 million (US$112 million) of “negative net exchange mpax is not yet looking to push into the burgeoning biosimilars Arate differences” caused Krka’ssales to decline by 0.8% to C1.19 Iarena, according to the US firm’spresident and chief executive billion in 2014. “A major proportion of negative exchange-rate officer,Fred Wilkinson. Quizzed by investors on howImpax plans to differencesresulted from the depreciation of the Russian rouble, and remain competitive in the US generics market as the US Food and mostly occurred at the end of the year,” the Slovenian firm noted. Drug Administration (FDA) works to clears its backlog of thousands Despite Russian sales growth in rouble terms, Krka reported sales in of generics filings, Wilkinson maintained that Impax would continue the market sliding by 5% to C282 million. The Slovenian group’s to aim for “alternative dosage forms and oral solids [in which] the operating profit improvedby22% to C277 million. technology itself is difficult”, thus limiting competition. Domestic sales dropped by atenth to C78.0 million, while falls “Wehavestayed away from [biosimilars], and Idonot think it of around 4% in both East Europe and Central Europe resulted in is appropriate for us to jump into that fray right now,”Wilkinson regional totals of C409 million and C273 million respectively (see observed. “But inevitably,” he concluded, “some time overthe Figure 1). As well as the Russian decline, falling sales in Kazakhstan lifecycle, you are going to have to get there.” and Ukraine more than offset arise of almost aquarter in Uzbekistan Moreover, he added, the US firm had “evaluated the injectables to reduce the East Europe total. Meanwhile, Central Europe suffered space”, buthad not “found the right opportunity to jump into that”. despite 4% growth in Poland to C125 million, as “legislative changes” “Weare still evaluating whether the [injectables] market will stay in the Czech Republic drove down prices and cut Krka’ssales by healthy, [or] whether it will go back to its previous commodity almost aquarter to C48.4 million and a6%decline to C40.3 million status,”Wilkinson stated. in the “key market” of Hungary followed austerity measures. Last year,Impax limited its generics pipeline to 46 projects –23 However, turnoverinSouth-East Europe grewby7%to C155 abbreviated newdrug applications (ANDAs) pendingUSapprovaland million after arise of afifth in Romania, while West Europe rose by 23 projects under development –following acost-cutting initiative. 11% to C251 million, drivenbyanincrease of more than aquarter in “About adozen” of the firm’sprojects under development were for Germany. In other markets, sales fell by 18% to C25.5 million. Prescription pharmaceutical sales that accounted for more than Division Annual sales Change Gross four-fifths of Krka’sgroup total were led by the firm’sAtoris (US$ millions) (%) margin (%) (atorvastatin), while the firm receivednew marketing authorisations Generics 549 +37.8 52.6 for 19 molecules or combinations in 2014. These included prolonged- Brands 47 -58.5 51.2 release quetiapine tablets, escitalopram tablets and pregabalin capsules. Krka has also just begun production at its newly-completed Impax 596 +16.5 52.5 55,000 sq mplant in Locna, Slovenia, in which the firm has since 2012 invested C200 million. “Once it is fully fitted with all technological Figure1:Breakdown by division of Impax Laboratories’ sales and gross margin in equipment, the plant will have the target capacity of 4.5 billion finished 2014 (Source –Impax) products per year,” the companyobserved, noting that the facility topical products, Wilkinson told investors. Arecent nod for lamotrigine represented “the largest investment in Krka’shistory”. orally-disintegrating tablets (Generics bulletin,6February 2015, Production has also nowstarted on three lines at anew active page 19) has left 22 ANDAs pending approval. ingredients plant in Krsko, Slovenia –with asecond module to be In 2014, launchinganauthorised generic of Sanofi’sRenvela added later this year –while the firm is still constructing a C135 million (sevelamer) tablets (Generics bulletin,2May 2014, page 14), coupled production and logistics facility in Russia that is expected to have with higher sales of “several keygenerics”, helped Impax to increase an annual capacity of 1.8 billion tablets and capsules. G sales through its Global Laboratories generics division by 37.8% to US$549 million. The business’ portfolio and pipeline will be further Region/ Annual sales Change Proportion of strengthened this year as Impax has just closed its US$700 million deal Product line (C millions) (%) total (%) for US-based generics player CorePharma (Generics bulletin,17 October 2014, page 1). The transaction –which requires Impax East Europe 409 -4 35 and CorePharma to divest twoproducts to Perrigo (see page 16) – Central Europe 273 -4 23 along with ANDAapprovals and both firms’ partnerships, will West Europe 251 +11 21 provide up to 17 generic launches this year,according to Wilkinson. South-East Europe 155 +7 13 Following the close of the deal, Impax announced that its Global Slovenia 78 -10 7 Laboratories generics division would be known as Impax Generics, Other 26 -18 2 while its brands unit would be called Impax SpecialtyPharma. Turnoverfrom Global Laboratories –which still lacks apermanent Krka 1,192 -1 100 head following the departure of Carole Ben-Maimon (Generics Prescription 991 +1 83 bulletin,3November 2014, page 27) –comfortablyoffset asales slide Non-prescription 122 -16 10 of almost two-fifths to US$47 million from Impax’ branded segment (see Figure 1), as group sales rose by 16.5% to US$596 million. Animal Health 47 +9 4 The firm’sincreased turnover, coupled with adrop in cost of Resorts, tourism, other 33 +1 3 goods and lower patent-litigation expenses, helped Impax to go from Figure1:Breakdown by region and product line of Krka’s group sales in 2014 aUS$6.39 million operating loss in 2013 to an operating profit of (Source –Krka) US$88.8 million. G

13 March 2015 GENERICS bulletin 7 Gen 13-3-15 Pgs. 2-10_Layout 1 11/03/2015 17:45 Page 8

COMPANY NEWS

BUSINESS STRATEGY/FIRST-HALF RESULTS BUSINESS STRATEGY/ANNUAL RESULTS Aspen almost ready Sagent is lookingat for trading in Japan deals on biosimilars

spen Pharmacare expects the operation it has establishedinJapan SinjectablesspecialistSagent Pharmaceuticals is looking at Ato start trading in July this year.The South African group said Umerger and acquisitions movesfor companies that have biosimilar Aspen Japan –inwhich GlaxoSmithKline (GSK) holds a25% stake– assets outside of the US, according to the firm’schairman and chief was“an important step towards the group establishing itself in that executive officer,JeffYordon. country,which is ranked second in the world by value of pharmaceutical While Sagent remained unwilling to invest the sums needed to sales”. Aspen is also “assessing Chinese market entry”. develop biosimilars, Yordon said the companyanticipatedhelping Having ayear ago announced its intention to target Japan developers to market such products. (Generics bulletin,21March 2014, page 6), Aspen agreed with GSK Generic approvaltimelines running to around four years in the to invest ¥2.5 billion (US$20.6 million) in aJapanese entity that will US were encouraging Sagent to look abroad where it could secure market both the South African group’sentire portfolio and abasket of authorisations more quickly,Yordon explained. Brazil, China, Russia off-patent brands and authorised generics provided by GSK (Generics and Turkey were all attractive markets in which the firm had hired bulletin,17October 2014, page 7). consultants to explore options, he stated, adding that Sagent would Stronger sales in Asia helped to counteract the negative effects also consider buying brands that fitted into its portfolio. of “disposals and licence terminations”, as well as of mandatory “I believe that China will be at price parity to the US by the end price cuts in Australia,asAspen’sturnoverinits Asia-Pacific region of next year,” Yordon commented,noting the huge volumes of rose by 3% to ZAR4.42billion (US$366 million) in the six months injectables used in China. “So it makes awhole lot of sense for us to ended 31 December 2014. But Aspen’soperating margin in the region be looking at entering that market in an aggressive manner once the slipped by 0.7 percentage points to 20.6% (see Figure 1). profit profile is the same or similar to the US.” Recent acquisitions, including the US$600 million purchase of “You have to have big capacity to servethat market,”Yordon 11 brands from Merck, more than doubled Aspen’sInternational continued. Therefore, he said, the firm waslooking at adding athird turnovertoZAR8.80 billion. Within that total, sales in Europe and production line at its 28,000 sq mSagent China Pharmaceuticals the Commonwealth of Independent States (CIS) were more than (SCP) facility in Chengdu, China. The SCP site is nowmaking three-times higher at around ZAR5.1 billion. Aspen has just agreed commercial batches of atracurium besilate following a‘CBE-30’ to expand its anticoagulants offering in Europe by acquiring product transferinDecember last year. Novartis’ Mono-Embolex(certoparin sodium) for US$142 million In its domestic market, the US companyhas just had to recall (Generics bulletin,27February 2015, page 27). six lots of atracurium vials due to sterility issues at its erstwhile Latin American International sales more than doubled to ZAR2.6 manufacturing partner Emcure. billion after Aspen paid Pfizer and Nestlé US$180 million for alocal infant-formula business. And turnoverinthe Rest of the World region Considering FDA approval for Montreal site rose by just overathird to ZAR0.9 billion, despite Aspen divesting Yordon said Sagent wasalso weighing whether to seek US Food US rights to Arixtra (fondaparinux) to Mylan in aUS$300 million and Drug Administration (FDA) clearance for the facility in Montreal, deal (Generics bulletin,19September 2014, page 19). Canada, that the firm picked up by acquiring Omega Laboratories for In the South African group’sdomestic market, strong private- US$82.7 million last year (Generics bulletin,17October 2014, page 3). sector and infant-formula sales pushed up turnoverby12% to ZAR4.31 Incorporating Omega’s portfolio of injectables, such as billion. Aspen said it had benefitted from “shifting market dynamics furosemide, glycopyrrolate,neostigmine and octreotide, from 1 towards generics”, aided by co-marketing agreements for keygenerics. October 2014 helped Sagent to raise its turnoverby18% to US$290 Ahigh-containment unit and apackaging upgrade at the firm’sfinished- million last year.Anti-infectivesand oncology drugs each contributed dose facility in Port Elizabeth, South Africa, are close to completion. 35%, or just overUS$100 million, of that total, with critical-care Supply constraints hampered turnoverinSub-Saharan Africa products contributing 30% or nearly US$90 million. where sales nevertheless grewby5%toZAR1.47 billion. Sevenlaunches during 2014 added US$13.8 million to Sagent’s Group turnoveradvanced by 51% to ZAR18.0 billion, matched sales. Yordon said the companyhad filed 15 abbreviated newdrug by a50% improvement in operating profit to ZAR4.32 billion, even applications during 2014, leaving 64 ANDAs across 42 molecules with exchange-rate losses of ZAR343 million. But higher financing costs pending approvalatthe end of the year.Another 15 ANDAs meant pre-tax profit rose by just overaquarter to ZAR3.11 billion. G representingfour products were approvedand awaiting launch, including five that were replacements for drugs previously covered Region Six-month sales Change Operating by aterminated supply and marketing agreement with Actavis. Drugs (ZAR millions) (%) margin (%) among Sagent’spipeline include iron sucrose and pentobarbital. Sagent’sgross margin fell by twopercentage points to 29.7%, International 8,804 +158 25.8 while the firm increased its product-development investment by almost Asia-Pacific 4,423 +3 20.6 athird to US$26.8 million. AUS$5.0 million termination fee from South Africa 4,307 +12 21.6 Actavis paid in 2013 wasalso afactor in Sagent’soperating profit Sub-Saharan Africa 1,467 +5 14.1 dropping by 39% to US$19.0 million. Eliminations -967 –– This year,the US companyexpects aturnoverofUS$325-US$375 Aspen Pharmacare18,033 +51 23.9 million. That forecast, Yordon explained, had been influenced by prospects for renewing keygroup purchasingorganisation (GPO) Figure1:Breakdown by region of Aspen Pharmacare’s sales and operating contracts such as Premier and Novation, as well as opportunities to margin in the six months ended 31 December 2014 (Source –Aspen) supply GPO private-label programmes. G

8 GENERICS bulletin 13 March 2015 MAY -EGA BIOS15 Fullpage Ad 297x210 -PRINT 002.pdf 123-02-2015 10:58:58 Gen 13-3-15 Pgs. 2-10_Layout 1 11/03/2015 17:45 Page 10

COMPANY NEWS

BUSINESS STRATEGY/ANNUAL RESULTS IN BRIEF CONCORDIA HEALTHCARE has agreed to pay Covis Pharma Kabi cuts its costs US$1.2 billion in cash for abasket of 18 branded and authorised generic drugs including Dibenzyline (phenoxybenzamine), Lanoxin (digoxin) and Nilandron(nilutamide). Legacy products and diabetes specialist Concordia said the acquired portfolio had combined sales to save C40m ayear last year of around US$140 million, around US$20 million more than Concordia’s2014 total turnover. Canada-based Concordia resenius Kabi has launched acost-cutting drive aimed at improving expects to generate around US$20 million of immediatesynergies Fproduction efficiencyand streamlining administrative structures, by eliminating distribution, general and administrative expenses. especially in Europe. It expects to incur implementation costs of around C100 million (US$108 million) this year,producingsavings IPCA LABORATORIES is poised to takemajority control of fellow of C10 million in 2015 and C40 million annually by 2018. Indian company Krebs Biochemicals and Industries.Through a Around two-thirds of the targetted savings are to be achievedin preferential share offering, Ipca will raise its holding in the Hyderabad- Europe, with the other third derivedfrom operationsinthe firm’s based producer from 13.1% to 29.8%. And an open offer worth Africa, Asia-Pacific and Latin America regions. Rs57.6 million (US$0.93 million) for 3.57 million shares at Rs54 per Group executive chairman Mark Schneider noted that Kabi’s share could add another 26.0%, taking Ipca’sholding up to 55.8%. operating margin had declined from apeak of around 20% in 2012 to 17.0% last year.While Kabi remained Fresenius’ most profitable FARMAK –which claims to be amarket leader in Ukraine, with business segment, its cost structure needed to be reduced to adjust to sales of US$122 million last year –said construction of its active issues such as alarger proportion of sales coming from lower-margin pharmaceutical ingredient (API) factory located in Shostka, medical devices, price cuts in China, easing drug shortages in the US Ukraine, “is nowcoming to afinal stage”. The 40,000 sq mfacility – and label restrictions on hydroxyethyl starch (HES) blood-volume which will comply with national and international good manufacturing expanders, he maintained. practice (GMP) standards –will start operating by the end of 2015. Setting mid-term targets for Kabi, Schneider said he expected the business segment to produce earnings before interest and tax (EBIT) TAKEDA has agreed to pay up to TRL300 million (US$114 million) growth of 6% to 10% at constant exchange rates –“without the to acquire13products in Turkey from local player Neutec. Under support of major acquisitions” –onorganic sales growth of between the terms of the deal, which is scheduled to close in March, 5% and 8%. The sales rise would be driveninpart by rolling out Istanbul-based Neutec will continuetomakethe gastroenterology, clinical-nutrition products in the US and emerging markets, as well metabolic, musculoskeletal and respiratory drugs. Separately,Takeda as by double-digit growth in China, where the company’ssales last has opened an office in Singapore that serves as the headquarters year reached around C550 million. of its Emerging Markets business unit that is led by Giles Platford.

Mid-termtarget of 3% to 5% sales growth BEXIMCO says its oral solid-dose facility in Tongi, Bangladesh, This year,Fresenius expects Kabi –which has just divested a has passed aUSFood and Drug Administration (FDA) inspection German compounding business with sales of C77 million last year without anyForm 483 observations of good manufacturing practice (Generics bulletin,27February 2015, page 8) –tocome in slightly (GMP) deficiencies. “This marks the first time the FDAhas conducted belowits mid-term target, with organic sales growth of 3% to 5% an audit of apharmaceutical facility in Bangladesh,”Beximco and aconstant-currencyEBIT rise of 4% to 6%. noted. From Tongi, the Bangladeshi firm has made its first exports Sales growth should be 3% to 5% in Europe on strong clinical to Australia by shipping pantoprazole. To fund newplant and nutrition demand and stable HES sales, with turnoverinemerging machinery for its production sites, Beximco has struck aUS$51.6 markets up around atenth on double-digit growth in China. ForNorth million loan agreement with Germany’sBHF-Bank. America, Kabi is forecasting between a3%fall and 3% growth, depending on factors including the number and timing of up to 10 NICHI-IKO increased its turnoverby22.3% to ¥95.9 billion generic injectablelaunches, howintravenous drug shortages develop, (US$791 million) in the nine months ended 31 December 2014, the impact of competition on Naropin (ropivacaine) and propofol, and aided by having introduced drugs including candesartan and the roll-out of neostigmine. levofloxacin in December last year.The Japanese generics specialist’s Intravenous drugs sales up by 4% on an organic basis to C1.81 operating profit kept pace with a22.2% rise to ¥7.88 billion. billion accounted for just overathird of Fresenius Kabi’ssales that increased by 3% to C5.15 billion last year,equivalent to 4% organic JUBILANT LIFE SCIENCES reported Pharmaceuticals turnover growth (see Figure 1). Lower use of HES blood-volume substitutesand ahead by 4% to Rs7.01 billion (US$112 million) in its financial an “easing of intravenous drug shortages in the US” hit not only Kabi’s third quarter ended 31 December 2014. Higher sales of active sales, butalso its EBIT,which fell by 6% to C873 million as research pharmaceutical ingredients(APIs) such as aripiprazole and of and development expenses rose by just overatenth to C276 million. G radiopharmaceuticals helped to offset pressure on contract- manufacturing revenues due to awarning letter issued by the US Region Annual sales Reported Organic Food and Drug Administration (FDA) against the Indian group’s (C millions) change (%) change (%) site in Spokane, US. Pricing pressure on advanced intermediates contributed to Life Science Ingredients sales falling by 3% to Europe 2,102 +2 +3 Rs7.44 billion as group turnoverstalled at Rs14.5 billion. Jubilant North America 1,531 +1 +1 has taken full control of its US affiliate Cadista following a Asia-Pacific 987 +6 +7 tender offer to minority shareholders. Latin America/Africa 526 +6 +14 Fresenius Kabi 5,146 +3 +4 ACTAVIS has secured shareholder approvalfor its planned US$66 billion acquisition of Allergan. G Figure1:Breakdown by region of Fresenius Kabi’s sales in 2014 (Source –Fresenius)

10 GENERICS bulletin 13 March 2015 Gen 13-3-15 Pgs. 11-14_Layout 1 11/03/2015 17:46 Page 3

MARKET NEWS

ANTI-COUNTERFEITINGMEASURES MARKET RESEARCH EGA hails ‘landmark’ US may risk stifling on counterfeit drugs biosimilar investment

European Medicines Verification Organisation (EMVO) that has dverse regulatory decisions and market risks in the nascent US Abeen establishedbythe European Generic medicines Association Abiosimilars market could impede biosimilarmarket share, and (EGA) in conjunction with several other European pharmaceutical even stifle biosimilar market entry altogether for several molecules, industry associations is a“landmark in the fight against counterfeit according to areport on the economic viability of US biosimilars medicines”, according to the EGA. that has just been published by Matrix Global Advisors. The US Developed with the European Federation of Pharmaceutical Generic Pharmaceutical Association (GPhA) said the study showed Industries and Associations (EFPIA), the Pharmaceutical Group of that “federal, state and international regulatory decisions could have the European Union (PGEU), wholesalers association GIRP and the asignificant impact on the viability of biosimilar market entry”. European Association of Euro-Pharmaceutical Companies (EAEPC), Matrix’ report presents three possible scenarios. In the “base-case the EMVOwould be a“keytool to combat the emergence of falsified scenario of the analysis –which includes manyfavourable assumptions medicines in the EU legitimate supply chain and improve patient about the market for biosimilars and assumes an average development safety”, the EGA stated. cost” –the report states that it would only be viable for agenerics Noting that the organisation “represents the culmination of four firm to develop and launch rivals to biologics with average annual years of intensive work towards adependable and secure pharmaceutical sales exceeding US$898 million. verification system”, the EGA said the EMVOwould “nowassume An alternative scenario that models potential regulatory,statutory responsibility for the European Hub, which links national verification and market impediments, biosimilars would only be viable for brands systems throughout Europe”. with annual sales of at least US$1.3 billion. Germanywould be the first EU member state to “contribute fully” But afinal scenario –that assumes lower researchand development to an “improvedEurope-wide verification system under the auspices costs for biosimilars without the second scenario’simpediments – of the EMVO”, the EGA noted. The organisation would “reinforce suggests that abiosimilar could break even providing that the target the value of the European Stakeholder Model, allowing end-to-end brand’sannual sales were more than US$627 million. verification of medicine packs from the point of manufacture, through “In short, the decision of abiosimilars manufacturer to enter wholesale distributors carrying out risk-based verification and the US market is more tenuous than commonly perceived,”Matrix pharmaciestothe dispensing point for patients, thereby securing states. “In anutshell,”the researcher finds, “evenunder favourable the entire supply chain”. G assumptions, manufacturers would likely invest only in biosimilars tied to the biggest-selling biologics.”Arobust US biosimilars market is not a“foregone conclusion”, the report warns. INTELLECTUAL PROPERTY Matrix identifies three categories of “potential impediments to biosimilarmarket uptake”. Regulatory burdens will depend on two LDCs seek TRIPSexception US Food and Drug Administration (FDA) decisions: “the naming conventions the agencyestablishes and the clinical testing the agency east developed countries (LDCs) should be exempt from providing may require biosimilars to repeat”. Statutory burdens include US state Lpharmaceutical patents and five-year data exclusivity for as long legislation that could restrict biosimilar substitution. And market risks as theyretain that status, according to arequest being circulated at the coverthe current lack of clarityoverhow health insurers and healthcare World Trade Organization (WTO) by Bangladesh on behalf of LDCs. programmeswill handle coverage of and reimbursement for biosimilars. Noting that awaiverfrom patent and data-exclusivity obligations “In addition,”Matrix states, “the perception of biosimilars among under the WTO’sagreement on trade-related aspects of intellectual- doctors and the general public will play asubstantial role in determining property rights (TRIPS) wasdue to expire on 1January 2016, biosimilarutilisation.”And even without these impediments, the market Bangladesh pointed out that “LDC members of the WTOcontinue researcher predicts, “biosimilars will be costly and time-consuming to to face massive health challenges from communicableand non- develop, requiring an estimated 8-10 years and US$100-200million”. communicable diseases”. Furthermore, LDCs also lacked an “adequate “A robust US biosimilars market for abroad spectrum of biologic technological base and local pharmaceutical manufacturing capacity”. products is unlikely,” Matrix concludes, even if biosimilar entry for “Patent protection contributes to high costs, placing manycritical blockbuster biologic products is viable. Ultimately,the report treatments outside the reach of LDCs,”the request states. “It is warns, “adverse decisionsbypolicy-makers and effective dissuasion imperative for LDCs to retain maximum policyspace to enable them to by biologics manufacturersnot only may impede biosimilarmarket confront their health burdens with effective and affordable strategies.” share, butmay stifle market entry altogether for manyproducts”. Articles 70.8 and 70.9 of the TRIPS agreement require WTO Ralph Neas, president and chief executive officer of the GPhA, members to provide patents and five-year market exclusivity for said it wasessential to ensure that “the nascent biosimilars pathway pharmaceuticals and agricultural chemicals. G in this country enables safe and timely patient access and patient savings”. One keyway in which the FDAcould encourage favourable IN BRIEF conditions, Neas suggested, would be to followEurope in adopting the existing international non-proprietary name (INN) conventions GERMAN REBATE TENDERS covered just overthree-fifths, or for biosimilars in the US. 348 million out of 570 million packs, of all off-patent medicines “GPhA is pleased to see the recent progress being made,”the dispensed through the country’sstatutory health insurance funds association concluded. The FDAhas recently followed the advice last year,according to IMS Health data. G of its Oncologic Drugs Advisory Committee in approving Sandoz’ filgrastim biosimilar (see front page). G

13 March 2015 GENERICS bulletin 11 Full Pg Adv.1 11-03-15_Layout 111/03/2015 10:01 Page 1

Sponsoring an Award will getyou noticedbythe global generics and biosimilars industries.

Contact [email protected] for more details.

Awards Presentation &Cocktail Reception. Madrid, Spain,Tu esday13October 2015

Visit www.generics-bulletin.com Email [email protected] Call +44 1564 777550

Awards sponsored by: Gen 13-3-15 Pgs. 11-14_Layout 1 11/03/2015 17:46 Page 5

MARKET NEWS

IN BRIEF REGULATORY AFFAIRS CANADIAN province British Columbia has announced that its PharmaCareprogramme has selectedAccel Pharma, Ranbaxy GPhA praises billto Canada and Septa Pharmaceuticals as “sole suppliers to PharmaCare for sevengeneric drugs, beginning 1April 2015”. This sole-supply deal would save the programme “more than C$2 million (US$1.61 million) ayear”, the province’shealth ministry stated. Accel will protect GDUFA fees provide alendronate, celecoxib, fluoxetine, quetiapine and topiramate, while Ranbaxy will supply escitalopram and Septa orodispersible bipartisanbill that would shield user fees paid to the US Food zolmitriptan. The deal lasts for ayear,atwhich point other suppliers Aand Drug Administration (FDA) from being clawed back, or will be able to submit price offers. sequestered, by the US Treasury has been hailed by the US Generic Pharmaceutical Association (GPhA), as well as by brand EMA –the European Medicines Agency–says that adjusted fees industry bodies PhRMA and BIO. formarketing-authorisation applicants that are due to come into The FDASafety Over Sequestration (SOS) Act reintroduced effect from the start of April are expected to represent a0.1% decrease by RepresentativesAnna Eshoo and Leonard Lance would ensure compared to the previous year.Noting that full details would be that the agencyretained all the user fees it collected from industry, published at the end of March, the agencyconfirmed that all even if the US Treasury tried to impose automatic spending cuts on applications receivedby31March would be charged at the current rate. agencies through sequestration. “User fees for generic drugs are 100% industry-supported and NORTHERN IRELAND could make“significant savings if doctors applied to the shared priorities established by the historic Generic Drug consistently prescribed lower-cost medicines which are as effective User Fee Act (GDUFA),”the GPhA’s president and chief executive as ones that are more expensive”, according to areport by the officer,Ralph Neas, pointed out. Such fees totalling more than country’spublic accounts committee. While the health service had US$300 million per year,hesaid, would be vital as the FDAworked made savings by encouraging doctors to prescribe generics, the to clear abacklog of around 4,000 pending generic applications. G committee acknowledged, there were still savings opportunities “if the lowest-cost versions of generic drugs were prescribed”. “If the most effective and least costly drugs had been prescribed,”the REGULATORY AFFAIRS committee found, “it would have saved£8.9 million (US$13.7 million) in 2012 and £5.1 million in 2013.” EMA asks industryabout ISO EU –European Union –national medicines authorities are being iscussions on creating aEuropean Medicines Agency(EMA) asked to participate in a European MedicinesAgency (EMA) Droadmap for converting the agency’s‘Article 57’ medicines database task force to implement international standards for the identification to ISO standards will nowinclude industry.The EMA is seeking input of medicinal products (IDMP) for human use. The IDMP standards on howtoimplement ISO identification of medicinal product (IDMP) finalised by the International Organization for Standardization (ISO) terminology in the European Union (EU) by July 2016. in 2012 established data elements, formats and technologies for the Through its roadmap, the agencywill outline howtoimplement unique identification of medicines, the EMA noted. This wasexpected asubstance, products, organisations and referentials (SPOR) master- to “simplify the exchange of information between regulatory data management system. authorities across the world”. International implementation guides General activities to be performed will include: conducting “a would become available in 2016, the agencystated, adding that a full gapanalysis” comparing the current XEVPRM standard with the strategy and ‘roadmap’ for the EU would be developed by the IDMP format; migrating data from the current Article 57 database to task force this year (see opposite). the master-data management system; and optimising current processes. At present, the EMA is discussing with the EU Network Data SWISSMEDIC –Switzerland’smedicines agency–and China’s Board (EUNDB) an operating model for exchanging information Food and Drug Administration (CFDA) have signed abilateral based on the IDMP format that is obtained from sources other than agreement to open “dialogue” between the twoauthoritieson marketing-authorisation holders. Once cleaned, such information health-related mattersincluding medicines.“Regular exchanges would be stored “in asingle repository”. shall increase each other’sunderstanding for the respective As of January this year,1,450 marketing-authorisation holders regulatory systems and legalframeworks in the twocountries as had listed around 385,400 products using the current format. G well as build mutual trust,”Swissmedic said.

ISPE –the International Society for Pharmaceutical Engineering – REGULATORY AFFAIRS will release preliminary data and findings from its quality metrics pilot programme at the organisation’s‘quality summit’ on 21-22 Ukraineimposes importduty April. “Responding to the US Food and Drug Administration’s (FDA’s) call for quality metrics,”the ISPE stated, “the summit will kraine’sgovernment says it will adopt “shortly” legislation that be an effective vehicle for communication between industry and the Uwill impose a5%surcharge on pharmaceutical imports for aperiod FDA.”The pilot data would provide insight on howquality might of one year.However,the legislation exempts “essential goods”. be measuredand howthis may affect pharmaceutical regulation, Expressing its concerns at the lack of aclear definition of “essential the ISPE promised. goods”, Ukraine’sAssociation of International Pharmaceutical Manufacturers (AIPM) called on the government to clearly specify EPO –the European Patent Office –says the number of biotechnology drug groups for which the additional import duties would apply. patent filings increased by 12.1% to 5,905 in 2014. At the same time, Furthermore, AIPM noted that manyimported brands had “no the number of “pharma” applications dropped by 5.4% to 5,270. G alternativesavailable in Ukraine”. This, the association warned, could lead to price increases. G

13 March 2015 GENERICS bulletin 13 Gen 13-3-15 Pgs. 11-14_Layout 1 11/03/2015 17:46 Page 6

MARKET NEWS

MARKET RESEARCH US advances drive growth in global market

13% turnoverincrease in the US drove up global generics sales Annual sales Change Proportion Aby atenth to US$195 billion in the 12 months ended September (US$ billions) (%) of total (%) 2014, according to IMS Health data. With annual sales of US$64.9 billion, the US made up athird of US 64.9 +13 33 the global generics market by value (see Figure 1). And the US China 23.9 +12 12 accounted for two-fifths of the global markets absolute sales gain Brazil 10.9 +17 6 during the 12-month period. China ranked second by value with sales ahead by 12% to Germany8.1 +5 4 US$23.9 billion, equivalent to just over12% of the global total. Third- France 7.2 -1 4 placed Brazil wasthe fastest-growing of the world’stop-10 generics India 6.9 +10 4 markets, although its 17% growth to US$10.9 billion still put sales UK 6.1 +7 3 in the country at less than half of those in China. Japan 5.8 +14 3 Germany’s5%rise to US$8.10 billion widened the gapwith Canada 4.8 ±0 2 fifth-placed France, which suffered a1%dip to US$7.22 billion. India matched the overall market with turnoverahead by atenth to US$6.88 Italy 4.2 +7 2 billion, ahead of the UK, Japan, Canada and Italy. Top10countries 142.8 +11 73 With combined turnover11% higher at US$143 billion, the top-10 Others 52.7 +9 27 countries by value represented almost three-quarters of the global total. Measured in standard units, the global generics market was Global 195.5 +10 100 significantly more fragmented, with the top-10 countries accounting for less than two-thirds of all global sales by volume that increased Figure1:Breakdown by countryofthe global generic medicines market that was valued at US$195 billion in the 12 months ended September 2014 (Source – by 5% to 1.02 trillion standard units. IMS Health) As with the value figures, the US led the waywith sales ahead by arelatively modest 3% to 187 billion units. The US’ 18.4% volume Annual volume Change Proportion share –compared to its 33.2% value share –suggests generics prices (standard unit billions) (%) of total (%) in the country are almost double the global average. India –ranked sixth by value –was the second-largest generics US 187.0 +3 18 market by volume, followed by China. And Japan’srapidly-expanding India 158.4 +6 16 generics market overtook Germanytotakefourth position following China 48.1 +8 5 13% volume growth to 43.7 billion units. Japan 43.7 +13 4 Presenting the data during the annual meeting of the US Generic Pharmaceutical Association (GPhA), Doug Long –vice-president of Germany40.7 +3 4 industry relations at IMS Health –pointed out that Pakistan ranked UK 40.2 +5 4 eighth by volume, and Bangladesh tenth. Brazil 37.6 +11 4 “Generics are taking an increased share in all markets,”Long Pakistan 34.2 +5 3 observed, noting that in the decade ended 2013, generics had gained Russia 30.8 +4 3 at least 10 percentage points of the retail prescription market in all major countries or regions apart from Canada. Bangladesh 27.0 +4 3 However, he warned, “buyers are for the first time exercising Top10countries 647.9 +6 64 leverage on the global market”. Highlighting recently-formed alliances, Others 369.1 +3 36 Long said 84% of the US generics market wasnow covered by four buying consortia: the Red Oak Sourcing joint venture between CVS Global 1,017.0 +5 100 and Cardinal; Walgreens with Alliance Boots and AmerisourceBergen; Figure2:Breakdown by countryofthe global generic medicines market McKesson with Celesio and Rite Aid; and the Econdisc consortium comprising 1.02 billion standardunits in the 12 months ended September 2014 involving Express Scripts, Kroger and Supervalu. G (Source –IMS Health)

IN BRIEF IN BRIEF EMA –the European MedicinesAgency–has confirmed that its BGMA –the British Generic ManufacturersAssociation –has called committee for human medicinal products (CHMP) has agreed to the onset of biosimilar competition on infliximab in the UK a re-examine some of the European marketing authorisations that “significant milestone in the development of the sector”. Warwick were recently recommended for suspension following concerns Smith, director general of the BGMA, said 2015 would be “a oversupporting data provided by GVK Biosciences. Hundreds of breakthrough year for biosimilars” with the launch of infliximab marketing authorisationsand dozens of generics firms were affected (Generics bulletin,27February 2015, page 1) heralding “a sea-change by the suspension recommendation (Generics bulletin,6February in their use”. Moving forward, Smith said, “appropriate mechanisms” 2015, page 17). Certain marketing-authorisation holders have since were needed to ensure that such medicines were best utilised. requested areview. “Upon receipt of the grounds for their requests,” Moreover, Smith noted, infliximab represented the first biosimilar the agencysaid, “the CHMP will start are-examination, which launches since the UK’sNational Institute for Health and Care will conclude within 60 days.” G Excellence (NICE) updated its biosimilars guidance earlier this year. G

14 GENERICS bulletin 13 March 2015 Gen 13-3-15 Pgs. 15-21_Layout 1 11/03/2015 17:46 Page 3

PRODUCT NEWS

CHOLESTEROL-LOWERINGDRUGS ANTIDEPRESSANTS Pfizer fights Lipitor Germany upholds its charges in Australia ruling on quetiapine

fizer wasnot guilty of offering anti-competitive inducements to straZeneca’sGerman version of European patent EP0,907,364 PAustralian pharmacists to stock up on the firm’sown generic Aprotecting Seroquel XR (quetiapine) extended-release tablets is version of its Lipitor (atorvastatin) brand ahead of patent expiry in invalid, Germany’sFederal Court of Justice has confirmed following May 2012, the country’sFederal Court has decided. the originator’sappeal against a2012 obviousness finding by the Justice GeoffreyFlick said the complainant, the Australian country’spatent court (Generics bulletin,23November 2012, page 1). Competition and Consumer Commission (ACCC), had failed to Teva –which wasforced to withdrawits extended-release establish that the originator had acted with the aim of “substantially quetiapine from the German market due to AstraZeneca’slegal action – lessening competition”. The ACCC had alleged that Pfizer had offered said it intended “to recoversubstantial legalcosts and damages”, significant discounts and rebates on previous sales of Lipitor if including US$48 million of lost revenues, from the originator.“The pharmacists ordered minimum volumes of the originator’sgeneric outcome also releasesTeva from potential damages for sales made version of the brand before patent expiry. since March 2012,”the Israeli group noted. “Prior to the loss of patent protection in May 2012,”the ACCC In its recently-released ruling, the Federal Court of Justice, or noted, “Lipitor wasprescribed to overone million Australians, with Bundesgerichtshof,said the technical problem addressed by annual sales exceeding A$700 million (US$550 million).” AstraZeneca’s‘364 sustained-release formulation patent wasdelivering amore effective delivery form of quetiapine. ‘Seeking to remain competitive’ “The patent court correctly came to the conclusion that askilled Noting that Pfizer had “relatively no prior experience” in person would have had cause to seek delivery forms through which Australia’sgenerics market, Flick said the originator wasrather quetiapine could be administered just once aday,” the panel of five “seeking to remain competitive in the market” by offering incentives Court of Justice judges stated, referencing prior-art documents for pharmacists to buyLipitor and the firm’sgeneric version of the including a‘Gefvert’article on desirable dosing schedules for cholesterol-lowering brand. immediate-release Seroquel IR. “The ACCC will carefully consider the judgement,”its chairman, Givenconcerns overpeaks in plasma concentration, the five judges Rod Sims, stated, adding that the watchdog had brought the case noted, askilled person would have to look for alternativestosimply “because it raised important public-interest issues regarding the conduct increasing the delivered dose of quetiapinefor achieving once-daily of apatent holder nearing expiry of that patent and what constitutes administration. Obvious alternatives, theysaid, included asustained- permissible competitive conduct”. G release formulationwith lower variations in plasma concentration. G

LITIGATION/OTCMEDICINES RB sued over Mucinex delay un’sURL Pharma and fellowIndian firm Mutual have sued SReckitt Benckiser in aPennsylvania district court after the originator allegedly refused to honour asettlement agreement under which it would supply Mutual with aUSauthorised generic of its Mucinex(guaifenesin) 600mg extended-release tablets once the first generic version of the cough and congestion remedy became available. “Both Mutual and consumers of extended-release guaifenesin products have been and continue to be harmed,”the firms insisted, pointing out that the originator had “expressly repudiated any obligation to supply Mutual with such tablets” after Perrigo introduced the first generic extended release guaifenesin in the US twoyears ago (Generics bulletin,5April 2013, page 2013). “In the absence of Reckitt’sbreach, Mutual’searlier market entry would have substantially benefitted Mutual in its competition with Perrigo,”the lawsuit states. “Now, as the result of Reckitt’s conduct, Mutual will be at asignificant disadvantage when it enters the generic market. Further,Reckitt’sconduct has prevented the development of abroad and vibrant generic market to compete with Reckitt’s600mg Mucinexproduct.” “The financial harm to Mutual resulting from Reckitt’s anticompetitive conduct is at least on the order of tens of millions of dollars,”the firms insisted.Mutual is seeking treble ‘actual’damages, direct and indirect damages “flowing from Reckitt’sbreach of the settlement agreement”, aruling ordering that the originator honour the settlement, and fees. G

13 March 2015 GENERICS bulletin 15 Gen 13-3-15 Pgs. 15-21_Layout 1 11/03/2015 17:46 Page 4

PRODUCT NEWS

DIABETES DRUGS/ANTIBIOTICS BIOLOGICALDRUGS Apotex wins acase Infliximab meeting is but pays on cefaclor postponed by FDA

potexhas convinced aCanadian Federal Court that apatent US Food and Drug Administration (FDA) meeting scheduled Aprotecting Servier’sDiamicron MR (gliclazide) 60mg modified- Afor 17 March to discuss Celltrion’sapplication for abiosimilar release tablets should not prevent the generics firm obtainingaNotice rivaltoJanssen’sRemicade (infliximab) monoclonal antibody has of Compliance (NOC), or marketing authorisation, for its ownversion. been postponed “due to information requests pending with the sponsor But in aseparate ruling, the same court has ordered Apotextopay of the application”. “A future meeting date will be announced in Eli Lilly C$106 million (US$85.2 million) plus post-judgement the Federal Register,” the agencystated. interest for infringing cefaclor process patents. The FDA’sArthritis Advisory Committee had been due to discuss Servier had sought to bar Apotexfrom getting an NOC for Celltrion’sbiologics license application (BLA) for its CT-P13 infliximab gliclazide modified-release tablets until after Canadian patent 2,629,670 candidate for arange of indications including Crohn’sdisease, expires on 24 April 2028. But Justice Yvan Roysaid Apotex’ tablets rheumatoid arthritis and ulcerative colitis. The South Korean company did not infringe the ‘670 patent because theydid not contain abinder had filed its biosimilar application in August last year (Generics described in the patent, nor did theyhavethe required identical in vitro bulletin,5September 2014, page 17). dissolution profile to the original. According to acomplaint Janssen has just filed against Celltrion “There is no agglutination –rather,Apotexuses compression and its partner Hospira in aMassachusetts district court, the FDA for its tablet,”Roy recognisedindismissing Servier’sinfringement accepted Celltrion’sBLA “on or about 7October 2014”. case on the binder. The legalaction argues that Celltrion and Hospira have “refused to follow” statutory patent-dispute resolution provisions and have Invalid for obviousness prematurely served a‘notice of commercial marketing’. It cites six Turning to Apotex’ invalidity attacks, Royfound the patent was US patents that expire between September 2015 and February 2027. obvious in light of prior art. “Apotexhas shown that the skilled “Defendants have insisted that [we] plaintiffs file this lawsuit before worker would have been able to combine the mosaic of prior art into the conclusion of the Biologics Price Competition and Innovation Act the claimed invention,”hesaid. “The step wasnot high –the gapwas (BPCIA) dispute-resolution process,”the action maintains. not broad.”Furthermore, there was“no evidence whatsoeverofutility” Pointing out that Celltrion and Hospira had failed to obtain in the ‘670 patent, as twobioequivalence studies cited by Server during declaratory judgements, Janssen says “defendants have nowproceeded the case were not alluded to or referenced in the patent’sspecification. to short-circuit the statutory process by withholding required information, Awarding damages against Apotexfor infringing eight Lilly and by refusing to participate to date in required statutory procedures,and Shionogi process patents by importing bulk cefaclor from Kyong Bo by serving apremature notice of commercial marketing”. In particular, and Lupin, Justice Russel Zinn said Lilly’slost profits before interest the originator claims the biosimilar developers have failed to provide were C$31.2 million. But pre-judgement interest of C$75.0 million details of their manufacturing process, have refused to enter into good- in the long-runningcase took the total damages to overC$106 million, faith negotiations overpatents and have announced commercial plus post-judgement interest at arate of 5.0% until paid. G marketing before obtaining regulatory approval. Patents asserted by Janssen include twocell-growth media patents – 7,598,083 and 6,900,056 –that expire on 7February 2027 and 5October 2022. Purification methods patent 6,773,600 expires on 4June 2023. DRY-MOUTHTREATMENTS/LIVER-DISEASEDRUGS Antibodies method patent 5,807,715 runs until 15 September this year,while fistulising Crohn’spatent 7,223,396 expires on 29 June Impax divests two to Perrigo 2016. Also asserted is antibody patent 6,284,471 that wasrecently mpax and CorePharma have agreed to divest the latter’srights to rejected by the US Patent and Trademark Office (USPTO) following Igeneric pilocarpine and ursodiol tablets to Perrigo as acondition re-examination(Generics bulletin,27February 2015, page 1). G of the US Federal Trade Commission (FTC) clearing the US$700 million acquisition of CorePharma by Impax that wasagreed last year (Generics bulletin,17October 2014, page 1). Under the proposed settlement –which is open to public comment until 6April –Impax and CorePharma must also provide “transitional services” and help Perrigo to obtain US approvalfor generic pilocarpine and ursodiol. Noting that only Actavis and Lannett currently supplied pilocarpine 5mg tablets for treating dry mouth in the US, the FTC said “Impax and CorePharma are the only likely newentrants into this market in the near future”. Impax, the FTC observed, wasone of four competitors in the US ursodiol market, along with Actavis, Glenmark and Par. But CorePharma was“the next likely entrant” into amarket for the liver- cirrhosis treatment in which supply shortages had “created an imbalance between supply and demand”. On 10 March, Impax announced that it had completed the US$700 million transaction (see page 7). G

16 GENERICS bulletin 13 March 2015 Gen 13-3-15 Pgs. 15-21_Layout 1 11/03/2015 17:46 Page 5

PRODUCT NEWS

HEPATITIS CDRUGS GASTROINTESTINAL DRUGS/ANTIVIRALS Gilead strikesdeals Ranbaxy failsincase with two on Sovaldi over US exclusivities

ylan and Natco Pharma have both struck licensing deals with anbaxy’smotion for apreliminary injunctionagainst the US Food MGilead for arange of sofosbuvir-based medicines. Rand Drug Administration’s(FDA’s) decision to rescind the firm’s Natco has signed an agreement with Gilead to manufacture and approvals and 180-day generic market exclusivity periods for market generic versions of hepatitis Ctreatments containing sofosbuvir esomeprazole and valganciclovir has been denied. Columbia District in 91 developing countries. The agreement covers sofosbuvir –the Judge Beryl Howell granted summary judgements to the FDAaswell active ingredient in Gilead’sSovaldi blockbuster –onits ownaswell as to interveners Dr Reddy’s, Endo and Teva. as in combination with ledipasvir or with the originator’sGS-5816 Howell’sruling wasfiled under court seal to allowthe parties to compound that is undergoing Phase III clinical trials. propose redactions.But in abrief order,against which Ranbaxy can Under the terms of the deal, the Indian firm can set its ownprice appeal, she said there was“no genuine dispute as to anymaterial fact”. for its generic versions. Natco will pay Gilead an undisclosed royalty In its suit, Ranbaxyhad claimed that the FDA’sdecision on 4 on sales “to support product registrations, medical education and November last year to strip the firm of exclusivity for generic versions training, safety monitoring and other essential business activities”. of Nexium (esomeprazole) and Valcyte (valganciclovir) had cost the Separately,Gilead has appointed Mylan as its exclusive distributor company“literally hundreds of millions of dollars” in lost sales. in India for Sovaldi 400mg and Harvoni (sofosbuvir/ledipasvir) “The agencyissued its decision with no prior notice to Ranbaxy,” 400mg/90mg tablets. Mylan plans to start distributing Sovaldi through the Indian companycomplained. its HepatoCare division during the second quarter of this year after Furthermore, Ranbaxy contended the FDAhad “no power” to Indian regulators approvedthe oral treatment in January.The two withdrawapprovals granted six years earlier.The Indian firm said it companies already have their ownlicensing and technology-transfer had secured tentative approvalfor its abbreviated newdrug application agreement for generic sofosbuvir,sofosbuvir/ledipasvir and sofosbuvir/ (ANDA) for esomeprazole capsules and valganciclovir in February GS-5816 in 91 developing countries. G and June 2008 respectively,within 30 months of filing both ANDAs. Ranbaxy planned to makefinished-dose esomeprazole and valganciclovir at its site in Paonta Sahib, India, with the bulk drug for the latter supplied from its plant in Dewas, India. Both facilities were OPIOID ANALGESICS subject to warning letters as well as to aconsent decree that required the firm’spending ANDAs to be audited for fraudulent data. CDER plans opioids guidance In November last year,the FDAdetermined that it had approved raft guidelines on “general principles for evaluating abuse- Ranbaxy’sANDAs in error “because of the compliance status of the Ddeterrent propertiesofgeneric solid oral opioid drug products” facilities referenced in the ANDAs at the time the tentative approvals have been added to alist of planned guidance documents that the US were granted” (Generics bulletin,14November 2014, page 20). The Food and Drug Administration’s(FDA’s) Center for Drug Evaluation agencythen gave final approvaltovalganciclovir ANDAs filed by and Research (CDER) intends to publish in 2015. The list also includes Dr Reddy’sand Endo, while Ranbaxy failed to persuade the Columbian four biosimilaritydraft guidances –including one on “demonstrating court to issue atemporary restraining order (Generics bulletin,5 interchangeability to areference product” –aswell as guidelines on December 2014, page 27). package insert labelling, refusals to receive abbreviated newdrug Teva has just launched the first generic alternative to Nexium in applications (ANDAs) and type-II drug master file (DMF) assessments the US, having had to alter the drug’slabelling following alate change (Generics bulletin,16January 2015, page 8). G by the originator (Generics bulletin,27February 2015, page 22). G

ONCOLOGY DRUGS BIOLOGICALDRUGS Actavis beats Alimta patent UK backs biosimilar infliximab ctavis’ generic version of Eli Lilly’sAlimta (pemetrexeddisodium) ospira’sInflectraand Mundipharma’sRemsima infliximab Adoes not infringe the originator’s vitamin regimen patent, Hbiosimilars are suitable treatments for moderate to severe ulcerative Germany’sCourt of Appeal has ruled in overturning aDüsseldorf colitis after conventional therapieshavefailed, according to a regional court’sfindings from last year (Generics bulletin,2May 2014, technology-appraisal guidance just released by the UK’sNational page 14). Actavis intends to market adipotassium salt form of the Institute for health and Care Excellence (NICE). chemotherapydrug once the German molecule patent expires in Noting that the twobiosimilars were approvedfor ulcerativecolitis December 2015, butLilly plans to appeal to Germany’sSupreme on the basis of extrapolated data, NICE recognised that “the European Court overthe European EP1,313,508 regimen patent that runs Medicines Agency(EMA) wascontent that the pharmacokinetics, until June 2021. efficacy, safety and immunogenicity profiles of the biosimilars were The German ruling mirrors anon-infringement decision handed similar to those of the reference product”. At the time of the appraisal, down by the English High Court last year in alandmark decision that it added, neither Inflectra nor Remsima had an approvedlist price. the court extended to coverpatents in France, Italy and Spain (Generics Launch list prices in Germanyfor Inflectra range between bulletin,6June 2014, page 17). An appeals hearing in the UK case C802.94 (US$871.68) for one 100mg powder for concentratevial beganon9March. Aseparate appeal is pending before the Technical to C3,920.04 for five.Those prices are around 6% lower than Board of Appeal of the European Patent Office (EPO). G Mundipharma’sentry list prices for Remsima. G

13 March 2015 GENERICS bulletin 17 Gen 13-3-15 Pgs. 15-21_Layout 1 11/03/2015 17:46 Page 6

PRODUCT NEWS

ANTIHYPERTENSIVES/ORAL CONTRACEPTIVES IN BRIEF STADA has launched ageneric version of Otsuka’s Abilify First US Tarka rivals (aripiprazole)inSpain. Available in 28-tablet packs of 5mg, 10mg and 15mg tablets, the schizophrenia treatment adds to aportfolio of antipsychotics that also includes olanzapine, quetiapine and risperidone. Meanwhile,Stada Spain has also introduced arival claimed by Glenmark to Pfizer’s Lyrica (pregabalin)capsules in 25mg, 75mg, 150mg and 300mg strengths. lenmark has begun shipping the first US rivals to AbbVie’sTarka G(trandolapril/verapamil) extended-release tablets in four strengths – ACTAVIS has broadened its topicals portfolio after launching aUS 1mg/240mg, 2mg/180mg, 2mg/240mg and 4mg/240mg –following rivaltoFougera’s Temovate (clobetasol)0.05% cream. The generics the expiry of US patent 5,721,244 on 24 February.Citing IMS Health companywill compete for ashare in the US market with approved data, the Indian firm said the branded antihypertensive had sales of abbreviated newdrug application(ANDA) holders Taro, G&W around US$23.5 million in 2014. Laboratories and the Sandoz affiliate itself, along with Akorn’s Glenmark had launched ageneric version of Tarka in the US Hi-Tech, which sells its generic clobetasol cream under the fantasy ‘at risk’ in 2010, butwas last year ordered to pay the US originator name Cormax. Citing IMS Health data, Actavis said US branded US$16.0 million in damages after an appeals court upheld a2011 New and generic sales of Temovate were around US$185 million for York district court ruling that found Glenmark’sversion infringed the the 12 months ended 15 January 2015. Meanwhile, Actavis has ‘244 patent (Generics bulletin,2May 2014, page 21). also receivedapprovalfrom the European Commissionfor its Meanwhile, the Indian firm has also introduced in the US ageneric Xydalba (dalbavancin)treatment for acute bacterial skin and version of Teva’s Seasonique (levonorgestrel/ethinylestradiol) oral skin-structure infections. contraceptive tablets under the brand name Ashlyna. The Indian companywill compete with Lupin’sDaysee version, and Actavis’ generic ANI PHARMACEUTICALS has furtheredits relationship with Teva (Generics bulletin,5August 2011, page 19) in aUSmarket that was and bolstered its “near-term generics pipeline” in the US after worth US$159 million last year,according to IMS Health data. G acquiring the Israeli firm’sapprovedabbreviated newdrug application (ANDA) for flecainide 50mg, 100mg and 150mg tablets for an undisclosed sum. Just overayear ago, the US player bought 31 ONCOLOGY DRUGS generics from Teva in adeal worth up to US$12.5million (Generics bulletin,10January 2014, page 3). Pointing out that flecainide had Galenicum rolls out in Peru sales of around US$39 million in 2014 according to IMS Health data, ANI said that it expected to “re-launch this product within the pain’sGalenicum says it is one of the first companiestointroduce next 12 months”. Generics players Amneal, Ranbaxy and Boehringer S‘bioequivalent’ drugs in Peru, ahead of pending legislation that Ingelheim’sRoxane also hold approvedANDAs for the heart will establish bioequivalence requirements in the country similar to disease treatment in all three strengths. those in other Latin American countries –such as Brazil, Chile and Mexico –aswell as in the US and Europe. ARTERIUM has introduced tranexamicacid 500mg/5ml solution Noting that it had initially launched oncology medicines, the for injection in Ukraine. The haemostatic agent –which was Spanish firm –which has an office in Peru –said it would “in the produced by the company’ssubsidiary Galychpharm in compliance next fewmonths” launch arange of central nervous system medicines. with European standards –isbeing marketed as Tramix. Treatments for heart disease and cardiovascular conditions will be introduced during the second half of the year. G ELI LILLY says it plans to launch biosimilar insulin glargine with its partner Boehringer Ingelheim later this year in Europe, once the compound patent for Sanofi’s Lantus brand expires. The CARDIOVASCULAR DRUGS European Commission granted the twofirms’ Abasria product a marketing authorisation last year (Generics bulletin,19September Mayne has deal on dofetilide 2014, page 1) following apositive European Medicines Agency (EMA) opinion.However,Lilly noted, legalproceedingswere ayne Pharma plans to launch dofetilide capsules in the US in underway in France related to the product, while UK proceedings M2016 after reaching an agreement with Pfizer to drop all litigation relating to device patents were recently resolved in Lilly’sfavour. concerning US patent 6,124,363 that protects its Tikosyn until 9 October 2018. This comes months after Pfizer sued the Australian ALVOGEN,Actavis and Parhavebeen sued by Santarus and Cosmo firm for filing an abbreviated newdrug application (ANDA) for Technologies overparagraph IV challenges to the originators’ Uceris generic versions of the antiarrhythmic agent, triggering a30-month (budesonide)extended-release tablets. Alvogen’slitigation cites three stay of final US Food and Drug Administration (FDA) approval US patents that expire on 9June 2020, while the lawsuits against (Generics bulletin,5December 2014, page 24). Actavis and Parassert five patents that expire on this date and a Describing the agreement as a“significant event for our US further US patent, 8,895,064, that is due to expire on 7September 2031. generics business”, Mayne’schief executive officer,Scott Richards, said the firm wasnow gearing up to launch dofetilide 0.125mg, 0.25mg and REX PHARMACEUTICALS has obtained Bulgarian approvalto 0.5mg capsules in the US with 180-day generic market exclusivity market its clonazepam 0.5mg and 2mg tablets. The generic rival “as early as 2016”. Mayne’sANDAisunder priority FDAreview. to Roche’s Rivotril anticonvulsant is being marketed under the UK-based firm Johnson Mattheywill be supplyingdofetilide Clonarex brand name. active pharmaceutical ingredient (API) to Mayne, and will share equally profits from sales of the drug upon launch. Citing data from NORMON has launched a75mg strength of risedronate in Spain. IMS Health, Mayne said Tikosyn had US sales of around US$150 The firm already markets a35mg version. G million last year. G

18 GENERICS bulletin 13 March 2015 Gen 13-3-15 Pgs. 15-21_Layout 1 11/03/2015 17:46 Page 7

PRODUCT NEWS

BIOLOGICALDRUGS EPILEPSY DRUGS Merck has plansfor Courtorders NHS to five filings by 2016 protect Pfizer patent

erck &Cointends to makeregulatory filings for biosimilar ngland’sNational Health Service (NHS) must issue guidance to Mversions of Enbrel (etanercept), Herceptin (trastuzumab), Humira Ethe country’s211 clinical commissioning groups (CCGs) and to (adalimumab), Lantus (insulin glargine) and Remicade (infliximab)by the NHS Business Services Authority instructing them that pregabalin the end of next year through the US-based originator’salliance with should only be prescribed for neuropathic pain under Pfizer’sLyrica Samsung Bioepis. All five programmesare currently in Phase III brand name, the UK’sPatents Court has ordered. clinical trials, and Merck is promising “others to follow”. Justice Richard Arnold –who had previously refused to grant Pfizer Submissions for the partners’ SB4 Enbrel rivalwill exclude the an injunction to stop Actavis from marketing pregabalin capsules, but US, the European Union (EU) and Japan, while the deal does not had decided adispute overPfizer’spain method-of-use patent should go include filing for their SB5 adalimumab and SB2 infliximab candidates to trial (Generics bulletin,27February 2015, page 25) –said requiring in the EU, Russia or Turkey,where Merck markets Remicade under the NHS to issue guidance was“the most efficacious, dissuasive and licence from Johnson &Johnson. cheapest solution” to Pfizer’sfears that its patent would be infringed As with their SB3 trastuzumab drug –for which the partners if pharmacists dispensed generics for the patented indication. plan to file during 2016 –Samsung Bioepis will be responsible for Instructingthe CCGs to distribute the guidance to general developing and manufacturing the biosimilars, while Merck will practitioners, and the NHS Business Services Authority to community handle commercialisation under the terms of an alliance formed pharmacists, by 6March, Arnold said the guidance to prescribe Lyrica twoyears ago (Generics bulletin,8March 2013, page 23). would end when Pfizer’sUKpart of European patent EP0,934,061 Merck will both manufacture and market the firms’ MK-1293 expired on 17 July 2017, or earlier if the patent were revoked. alternative to Sanofi’sLantus diabetes blockbuster. Unveiling Merck’spipeline during aCowen and Company Keogh letter aided appeal investors’ conference, the firm’spresident of global human health, Arnold noted that NHS England’snational medical director, Adam Schechter,said biosimilars offered “a good strategic fitwith our Bruce Keogh, had written to Pfizer declining to express aviewon global commercial capabilities” in core therapeutic categories such as howpregabalin should be prescribed. The originator then sought an diabetes and oncology. G order requiring NHS England to issue guidance. Keogh’sletter,he noted, had been afactor in the Court of Appeal allowing Pfizer to appeal against the Patent Court’srefusal to grant an injunction. In mid-February,Arnold observed, Pfizer had sued Dr Reddy’s and Teva for infringingthe ‘061 patent, seeking injunctions against both generics firms. Reddy’s, along with Actavis, launched pregabalin capsules in mid-February,joining Consilient Health on the market. But Teva has yet to obtain amarketing authorisation. “The legitimate interests of the generic pregabalin suppliers are protectedbythe terms of the order,” Arnold insisted. Actavis, Reddy’s and Teva were each covered by undertakings on damages required from Pfizer,hepointed out, as were NHS England and the UK Department of Health. Rejecting Pfizer’sobjections, he said the generics firms could be disadvantaged if the patent wasfound invalid or the guidance led to Lyrica being dispensed instead of generics for non-infringing indications. In Wales, Arnold noted, NHS chief pharmaceutical officer Roger Walker had pledged to write to health boards to update them on the patent situation, as well as to offer them “his personal view on howtheyshould act”. G

BIOLOGICALDRUGS EMA informs on biosimilars xplaining “the science behind biosimilars”, howtheyare evaluated Eby regulators and “howtobridge the scientific evaluation with clinical reality and public acceptability” wasthe focus of abiosimilars information session that the European Medicines Agency(EMA) hosted on 5March. Aimed at organisations representing healthcareprofessionals, patients and consumers, participation wasbyinvitation only.However, the European agencyplans soon to makepresentationsfrom the session available publicly. G

13 March 2015 GENERICS bulletin 19 Gen 13-3-15 Pgs. 15-21_Layout 1 11/03/2015 17:46 Page 8

PARAGRAPH IV WATCH Ella challenge may stretch beyond sales

eneric-drug development can be atime-consuming enterprise, with Gyears of work and investment necessary before the submission KEY DETAILS: ELLA of an abbreviated newdrug application(ANDA) to the US Food and Brand: Ella Drug Administration (FDA). Heavy competition has drivenmanyUS companies to seek the potentially lucrative 180-day generic drug Active ingredient: ulipristalacetate exclusivity that may be awarded to the first filer of an ANDAthat Delivery form: 30mg tablets includes aparagraph IV certification of patent invalidity or non- infringement. Reference drugs covered by afive-year NewChemical Brand owner: Laboratoire HRA Pharma Entity (NCE) exclusivity offer aknown filing date –four years from the date of first FDAapproval, on the so-called NCE -1 date –that will First paragraph IV 13 August 2014 ensure first-filer status. filing submitted to FDA: With the time necessary for development in mind, generics companies must sometimes makethe decision to target anew product Known paragraph IV filers: Teva for ageneric challenge before the true commercial prospects of the US patents at issue – 8,735,380 –20February 2029 drug are clear.Market projections and overall portfolio strategy must 8,512,745 –14February 2030 stand in for direct evidence of commercial potential. In some cases, 8,426,392 –12June 2030 considerations beyond simple sales potential may drive continued pursuit of generic approval. Teva’s patent challenge to Laboratoire Other Orange Book patents: 8,962,603 –12June 2030 HRA Pharma’semergencycontraceptive Ella (ulipristal acetate) tablets may be one such case. District court locations: Delaware Ella wasfirst approvedinAugust 2010 and marketed in the US through Actavis’ Watson. In March 2014, HRA Pharma announced Litigation references: Laboratoire HRA Phama vs acommercial partnershipwith family-planning supplier Afaxys in a Teva Pharmaceuticals USA – bid to improve access to the emergencypill. “US sales of Ella appear 1:15-cv-00045 to have been extremely modest, with IMS reporting 12-month Figure1:Paragraph IV challenges to LaboratoireHRA Pharma’s Ella (ulipristal ulipristalacetate sales of under US$2.5 million through the end of acetate) tablets in the US (Source –Thomson Reuters) September 2014,”observes Thomson Reuters, which maintains a database of paragraph IV challenges and resulting litigation. Yet, despite Active Brand Earliest ANDA the lack of commercial success, the FDAreports that an ANDAfor ingredient name submission date ageneric version of Ella wassubmitted on 13 August 2014, which wasthe first day possible, giventhat NCE exclusivity for ulipristal Ioflupane I-123 Datscan 14 January 2015 acetate expires on 13 August 2015. Teva provided notice of its Spinosad Natroba 18 January 2015 paragraph IV certification in December and HRA duly filed apatent- Vilazodone Viibryd 21 January 2015 infringement suit in January,asserting three patents listed against Azilsartan medoxomil Edarbi 25 February 2015 Ella in the FDA’sOrange Book. Atrial is set for February 2017. Azilsartan/chlorthalidone Edarbyclor 25 February 2015 “GivenElla’slow sales, it is not surprising that no other challengers Roflumilast Daliresp 28 February 2015 have emerged thus far,”comments Thomson Reuters. “Unless market Gadobutrol Gadavist 14 March 2015 conditions change significantly,itisunlikely that generics could recover Gabapentin enacarbil Horizant 6April 2015 development and legalcosts for several years.” Vandetanib Caprelsa 6April 2015 ForTeva,the decision to push forward with its challenge to Ella may have as much to do with the broader emergencycontraception Abiraterone acetate Zytiga28April 2015 market as with generic ulipristal acetate itself. “While the decision to Empagliflozin/linagliptin Glyxambi 2May 2015 target Ella might have occurred before it became clear that it wasnot Linagliptin Tradjenta 2May 2015 arich generic target, Teva is invested in emergencycontraception Linagliptin/metformin Jentadueto 2May 2015 through its Plan Bproducts,”Thomson Reuters points out. “Although Boceprevir Victrelis 13 May 2015 generic versions of Plan Bare available, Teva claims it is the only Emtricitabine/rilpivirine/tenofovir Complera 20 May 2015 companytohaveconducted actual-use and label-comprehension Rilpivirine Edurant 20 May 2015 studies required by the FDAfor sale without age or point-of-sale Telaprevir Incivek23May 2015 restrictions. Teva’s status as the first-to-file for Ella could work to Fidaxomicin Dificid 27 May 2015 mitigate against further market erosion upon the approvalofa generic version of Ella.” Ezogabine Potiga10June 2015 As Figure 2shows, brands including Daliresp (roflumilast), Figure2:Active ingredients subject to new chemical entity (NCE) exclusivities for Incivek(telaprevir) and Zytiga(abiraterone) face NCE-1 dates and which abbreviated new drug applications (ANDAs) can be submitted between possible paragraph IV challengesduring the first half of this year. G January2015 and June 2015 (Source –Thomson Reuters)

Thomson Reuters draws on strategic intelligence and competitive analysis information on the US generics industry to create Newport Premium™,the criticalproduct-targeting and global business-development system from the industry authority on the global generics market. Forfurther details contact Benjamin Burck, Thomson Reuters API Intelligence, 215 Commercial Street, Portland, Maine 04101, USA. Tel: +1 207 808 7977. Fax: +1 207 871 9800. E-mail: [email protected]. Website: scientific.thomsonreuters.com/newport.

20 GENERICS bulletin 13 March 2015 Gen 13-3-15 Pgs. 15-21_Layout 1 11/03/2015 17:46 Page 9

PRODUCT NEWS

BIOLOGICALDRUGS OSTEOPOROSIS DRUGS Biocad plans rival to US Atelviapatents infliximab in Russia aredeclared invalid

iocad has announced that it plans to launch the country’sfirst ey claims in Actavis’ US patents that protect its Atelvia (risedronate) BbiosimilarrivaltoJanssen’sRemicade (infliximab) in Russia in K35mg delayed-release tablets are invalid, aUSdistrict court has 2017. Noting that it had invested US$15 million in developing its determined. Teva,which had admitted infringement by its abbreviated version of the rheumatoid arthritis treatment –which is currently newdrug application(ANDA) for ageneric version of the osteoporosis undergoing clinical trials in compliance with European Medicines treatment in postmenopausal women, convinced aNew Jerseydistrict Agency(EMA) recommendations –the companysaid it expected court that claim 16 of US patent 7,645,459 and claim 20 of US patent to capture at least a50% share of Russia’sinfliximabmarket. 7,645,460 –both of which were due to expire on 9January 2028 – At present, Biocad’schief executive officer,Dmitryi Morozov, were obvious in light of prior art. stated, the annual cost of treatment in Russia for 100mg of infliximab Prior to the ruling, Actavis had dropped all asserted claims of per patient wasaround RUB1.5 million (US$24,000). However, he Atelvia’sother Orange Book-listed US patent –8,246,989 –that expires emphasised, only atenth of Russia’s150,000 rheumatoidarthritis on 16 January 2026, along with all claims of the ‘459 and ‘460 patents patients were eligible to receive such treatment. aside from claim 16 and claim 20 respectively. “By pricing our infliximab at least 15% cheaper than the original Allegations brought by Teva that these twoclaims were also drug”, he anticipated, “the government will be able to significantly invalid due to anticipation failed, however. increase its procurement of the drug, thereby improving patients’ Atelvia combines 35mg of risedronate sodium with 100mg of a access to the treatment.” calcium-blocking agent, disodium EDTA, to bind metal ions in food, Biocad has also revealed plans to launch its rivaltoRoche’s ensuring the active ingredient is not blocked when apatient has eaten. Avastin (bevacizumab) in the second half of this year (Generics NewJerseyDistrict Judge Faith Hochbergsurmised that aprior-art bulletin,27February 2015, page 25). G document –referred to in the ruling as the ‘Brazilian application’ – had disclosed using 35mg of risedronateand “a preferred range of disodium EDTAequivalent to between 20mg and 175mg”. ANTIFUNGALS “The selection of 100mg wasnot critical; there is no special benefit to choosing 100mg rather than another amount within the NZ’s Pharmac sets out tender prior-art range,”Hochberginsisted. “Considering the levelofskill in the art and the scope and content ultichem’snystatin 24ml bottle will be the only version subsidised of prior art,”Hochbergcommented, “there is clear and convincing Mby NewZealand’spharmaceutical management agency, Pharmac, evidence that aperson of ordinary skill in 2005…would have known from 1February 2016 in hospitals –and from 1May 2016 in pharmacies that EDTA’schelation mechanism would eliminatethe bisphosphonate –until 30 June 2017, following atender award by the agency. Aspen’s food effect.”“The claims are thus acombination of known elements, Nilstat brand will be subject to areference price of NZ$2.55 (US$1.88) arranged in aknown way, to produce expected results,”she concluded. in pharmacies from 1February 2016 before it is delisted. Actavis’ president and chief executive officer,Brent Saunders, Meanwhile, several other drugs were awarded sole-supply deals said the companywas “disappointed” with the ruling and “strongly that will see them listed with anew subsidy from 1July this year disagreed with the district court’sdecision”. Moreover, he added, before becoming the only versions reimbursed by Pharmac from 1 Actavis would “evaluate all available options to defend our intellectual- October when other versions are delisted. property rights on Atelvia, including an appeal”. These include presentations such as Mylan’satenolol 50mg and Separate litigation surrounding paragraph IV patent challenges 100mg tablets and entacapone 200mg tablets; Apotex’ azithromycin sent to Actavis by Impax (Generics bulletin,1November 2013, 250mg and 500mg tablets, ciclopirox 8% nail solution and page 14) and Ranbaxy had been previously resolved by individual clomipramine 10mg and 25mg tablets; Sandoz’ cefalexin 25mg/ml settlements that allowthe generics firms to launch rivals to Atelvia on and 50mg/ml oral liquid; Multichem’senalapril 5mg, 10mg and 9July 2025. US player Amneal –which twoyears ago acquired a 20mg tablets; and Douglas’ hydrocortisone 5mg and 20mg tablets. risedronateANDAfrom Actavis as part of the latter’s agreement to Mylan’sbetamethasone 0.1% cream and ointment will have buyWarner Chilcott (Generics bulletin,4October 2013, page 5) – their subsidies modified from 1April this year and will be the sole may also launch its generic version on that date according to a subsidised versions from 1July. G settlement reached last year. G

ALZHEIMER’SDISEASE DRUGS MIGRAINE TREATMENTS Acino claims rivastigminewin French répertoire adds apair cino believesithas secured acompetitive advantage after a reference group that includes generic rivals to Almirall’sAlmogran Aregional court in Munich, Germany, confirmed that its generic A(almotriptan)12.5mg tablets has been added to France’s répertoire rivastigmine patches do no infringe anyvalid patents or utility models. of equivalents following adecision by local medicines agencyANSM. The Swiss firm –which launched its once-daily rivastigmine patches Local firm Biogaran is among the companies with generic versions in Germanytwo years ago –also supplies the Alzheimer’sdisease listed in the group, along with Mylan, Sandoz and Teva.Atthe same treatment from its plant in Miesbach, Germany, to marketing time, Aurobindo has had its amoxicillin 250mg capsules listed in anew partners in Italy,the Netherlands, Spain and the UK. G group that has GlaxoSmithKline’sClamoxyl as its reference brand. G

13 March 2015 GENERICS bulletin 21 Gen 13-03-15 Pg. 22_Layout 1 11/03/2015 17:47 Page 2

EVENTS

MARCH 16-19 September 24-26 March ■ 18th IGPAAnnual Conference ■ World-China Toronto, Canada Generics Forum This three-day event is being organised by the Canadian Generic Pharmaceutical Association. It is the annual joint meeting of the Canadian, European, Japanese, Jordanian, Shanghai,China South African and US generics industry associations, the CGPA, EGA, JAPM, JGA, NAPM “World-China Generics Forum (WCGF)” and GPhA. Pharmaceutical executiveshavethe opportunity to takepart in conference calls for high-quality and high-end generics, workshops, and listen to industry experts discuss current issues regarding the international focusing on the improvement of generics pharmaceutical sector during afull schedule of plenary sessions. quality and transition from imitation to Contact:Julie Ta m, CGPA.Tel:+1416 223 2333. innovation. WCGF will provide E-mail: [email protected]: www.igpa2015toronto.com. communication and exhibition platforms for chemical drug professionals in China and abroad and promote international 20-21 April conference will include biosimilar cooperation and interaction. ■ 3rdAnnual Biosimilars & development and regulation, clinical studies, reimbursement and legal strategies. Contact: Violet Chang. Biobetters Congress Tel: +86 21 51869310. London, UK Contact:Terrapinn. Tel: +1 212 379 6322. E-mail: [email protected]. This event will address topics including Register onlineatwww.wcgenericsforum.com. E-mail: [email protected]. market access and strategies. Presentations Website: www.terrapinn.com. will provide information on emerging 23-24 March markets as well as global commercialisation ■ EU Biosimilar Registration strategies. The development of biosimilars JUNE and biobetters will be the focus of day two. and Marketing Requirements 8, 9-10 June London, UK Contact:OxfordGlobal. Tel: +44 1865 248455. ■ 6th European An interactive two-day training course E-mail: [email protected]. GMP Conference that will look at practical solutions on Website: www.oxfordglobal.co.uk. howtogain regulatory approval through Heidelberg, Germany fast, compliant registration applications. This two-day conference will discuss 23-24 April Contact:Informa UK. current and planned changes to the good Tel: +44 20 7017 7481. ■ 13th EGA International manufacturing practice (GMP) regulation. E-mail: [email protected]. BiosimilarsConference Contact:Concept Heidelberg. Website: www.pti-global.co.uk. London, UK Tel: +496221 84 44 34. E-mail: [email protected]. This meeting is organised by the EGA Website: www.gmp-conference.org. 26-27 March and will covertopics including industry ■ 11th EGA Legal developments and regulatory issues for 9-11 June Affairs Forum the biosimilars industry. ■ 21st EGA Annual Conference Brussels,Belgium Contact:Lucia Romagnoli, GPAConferences. Tel: +44 7562 876 873. Berlin,Germany This is atwo-day event organised by E-mail: [email protected]. The EGA’s three-day annual conference the European Generic medicines Register onlineatwww.egagenerics.comor will look at topics including the current Association (EGA) which will look at www.egaevents.org. regulatory environment. issues including litigation, regulatory matters and patent settlements. Contact:Lucia Romagnoli, GPAConferences. 30 April Tel: +44 7562 876 873. Contact:Lucia Romagnoli, GPAConferences. ■ EMA/EGA Joint Workshop E-mail: [email protected]. Tel: +44 7562 876 873. Register onlineatwww.egagenerics.comor E-mail: [email protected]. London, UK www.egaevents.org. Register onlineatwww.egagenerics.comor Looking at regulatory expectations in www.egaevents.org. advance of newguidelines, topics introduced 11-12 June by national regulators and industry speakers Annual Biosimilars Summit APRIL will include modified release products, ■ transdermal products and line extensions. Berlin,Germany 13-15 April Contact:Lucia Romagnoli, GPAConferences. The keypoints covered at this two-day Tel: +44 7562 876 873. event will include the evolving landscape ■ DIA 27th Annual E-mail: [email protected]. in the European Union (EU), regulatory EuroMeeting Register onlineatwww.egagenerics.comor advice and global clinical biosimilar trials. www.egaevents.org. Paris,France Contact:Vonlanthen Group. Issues to be covered at this three-day Tel: +420 267 224 122. event include innovation, clinical trials MAY E-mail: [email protected]. legislation and medical devices. There Website: www.vonlanthengroup.com. will be speakers from firms including 27-28 May2015 SAVE THE Amgen and Sanofi. ■ World Biosimilar DATE ... Contact:DIA. Congress USA Tel: +41 61 225 5151. Tu esday 13 October 2015 E-mail: [email protected]. SanDiego,USA Madrid, Spain. Website: www.diaeurope.org. Topics looked at during this two-day

22 GENERICS bulletin 13 March 2015 Gen 13-3-15 Pg. 23_Layout 1 11/03/2015 17:48 Page 3

PRICE WATCH ...... UK Digoxin and trimethoprim prices take off ome of the highest-evermonthly price rises were recorded for 200mg were £2.01 and £5.19, which compared with concessionary Strimethoprim in February,and those for digoxin were not far prices of £3.10 and £7.25, and Drug Tariffprices of £0.44 and £1.03. behind. Independent pharmacists and dispensing doctors were paying Digoxin prices were alittle tighter.Independent pharmacists last month more than eight-times the trade price for 28-tablet packs would have had to pay on average £4.63, £4.77 and £4.72 for 62.5µg, of trimethoprim 100mg theyhad been in January.Similarly,the average 125µg and 250µg packs of 28 digoxin tablets, buttheywould have trade price of the 200mg strength wasmore than five-times higher. only been reimbursed £4.20, £4.99 and £4.36 even at the concessionary Digoxin prices also rocketed in 14-count packs (see Figure 2). prices. This would have meant them making dispensing losses on The Department of Health reacted quickly by granting price the lowest and highest strengths. These would have been small, concessions for the twoingredients, which meant pharmacists were however, compared with those theywould have incurred at Drug not out of pocket. Both ingredientswere included in the monthly Tariffprices of £1.44,£1.07 and £1.01. list of products that would be reimbursed at more than Drug Tariff Price movements among recent launches were small for the most prices. Trimethoprim 100mg tablets in 28-count packs were priced part, with only the average price rise for irbesartan reaching double on average at £4.18 (US$6.40) in the market, butwould be reimbursed figures (see Figure 1). Even the most severe price falls were relatively at £7.55. This compared to £0.92 in the Drug Tariff. The equivalent modest (see Figure 3). Lansoprazole and omeprazole continued to average trade prices for 6-and 14-count packs of trimethoprim attract the most price offers among ‘fast movers’ (see Figure 4). G

RECENT LAUNCHES BIGGEST RISERS Product/Strength/Pack size Lowest Change Average Change Product/Strength/Pack size Lowest Change Average Change price (%) price (%) price (%) price (%) Amorolfine lacquer 5% 5ml £3.50 -3 £5.01 -3 Trimethoprim tabs 100mg 28 £0.23 ±0 £4.18 +748 Atorvastatin tabs 20mg 28 £0.49 ±0 £0.79 -8 Trimethoprim tabs 200mg 14 £0.20 +33 £5.19 +410 Candesartan tabs 8mg 28 £0.36 ±0 £0.81 +3 Digoxin tabs 250µg 28 £2.45 +880 £4.72 +249 Cilostazol tabs 100mg 56 £5.90 -33 £15.66 +2 Digoxin tabs 125µg 28 £2.45 +880 £4.77 +202 Cyclizine tabs 50mg 100 £7.61 -2 £10.53 -2 Trimethoprim tabs 200mg 6£0.59 +31 £2.01 +165 Desloratadine tabs 5mg 30 £0.25 -17 £0.79 +6 Digoxin tabs 62.5µg 28 £0.95 +12 £4.63 +142 Desogestrel tabs 75µg 84 £1.63 -1 £2.61 +3 Donepezil tabs 10mg 28 £0.56 ±0 £1.13 -2 BIGGEST FALLERS Entacapone tabs 200mg 30 £4.46 -2 £5.38 +2 Product/Strength/Pack size Lowest Change Average Change Escitalopram tabs 10mg 28 £0.53 -15 £1.09 -5 price (%) price (%) Hydroxychloroquine tabs 200mg 60£3.18 -1 £4.15 +1 Irbesartan tabs 75mg 28 £0.35 -13 £0.78 +16 Glimepiride tabs 3mg 30 £0.31 ±0 £0.76 -42 Latanoprost eyedrops .005% 2.5ml £0.89 ±0 £1.61 +2 Ondansetron tabs 8mg 10 £1.80 ±0 £4.43 -28 Memantine tabs 10mg 28 £0.95 -3 £2.04 -9 Galantamine XL caps 24mg 28 £6.92 ±0 £12.91 -25 Montelukast tabs 10mg 28 £0.97 -3 £1.57 +1 Quinapril tabs 10mg 28 £0.59 -13 £1.13 -24 Naratriptan tabs 2.5mg 6£1.13 -6 £1.51 -4 Quinapril tabs 5mg 28 £0.55 -5 £1.21 -24 Quetiapine tabs 25mg 60 £0.57 +27 £1.17 +2 Valsartan tabs 320mg 28 £5.31 -12 £8.64 -22 Rabeprazole tabs 10mg 28 £1.17 -12 £1.85 ±0 Raloxifene tabs 60mg 28 £3.50 ±0 £5.16 -2 FAST MOVERS Riluzole tabs 50mg 56 £13.75 -2 £25.08 ±0 Price offers as at 28 February Rizatriptan tabs 10mg 3£0.86 ±0 £2.57 ±0 Product/Strength/Pack size December January February Sildenafil tabs 100mg 4£0.36 -3 £0.68 +3 Telmisartan tabs 80mg 28 £0.79 -1 £1.81 -4 Omeprazole caps 20mg 28 126 159 160 Tolterodine tabs 2mg 56 £1.45 ±0 £2.37 -1 Lansoprazole caps 30mg 28 100 149 144 Zolmitriptan tabs 2.5mg 6£0.42 ±0 £0.95 -4 Simvastain tabs 40mg 28 91 144 134 Fluoxetine caps 20mg 30 102 137 122 Figure1(above): Comparison between the periods 1-31 Januaryand 1-28 February 2015 of UK trade prices of the most recently-launched generics listed in categoryM Naproxen tabs 500mg 28 85 120 117 of the Drug Tariffofpharmacy-reimbursement prices. Averages calculated from at least Amitriptyline tabs 25mg 28 97 109 116 38 data points. Figure2(top right) and Figure3(centreright): Biggest average trade-price changes between 1-31 Januaryand 1-28 February2015. Averages Warfarin tabs 1mg 28 96 124 116 calculated from at least 17 data points. Figure4(bottom right): Ranking of fastest- Tramadol caps 50mg 100 101 125 114 moving products subject to the most price offers made to independent UK pharmacists Citalopram tabs 10mg 28 98 118 113 (one strength per ingredient; offers recorded by 28 February). Data for Figures 2, 3 and 4fromabasket of about 750 commonly-dispensed generics. Recently-launched Gabapentin caps 300mg 100 87 108 112 products in Figure1excluded from Figures 2and 3(Source –WaveData).

WANT MORE LIKE THIS? Detailed product price comparisons and other price analyses are available at www.wavedata.net. To find out more about subscribing, please email your contact details to [email protected] and quote ‘GB online enquiry’ in the title line. ■ Forfurther information see www.wavedata.co.uk.Alternatively,contact Charles Joynson at WaveData Limited, UK. Tel: +44 (0)1702 425125.E-mail [email protected].

13 March 2015 GENERICS bulletin 23 Gen 13-3-15 Pgs. 24-25_Layout 1 11/03/2015 17:48 Page 2

MARKET RESEARCH Sovaldi recasts US specialty as generic price rises hold

As the US pharma veninthe huge US pharmaceuticals market, Brand Annual sales Change Market only ahandful of brands can boast annual sales (US$ millions) (%) share(%) market growsat Eof more than US$5 billion. And only one has double-digit rates, achievedthat status after just one year on the market Abilify 7,725 +19.7 2.1 –Gilead’sSovaldi (sofosbuvir) cure for hepatitis C. Sovaldi 7,570 –2.1 the generics sector “Sovaldi is the single biggest launch in the history Humira 7,005 +28.0 1.9 of the US pharmaceutical market, with annual sales of is keeping pace, Nexium 6,016 -1.8 1.6 about US$8 billion,”highlighted Doug Long, vice- Crestor 5,808 +9.0 1.6 president of industry relations at IMS Health. Very soon, according to the latest Enbrel 5,419 +15.8 1.5 he said, Sovaldi would overtakeAbilify (aripiprazole) Advair Diskus 4,857 -5.7 1.3 IMS Health data. antipsychotic agent as the leading US prescription brand. Presenting the latest US industry data and Remicade 4,487 +8.9 1.2 Aidan Fry reports. developments during last month’sannual meeting of the Lantus Solostar 4,343 +45.3 1.2 US Generic Pharmaceutical Association (GPhA), Long Copaxone 3,833 +2.6 1.0 said Sovaldi’srapid rise had illustrated several trends. Top1057,062 +29.5 15.5 Firstly,heoutlined, the hepatitis Cmedicine had Others 311,722 –84.5 been instrumental in returning the US pharma market to double-digit value growth. Secondly,the brand had US pharma market 368,784 +12.4 100.0 accentuated the debate overpricing and relative value Figure1:Sales of the best-selling prescription brands in the US of pharmaceuticals versus other treatment options.And in the 12 months ended November 2014 (Source –IMS Health) thirdly,ithad exposed relatively short lifecycles for older,less effective treatments. typically for chronic diseases, initiated by aspecialist “If you use one word to describe 2014, it would and required special handling, distribution, reimbursement be Sovaldi,”hemaintained. or patient counselling –increasinglybeing delivered With US sales of US$7.57 billion in the 12 months orally as small molecules,rather than as injectables. ended November 2014, Sovaldi –which entered the DrivenbySovaldi and biological drugs such as market in December 2013 –had within less than ayear Humira (adalimumab) and Remicade (infliximab), US become the country’ssecond best-selling medicine, specialty brands sales grewby25.1% in the 12 months Long noted (see Figure 1). ended November 2014, the latest IMS Health data shows. This had presented amajor headache for payers, In total, brands turnoverincreased by 12.0%, while who were faced with abill of US$84,000for Sovaldi generics sales –disaggregating branded generics plus another US$32,000 for Janssen’scompanion drug, between brands and generics –climbed by 14.2%, or Olysio (simeprevir). “People are picking sides,”Long by US$8 billion, to US$65 billion. The total US pharma observed. “This is the first time you are seeing payers market expanded by 12.4% to US$369 billion. exerting real control.” Over the same period, the number of generic Sovaldi’shuge success had effectively forced other prescriptions dispensed advanced by just 4.0% to around hepatitis Cdrugs, such as Vertex’ Incivek(telaprevir) 3.5 billion, carrying the overall US pharma market to a and Merck &Co’sVicrelis (boceprevir) offthe market 1.9% volume rise on arelatively weak flu season and just four years after theyhad been launched, Long an “average” allergy season. Generics accounted for commented. And with Gilead having already rolled 82.0% of all prescriptions, butrepresented just 17.6% out its Harvoni (sofobuvir/ of prescription drug costs in the 12-month period. ledipasvir) follow-up to “Double-digit dollar growth is back, caused by 40 2015-2018 exposure: US$78.4 billion
 Sovaldi, the potential for innovation and list-price increases,”Long remarked. 35 32.8 major brands to slip into And those rises were not limited to patented brands. therapeutic obscurity “If you look back in history,weused to have 30  27.7 within afew years, rather generic price deflation. Nowwehaveprice inflation,” 25 than decades, presented he said. Research by AmerisourceBergen found that 20.7 challenges to generics the average wholesale price of ageneric had 20 18.9  16.6 firms as theyidentified increased by 15% in the year to June to US$10.96. 15 development targets. Speculating on potential reasons for the generic 10.3 11.0 11.1

Sales (US$ billions) What all the hepatitis price inflation, Long put forward three causes: 10  Ctreatments named have increased regulatory,quality and other costs; customer 5 in common is that theyare consolidation; and fewer new-product launches. administered orally as “With the increased scrutinyfrom the US Food and 0 2011 2012 2013 2014 2015 2016 2017 2018 tablets or capsules. Long Drug Administration (FDA), manufacturers need to said this demonstrated an invest more into their quality systems,”Long recognised. Figure4:Annual sales value of US drugs –excluding biologicals – that were, or will be, exposed to generic competition in the years emerging trend of specialty Supply disruptions caused by quality problems created between 2011 and 2018 (Source –IMS Health) drugs –those that were opportunitiesfor competitorstoraise prices and recoup

24 GENERICS bulletin 13 March 2015 Gen 13-3-15 Pgs. 24-25_Layout 1 11/03/2015 17:48 Page 3

MARKET RESEARCH

their investments, he said, adding that other costs such Having split out branded generics, Long said as user fees and risk evaluation and mitigation strategies Teva –the seventh-largest pharma player in the US – (REMS) were also adding to companies’costs. led the wayinterms of unbranded generics sales with Amid customer consolidation among wholesalers a12.9% market share (see Figure 2). Manyofthe and retailers that wascreating greater purchasing top-10 companies had registered double-digit sales power,manufacturers were making profits where they growth in the 12 months ended November 2014, he could. “Manyare thinkingtheymay as well raise highlighted. “Wesaw big growth from Teva,Sandoz, their prices and see if theystick,”Long commented. Sun, Endo, Lupin and Dr Reddy’s,”Long commented. While generic price inflation wasakey topic for As with the overall generics market, volume growth US pharmacies, wholesalers and payers, generics by prescriptions of unbranded generics dispensed was manufacturers were occupied by howtooptimise more muted, although several Indian companies –such their portfolios, howtohandle purchasing alliances and as Lupin, Zydus, Aurobindo, Reddy’s, Hetero’sCamber howtodeal with OTCswitches such as for Flonase and Sun –made notable advances (see Figure 3). (fluticasone), Long said. Firms were also pondering “It wasnot abad year for generics, considering “There are some very adding branded drugs to their offerings, reducing that there wasnocompetition to Nexium or Copaxone taxes through inversion-led acquisitions, and being (glatiramer acetate), and celecoxib generics only arrived big opportunities in forced to makechanges to labels under the FDA’splans late in the year,” Long opined. And with Nexium and 2015 and 2016” to impose the same requirements as on brand owners. Copaxone on the block this year –along with Abilify Changes in the scheduling of certain controlled and Namenda (memantine) –2015 could be even better, substances were also causing headaches for some firms, especially if the first US biosimilar reached the market. with more stringent restrictions around hydrocodone “There are some very big opportunities in 2015 combinations being reflected in volume sales of and 2016,”Long noted, highlighting Advair Diskus hydrocodone/acetaminophen dropping by 6.5% to (fluticasone/salmeterol), Benicar (olmesartan) and 121 million prescriptions in the year to November 2014. Crestor (rosuvastatin),aswell as ProAir (albuterol), Over the same period, atorvastatin prescriptions Seroquel XR (quetiapine) and Tamiflu (oseltamivir). rose by 19.3% to 80.2 million, taking share away from As Figure 4shows, brands with combined annual simvastatin, which suffered a9.2% slide to 72.3 million US sales of overUS$78 billion face patent expiry prescriptions. Viewed by therapeutic category,human between 2015 and 2018. insulins and antipsychotics showed double-digit value Atotal of 41 newmolecular entities approvedby advances, butsales of proton-pump inhibitors fell by the FDAlast year –42were launched –was the most 8.2%, even though generic competition to Nexium for more than adecade, Long observed, ensuring that (esomeprazole) failed to arrive until February 2015. generics firm had plenty at which to takeaim. G

Annual sales Change Share Prescriptions Change Share (US$ millions) (%) (%) (millions) (%) (%) Teva 8,275 +21.9 12.9 Teva 538 -4.3 12.6 Mylan 7,009 +4.9 10.9 Mylan 342 -7.8 8.0 Actavis 5,737 -8.2 9.0 Novartis/Sandoz304 +13.6 7.1 Sandoz 5,076 +19.8 7.9 Actavis 301 -9.2 7.0 Sun Pharma 2,654 +14.5 4.1 Endo 237 +13.6 5.5 ParPharma 1,906 -10.9 3.0 Lupin 187 +7.4 4.4 Endo 1,845 +63.0 2.9 Amneal 149 +9.2 3.5 Lupin 1,809 +29.9 2.8 Pfizer/Greenstone 133 -8.3 3.1 Dr Reddy’s1,687 +22.2 2.6 Zydus 116 +15.8 2.7 Hospira 1,438 +6.4 2.2 Aurobindo 106 +12.5 2.5 Top1037,436 +11.2 58.5 Top102,413 +0.9 56.4 Apotex1,378 +11.2 2.2 Dr Reddy’s99+7.2 2.3 Perrigo 1,335 +11.7 2.1 Boehringer/Roxane 92 +5.8 2.1 Mallinckrodt 1,333 +29.3 2.1 Apotex92+17.0 2.1 Greenstone (Pfizer) 1,258 +2.9 2.0 Camber (Hetero) 80 +18.9 1.9 Roxane (Boehringer)1,245 +24.6 1.9 Sun Pharma 64 +7.2 1.5 Amneal 1,223 +43.8 1.9 Mallinckrodt 63 -24.0 1.5 Prasco 1,025 +50.5 1.6 Daiichi Sankyo/Ranbaxy 62 -18.1 1.4 Impax 944 +40.7 1.5 AstraZeneca 60 -4.6 1.4 Fresenius Kabi 892 -4.8 1.4 International Labs 58 +13.8 1.4 Glenmark 837 -2.7 1.3 GlaxoSmithKline 50 -10.5 1.2 Top2048,905 +12.8 76.4 Top203,134 +0.9 73.3 Total US market 64,040 +14.5 100 Total US market 4,277 +1.9 100

Figure2:Top 20 generics companies in the 12 months ended Figure3:Top 20 companies in the 12 months ended November November 2014 by the value of their unbranded generics 2014 by the number of prescriptions dispensed in the US turnover in the US (Source –IMS Health) (Source –IMS Health)

13 March 2015 GENERICS bulletin 25 OTC Sister Ad AUGUST 2014_Generics Sister Advert 03/09/2014 10:08 Page 1 Allthat’shappening in consumer healthcare

WrittenbyOTC specialists from an OTCindustryperspective Thebest decision-makers in theOTC industry don’t have thetime to go looking for good information.Theylet it come to them.Theysubscribe to OTC bulletin. GOOD VALUE Jointhousands of subscribers from competitor companiesinover35countries whoare Individual subscriptionrates already benefitting from commercialintelligence aboutbusiness opportunitiesinthe startfromjust global non-prescription medicinesand dietary supplements markets. £975

INDIVIDUAL SUBSCRIPTIONS An annual subscriptioncomprises: n 20 OTC bulletin newsletters; n AND at least 45 weekly news@OTCbulletin electronicnewsflashes containing the week’s top news stories(currentlydelivered by email). CHOICE OF FORMATS The 20 OTC bulletin newslettersare available: n EITHER as thedigital OTC bulletin-i for online access by desktop AND tablet and smartphone. These mobile devices can have Apple or Androidoperating systems. n OR in traditional hard-copyprint format, delivered by airmail; CORPORATESUBSCRIPTIONS Acorporatesubscription provides location-,country- or company-wide access to OTC bulletin-i. Contact [email protected].

AVAILABLE INSTANTLYWORLDWIDE OTC bulletin-i is the digital i-edition of OTC bulletin.Now available online for desktop access, it delivers the latest OTC bulletin on the day of publication with no postal delay.Italso comes –atNOEXTRA CHARGE –asanapp for mobile access by tablet and smartphone. OTC bulletin-i subscribers also get access to afully-searchable archive.This contains overfiveyears of OTCnewsand analysisinmore than 100 back issues. These offer an invaluable resource for researching marketingopportunities, benchmarking competitivestrengths, evaluating regulatory changes and assessing product developments. Existing subscribers canget 20% OFF when theyupgrade theirsubscriptions to include OTC bulletin-i.Contact [email protected].

Take out asubscriptionTODAY at www.OTC-bulletin.com or contact: [email protected]

Bulletin PublishingGroup, OTCPublications Ltd, 4Poplar Road, Dorridge, SolihullB93 8DB, UK. (Tel: +44 (0)1564 777550; Fax: +44 (0)1564 777524). Registered in England No: 2765878. VATNo: GB 608 0432 69 Gen 13-3-15 Pg. 27_Layout 1 11/03/2015 17:49 Page 3

PEOPLE

APPOINTMENTS PROMOTIONS Girardismade head Ruepp takes the lead of Sandoz in France at Germany’s Aristo

andoz has appointed Frédéric Girard to become president of erman generics player Aristo Pharma has promoted its head of Sthe firm’sFrench operation.Hereplaces Frédéric Collet,who Gbusiness development, Kristian Ruepp,tomanaging director has become country head of parent companyNovartis’ oncology and board member with responsibility for business development, division in France. Girard joins Sandoz from Novartis Pharma in licensing and research and development. He succeeds Stephan Walz, France, where he wasdirector of the firm’sprimary care franchise. who has left the Berlin-based company. Sandoz noted that Girard had “more than 20 years’ experience Aristo has also brought in Sabine Brand as head of production in pharma, including keyleadership roles”. These included several and quality control. She waspreviously head of quality assurance for positions within the Servier group, where Girard has served as chief Western Europe at Sandoz. Brand and Ruepp form afour-member executive officer in the UK, general manager in Russia, general manager management board along with finance and administration director Anton in Slovakia and deputy regional operations manager for Central Europe. Karremann and marketing and distribution director Stefan Koch. G Girard has also held positions with the Russian subsidiary of AstraZeneca, and, before joining Novartis in 2013, wasmanaging director of orthopaedics specialist the Gibaud Group. RECRUITMENT After being appointed to lead Sandoz France, Girard has also joined local generics industry association Gemme as vice-president of FDA looks for deputy at OGD medical affairs for hospital drugs and biosimilars, replacing Collet. Gemme is led by Biogaran’s Pascal Brière as president. candidate who can “provide oversight of the Office of Generic Stéphane Joly,president of French generics firm Cristers, is Gemme’s ADrugs (OGD) activities related to the implementation and meeting vice-president for economic affairs, while Teva France’spresident, of Generic Drug User Fee Amendments (GDUFA) goals” is being Erick Roche,isvice-president of general affairs. sought by the US Food and Drug Administration (FDA) to become EG Labo’spresident, Pascal Faye,isGemme’streasurer and deputy director of the OGD. secretary-general,while Substipharm’s Léopold Berthier is the Providing “oversight of review-management activities to ensure committee representative for member companies. G ahighly efficient and effective reviewprocess” will be akey responsibility,along with overseeing technical and administrative aspects of the OGD and representing the Office –and its recently- appointed permanent director,Kathleen Uhl (Generics bulletin,6 February 2015, page 31) –indealing with industry,FDA officials and other government agencies. G

APPOINTMENTS TWinames Guilder as chief aiwan’sTWi Pharmaceuticals has appointed the president of its TUS subsidiary, Tina Guilder,toalso become the group president and chief executive officer from the start of April as part of plans to “enhance the strategic move to commercialise its products in the US market”. She replaces Calvin Chen,who will become Guilder’s “special advisor” and will also remain president of TWiBiotechnology. Meanwhile, EvaHo has been named as TWi’schief financial officer. Before joining TWi, Guilder wasvice-president of business development and alliance management for Teva’s US operations. Her “18 years of experience in the pharmaceutical and healthcareindustry” – including “extensive operational experience in the US generics market” –would help transformTWi into a“world-class specialty generic pharmaceutical company”, the firm said. TWiplans to launch several products in the US under its ownlabel later this year (Generics bulletin,27February 2015, page 23). G IN BRIEF PFIZER has appointed Jonathan Emms to become global marketing lead for its Global Established Pharmaceutical (GEP) business. Emms waspreviously managing director and head of the originator’s global innovative pharmaceutical business in the UK. G

13 March 2015 GENERICS bulletin 27 Generics House Ad AUGUST 2014_Layout 103/09/2014 10:04 Page 1

Generics bulletin print

Generics bulletin-i digital

News@Genericsbulletin electronic newsflash

INDIVIDUAL SUBSCRIPTIONS The bestdecision-makersinthe genericsindustrydon’thave the An annual subscription comprises: time to go lookingfor goodinformation. Theylet it cometothem. n 20 Generics bulletin newsletters; TheysubscribetoGenerics bulletin. n ANDatleast 46 weekly Join thous News@Genericsbulletin electronic andsofsubscribers from competitor companies in newsflashescontaining the week’stop nearly 60 countries whoare alreadybenefitting from commercial news stories (currently delivered by email). intelligence about business opportunities in theglobal generic medicinesand biosimilars markets. CHOICE OF FORMATS The 20 Generics bulletin newsletters GOOD VALUE -Individual subscription rates start from just£895 are available: n EITHER as the digital Generics bulletin-i for online access by desktop ANDtablet and smartphone. These mobile devices can have Apple or Androidoperating systems; AVAILABLEINSTANTLY WORLDWIDE n OR in traditional hard-copyprint format, Generics bulletin-i is the digital i-edition of Generics bulletin. delivered by airmail; Nowavailable online for desktop access,itdelivers the latest Generics bulletin on the day of publication withnopostal delay.Italso comes –atNOEXTRA CORPORATE SUBSCRIPTIONS CHARGE –asanapp for mobile access by tablet and smartphone. Acorporate subscription provides location-, Generics bulletin-i subscribers also get access to afully-searchable archive.This contains over country- or company-wide access to five years of generics news and analysisinmore than 100 back issues. These offer an invaluable Generics bulletin-i. resource for researching marketing opportunities,benchmarking competitivestrengths, evaluating regulatory changes and assessing product developments. Contact [email protected]. Existingsubscribers can get 20% OFF when theyupgrade theirsubscriptions to include Generics bulletin-i.Contact [email protected].

Take out asubscription TODAYatwww.Generics-bulletin.com or contact: [email protected]

Bulletin PublishingGroup, OTCPublications Ltd, 4Poplar Road, Dorridge, SolihullB93 8DB, UK. (Tel: +44 (0)1564 777550; Fax: +44 (0)1564 777524). Registered in England No: 2765878. VATNo: GB 608 0432 69