www.generics-bulletin.com

Bulletin Publishing Group 4 Poplar Road, Dorridge, Solihull B93 8DB, UK Tel: +44 (0)1564 777550 Fax: +44 (0)1564 777524 E-mail: [email protected]

COPYRIGHT NOTICE This publication must not be forwarded, exported, distributed or circulated by any means or in any format to persons including clients outside the direct employment of your Company. You may distribute the publication internally, but you may incorporate only insubstantial extracts, abstractsbulletin or summaries into presentations, providing Generics is identified as the source of the information. bulletin bulletin The publication/s, Generics and/or News@Generics , in PDF and/or HTML format, are supplied to you strictly under the terms and conditions of the Global Licence agreement between your Company and OTC Publications Ltd, the copyright holder of the publications.

The publication/s are the intellectual property of the Publisher, OTC Publications Ltd and are protected by English copyright, trademark and other laws.

Bulletin Publishing Group is a division of OTC Publications Ltd Registered Office: 4 Poplar Road, Dorridge, Solihull B93 8DB, UK. Registered in England No 2765878 Gen 1/11/13 Pg. 1_Gen 18/11/05 Pg. 1 30/10/2013 19:41 Page 1

1November 2013

COMPANY NEWS 2 Levinsteps down from Wockhardt loses UK GMP certifications 2 McKesson movesfor Celesio in Europe 3 Actavis has deadline forEuropean decision 3 PharmstandardOTC grows 4 leadership role at Teva ahead of spin Te va cuts portfolio in Japan by 81 drugs 5 Ranbaxy’sfortunes varyacross Europe 5 eva’spresident and chief executive officer,Jeremy Levin, has stepped down from the Trole with immediate effect, the Israeli company has announced. “The board has named Sandoz outstrips global markets growth 6 Eyal Desheh, Teva’s executive vice-president and chief financial officer,tofill the role of Biocon awaits Indian 8 president and chief executive officer on an interim basis,”Tevanoted, adding that the firm trastuzumab approval had “formed acommittee that will promptly begin to search forapermanent successor”. Phillip Frost, chairman of Teva’s board, acknowledged that Levin and the board had been MARKET NEWS 9 “truly aligned” on the firm’sstrategy,but had “different views” overhow best to pursue it. These differences revolved around “nuances” and “subtleties”, Frost said, butwere not able to Industryurges WHO to use 9 be resolved. He said the firm’smanagement team was“fully committed to the implementation common INNs of Teva’s strategy,including the development of newcompounds, making strategic acquisitions, Canada’sCGPAhas mixed viewonCETA 9 forming joint ventures and the planned acceleration of the company’scost-reduction programme”. UK seeks clarity over 10 The Israeli firm recently announced plans to slash around 5,000 jobs –more than atenth widening SPC scope of its global workforce –bythe end of next year in abid to produce annual cost savings of REMS sample case will continue in US 11 US$2.0 billion by 2017 (Generics bulletin,18October 2013, page 1). This formed part of a German companies arehurtbyrebates 11 global restructuring programme outlined by Levin at the end of last year (Generics bulletin, 11 January 2013, page 24). PRODUCT NEWS 12 Since then, the firm has announced the creation of aGlobal Specialty Medicines group to encompass the group’sproprietary brands (Generics bulletin,3May 2013, page 26) and has FDAfinds fault with second 12 cancelled abiosimilars joint venture with Lonza (Generics bulletin,9August 2013, page 5). Teva US bupropion also recently suffered alegal setback that could see US rivals to its Copaxone (glatiramer acetate) blockbuster launch as early as May next year (Generics bulletin,9August 2013, page 1). Stada will license Apotex’ EU filgrastim 14 “It is obvious that Teva is going through atransition period,”Desheh stated, adding that Arrowtakes aim at eight French targets 14 he had “full confidence in the ability of Teva’s management and employees to achieve our Te va drops dossier 15 goals and execute the strategy laid out for the company”. G forUSlipegfilgrastim Stada buys Russian Aqualor sea sprays 15 Te va Canada loses on zoledronic acid 17 Canadagets two-year extensions FEATURES 20 wo-year patent-term extensions for Canadian pharmaceutical patents have been agreed by TCanada and the European Union (EU) as part of acomprehensive economic and trade Stada sets great storeby20agreement (CETA). The agreement also includes aBolar-type provision that will allowCanadian lureofeastern promise generics firms to manufacture products for export during anypatent-term extension period, as European companyStada is looking well as measures aimed at ending the possibility of generics firms being sued more than once eastwards towards Asia and the by originatorsoverthe same brand patents. Aspokesperson for the Canadian Generic Commonwealth of Independent States Pharmaceutical Association (CGPA) told Generics bulletin that the association knewof (CIS) for growth. Aidan Fry reports. “no CETAprovisions regarding pharmaceutical intellectual property that apply to the EU”. Noting that the deal constituted an “agreement in principle”, the CGPAsaid that it could REGULARS takeuptothree months before the full text of the deal waspublished. Canada and the EU must then conduct alegal reviewofthe document before it can be signed and ratified. Paragraph IV Watch – Savella 16 Jim Keon, president of the CGPA, said the association was“disappointed by the inclusion Events – Our regular listing 18 of apatent-term extension in CETA, butwelcomes the government of Canada’scommitment Price Watch UK – Our in-depth 19 to cap the maximum length of extension at twoyears and include other essential safeguards”. look at pricing trends in the UK Meanwhile, Keon said the CGPAwas pleased that the government had committed to “additional safeguards and reforms to Canada’spharmaceutical intellectual-property regime” that would People – Polpharma’sGlinka 23 “provide greater business certainty” for local generics manufacturers. “The specific implementation leads Mylan Europe details will be crucial to the success of these critical reforms,” Keon stated. G Forfurther details of the CGPA’sreaction to CETA, turntopage 9. Gen 1/11/13 Pgs. 2-8_Layout 1 30/10/2013 19:42 Page 2

COMPANY NEWS

MANUFACTURING/SECOND-QUARTERRESULTS Wockhardt loses UK GMP certifications

he UK’sMedicines and Healthcare products Regulatory Agency Region Second-quarter sales Change Proportion T(MHRA) has withdrawn good manufacturing practice (GMP) (Rs millions*) (%) of total (%) certificates it had previously issued for Wockhardt’sIndian solid-dose facilities in Chikalthana and Kadaiya. Forboth plants, the UK regulator US 5,220 -19 43 has issued restricted certificates that permit production only of ‘critical’ India/Emerging 3,440 -7 29 drugs that are at risk of market shortage. Furthermore, the MHRA ordered Wockhardt to recall from UK 2,390 +5 20 pharmacies, clinics and wholesalersfivenon-critical, prescription- Ireland 340 -37 3 only drugs made at the Chikalthana site. The recalleddrugs –all in France 290 -18 2 tablet form –are amiloride 5mg, clarithromycin 250mg and 500mg, Other 290 –2 gliclazide 80mg, quinine sulphate 300mg and tamsulosin pinexel400µg. Europe 3,310 ±0 28 The firm also voluntarily recalled several own-label OTCpainkillers. Wockhardt 11,970 -11 100 Wockhardt estimated that the effect of the MHRA’s actions over the Chikalthana plant would reduce its turnoverby£9million (US$15 *rounded to the nearest Rs10 million million) on an annualised basis. Figure1:Breakdown by region of Wockhardt’s sales in its financial second Citing “concerns overthe continuity of supply”, the MHRA said quarter ended 30 September 2013 (Source –Wockhardt) it wasallowing Wockhardt to continue to provide UK patients with 10 prescription-only medicines made at the Chikalthana site. plant. Audits of Indian plants in Baddi, Bhimpore and Shendra had Wockhardt has not learned which critical drugs the UK regulator produced only minor observations, as had separate MHRA and FDA will permit it to makeatthe Kadaiya plant following an inspection inspections of the firm’ssite in Wrexham, UK. in September this year.“The impact on existing business will only be The US import alert on the Waluj facility contributed to a19% known once the companyreceivesfurther communication from the local sales fall to Rs5.22 billion (US$87 million), equivalent to a MHRA,”stated Wockhardt, which added that the total annual value 26% dollar slide. Lower metoprolol prices were also afactor.Of53 of exports from Kadaiya to the UK was£18 million. abbreviated newdrug applications (ANDAs) pendingapproval, 43 had In July,the MHRA recalled16drugs made at Wockhardt’s been filed from either the Chikalthana or Waluj site, the firm noted. manufacturing site in Waluj, India, due in part to arisk of cross- Wockhardt’sreported 5% sales rise to Rs2.39 billion in the UK contamination (Generics bulletin,9August 2013, page 3). The same equated to a2%local-currencydecline due to product recalls and just site is the subject of aUSFood and Drug Administration (FDA) import one launch during the quarter.The Indian firm said its turnoverinIreland alert. Wockhardt said it had enlisted the consultant Lachman, which had plummeted by 37% to Rs340 million on lower prices as the country had completed a“baseline assessment”atWaluj, trained staffonGMP transitioned from abrand-led to asubstitution-drivenmarket. French requirementsand data integrity,and wasoverseeing remediation plans. sales tumbled by 18% to Rs290 million (see Figure 1). Presenting financial results for its second quarter ended 30 Asuspension of dextropropoxyphene –against which Wockhardt September 2013, Wockhardt said it had undergone “11 regulatory is appealing –contributed to a2%fall in India, while the firm blamed inspections in 12 weeks”. While the MHRA’s audits of the Chikalthana supply shortages amid increased quality oversight for its total turnover and Kadaiya sites had resulted in major observations, eight inspections in India and other emerging markets falling by 7% to Rs3.44 billion. had been passed with no or only minor observations, while the firm The group’spre-tax profit declined by more than three-quarters wasawaiting the outcome of the FDA’sinspection of the Chikalthana to Rs1.30 billion on group turnover11% lower at Rs12.0 billion. G

1November 2013 Issue 201 SUBSCRIPTIONS Te rms &Conditions: No partofthis publication maybe Individual subscriptions: Asubscription to copied, reproduced, stored in aretrieval system, distributed Editor: Aidan Fry GENERICS bulletin includes this hard-copy or transmitted by anymeans, including electronic,mechanical, newsletter published 20 times ayear –twice monthly, photocopying or recording, without the prior written Deputy Editor: David Wallace permission of the publisher,orunder the terms and conditions except monthlyinJuly, August, December and Business Reporter: Dean Rudge of aGlobal Site Licence or of alicence issued by the Copyright January, and delivered by air mail –and afreeweekly Licensing Agency (CLA) in London, UK, or rights bodies in Production Controller: Debi Minal email newsflash News@Genericsbulletin published other countries that have reciprocal agreements with the CLA. Production Editor: Jenna Lawrence 46 times ayear.Annual subscriptions in Europe cost £590 (additional copies at the same address £365); Neither maythis publication be exported, distributed or Director of Subscriptions: ValDavis outside Europe £620 (£395). Single copies cost £50 circulated by anymeans outside the staff who work at the Managing Director: MikeRice each. Subscription rates maybeadjusted to coverany address to which it is sent by the publisher without the prior written permission of the publisher. period and can be backdated. Subscriptions mayonly be cancelled at expiry. Editorial enquiries: GENERICS bulletin, While due carehas been taken to ensurethe accuracy of information contained in this publication, the publisher makes 4Poplar Road, Dorridge,Solihull, Corporate subscriptions: Global Site Licences are no claim that it is free of errorand disclaims anyliability West Midlands B93 8DB, UK. available to companies.These provide in-house whatsoeverfor anydecisions or actions taken as aresult electronic access forstaff to Generics bulletin and of its contents. Website: www.generics-bulletin.com [email protected] ask foraquotation. ® Such licences aresupplied strictlyonthe condition ©OTC Publications Ltd.All rights reserved. Generics bulletin Te l: +44 (0)1564 777550 is registered as atrademark in the European Community. that both publications arethe intellectual property of Fax: +44 (0)1564 777524 the copyright holder,OTC Publications Ltd, and are ISSN 1742-0784. E-mail: [email protected] protected by copyright, trademark and other laws. Companyregistered in England No 2765878.

Advertising enquiries: Subscription enquiries: Printed by Warwick Printing CompanyLimited, As above,[email protected] As left, or [email protected] Leamington Spa CV31 1QD, UK.

2 GENERICS bulletin 1November 2013 Gen 1/11/13 Pgs. 2-8_Layout 1 30/10/2013 19:42 Page 3

COMPANY NEWS

BUSINESS STRATEGY/THIRD-QUARTER RESULTS MERGERS&ACQUISITIONS/DISTRIBUTION Actavis has deadline McKesson moves to for European decision buy Europe’s Celesio

ctavis will decide by the end of the year whether to sell or restructure eneric purchasing efficiencies are central to the US$275-US$325 Asome of its businesses in western Europe, according to Siggi Gmillion of annual synergy savings that McKesson believesitwill Olafsson, president of the firm’sActavis Pharma generics division. be able to achieve by taking control of European wholesaling and Having announced earlier this year that the firm wasconsidering “a pharmacyretailing group Celesio in atransaction valued at US$8.3 range of strategic alternatives” including “possible divestiture” for units billion. The combined companywill generate an annual turnoverof in certain markets (Generics bulletin,9August 2013, page 1), more than US$150 billion from operations in over20countries, and Olafsson confirmed that the “process is going well”, adding that the will employmore than 81,500 staff. firm expected to confirm the outcome by the end of 2013. “The principal and primary driverofour synergies is going to be Meanwhile, Actavis’ president and chief executive officer,Paul supply-chain and sourcing activities,”McKesson’spresident and chief Bisaro, said the firm wasalso “in the process of actively integrating executive officer,John Hammergren, told investors. “Weget global Warner Chilcott into our specialty brands business”, having closed scale immediately,” he added. the acquisition of the women’shealth specialist at the start of October “From asupply-chain perspective,” Hammergren stated, “those (Generics bulletin,4October 2013, page 5). The firms were “on synergies are really craftedaround models where McKesson has more track to achieve more than US$400 million” in synergies, Bisaro noted. of an influence overthe relationship between the choice of particular Actavis achievedsales that advanced by 57% to US$2.01 billion generics manufacturer and the customer’sability to sell it through.” in the third quarter of 2013. This waslargely due to the merger of Noting that generics buying wasfragmented in both the US and Europe the former Watson business with Actavis, butwas also drivenby between wholesalersand retailers, he said the combined group would product launches that included US rivals to Suboxone(buprenorphine/ exercise most influence where payers and governments did not mandate naloxone) sublingual tablets and Lidoderm (lidocaine) patches. These the use of particular generics. launches “more than offset lower sales of our authorised generic version Refusing to quantify the combined group’sgenerics purchasing of Concerta (methylphenidate) as aresult of expected competition”, power,Hammergren stated: “Manufacturing partners will benefit from Actavis observed, helping the Actavis Pharma division to growby stronger relationships that are more consistently implemented on a more than two-thirds to US$1.55 billion (see Figure 1). global basis and provide opportunitiestoincrease market share Full-year group sales –including Warner Chilcott from 1October globally.” He identified an opportunity in Europe to “improve the –were expected to reach around US$8.6 billion, Actavis forecasted, profitabilityofour operations as generics are more widely consumed”. noting that Warner Chilcott had achievedsales of US$1.8 billion in “Retail for Celesio –inthe markets in which it owns stores –has the first nine months of this year.Adjusted earnings before interest, been avery successful strategy,and the Lloyds [pharmacy] brand has tax, depreciation and amortisation would be around US$2.23 billion. performedquite well,”Hammergren continued. However, he added, Since the start of 2013, Actavis has filed 32 newabbreviated new McKesson had no plans to enter directly the US or Canadian retail drug applications (ANDAs), including 16 possible first-to-file arenas. “You don’tcompete with your customers,”hesaid, pointing opportunities, such as the firm’srecent paragraph IV challenges to to the “channel conflict” that Celesio had experienced before it sold Nucynta ER (tapentadol) extended-release tablets and Suboxonefilm. the mail-order pharmacyDocMorris. Manyofthe German group’s “Weare firing on all cylinders,”commented Olafsson, noting that the challenges, Hammergren believed, had been “self-inflicted, related to firm was“spending more time, moneyand resources on generic the deployment of capital”. development than ever”. Actavis launched atotal of 509 products in Over the past five years, Celesio’sturnoverfrom its operations the first nine months of the year,including Lynlor (oxycodone) in Europe and Brazil has grown by less than 1% per year on average capsules in the UK (Generics bulletin,6September 2013, page 22). to reach C22.3 billion (US$30.7 billion) in 2012. Of that total, C18.8 Among Actavis’ pipeline is aUSrivaltoGlaxoSmithKline’sAdvair billion came from around 130 wholesale branches in 12 European (fluticasone/salmeterol) respiratory brand for which the US Food and countries and Brazil, while the remaining C3.46 billion wasgenerated Drug Administration (FDA) recently published bioequivalence guidance through the group’snetwork of about 2,200 retail pharmacies in (Generics bulletin,20September 2013, page 1). Olafsson said Actavis Belgium, Ireland, Italy,Norway,Sweden and the UK. had identified its device and hoped to reach Phase III development In its financial year ended 31 March 2013, McKesson’sturnover soon, adding that he expected the timing of anyfuture launch to slipped back slightly to US$122 billion, the vast majority of which depend on howquickly the FDAprocessed ANDAs. At the current wasgenerated in the US and Canada. The US-based group supports rate, he predicted, it could takeuntil 2018 to receive approval, but 3,160 HealthMartindependent pharmacyfranchises,owns the Northstar if the rate improved, alaunch could come as soon as 2016. G generics label and offers the OneStop generic rebates programme.The vast majority of its turnovercomes through its Distribution Solutions Segment Third-quarter sales Change Operating division that is led by Paul Julian and will incorporateCelesio. (US$ millions) (%) margin (%) McKesson has agreed to acquire the 50.01% stakeheld by Celesio’smajority shareholder,Franz Haniel &Cie (Generics bulletin, Actavis Pharma 1,552 +69 33.4 18 October 2013, page 5). The US group will launch parallel voluntary Specialty Brands 154 +27 12.1 public-tender offers for Celesio’spublicly-traded shares and convertible Anda Distribution 307 +26 3.6 bonds at C23.00 per share. It expects to takeoperational control and close the deal –which is subject to antitrust approvaland securing at Actavis 2,013 +57 7.7 least 75% of Celesio’sshares –during its financial year starting on Figure1:Breakdown by business of Actavis’ group sales in the thirdquarter of 1April 2014. The annual synergies of US$275-US$325 million are 2013 (Source –Actavis) to come by the fourth year after closing. G

1November 2013 GENERICS bulletin 3 Gen 1/11/13 Pgs. 2-8_Layout 1 30/10/2013 19:42 Page 4

COMPANY NEWS

RESULTSFORECAST NINE-MONTHRESULTS Methylphenidate will PharmstandardOTC bolster Mallinckrodt grows ahead of spin

allinckrodt expects its generic version of Janssen’sConcerta harmstandard said sales of the 27 OTCbrands that it is spinning M(methylphenidate) extended-release tablets to contribute “at least Poffinto aseparate business grewby19% to RUR10.2 billion US$120 million” to group turnoverinthe US firm’sfinancial year (US$320 million) in the first nine months of this year.Having recently ending on 26 September 2014. The US firm will on 7November reveal secured shareholder support for the spin-off(Generics bulletin,18 whether it reached its target of achieving US$135-US$150 million October 2013, page 5), the Russian firm plans to buyback shares from in sales of the attention deficit hyperactivity disorder (ADHD) treatment eligible shareholders and file tax documents this month ahead of the in its financial year ended September 2013. newly-created, publicly-listed OTCPharm unit becoming fully Chief financial officer Matt Harbaugh said the US$120 million operational in February or March next year. forecast included the impact of competitionfrom KUDCo’sversions, OTCPharm will also incorporate BeverPharmaceutical, the and also factored in apotential generic launch by Impax. Harbaugh companythat Pharmstandard bought for US$590 million to secure a said the guidance also included Mallinckrodt introducing an 18mg “long-term, fixed-cost supply of criticalactive pharmaceutical ingredients strength of the ADHD drug. (APIs)” for twoofits flagship OTCbrands, Arbidol (umifenovir) and The firm’sExalgo (hydromorphone) analgesic brand, Harbaugh Aphobazolum (afobazole). noted, faced imminent competition from Actavis’ generic rival Includingaround RUR1.7 billion from unbranded products that (Generics bulletin,8March 2013, page 19). will not be taken overbyOTCPharm, Pharmstandard’snine-month In the 12 months to September 2014 –Mallinckrodt’sfirst full OTCsales increased by 17.3% to RUR11.9 billion (see Figure 1). The financial year following its spin-offfrom Covidien –sales by the firm’s firm –which claims to be Russia’sOTC market leader –said akey Specialty Pharmaceuticals brands and generics segment are forecasted to be US$1.22-US$1.27 billion. The Global Imaging segment will Nine-month sales Change Proportion contribute US$885-US$930 million to group turnoverthat Mallinckrodt (RUR millions) (%) of total (%) anticipates will be in the US$2.15-US$2.25 billion range. OTC11,920 +17.3 42 Research and development spending is set to equate to between Prescription 4,543 +24.7 16 6% and 8% of turnover. The firm has plans roughly to double the size Own pharma 16,463 +19.3 58 of its US salesforce to around 400 representativesasitprepares to launch upon approvalits MNK-795 and MNK-395 formulations. The Third-party products 10,678 -32.6 37 former is an extended-release oral combination of oxycodoneand APIs 747 +20.8 3 acetaminophen –the active ingredients in Percocet –with tamper-resistant Medical equipment 679 +6.1 2 properties, while the latter is adiclofenac 2% topical solution. G Pharmstandard 28,567 -7.6 100

Figure1:Breakdown by product type of Pharmstandard’s sales in the first nine BUSINESS STRATEGY months of 2013 (Source –Pharmstandard) driverofits OTCgrowth had been arise of afifth in sales of its largest Agila Biotech becomesStelis brand, the antiviral agent Arbidol. Pharmstandard also enjoyed double- trides Arcolab has rebranded its Agila Biotech business as Stelis. digit increasesinturnoverfrom OTCbrands includingComplivit SThe renaming includes the firm’sbiotech operations in Malaysia, vitamins and mineralsand the Amixin (tilorone)antiviral drug. where the firm is building afacility in Johor to produce recombinant Prescription turnoverahead by almost aquarter to RUR4.54 proteins and monoclonal antibodies (mAbs). Strides expects the billion included sales of the Phosphoglivand Biosulin insulin brands Malaysian site to come on-stream by the end of next year (Generics that increased by 13% to RUR811 million and by 19% to RUR439 bulletin,5April 2013, page 7). million, respectively.The firm also enjoyed double-digit growth from Having pushed into the biotech space in 2010 by acquiring prescription brands including the Combilipen vitamin B1 brand, the Inbiopro, Strides gained apipeline of eight biosimilar candidates, five codeine-based brand Pentalgin and the azithromycin antibiotic Azitrox, of which were mAbs in the oncology sector.Earlier this year,the while turnoverfrom the company’sdiabetes treatment Formetine Indian firm –which is developing drugs based on both mammalian (glimepiride) reached RUR168 million. and microbial expression platforms–formed ajoint venture with But the Russian company’sturnoverfrom brands distributed for US-based biotech firm Pfenextodevelop, manufacture and market six third parties tumbled by nearly athird to RUR10.7 billion. The firm biosimilars, including arivaltoBayer’sinterferon-beta brand Betaseron attributed this fall to the Russian government having pushed back – (Generics bulletin,3May 2013, page 7). towards the end of this year –procurement tenders for drugs such as Stelis has just struck aresearch-collaborationagreement with bortezomib, eptacog alfaand rituximab. This more than halved to Singapore’sBio-Scaffold Internationaltodevelop 3D-printed devices RUR5.40 billion Pharmstandard’stender-driventhird-partyrevenues, loaded with bone morphogenetic proteins (BMPs) and stem cells. more than outweighing third-party turnoverinthe retail sector that rose Agila Biotech is excluded from Strides’ proposed sales of its Agila by afifth to RUR5.28 billion on strong sales of Atimos (formoterol), injectables division to Mylan for up to US$1.85 billion. Shortly after Reduksin (sibutramine) and Tamiflu (oseltamivir). India’sForeign Investment Promotion Board (FIPB) had cleared the Even with API turnoverahead by afifth to RUR747 million –and transaction, the US Federal Trade Commission (FTC) told Mylan it must medical equipment sales 6% higher at RUR679 million –the third- divest rights to 11 marketed or pipeline drugs as acondition of securing party fall caused Pharmstandard’sgroup turnovertoslide by almost approvalfor the deal (Generics bulletin,4October 2013, page 3). G 8% to RUR28.6 billion. G

4 GENERICS bulletin 1November 2013 Gen 1/11/13 Pgs. 2-8_Layout 1 30/10/2013 19:42 Page 5

COMPANY NEWS

THIRD-QUARTER RESULTS BUSINESS STRATEGY Ranbaxy’s fortunes Teva cuts portfolio varyacross Europe in Japan by 81 drugs

anbaxy Laboratories experienced amixed performance from its eva is cutting 81 products from its portfolio in Japan –around 15% REuropean operations in the third quarter of this year. Tof its current Japanese portfolio of 539 drugs –due to supply issues. The Indian company’sturnoverinEastern Europe and the The Israeli firm said the discontinued Japanese portfolio consisted Commonwealth of Independent States (CIS) advanced by 43% to Rs4.77 mainly of products it had gained through its acquisition of local firm billion (US$78.0 million) –equivalent to a24% constant-currencyrise Taiyo twoyears ago (Generics bulletin,20May 2011, page 1). (see Figure 1) –on“product launches and volume growth of our existing Following areviewofits portfolio, Teva –which earlierthis year portfolio” in Eastern Europe, as well as a“strong OTCperformance” installed former Eli Lilly executive Ichiro Kikushige as chief executive in several CIS countries. officer of its Japanese Teva Seiyaku operation (Generics bulletin, But Ranbaxy’ssales in Western Europe tumbled by 18% to Rs2.02 19 April 2013, page 23) –said that it had pruned its portfolio to ensure billion, which the firm said equated to a31% constant-currencydecline. “a stable supply system” for patients and healthcare professionals. However, the Israeli group said it possessed enough stock of its current Third-quarter sales Reported Constant-currency portfolio to meet demand until 31 March 2014, and was“fully equipped” (Rs millions) change (%) change (%) to supply alternative products. Furthermore, Teva said it intended by 2018 to increase the North America 8,754 -5 -15 proportion of its Japanese portfolio manufactured in-house –excluding India 5,748 ±0 ±0 biosimilars and speciality products –to“more than 90%”. By the same Eastern Europe, CIS 4,771 +43 +24 time, the Israeli firm plans to double its production capacity in Japan Western Europe 2,023 -18 -31 to ensure supply levels meet rising demand. G Africa, Middle East 2,458 +9 +4 Asia-Pacific and 2,275 +21 +14 Latin America APIs/others 1,474 -19 -28 MANUFACTURING Ranbaxy 27,502 +3 -6 Hospira opens US quality lab Figure1:Breakdown by region and business of Ranbaxy’s sales in the third ospira has officially opened aquality and analytical-testing quarter of 2013 (Source –Ranbaxy) Hlaboratory at its troubled US manufacturing facility in RockyMount, The Indian companysaid its focus in the region –where France, North Carolina. The site is currently the subject of awarning letter Germanyand the UK are its leading markets –was on profitability. originallyissued by the US Food and Drug Administration (FDA) TurnoverinNorth America fell by 5% to Rs8.75 billion, even three years ago and maintained following are-inspection earlier this including apositive 10 percentage-point exchange-rate effect. Ranbaxy year (Generics bulletin,22March 2013, page 3). said it had seen aweaker effect from US exclusivity periods after the The laboratory –which will house 200 staff, responsible for testing prior-year quarter’sboost from atorvastatin, butstressed that its Absorica more than 450 products –forms part of an investment of more than (isotretinoin) brand had enjoyed “strong prescriptiongrowth”. US$200 million that Hospira is making in the 130,000 sq mRocky Ranbaxy recently receivedaboost in the US when the Food Mount site that the firm says is “one of the world’slargest generic and Drug Administration (FDA) issued an Establishment Inspection injectables manufacturing facilities”. Report (EIR) that officially closed out an inspection of the firm’sOhm “Through advanced technology and additional space, we have been plant in NewBrunswick,New JerseyinDecember 2012. able gradually to increase our production levels and ensure more However, the FDAalso placed the company’splant in Mohali, consistent release of products,”stated the firm’svice-president of India under import alert and subjected it to certain provisions of a operations at RockyMount, Marty Nealey. G consent decree that covers Ranbaxy’ssites in Dewasand Paonta Sahib, India (Generics bulletin,20September 2013, page 3). The Indian firm’sturnoverinits domestic market –where it has MANUFACTURING just receivedclearance to market its Synriam (plasmodium vivax) malaria treatment –almost stalled at Rs5.75 billion as sales were “impacted Pliva unveils oral-solids facility by pricing policyand trade-related supply disruptions”. “Strong performances in Australia, Brazil, Myanmar and the liva has opened an oral-solids plant in Zagreb, Croatia. The Teva Philippines” –aswell as beneficial currencyshifts –lay behind a21% Psubsidiary invested approximately US$100 million into the facility, sales rise to Rs2.28 billion in Ranbaxy’sAsia-Pacific and Latin America which will increase Pliva’s tablets and capsules capacity by 25%, or region. Just overhalf of areported 9% turnoverrise to Rs2.46 billion about 2billion units per year. in the firm’sAfrica and Middle East region wasdue to exchange-rate The investment covered the cost of transferring operationsfrom fluctuations as sales were “impacted by reduced tender quantities”. Pliva’s pilot plant to the newfacility,the Croatian firm said, as well as an “Changes in regulations and lower demand” led to a19% reduction investment in increasing its production capacity for sterile delivery forms. in turnoverfrom active pharmaceutical ingredients(APIs) and related Noting the US$20 million investment in sterile manufacturing, products. Ranbaxy said that equated to a28% constant-currencyslide. Pliva’s president, Tihomir Oreskovic, said the plant would supply Group turnoverrose by 3% to Rs27.5 billion, butthe firm posted a largely European Union (EU) and US markets. Production at the facility pre-tax loss of Rs3.91 billion on aRs695 million settlement provision would begin as soon as it receivedapprovalfrom the US Food and Drug and Rs3.63 billion of foreign-currencylosses. G Administration (FDA) and other regulatory agencies, he added. G

1November 2013 GENERICS bulletin 5 Gen 1/11/13 Pgs. 2-8_Layout 1 30/10/2013 19:42 Page 6

COMPANY NEWS

THIRD-QUARTER RESULTS Sandoz outstrips global markets growth

andoz says it is outpacing the generics market in all geographic Region Third-quarter sales Reported Constant-currency Sregions around the world. The company’sglobal sales advanced (US$ millions) change (%) change (%) as reported, and on aconstant-currencybasis, by 11% to US$2.27 billion in the third quarter of this year.Anegative six percentage-point Europe 1,127 +12 +8 impact from price erosion wasmore than outweighed by a17-point US 718 +14 +14 volume gain, including four points from the US$1.5 billion acquisition Asia, Africa, Australasia 280 +9 +15 of US dermatology specialist Fougera in July 2012. Canada, Latin America 148 -3 +5 Commenting on the company’sthird-quarter results, Sandoz’ global Sandoz 2,273 +11 +11 head, JeffGeorge, told Generics bulletin that Fougera wasperforming “nicely ahead of expectations”. Fougera’snystatin/triamcinolone Established Markets 1,669 +12 +10 cream wasjust one of several recent launches that had contributed to Emerging Markets 604 +9 +11 the “very good start” by Sandoz’ newUSmanagement team led by Peter Goldschmidt (Generics bulletin,12July 2013, page 23). George Figure1:Breakdown by region of Sandoz’ sales in the thirdquarter of 2013 (Source –Novartis) also highlighted strong sales of generic Metrogel (metronidazole) 1% topical gel following afirst-to-market launch through apatent-litigation George hailed a“good performance from our flagship products”, as well settlement, as well as of the authorised generics of oncology brands as the impact of pursuing amultiple brand strategy with Hexal in retail Temodar (temozolomide) and Vidaza (azacitidine). generics and OTCsectors, with discount label 1A Pharma, and with “Our US operation conducted 25 launches in the first nine months the Sandoz speciality unit that includes biosimilars. of this year,more than in all of 2012,”George observed. Those launches George said Sandoz’ sales had also increased ahead of the local more than offset the effect of having introduced an authorised generic markets in manyemerging countries. Emerging markets accounted for of Novartis’ DiovanHCT (valsartan/hydrochlorothiazide) last year,as around 27% of the firm’sturnoverinthe third quarter (see Figure 1). US retail generics and biosimilars sales rose by 12% to US$665 million. Turkey and Ukraine contributed to a7%constant-currencysales Addressing manufacturing deficiencies at Sandoz facilities in North rise in Central and Eastern Europe (CEE). George said Sandoz had America and Europe, George said the companywas “on track” to meet been Russia’sleading generics player for the past four months, having all of its commitments to the FDA. overtaken local firm Pharmstandard. The company’sthird-quarter sales of retail generics, biosimilars Strong performances in Francophone West Africa, as well as in and oncology injectables in North America rose by atenth, compared North African countries such as Algeria and Egypt, lay behind 11% to an estimated generics market decline of 3%. The market decline constant-currencygrowth in the Middle East and Africa. wasdue largely to provincial cost-cutting measures in Canada, where On the same basis, Sandoz’ turnoverinthe Asia-Pacific region the local market contracted significantly as Sandoz suffered a6% climbed by 17%, aided by the firm’s“23rd consecutive quarter of constant-currencysales slide. double-digit growth” in Japan, where sales movedahead by 28% A13% third-quarter constant-currencysales rise in Western Europe, following several successfulproduct launches.George noted that a excluding Germany, formed part of a“sustained strong performance revamped management team in China had produced 29% sales growth. from Nick Haggar and his team”, George noted. The regional operation, Strong sales in Argentina, Brazil, Mexico and Venezuela contributed he said, had benefitted from first-to-market launches of methylphenidate to a23% constant-currencyrise in Latin America (see Figure 2). in several countries,aswell as from introducing generic forms of Ebixa George highlighted a“terrific performance” by Ameet Mallik and (memantine) and Nasonex(mometasone). his team in increasing global biosimilars turnoverbyaquarter to Growth had been drivenbyFrance, Italy,the Netherlands and the US$106 million. Zarzio (filgrastim) had achievedthe “important UK, he said, offset in part by difficult trading conditions in Spain amid milestone” of becoming the “the most prescribed filgrastim in Europe, the partial implementation of tenders in Andalusia and monthly pricing after overtaking its reference product,Neupogen, and market leader revisions that required pharmaciststodispense the lowest-price generic. Granocyte”. The brand had captured 27% of Europe’sdaily granulocyte- In Germany, Sandoz posted a3%constant-currencyadvance to colonystimulating factor (G-CSF) market by volume, he said. US$302 million, “despite an estimated net market decline of 7%”. Binocrit (epoetin alfa) had secured double-digit market shares in both the oncology and nephrology sectors, and become market leader in Germany. George also welcomed positive feedback on the SurePal Region Third quarter Nine months device for Omnitrope (somatropin) that the firm is rolling out in Europe, Sandoz Market Sandoz Market starting in the UK (Generics bulletin,4October 2013, page 19). change (%) change (%) change (%) change (%) Biosimilars sales reached US$301 million in the first nine months of North America +10 -3 +3 -1 this year as Sandoz’ group turnoverincreased by 7% to US$6.75 billion, Latin America +23 +8 +18 +8 despite adecline of more than US$200 million in US enoxaparin sales. Western Europe* +13 +6 +13 +6 Excluding US$304 million for amortisation of intangible assets, Germany+3-7+2-4 US$95 million of legalprovisions and US$20 million of intangible CEE +7 +4 +11 +4 impairments, Sandoz’ nine-month ‘core’ operating margin edged up to 17.3%. On the same basis, the firm’sthird-quarter core margin fell by Middle East, Africa +11 +7 +15 +7 almost apercentage point to 16.6%. Asia-Pacific +17 +6 +12 +8 As reported, Sandoz’ third-quarter and nine-month margins fell *excluding Germany by 1.6 points and 1.7 points respectively to 10.6% and 11.1%. These margin declines were due in part to US$59 million of exceptional Figure2:Breakdown by region of Sandoz’ constant-currency sales growth in the third- quarter and first nine months of 2013, compared with Sandoz’ estimates of regional income in the prior-year third quarter and the US$95 million of one- net market growth calculated from IMS Health gross sales data (Source –Novartis) time legalprovisions in the first nine months of 2013. G

6 GENERICS bulletin 1November 2013

Gen 1/11/13 Pgs. 2-8_Layout 1 30/10/2013 19:42 Page 8

COMPANY NEWS

SECOND-QUARTERRESULTS IN BRIEF SANDOZ has been sued in the NewYork Supreme Court by Bioconawaits Indian Shareholder Representative Services,agroup purportedly representingformer shareholdersofthe Oriel Therapeutics respiratory business that Sandoz acquired three years ago (Generics bulletin, 18 June 2010, page 3). The plaintiffisasserting claims including trastuzumab approval fraud and negligent misrepresentation against Sandoz and two affiliates, as well as against one current and one former employee of iocon is awaiting Indian regulatory approvalfor its follow-on the company. As well as punitive damages, the plaintiffisseeking Bversion of Herceptin (trastuzumab)inthe near future, based on US$335 million in compensatory damages. Sandoz’ global head Jeff aPhase III clinical trial that the Indian firm conducted. Meanwhile, George described the cases as “essentially are-filing of acomplaint the companysays it is making good progress on the biosimilar that wasdenied overayear ago”. The companydenies the allegations. candidates it is developing through its alliance with Mylan. In its financial second quarter ended 30 September 2013, strong LUPIN has applied to the ReserveBank of India for permission to demand for follow-on recombinant insulin and insulin glargine in increase the firm’s shareholding limit for foreign institutional emerging markets helped to raise Biocon’sBiopharmaceuticals sales investors from 33% to 49%. by afifth to Rs4.47 billion (US$72.7 million). The Indian firm’s domestic Branded Formulations turnoveradvanced by 9% to Rs990 ORION said turnoverbyits off-patent Specialty Products division million as it launched the psoriasis treatment Alzumab (itolizumab). increased by 4% to C279 million (US$384 million) in the first nine Strong contract-researchrevenues contributed to a17% increase months of 2013, even though sales of generic entacapone almost in group turnovertoRs7.53 billion (see Figure 1). Biocon’spre-tax halved to C7million. The Finnish firm said its prescriptionsales had profit improvedby15% to Rs1.38 billion. G risen in its domestic market, while Specialty Products had accounted for the majority of human pharmaceuticals turnoverinEastern Europe and Russia that advanced by 14% to C50 million. Third-party sales Second-quarter sales Change Proportion by the group’sFermion active pharmaceutical ingredients (APIs) unit (Rs millions*) (%) of total (%) climbed by 27% to C46 million. Group turnover–including proprietary Biopharmaceuticals 4,470 +20 59 brands and animal health –edged ahead by 1.1% to C734 million. Indian Formulations 990 +9 13 VALEANT has agreed to pay Anacor just overUS$142 million to Contract Research 1,880 +46 25 settle adispute overdrug-development contracts that involved the Other 190 -62 3 Medicis business that Valeant acquired at the end of last year. Biocon 7,530 +17 100 US GENERICS FIRMS including Actavis, Mylan and Teva face *rounded to the nearest Rs10 million litigation in aLouisiana district court overallegations theyimproperly

Figure1:Breakdown by division of Biocon’s sales in its financial second quarter claimed Medicaid reimbursements for unapproveddrugs. ended 30 September 2013 (Source –Biocon) HYPERMARCAS has obtained board clearancetorepurchase up to US$300 million of corporate bonds.The Brazilian company– BUSINESS STRATEGY which has movedits administrative offices to anew address in São Paulo –said buying back the bonds would decrease its “foreign Finox raises funds for studies currencyexposure and the overall indebtedness of the company”. iosimilars developer Finox Biotech has secured acapital increase CELLTRION “cannot accept” adecision by South Korea’sSecurities & Bof SFr22 million (US$25 million) following ashareholders’ meeting. Futures Commission (SFC) to recommend prosecution of the The Swiss firm’smajority shareholder,Willy Michel, contributed biosimilardeveloper’slargest shareholder,Seo Jung Jin. “Celltrion around SFr12 million, and BV Group another SFr10 million. has neverleaked anyundisclosed materials nor made illegalprofits Gavin Jelic-Masterton –who recently became the firm’schief from share trading,”the South Korean firm insisted in responseto executive officer (Generics bulletin,12July 2013, page 23) – the SFC’sallegations of share-price manipulation. commented: “This shareholders’ agreement for the capital raise is an important milestone in the history of the company, as it will allow ABDI IBRAHIM has started building a manufacturing facility in Finox Biotech to push ahead with our pivotal study in the US, which Kazakhstan through an alliance with its local affiliate Global Pharm. is the world’sbiggest market for recombinant follicle stimulating Last year,the Turkish companybought 60% of Global Pharm’sshares hormone (rFSH).”Furthermore, he said, the funds would provide “the (Generics bulletin,19October 2012, page 3). Abdi Ibrahim expects financial platform”from which to launch its Bemfola rFSH biosimilar the good manufacturing practice (GMP) compliant plant –which candidate in Europe. includes development laboratories –tobeoperational by the end of The Swiss companysubmitted amarketing authorisation 2014, helping it to meet Global Pharm’ssupply contract for around application (MAA) for Bemfola to the European Medicines Agency 130 drugs with Kazakhstan’sgovernment. “This partnership (EMA) late last year,using Gonal-F as the reference product and a agreement is astep towards our goal to be aglobal player,” stated “single-use, one-a-day disposable” injector pen as the delivery device the Turkish firm’schairman, Nezih Barut. (Generics bulletin,11January 2013, page 19). It expects to receive an opinion from the EMA’s committee for human medicinal products NIPPON CHEMIPHAR has cut its operating profit forecast for its (CHMP) “by end of the first quarter of 2014”. financial year ending 31 March 2014 by 25% to ¥3.00 billion In the US, the firm has agreed a‘special protocol assessment’ (US$30.6million). The Japanese firm has also reduced its turnover with the Food and Drug Administration (FDA) on conducting apivotal guidance by 2.4% to ¥32.0 billion. G phase III clinical study.That trial, entitled FIN3002, is underway. G

8 GENERICS bulletin 1November 2013 Gen 1/11/13 Pgs. 9-11_Layout 1 30/10/2013 19:43 Page 3

MARKET NEWS

INTELLECTUAL PROPERTY BIOSIMILARS Canada’s CGPAhas Industryurges WHO mixed view on CETA to use commonINNs

wo-year patent-term extensions agreed by Canada and the European nternational non-proprietary names (INNs) for biologics should also TUnion (EU) as part of acomprehensive economic and trade agreement Ibe used globally for the drugs’ biosimilarcounterparts, the World (CETA) “fall short of the European Commission’soriginal unnecessary Health Organization (WHO) has been urged by representativesof demands on behalf of brand-name drug companies, butwill still the generics industry. delay market entry of cost-saving generic prescription medicines in At the WHO’sconsultation on INNs that washeld on 22-24 Canada”, according to Jim Keon, president of the Canadian Generic October in Geneva,Switzerland, the European Generic medicines Pharmaceutical Association (CGPA). Association (EGA) and the US Generic Pharmaceutical Association As well as allowing two-year patent-term extensions, the agreement (GPhA) reiterated their opposition to suggestions that biosimilars included proposals aimed at “ending the practice of dual litigation”, should use unique INNs to distinguish them from reference brands. Keon pointed out, adding that such areform had been advocated by “Proposals to introduce anew naming convention with different the CGPA“for several years”. “Currently,Canada is the only country INNs will create confusion, are likely to compromisepatient safety and that allows brand-name pharmaceutical companies to sue generic will limit patient access to biologics,”warned the EGA’s JoergWindisch. pharmaceutical companies multiple times on the same patents,”Keon “Furthermore,”headded, “a newconvention that discriminates against pointed out, referring to the co-existence in Canada of standard patent biosimilars will also impact the realisation of substantial cost savings.” litigation and the country’sPatented Medicines (Notice of Compliance) Meanwhile, the GPhA’s president and chief executive officer, patent-linkage system (see front page). Ralph Neas, insisted that it was“critical that anydecision on naming these products does not jeopardise the enormous opportunity to put First trade deal with exportexception manyoftoday’smost life-changing medicines in reach for millions Moreover, Keon noted, “CETAalso sets an international precedent more patients”. Biosimilars were by definition “highly similar” to as the first trade agreement that permits an exception under the period reference biologics and had “no clinically meaningfuldifferences that of patent extension for the production and other activities related to require aunique name”, Neas stated, adding that the US association the export of generic medicines”. The association commended the was“pleased that the WHO is taking athoughtful and deliberate Canadian government for “recognising the importance of generic approach to reviewing this issue”. pharmaceutical manufacturing to the domestic economy” through this Addressing arguments that unique INNs for biosimilars could aid advanced manufacturing Bolar-type provision. pharmacovigilance, the EGA pointed out that “high levels of traceability The CGPAnoted CETAwould not increase domestic data protection. and pharmacovigilance accuracyhavebeen achievedwhere biosimilar It had previously warned that EU proposals to provide patent-term and reference medicines share the same INN”. extensions and increase data protection could delay generic entry in Instead, unique brand names should continuetobeused for all Canada by 3.5 years on average and add C$2.8 billion (US$2.71 billion) biologics, the EGA suggested, insisting that these were “the best unique to prescription drug costs (Generics bulletin,4March 2011, page 16). identifier for patients and healthcare professionals”. If certain countries However, the association acknowledged that the extra costs and chose not to allowbrand names to be used when prescribingbiologics, delays to generic competition that would result from the final agreed the EGA proposed, “a newproduct identifier could be introduced by the measures “will depend on the specific manner in which theyare WHO” which would be separate from the INN, apply to both biosimilars implemented by the government of Canada”. G and brands, and be applied retrospectively to all biologics. The European Union (EU) already had “a very robust framework for clear and unambiguous identification of all biologicals”, concluded the EGA’s senior director of scientific affairs, Suzette Kox. “Consequently, REGULATORY AFFAIRS no change is needed as regards the naming of biosimilar products.” FDA sets out GDUFApriorities Hospira’schief scientific officer,Sumant Ramachandra,also spoke at the consultation meeting in favour of common INNs. Noting that aining abetter understanding of patient perceptions of generic drug the decision “could makeorbreak the success of these products”, Gquality and effectiveness, researching newbioequivalence methods Ramachandra warned that if aproduct’sname did not communicate and pathways for locally-acting drugs and ensuring therapeutic to clinicians that the product wasconsidered biosimilar, doctors would equivalence across all dosage forms and routes of delivery are among be less likely to prescribe biosimilars, “or worse, confusionabout the scientific regulatory priorities for the US Food and Drug biosimilarnames could lead to prescribing errors”. Administration (FDA) in its 2014 financial year.. “Safety and accessibility are best ensured when abiosimilar shares Under the terms of the Generic Drug User Fee Amendments the same non-proprietary name,”Ramachandra stated. Hospira’sdata (GDUFA) of 2012 (Generics bulletin,13July 2012, page 9), the FDA indicated that “the vast majority” of adverse events relating to biosimilars has drawn up an annual list of research areas that, according to were reported with both the brand name and the INN, he added. industry and stakeholder input, require more focus. “Having different standards for naming abiosimilar in each country Also cited as apriority for 2014 is research to ensure that complex will undermine the point of having non-proprietary names in the first generics are available in all product categories and for all reference place,”Ramachandra observed, “creating further confusion for clinicians listed drugs (RLDs). Meanwhile, post-marketing evaluation of generics and patients across the globe, especially in the evolving globalisation will include verifying equivalence “in therapeutic areas where there of medical practices.”Ifthe WHO, the US Pharmacopeia (USP) or is concern expressed about substitutability of generic drugs”. These the US Food and Drug Administration (FDA) were to support different include anti-epileptic drugs, immunosuppressants, bupropion, attention INNs for biosimilars,heconcluded, it would “set aprecedent that will deficit hyperactivity disorder drugs and cardiovascular medicines. G have grave ramifications”. G

1November 2013 GENERICS bulletin 9 Gen 1/11/13 Pgs. 9-11_Layout 1 30/10/2013 19:43 Page 4

MARKET NEWS

INTELLECTUAL PROPERTY IN BRIEF EMA –the European Medicines Agency–has launched anew UK seeks clarity over version of the European Clinical Trials Database (EudraCT). The latest iteration “marks the initial step of aprocess through which summary clinical trial results will be made publicly available through the European Union’s(EU’s) Clinical Trials Register”, the EMA wideningSPC scope said. Further updates will takeplace in 2014 to provide “improved functionalities” for industry and EU regulators. hether the scope of supplementaryprotection certificates (SPCs) Wcan be extended by amending the basic patents on which they SOUTH AFRICA should incorporate aspects of the international are based during the SPC application process is among ahost of agreement on Trade Related Aspects of Intellectual Property Rights queries that have been referred to the Court of Justice of the European (TRIPS) into its national law, according to areport by the United Union (CJEU) by the Patents Court of England and Wales. Nations Development Programme (UNDP). The country could benefit As part of adispute involving Actavis overSPCs protecting from adopting“an enabling legaland regulatory environment across Boehringer Ingelheim’sMicardis (telmisartan) and MicardisPlus patent, competition and medicines law”, the report states, suggesting (telmisartan/hydrochlorothiazide), Judge Colin Birss asked the CJEU that astricter patentability standard could increase competition and whether the validity of the combination SPC –which is based on the reduce prices. Lobbying group the Treatment Action Campaign UK part of telmisartan’sEuropean Patent EP0,502,314 –should be (TAC)also criticised South Africa’s“excessive”number of patents affected by the fact that the ‘314 patent had been amended explicitly to in areport drawn up to illustrate howthe country’sintellectual-property identify the combination of the twoingredients. rights stifle public access to vital medicines. At the suggestion of the UK Intellectual Property Office (IPO), the amendment had been made after Boehringer had applied for the EPO –the European Patent Office –has revised certain provisions combination SPC, butbefore the SPC wasgranted. of the European Patent Convention to remove the 24-month time Actavis claimed that the combination SPC –which expires on limit for filing divisional patent applications, allowing such applications 30 January 2017 –was invalid, Birss noted. However, in referring the to be filed as long as the earlier parent application is pending. “The question to the CJEU, he stated that “if the amendment is alawful decision enters into force on 1April 2014 and will apply to divisional amendment, then Ican see no good reason whyitmatters from the point applications filed on or after that date,”the EPO stated. An additional of viewofthe validity of an SPC when the amendment took place”. fee for filing divisional applications will also be introduced. Among other questions referred to the CJEU, Birss asked for clarity overwhether the IPO had been correct to suspend Boehringer’s INDIA will retain its “explosive growth in generics exports” over application for the combination SPC and advise the originator to amend the next fewyears, according to areport published by agovernment the ‘314 patent specifically to include the combination of telmisartan trust, the India Brand Equity Foundation.Noting that generics and hydrochlorothiazide before granting the combination SPC. “I can exports had grown annually by almost aquarter –24% –overthe see nothing wrong with what the IPO did in this case,”Birss stated. past four years, the report states that overall pharmaceutical exports Birss also asked the CJEU whether the validity or duration of the are expected to enjoyacompound annual growth rate (CAGR) of combination SPC should be affected by an earlier SPC for telmisartan 20% overthe next five years. alone that had been based on the same patent. However, he stated: “I would be surprised if there could be said to be anybasis in the [European BIO –the US Biotechnology Industry Organization –isurging SPC] regulation for giving an otherwise valid SPC alesser term than lawmakers in the US state of Indiana to adopt legislation that would it would otherwise be entitled to for this sort of reason”. G require pharmacists dispensing biosimilars in place of branded equivalents to notify prescribers of the change. “Due to the complexities of biologic medications, existing state laws governing MARKET RESEARCH generic substitution should not be applied to biosimilars, and we must address this issue prior to biosimilars coming to market,”BIO GPhA welcomesNCPAstudy insisted. Similar legislation wasrecently blocked by California’s governor (Generics bulletin,18October 2013, page 9), while ndependent community pharmacists in the US dispense generics several other US states have previously blocked such provisions. I77% of the time, according to areport published by the National Community Pharmacists Association (NCPA). US SENATORS have asked the US Food and Drug Administration Welcoming the report –which also highlighted pharmacists’ (FDA) to clarify whether the agencyintends to change its position increasing focus on “helping patients stick to their medication and on naming conventions forbiosimilars after it removedanearlier saving moneythrough the appropriate use of lower-cost generic drugs” statement on the subject from its website. Noting that the country’s –the US Generic Pharmaceutical Association (GPhA) described Congress had “rejected astatutory requirement that biosimilars must community pharmacies as “valued partners” in “ongoing efforts to be givenunique international non-proprietary names (INNs)” when lower health costs”. formulating the BiologicPrice Competition and Innovation Act, six Noting that the figure of 77% represented“an increase from years senators wrote to FDACommissioner Margaret Hamburgtoinsist that past and arecord high”, the GPhA said access to generics wascritical, “no unique name should be required for an FDA-approvedbiosimilar”. especially among the “low-income subsidy population” of health insurance programme Medicare. “One reason whyadherence WTO –the World Trade Organization –has proposed extending continues to be achallenge for manypatients is the high cost of brand the deadline for countries considering a public health amendment name therapies,”the generics association pointed out. to the agreement on Trade Related Aspects of Intellectual Property Moreover, NCPAnoted that “community pharmacistsroutinely Rights (TRIPS) for twoyears until 31 December 2015, so that consult with physicians about proper prescription drug therapy, and more countries can accept it. The amendment removesobstacles pharmacists’ recommendations for generic drug use are accepted to countries issuing compulsory licences for generics. G 83% of the time”. G

10 GENERICS bulletin 1November 2013 Gen 1/11/13 Pgs. 9-11_Layout 1 30/10/2013 19:43 Page 5

MARKET NEWS

PRICING&REIMBURSEMENT LITIGATION German companies REMS samplecase arehurtbyrebates willcontinue in US

erman generics companies paid almost C110 million (US$151 US legalbattle overwhether originatorscan refuse to supply Gmillion) in mandatory rebates to health insurance funds in the first Asamples of their drugs for bioequivalence testing by citing risk half of this year,according to IMS Health data cited by local generics evaluation and mitigation strategy (REMS) requirements will proceed industry association, Pro Generika. The equivalent figure for all of to the discovery stage. NewJerseyDistrict Judge Noel Hillman on 2012 was C218 million. 21 October denied amotion filed by originator Actelion for ajudgement Since April 2006, generics and off-patent brands have been subject on the pleadings and for dismissal of counterclaims brought by generic to a10% mandatory rebate on their ex-factory price unless theyare litigants Actavis, Apotexand Roxane. priced at least 30% belowthe applicable reference price. The Swiss originator had asked the court for adeclaratory Pro Generika pointed out that the C218 million paid by firms last judgement “declaring that Actelion has no duty to deal with Apotex year had come on top of the C2.4 billion that Germany’sfederal or Roxane” and that it wasunder no obligation to supply samples of ministry of health said the funds had savedin2012 through tender its Tracleer (bosentan) brand to the generics firms (Generics bulletin, contracts, largely at the cost of the generics industry.The association 1October 2012, page 17). Actelion argued that supplying samples noted that sales of generics and biosimilars through German statutory would contravene the strictures of the REMS programme applied to health insurance funds totalled C4.6 billion at ex-factory prices last year. the treatment for pulmonary arterial hypertension. The case has since According to Pro Generika, calculating the 10% mandatory rebate been extended also to coverActelion’sZavesca (miglustat) brand for caused “considerable bureaucracycosts” for funds, pharmaciesand treating Gaucher disease. generics firms. Giventhat the funds were sitting on “a financial cushion Ordering that the lawsuit should progress to the discovery stage, of almost C30 billion”, the rebate wasunnecessary and should be Hillman granted leave for both the US Federal Trade Commission dropped, the association argued. G (FTC) and the US Generic Pharmaceutical Association(GPhA) each to appear as afriend of the court, or amicus curiae.The FTC had told the court: “Actelion’slegal position, if adopted by the court, could pose PRICING&REIMBURSEMENT asignificant threat to competition in the pharmaceutical industry.” (Generics bulletin,22March 2013, page 9). MSF urges Brazilian reforms Asimilar lawsuit has been brought by Intas in aFlorida district court overAcorda preventing the generics firm from buying samples Braziliangovernment report urging reforms to the country’s patent of the Ampyra (dalfampridine)multiple-sclerosis drug (Generics Aregime that would improve access to generics has been welcomed bulletin,19April 2013, page 13). by humanitarian group Médecins Sans Frontières (MSF). The Meanwhile, the US Food and Drug Administration (FDA) has parliamentary committeereport recommends improving generic denied requests in acitizen petition filed by Prometheus Laboratories competition and reducing drug prices by introducing stricter criteria urging the agencytoestablish standards and processes for single, shared for patentability,aswell as amore robust patent opposition system. REMS systems. The originator had argued that the requirement for both It also suggests that Brazil’sgovernment should be able to issue generics firms and brand companiestouse single, shared systems was compulsory licences to import or produce generics. “unprecedented” in its requirement that competitors worked together “The patent lawreform process in Brazil can be seen as part of “as business partners”. an international momentum where middle-income countries are facing “The agencyiscontinuing to evaluate whether rulemaking or unaffordable prices for medicines and increasingly taking measures guidance relating to single, shared system standards and processes to overcome the patents that price drugs out of reach,”said MSF would be useful,”the FDAsaid. The agencyalso denied Prometheus’ Brazil’sexecutive director,Susana de Deus. request that the agency“refrain from granting awaiverofthe single, “If the reforms proposed by Brazilian legislators are approved shared system requirement for Lotronex(alosetron) without providing and implemented,”she added, “it could encourage other countries to Prometheus with adequate notice that awaiverrequest wassubmitted takeaction against the rising cost of medicines and consider and an opportunity to participate in the process of determining whether reforming their patent laws.” G the waiver should be granted”. G

MARKET RESEARCH MARKET RESEARCH Portuguese penetration peaks South Africa proposes savings ore than one in every four medicines sold in Portugal between nnual savings of ZAR400 million (US$40.7 million) could be MJanuary and August 2013 wasageneric, according to data Arealised in South Africa by substituting 5% of brands dispensed published by the country’smedicines agency, Infarmed. Volume sales for ageneric, according to the country’sNational Association of during the period rose by 13.9% to 45.3 million, giving generics a Pharmaceutical Manufacturers (NAPM). While 70% of off-patent brands 44.2% share of the available market and a27.8% share of the total nowhad generic rivals, the association noted, “only about 55% of medicines market. The latter figure represented arise of overthree generic medicines by volume are being regularly prescribed”. percentage points compared with the prior-year period’s24.7%. Generics accounted for two-thirds of the ZAR1.1 billion South Africa Meanwhile, turnoverfrom generics rose by 6.9% to C312 million spent on off-patent drugs in 2012, NAPM said, adding that the average (US$430 million), or 18.6% of the total market by value. G brand price of ZAR213 wasthree-times that of ZAR68 for generics. G

1November 2013 GENERICS bulletin 11 Gen 1/11/13 Pgs. 12-17_Layout 1 30/10/2013 19:43 Page 2

PRODUCT NEWS

BIOSIMILARS ANTIDEPRESSANTS Epirus makes deal for FDA finds fault with Brazilian biosimilars secondUSbupropion

pirus Biopharmaceuticals will collaborateondeveloping, uproprion 300mg extended-release tablets manufactured by Actavis’ Emanufacturing and marketing biosimilars in Brazil with local player Bformer Watson business in the US are “not therapeutically Orygen Biotecnologia, according to adeal struck between the two equivalent” to Valeant’sWellbutrin XL brand, the US Food and Drug companies. Orygen –ajoint venture between Brazil’sEurofarma Administration (FDA) has concluded. Ayear ago, the agencyhad found Laboratórios and Biolab Sanus Farmaceutica –will help Epirus to that Teva’s version of the product –manufactured by Impax –was not register its ‘BOW015’ biosimilarinfliximabcandidate locally,aswell therapeutically equivalent to the brand (Generics bulletin,19October as developing “additional biotechnology products for manufacture and 2012, page 1). commercialisation in Brazil”. “Watson has agreed to voluntarily withdrawthis product from the Noting that it had recently announced “successful Phase III data distribution chain,”the FDAnoted. The agencyadded that it had for BOW015”, Epirus said it would transfer technology and completed areviewofgeneric bupropion 300mg extended-release manufacturing systems to Orygen so that the firm could construct a tablets and had confirmed that three other versions –manufactured by production plant and manufacture the rivaltoJanssen’sRemicade in Actavis, Mylan and Par–were equivalent to the antidepressant brand. Brazil. ForBOW015 –aswell as the additional biotech products – “The FDAhas changed the therapeutic equivalence code for the Orygen will have exclusive rights in Brazil, while Epirus will retain Watson product from AB –therapeutically equivalent –toBX, indicating exclusive rights for all other global markets. that data are insufficient to determine therapeutic equivalence,”the Epirus said it would “earn up to US$275 million in upfront, agencystated, adding that it “does not anticipate adrug shortage”. milestone and royalty payments and service-based fees”. G In 2012, abioequivalence study by the FDAhad demonstrated that Teva’s Budeprion XL 300mg tablets “fail to release bupropion into the blood at the same rate and to the same extent as Wellbutrin XL 300mg”. The agencyhad previously approvedthe product based on BONE-DISEASE DRUGS/OSTEOPOROSIS DRUGS bioequivalence studies comparing the 150mg strength to Wellbutrin XL 150mg. These results were then “extrapolatedtoestablish bioequivalence US Reclast case is limited of the 300mg product”. “This extrapolation did not provide the right ovartis cannot assert literal or induced infringement of US method- conclusion,”the FDAlater acknowledged. Nof-use patent 8,052,987 against several generics firms that have Mylan and Parhad already receivedFDA approvalearlier this sought abbreviated newdrug application(ANDA) approvals for year for supplementary abbreviated newdrug applications (sANDAs) zoledronic acid as atreatment for Paget’sdisease, NewJerseyDistrict that were submitted to the agencytoconfirm the bioequivalence of Judge Susan Wigenton has ruled. The ANDAfilers had submitted their bupropion 300mg extended-release tablets with Wellbutrin XL ‘section viii’ carve-outs for the osteoporosis indicationofNovartis’ (Generics bulletin,6September 2013, page 22). G Reclast brand that is covered by the ‘987 patent. According to Wigenton, Novartis’ literal and induced infringement arguments must be dismissed because the originator had not shown that EPILEPSY DRUGS the section viii carve-outs were misleading or improper.Furthermore, she said, Novartis had not proventhat the generics firms had taken “affirmative steps to foster infringement”. Hospira lines up levetiracetam However, Wigenton said she could not at this stage of proceedings centralised European Union (EU) marketing-authorisation application determine whether using the generics for the non-patented treatment Asubmitted by Hospira for levetiracetam concentrate has received of Paget’sdisease wassufficiently “substantial” to avoid contributory apositive opinion from the European Medicines Agency(EMA). infringement. Novartis claimed Paget’sdisease accounted for only The EMA’s committee for human medicinal products (CHMP) said 0.3% of prescriptions for Reclast. Hospira’sgeneric version of UCB’sKeppra (levetiracetam) 100mg/ml Apotex–one of several generic litigants along with Accord, concentrate for solution should be approvedasamonotherapyfor Actavis, Sun and Wockhardt, amongst others –persuaded Wigenton treating partial onset seizures for adults and adolescents aged 16 years to takeaccount of the US Food and Drug Administration’s(FDA’s) and above who had been newly diagnosed with epilepsy,aswell as recent response to Novartis’ citizen petition. This stated that the agency adjunctive therapyofyounger epilepsy patients. could approve zoledronic acid ANDAs that carved out the patented As Levetiracetam Hospira would be administered intravenously osteoporosis use. G and be 100% bioavailable, the CHMP noted, no bioequivalence study wasrequired. The European Commission typically acts on the CHMP’s IN BRIEF opinions within 67 days. The CHMP has also said intravenous nicardipine should only be ACTAVIS has been sued by Dowand Valeant in the US after filing used to treat acute, life-threatening high blood pressure, butnolonger an abbreviated newdrug application (ANDA) containing a for indications linked to anaesthesia and surgery.The UK had triggered paragraph IV challenge to apatent protecting the originators’ Acanya asafety reviewafter it receivedageneric marketing-authorisation (clindamycin/benzoyl peroxide)1.2%/2.5% gel until 2029. Asecond application for an intravenous form of the antihypertensive agent. patent covering the brand expires on 31 March 2015. Noting that the Separately,the CHMP has confirmed, following are-examination, acne treatment had annual US sales of around US$62 million, Actavis its recommendation to restrict the dose and duration of use of said it believeditmay be entitled to 180-day exclusivity for its generic.G metoclopramide due to “potentially serious neurological side effects”. Oral solutions, the committee said, should be no stronger than 1mg/ml. G

12 GENERICS bulletin 1November 2013

Gen 1/11/13 Pgs. 12-17_Layout 1 30/10/2013 19:43 Page 4

PRODUCT NEWS

PRODUCT LAUNCHES BIOSIMILARS Arrowtakes aim at Stada will license eight French targets Apotex’EUfilgrastim

ight products in 11 presentations have been launched by Actavis’ tada has struck adeal with Apotextolicense the Canadian firm’s EArrowsubsidiary in France. Sold under the Actavis label, captopril/ SGrastofil (filgrastim) biosimilar version of Amgen’sNeupogen hydrochlorothiazide 50mg/25mg tablets are rivals to Bristol-Myers brand in the European Union (EU). Noting that the German firm Squibb’sEcazide and Sanofi’sCaptea brands, while the generics firm would “assume sales of the biosimilarfor nearly all EU countries”, has also introduced aversion of Pfizer’sZoxan (doxazosin) 8mg Stada said it planned to begin selling the product from 2014. prolonged-release tablets. Grastofil has just receivedapprovalfrom the European Commission, Arrowhas also launched ageneric version of Abbott’sFloxyfral following apositive opinion from the European Medicines Agency’s (fluvoxamine) tablets in 50mg and 100mg strengths,aswell as (EMA’s)committee for human medicinal products (CHMP) earlier levocetirizine 5mg tablets equivalent to UCB’sXyzall antihistamine. this year (Generics bulletin,9August 2013, page 18). The product Metoprolol 100mg tablets will compete with Daiichi Sankyo’s represented “an inexpensive alternative therapythat doctors, patients Lopressor and AstraZeneca’sSeloken brands, while Arrowhas also and even the public healthcare system will benefit from”, Stada said. introduced ageneric version of Merck, Sharp &Dohme’sNorset “With Grastofil, we are consequently following our strategy of (mirtazapine) brand in the form of 15mg orodispersible tablets. selectively in-licensing biosimilars from high-profile partners,”stated Meanwhile, spironolactone tablets in 25mg, 50mg and 75mg Stada’svice-president of biotechnology,Michael Mack. “The agreement strengths are rivals to Pfizer’sAldactone. And Arrowisalso competing with Apotexputs us in the position to expand our portfolio with a with Novartis’ antifungal Lamisil (terbinafine) 1% cream. high-qualitybiosimilar at very favourable conditions,”Mack added, Arrowalso recently launched aFrench rivaltoJanssen’sDurogesic insisting that both companies would benefit from the German firm’s (fentanyl) patches in four strengths, as well as adedicated portfolio of “excellent international sales structures and comprehensive experience orthopaedic products (Generics bulletin,18October 2013, page 14). G in the European market”. Noting that Grastofil would be available in pre-filled syringes with twodifferent concentrations –30MU/0.5ml or 48MU/0.5ml –for ANTIRETROVIRALS intravenous or subcutaneous injection, Mack observed that “the effectiveness, tolerability and quality of Grastofil are comparabletothe Efavirenz patent blocks Mylan original product within the approvedarea of application”. Biosimilarity with Amgen’sNeupogen neutropenia treatment had been demonstrated ylan has failed to convince Delaware District Judge Leonard in “comprehensive comparative studies”, he stated. G MStark that US patent 6,673,372 –which protects certain crystalline forms of efavirenz –isanticipatedorinvalid for lack of enablement IN BRIEF and written description. Furthermore, Stark said, Mylan infringed a keyclaim of the patent, which expires on 10 June 2019. FDA –the US Food and Drug Administration –isplanning to Since March 2011, Mylan has held tentative abbreviated newdrug reclassify hydrocodone combination products from schedule III application (ANDA) approvalfor its rivaltoBristol-Myers Squibb’s of controlledsubstances into schedule II, which would increase (BMS’) Sustiva (efavirenz) 600mg antiretroviral tablets. controls on all such products. “In recent years, the FDAhas become “BMS has proventhat all of the limitations of claim 18 [of the increasingly concerned about the abuse and misuse of opioid ‘372 patent] are present in Mylan’sANDAproduct,”Stark stated. products,”the agencystated, adding that it would submit formal Addressing Mylan’sinvalidity arguments, Stark said that the recommendations to the US Department of Health and Human differential scanning calorimetry (DSC) peak for the patented Services by early December.Meanwhile, the FDAhas just approved polymorph wassufficiently different to that of aprior-art crystal form extended-release hydrocodone capsules made by Zogenix to be to avoid anticipation. Nor,hesaid, did claim 18 fall for being indefinite. marketed under the ZohydroERbrand name. It did not fail to teach askilled person howtomakethe polymorph, or fail to meet written-description standards. G TEVA has succeeded in convincing afederal court in Ontario, Canada, to support an earlier ruling allowing the companytoseek damages from Pfizer for keeping the generics firm’srivaltoNorvasc ORAL CONTRACEPTIVES (amlodipine)off the market between 2006 and 2009. Teva’s Ratiopharm had in 2009 successfullyinvalidated akey patent Canada’sCobalt loses on Yaz protecting the brand (Generics bulletin,1August 2009, page 17). obalt Pharmaceuticalshas failed to convince afederal court in JB CHEMICALS &PHARMACEUTICALS says it will launch COntario, Canada, that it should be granted anotice of compliance generic tinidazole 250mg and 500mg tablets in the US in the first –effectively amarketing authorisation –for arivaltoBayer’sYaz quarter of 2014 after receiving US Food and Drug Administration (FDA) (drospirenone/ethinylestradiol) 3mg/20mg tablets. approval. JB is making the antibiotic at its plant in Panoli, India. Cobalt had claimed that Canadian patents 2,179,728 and 2,382,426 were invalid or not infringed by its proposed generic. But while the IMPAX has been sued overanabbreviated newdrug application court accepted the generics firm’sargument that certain claims of the (ANDA) containing aparagraph IV certification it has filed in the US ‘728 patent were “not patentable because theyare directed to amethod for ageneric rivaltoWarner Chilcott’s Atelvia (risedronate)35mg of medical treatment”, it rejected Cobalt’sclaims that the ‘426 patent delayed-release tablets. US patents protect Atelvia until January 2028. G lacked utility and wasobvious, insufficient and ambiguous. G

14 GENERICS bulletin 1November 2013 Gen 1/11/13 Pgs. 12-17_Layout 1 30/10/2013 19:43 Page 5

PRODUCT NEWS

OTCPRODUCTS BIOLOGICALDRUGS Stada buys Russian Teva dropsdossier Aqualor sea sprays for US lipegfilgrastim

tada Arzneimittel is set to expand its OTCportfolio in Russia by eva has withdrawn its pending US biologics license application Sacquiring the Aqualor brand of seawater-based sprays and drops T(BLA) for its XM22 lipegfilgrastim long-acting granulocyte-colony for C131 million (US$180 million) in cash, 83% of which will be payable stimulating factor (G-CSF). “Teva decided to prioritise its efforts and upon completion, and the other 17% within 12 months of closing. provide greater focus on investigating one long-acting G-CSF,” a Stada expects to close the deal –which does not include any companyspokesperson told Generics bulletin.“Therefore, we decided facilities or transfer of employees from the vendors, Cyprus’ Butterwood to proactively withdrawthe BLA filing in the US for XM22 and focus Holdings and Moscow’sPharmamed –inthe first quarter of 2014. on balugrastim,”she stated. The deal will give Stada arange of 10 Aqualor-branded OTC Balugrastimisaonce-per-cycle recombinant G-CSF that is fused medical devices for adults, children and infants. These sprays and drops to human albumin. Teva says albumin fusion is “a clinically-validated are used to treat conditions including sinusitis and sore throat. technology that extends product half-life, allowing for infrequent Russian sales of Aqualor products amounted to approximately dosing, better tolerability and lower cost”, while it also “improvesdrug C28 million in 2012, Stada pointed out, and generated an earnings design, potentiallylowering immunogenicity risk”. before interest, tax, depreciation and amortisation (EBITDA) margin Last year,Teva said it had completed Phase III clinical trials for that was“significantly above”the average margin generated by other both balugrastimand lipegfilgrastim. “In both Phase III breast-cancer products within its Branded Products division. On an adjusted basis, the studies,”the Israeli firm stated, “the primary endpoint wasachieved division’sEBITDAmargin in the first half of this year was32.8%. –demonstrating areduction in the duration of severe neutropenia in Since its launch in 2007, Stada noted, Aqualor had become one cycle 1.”Efficacyand safety metricswere comparable to pegfilgrastim, of Russia’sleading brands in the seawater products category,which it added (Generics bulletin,13July 2012, page 14). had grown by 34% on average for each of the past five years. Earlier this year,Teva’s chief scientific officer,Michael Hayden, Branded self-medication products are “especially strategically said the companywould launch balugrastim–for which Teva just important” for Stada as it seeks to expand eastwards and to reduce started aPhase II paediatricdosing trial –“towards the end” of 2013. its dependence on volatile generics markets (see page 20). G Under the terms of aUSpatent-litigation settlement with Amgen, Teva has agreed not to market balugrastimorits short-acting tbo-filgrastim before 10 November 2013 (Generics bulletin,5August 2011, page 1). KIDNEYDISEASE DRUGS Teva had secured US Food and Drug Administration (FDA) approvalfor tbo-filgrastim–since giventhe brand name Granix –just Prasco strikes Fosrenol deal overayear ago as astandalone BLA, rather than as abiosimilar to Amgen’sNeupogen (Generics bulletin,14September 2012, page 1). rasco has struck an exclusive US deal to distribute an authorised In responsetoTeva dropping its lipegfilgrastimBLA, Amgen has Pgeneric of Shire’sFosrenol (lanthanum carbonate) 500mg, 750mg dismissed its lawsuit with Teva overUSpatent 8,058,398 (Generics and 1g chewable tablets. The authorised generics specialist will be bulletin,6September 2013, page 21). “If circumstances change,”the able to launch in response to the first generic entering the US market. originator stated, “we can re-file the lawsuit.”Amgen claims to have Mylan had in 2009 claimed first-to-file status by challenging US US intellectual-property protection for pegylated forms of filgrastim patent 5,968,976, which protects Fosrenol until 26 October 2018 “through to the end of 2015”. (Generics bulletin,3April 2009, page 15). Shire settled litigation with Amgen’sNeulasta (pegfilgrastim) original achievedUSsales of Mylan, Alkem and Natco, allowing them to launch upon abbreviated US$905 million in the third quarter of this year,while Neupogen newdrug application(ANDA) approval. Another settlement allows Teva’s (filgrastim) added another US$409 million, includingaUS$155 million Barr to launch on the earlier of another generic entering the market or order from the US government. 1October 2021. No generics of Fosrenol have been approvedtodate. G In the European Union (EU), Teva recently receivedacentralised marketing authorisation for its XM22 lipegfilgrastim drug under the Lonquexbrand name. This approval–which allows Teva to launch in all 28 EU member states, as well as Iceland, Liechtenstein and Norway –came around eight weeks after the European Medicines Agency(EMA) gave apositive opinion (Generics bulletin,7June 2013, page 1). The firm recently obtained aprice listing in Germany (Generics bulletin,20September 2013, page 16). Meanwhile, Amgen –which is currentlyenrolling psoriasis patients for apivotal clinical study for abiosimilar rivaltoAbbVie’sHumira (adalimumab)–will from 1January 2014 regain rights to Neupogen and Neulasta in around 100 countries outside of the US and European Union (EU). Roche has since 1989 held rights to filgrastim and pegfilgrastiminEastern Europe, Latin America, Asia, the Middle East and Africa under alicence from Amgen’sjoint venture with Kirin. “These markets account for about US$200 million Neupogen and Neulasta sales, and will provide aplatform for future product launches,” stated Amgen. Roche will act as an interim distributor for the brands in certain countries. G

1November 2013 GENERICS bulletin 15 Gen 1/11/13 Pgs. 12-17_Layout 1 30/10/2013 19:43 Page 6

PARAGRAPH IV WATCH Savella’s prospects give little to savour

ncreating afive-year newchemical entity (NCE) exclusivity period, IUS legislators were aiming to encourage the development of new KEY DETAILS: SAVELLA compounds and to protect the investment made in bringing them to Brand: Savella market. Not only does the NCE exclusivity prevent the approvalof Active ingredient: milnacipran hydrochloride anygeneric version of aprotected drug for five years from the date of first approval, it also prevents the submission of an abbreviated Delivery form: 12.5mg, 25mg, 50mg and 100mg tablets newdrug application(ANDA) during that period, thus delaying Brand owner: Forest Labs (licensed from Cypress) competition well beyond the five-year exclusivity term. Annual brand sales: US$105 million However, if an ANDAincludes aparagraph IV certification –stating that one or more patents are invalid, unenforceable or not infringed –it First paragraph IV 14 January 2013 may be submitted exactly one year before the expiration of the applicable filing submitted to FDA: NCE exclusivity,onthe so-called‘NCE minus one’ (NCE-1) date. Known paragraph IV Amneal, Apotex, First Time US Generics, Under the Hatch-Waxman legislative framework, generic applicants filers: Hetero, Lupin, Mylan, Par, Ranbaxy are encouraged to file patent challenges as early as possible by the potential benefit of a180-day generic market exclusivity that may Patents at issue – 6,602,911 –14January 2023 be granted to the first filer of aparagraph IV patent challenge. For 7,888,342 –5November 2021 products protected by an NCE exclusivity,the NCE-1 date serves as 7,994,220 –19September 2029 acertain date upon which ANDAfilers may submit an application, Other patents – 6,992,110 –5November 2021 secure in the knowledge that theywill be afirst filer.Asaresult, NCE District court location: Delaware products have drawn ANDAfilers likemoths to aflame, possibly attracting more challenges than might otherwise have been made based Litigation reference: Forest vs Amneal –1:13-cv-01737 upon other considerations. Forest’sSavella (milnacipran hydrochloride) Forest vs Apotex–1:13-cv-01602 tablets, afibromyalgia treatment licensed from Cypress BioScience, Forest vs First Time –1:13-cv-01642 is just the most recent example of this phenomenon. Forest vs Hetero –1:13-cv-01603 The January 2009 authorisation of Savella tablets marked the first Forest vs Lupin –1:13-cv-01604 approvalofthe milnacipran compound in the US. The resulting NCE Forest vs Mylan –1:13-cv-01605 exclusivity will expire on 14 January 2014. Since its introduction, Forest vs Par–1:13-cv-01606 Savella has produced modest results in the marketplace. US sales in Forest vs Ranbaxy –1:13-cv-01607 the 12 months ended 31 March 2013 were just under $105 million, Figure1:Paragraph IV challenges to Forest Labs’ Savella (milnacipran hydrochloride) up slightly from $103 million during the previous 12-month period. tablets in the US (Source –Thomson Reuters) Predictably,the US Food and Drug Administration (FDA) reports that at least one ANDAfor milnacipran hydrochloride tablets wasfiled Active Brand Earliest ANDA on the NCE-1 date, and it appears likely that several were submitted ingredient name submission date on 14 January this year.On23September 2013, Forest and Royalty Pharma –the owner of Cypress BioScience –filed patent-infringement Romidepsin Istodax 5November 2013 suits against Apotex, Hetero, Lupin, Mylan, Par, and Ranbaxy,alleging Capsaicin Qutenza 5November 2013 infringement of three of the four patents listed for Savella in the FDA’s Fampridine Ampyra 22 January 2014 Orange Book (see Figure 1). Then on 2October,Forest and Royalty Liraglutide Victoza 25 January 2014 filed asimilar suit against First Time US Generics, acontract Velaglucerase alfaVpriv26February 2014 manufacturing companythat has not previously been involved in Hatch- Carglumic acid Carbaglu 18 March 2014 Waxman litigation (Generics bulletin,18October 2013, page 21). Polidocanol Asclera 30 March 2014 Subsequently,on21October,Forest and Royalty sued Amneal over its ANDAfor ageneric version of Savella. Figure2:Active ingredients subject to new chemical entity (NCE) exclusivities for “With hindsight, it is tempting to speculate that the companies which abbreviated new drug applications (ANDAs) can be submitted between November 2013 and March 2014 (Source –Thomson Reuters) which targeted Savella for generic development could have predicted the heavy competition and devoted their resources elsewhere. As an NCE-1 Reuters observes. “Asitstands, with future sales likely to be divided opportunity,itwas perhaps too obvious atarget,”comments Thomson among multiple players and prices diminished by the inevitable erosion, Reuters, which compiles adatabase of paragraph IV challenges and Savella does not appear to offer much promise of alucrative generic associated litigation. Savella’soral solid formulation seems unlikely to payoff, even if the patent challenges are successful.” have presentedmuch of abarrier and the active ingredient is widely As Figure 2shows, November brings NCE-1 dates for Celgene’s available, with over10drug master files (DMFs) currently active. Istodax (romidepsin) powder for injection and Acorda’sQutenza “If Savella’srelatively lowsales were thought to be adeterrent (capsaicin)patches, while Ampyra (fampridine) extended-release tablets to some filers, one could counter by pointing to numerous challenges and Victoza (liraglutide) solution for injection face potential paragraph IV to products with even less enticing financial prospects,”Thomson filings in January next year. G

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: +1 207 871 9700 x35. Fax: +1 207 871 9800. E-mail: [email protected]. Website: scientific.thomsonreuters.com/newport.

16 GENERICS bulletin 1November 2013 Gen 1/11/13 Pgs. 12-17_Layout 1 30/10/2013 19:43 Page 7

PRODUCT NEWS

IN BRIEF ONCOLOGY DRUGS/OSTEOPOROSIS DRUGS ACCORD HEALTHCARE has failed to have claims 1to22ofUS patent 7,772,209 ruled invalid through an inter partes review before Teva Canadaloses the US Patent and Trademark Office (USPTO). In rejecting Accord’s petition as “time-barred”, the USPTOsaid Lilly had first sued the Intas affiliate in January 2012, so the reviewfell outside of the permissiblelimit of one year from an infringement complaint being on zoledronic acid filed. The ‘209 patent protects the originator’s Alimta (pemetrexed) brand until 24 May 2022, including six-month paediatricexclusivity. eva has failed to convince Canada’sFederal Court of Appeal that It did not matter,the USPTOruled, that Lilly had sued Accord Talower court had been incorrect to prohibit the companyfrom separately overdifferent formulations of Alimta. securing anotice of compliance –effectively amarketing authorisation – for zoledronic acid 4mg/5ml and 5mg/100ml injectable formulations. RESOLUTION CHEMICALS can continue to prepare for imminent According to Teva,the lower-court judge had erred in his analysis UK litigation seeking revocation of Lundbeck’ssupplementary of the obviousness of Canadian patent 1,338,937. But the panel of three protection certificate (SPC) for its Cipralex (escitalopram) appeal judges said the Israeli firm had failed to establish that the lower- antidepressant (Generics bulletin,9August 2013, page 17). Justice court judge had “made an overriding and palpable error in his appreciation Richard Arnold declined Lundbeck’scall for him to recuse himself of the evidence”. The ’937 patent expires on 25 February next year. because he knewone of the expert witnesses called by Resolution, “There are clear indications that the judge wasalert and alive and thus might be biased subconsciously.But Arnold said there was to the issues raised, butinthe end, simply did not agree with the no “real possibility” of him being biased during an eight-day trial appellant’sanalysis of the evidence,”the panel said in dismissing scheduled to begin on 11 November. Teva’s appeal against the earlier ruling. This had found that the ‘937 patent’sinventors had “made and tested the [zoledronate] compound APOTEX has succeeded in having struck out portions of affidavits before the Canadian application wasfiled, and found it to be useful”. supplied by Pfizer’sexpert witnesses in alegal dispute overCanadian While it upheld the ‘937 patent, the lower federal court in Ontario patent 2,177,576, which protects Pfizer’s Celebrex (celecoxib)anti- ruled that Canadian patent 1,338,895 wasinvalid for lack of utility inflammatory agent. Noting that the twofirms had disagreed on (Generics bulletin,5April 2013, page 14). There wasnothing in the what constituted factual evidence that should have been disclosed, description of the ‘895 patent, it said, to suggest that all members of a Judge Kevin Aalto awarded costs against Pfizer as the originator class of 1.2 million compounds identified in the patent had utility. G had been responsible for “much of the mischief that has transpired”.

MYLAN did not infringe US patent 5,741,510 by filing an abbreviated newdrug application(ANDA) for ageneric version of Endo’s ANTIDEPRESSANTS Lidoderm (lidocaine)transdermal patch, according to aconsent decree entered in aDelaware district court. Mylan’sallegation that US upholds Aplenzinpatents the ‘510 patent wasinvalid wasdismissed without prejudice. Each our US patents protecting Valeant’sAplenzin (bupropion party bore its owncosts. Actavis introduced the first US generic of Fhydrobromide) have been confirmed as valid by aUSCourt of Lidoderm in mid-September under the terms of apatent-litigation Appeals. The decision upholds a2011 ruling by asouthern Florida settlement with Endo (Generics bulletin,20September 2013, page 7). district court that Actavis’ former Watson operation had “not provedby clear and convincing evidence” that askilled artisan “would have EAGLE PHARMACEUTICALS has infringed US patent 8,445,524 reasonably expected abupropion hydrobromide formulation to have by filing anew drug application (NDA) for bendamustine 100mg/4ml improvedstability overbupropion hydrochloride formulations”. The liquid concentrate, according to alawsuit filed by Teva’s Cepahlon patents run until 27 June 2026. in aDelaware district court. The ‘524 patent protects Cephalon’s “Valeant’sclaimed inventions have significant unexpected Treanda powder and solution for injection until 26 September 2029, advantages overthe bupropion hydrochloride formulations,”the district including six-month paediatric exclusivity.“Eagle’suse of the solid court found. These included “a longer –doubled –shelf life, reduced form of bendamustine hydrochloride in the manufacture of Eagle’s risk of seizures, the ability to formulate asingle tablet at all dosage bendamustine product infringes one or more claims of the ‘524 strengths –including the highest dosage –improvedresistance to dose patent,”according to documents filed by Cephalon as part of its dumping and easier manufacturability”. Furthermore, the court lawsuit overthe leukaemia treatment. concluded, “the fact that three other companies, including Watson, have copied Aplenzin despite the availability of bupropion hydrochloride STADA has introduced the migraine remedy rizatriptan in Spain in supports afinding of non-obviousness”. G packs of twoand six orodispersible tablets. The generic is equivalent to Merck, Sharp &Dohme’s Maxalt Max brand. Between 12% and 16% of Spanish people suffered from migraines, estimated Stada, UROLOGY DRUGS which also markets zolmitriptan in Spain. Sandoz can pursue silodosin AGILA SPECIALTIES has been sued by Cubist in aDelaware district court overthe Indian firm’sparagraph IV challenges to four patents andoz can continue to pursue abbreviated newdrug application protecting the originator’s Cubicin (daptomycin)injectable antibiotic. S(ANDA) approvalfor ageneric version of Actavis’ Rapaflo Twoofthe four patents expire on 24 September2019, and the other (silodosin) capsules.The US Food and Drug Administration (FDA) has twoon28November 2020. Cubist said it had filed the lawsuit within denied acitizen petition in which Actavis demanded that the agency 45 days of receiving anotification letter from Agila, thereby triggering revise guidance to require ANDAapplicants to demonstrate an automatic 30-month stay of approvalfor Agila’sabbreviated bioequivalence with both silodosin and its metabolite KMD-3213G. newdrug application (ANDA). G It wassufficient, the FDAsaid, to measure KMD-3213G and provide metabolitedata to support bioequivalence to silodosin. G

1November 2013 GENERICS bulletin 17 Gen 1/11/13 Pg. 18_Layout 1 30/10/2013 19:44 Page 2

EVENTS

NOVEMBER generics, biosimilars, OTCproducts, 19-21 February medical devices and food supplements. ■ GPhA 2014 Annual Meeting 11-14 November Contact:Raucon. Florida, USA ■ 8th Generics Asia Tel: +49 6222 9807 0. This three-day meeting of the US Generic E-mail: [email protected]. Singapore Pharmaceutical Association (GPhA) will Website: www.europlx.com. This four-day event will coverissues such look at regulatory issues and the challenges as strategic partnerships, market access, and opportunities for the generics industry. product portfolios, supergenerics, branding JANUARY There will also be networking opportunities. and marketing, as well as pricing policies. 22 January Contact:GPhA. Contact: IBC Asia. Tel: +1 202 249 7100. Tel: +65 6508 2401. ■ 7th EGA Pharmacovigilance E-mail: [email protected]. E-mail: [email protected]. Discussion Forum Website: www.gphaonline.org. Website: www.generics-asia.com. London, UK This European Generic medicines Association MARCH 12-13 November (EGA) event will takethe form of a ■ 2nd Annual World Biosimilar discussion forum and look at topics including 18-19 March Congress Europe legislation and risk-management plans. ■ 10th EGA Legal Geneva, Switzerland Contact:Cristina Romagnoli, GPAConferences. Affairs Forum Tel: +377 93 501 348. This two-day event will discuss topics such Brussels,Belgium as production, regulation, clinical trials, E-mail: [email protected]. Register onlineatwww.gpaconferences.com. This two-day EGA event will look at comparability and to-market models for the issues including intellectual property, international biosimilars industry. 23-24 January litigation, regulatory matters, patent Contact:Terrapinn. settlements and the European unified ■ 13th EGA Regulatory& Tel: +44 207 092 1000. patent court. The forum will also offer E-mail: [email protected]. Scientific Affairs Conference networking opportunites. Website: www.terrapinn.com. London, UK Contact:Cristina Romagnoli, GPAConferences. This two-day conference will followthe Tel: +377 93 501 348. 19-21 November EGA’s Pharmacovigilance Forum. The event E-mail: [email protected]. ■ World Generic Medicines will look at regulatory developments, generic Register onlineatwww.gpaconferences.com. Congress Americas 2013 medicines development and bioequivalence, Boston, USA and electronic submissions. Both meetings 25-27 March are to be held at the same venue in London. Focusing on issues including policyupdates, ■ DIA 26th Annual IP developments, commercial strategies for Contact:Cristina Romagnoli, GPAConferences. EuroMeeting biosimilarsand building market share, this Tel: +377 93 501 348. E-mail: [email protected]. Vienna, Austria three-day event is co-located with the Register onlineatwww.gpaconferences.com. Issues covered at this three-day meeting of Biosimilar Drug Development Conference. the Drug Information Association (DIA) Contact:Health Network Communications. FEBRUARY will include clinical research, regulatory Tel: +44 207 608 7055. topics, active substances, drug development E-mail: customerservices@healthnetwork and globalisation. communications.com. 6-7February Contact:DIA. Website: www.healthnetwork ■ 6th Pharmeet communications.com. Tel: +41 61 225 5151. Marrakech, Morocco E-mail: [email protected]. This two-day event is designed to offer Website: www.diaeurope.org. 25-26 November delegates the opportunity to network as ■ EuroPLX 53 well as the chance to strikelicensing Barcelona, Spain deals for awide range of products, APRIL This conference will provide aforum for including biosimilars. 1-4April business-development decision makers to Contact:PharMeet. ■ World Generic Medicines discuss and negotiate collaborative Tel: +34 91 637 0660. agreements in licensing, marketing and E-mail: [email protected]. Congress Europe 2014 distribution of patented medicines, Website: www.pharmeet.com. London, UK This is afour-day conference which is to 9-11 December 2013 be co-locatedwith the Biosimilar Drug Development event. The conference will ■ 16th IGPAAnnual Conference look at topics including commercial Brussels,Belgium strategies, intellectual-property This three-day conference is being organised by the European Generic developments and international markets, medicines Association (EGA) and is the global event of the worldwide generics industry. and will provide global policyupdates. It is the annual joint meeting of the Canadian, European, Japanese, South African and US Contact:Health Network Communications. generics industry associations, the CGPA, EGA, JGA, NAPM and GPhA. Topics to be Tel: +44 207 608 7055. covered at this year’sconference will include market trends and regulatory developments E-mail: customerservices@healthnetwork Contact:Cristina Romagnoli, GPAConferences.Tel:+377 93 501 348. E-mail: [email protected]. communications.com. Website: www.igpagenerics.comorwww.gpaconferences.com/igpa13.htm. Website: www.healthnetwork communications.com.

18 GENERICS bulletin 1November 2013 Gen 1/11/13 Pg. 19_Layout 1 30/10/2013 19:44 Page 3

PRICE WATCH ...... UK Sildenafil comes in at under £1 per pack ildenafil has been added to our ‘fast movers’ this month to reflect At that time, the lowest recorded trade price for four-tablet packs Stheerectile-dysfunction treatment’sswift move to category Mof of sildenafil 100mg was£0.71, compared with abrand price of £23.50. the Drug TariffinOctober.Launched only in June, the generic equivalent Last month, that price too had fallen to £0.50 (see Figure 1). Pharmacists’ to Pfizer’sViagra had taken alittle overthree months to move through dispensing profit margins were 48% on average, based on aDrug the reimbursement categories since the original’ssupplementary Tariffprice of £1.55,and 68% at the lowest trade price. protection certificate (SPC) expired. The rapid transition to getting a Alfuzosin 2.5mg tablets in 60-count packs, launched in September pharmacyreimbursement price based on actual market prices –rather 2007, have been removedfrom the fast movers to makeway for sildenafil. than the brand’strade price or aprice based on Actavis and Teva’s Elsewhere, prices for 28-tablet packs of rabeprazole 10mg suffered formal price lists –reflected sildenafil’sdramatic price fall at launch. double-digit falls, while those for lercanidipine 10mg went the other Prices for four-tablet packs of sildenafil 25mg fell from £16.59 way. Valaciclovir 500mg tablets sawthe biggest price falls (see Figure 2), (US$26.53) to £0.50,adrop of 97% (Generics bulletin,18October while for the second month running, propanolol 10mg and 40mg tablets 2013, page 23). While pharmacists were being reimbursed at the brand’s experienced some steep price rises (see Figure 3). But only the latter trade price, their dispensing profit margin too was97%. had been givenaprice concession of £3.51 by 25 October. G

BIGGEST FALLERS BIGGEST RISERS Product/Strength/Pack size Lowest Change Average Change Product/Strength/Pack size Lowest Change Average Change price (%) price (%) price (%) price (%) Valaciclovir tabs 500mg 10 £1.99 ±0 £3.86 -42 Propranolol tabs 10mg 28 £0.22 +29 £1.60 +272 Valaciclovir tabs 500mg 42 £8.99 +12 £14.40 -42 Propranolol tabs 40mg 28 £0.33 +38 £2.93 +115 Risperidone tabs 6mg 28 £0.99 +15 £3.92 -32 Prednisolone tabs 1mg 28 £0.24 +50 £0.77 +96 Rivastigmine caps 1.5mg 56 £5.18 -3 £10.26 -29 Indapamidetabs 2.5mg 28 £2.59 +15 £6.75 +86 Rivastigmine caps 3mg 56 £7.27 -9 £10.97 -25 Gabapentin caps 300mg 100 £3.87 +11 £7.87 +55 Glycerin adult suppositories 4g 12 £0.42 ±0 £0.60 -25 Indapamidetabs 2.5mg 56 £5.59 +22 £12.98 +48

Figure1(below): Comparison between the periods 1-30 September 2013 and 1-22 September 2013 and 1-22 October 2013 in lowest and average UK trade prices of October 2013 of the lowest and average UK trade prices of fast-moving generics. about 748 commonly-dispensed generics. The basket specifically excludes the ‘fast Each average price was calculated from at least 31 data points. Figure2(above) movers’ shown below,but includes other presentations of the same products. Each and Figure3(above right): Biggest changes recorded between the periods 1-30 average price was calculated from at least 14 data points (Source –WaveData).

FAST MOVERS FAST MOVERS Product/Strength/Pack size Lowest Change Average Change Product/Strength/Pack size Lowest Change Average Change price (%) price (%) price (%) price (%) Anastrozole tabs 1mg 28 £1.13 +4 £1.69 -35 Pioglitazone tabs 15mg 28 £0.53 -7 £0.98 -4 Atorvastatin tabs 20mg 28 £0.49 ±0 £0.70 -1 Pramipexole tabs 700µg 30 £1.64 -1 £3.00 +1 Bicalutamide tabs 50mg 28 £1.25 -2 £2.59 -1 Quetiapine tabs 25mg 60 £0.59 -8 £1.02 -6 Buprenorphine tabs 2mg 7£1.30 -12 £1.99 -5 Rabeprazole tabs 10mg 28 £1.46 -27 £1.96 -16 Candesartan tabs 8mg 28 £0.73 -18 £1.20 -4 Riluzole tabs 50mg 56 £36.75 -6 £47.59 -8 Clopidogrel tabs 75mg 28 £1.09 -1 £1.32 -3 Risedronate tabs 35mg 4£0.47 -2 £0.68 -1 Cyclizine tabs 50mg 100 £9.49 -6 £12.01 +3 Risperidone tabs 2mg 60 £1.11 +7 £1.81 -1 Desloratadine tabs 5mg 30 £0.75 -12 £1.03 -8 Sildenafil tabs 100mg 4£0.50 -4 £0.80 -7 Donepezil tabs 10mg 28 £0.79 +27 £1.56 +4 Terbinafine cream 1% 15g £1.21 ±0 £1.54 +2 Dorzolamide eyedrops 2% 5ml £1.15 ±0 £1.76 +3 Tolterodine tabs 2mg 56 £1.85 -3 £2.63 -9 Entacapone tabs 200mg 30 £5.95 -3 £7.29 -9 Topiramate tabs 25mg 60 £0.89 +1 £2.08 +15 Esomeprazole tabs 40mg 28 £3.25 -18 £4.94 -9 Trandolapril caps 2mg 28 £0.93 -4 £1.35 -4 Exemestane tabs 25mg 30 £2.90 -2 £5.22 -1 Valsartan caps 80mg 28 £0.82 -2 £1.41 +8 Finasteride tabs 5mg 28 £0.68 ±0 £0.98 +2 Venlafaxine tabs 75mg 56 £1.60 ±0 £2.18 +2 Irbesartan tabs 75mg 28 £0.58 -9 £0.81 +1 Zolmitriptan tabs 2.5mg 6£0.46 -8 £0.99 -2 Latanoprost eyedrops .005% 2.5ml £0.86 +5 £1.28 -10 Lercanidipine tabs 10mg 28 £0.69 +13 £1.19 +13 WANT MORE LIKE THIS? Letrozole tabs 2.5mg 14 £0.99 +24 £1.48 +4 Detailed product price comparisons and other price analyses are Levetiracetam tabs 500mg 60 £1.15 +16 £3.26 -2 available at www.wavedata.net. Losartan tabs 100mg 28 £0.55 ±0 £0.83 -7 To find out more about subscribing, please email your contact details to Montelukast tabs 10mg 28 £1.30 -10 £1.75 -6 [email protected] and quote ‘GB online enquiry’ in the title line. Mycophenolate tabs 500mg 50 £8.70 -3 £10.57 +7 ■ Forfurther information see www.wavedata.co.uk. Naratriptan tabs 2.5mg 6£0.72 +4 £1.37 -4 Alternatively,contact Charles Joynson at Nebivolol tabs 5mg 28 £0.71 ±0 £1.18 -3 WaveData Limited, UK. Tel: +44 (0)1702 425125. Olanzapine tabs 5mg 28 £0.36 -8 £0.69 -7 E-mail [email protected].

1November 2013 GENERICS bulletin 19 Gen 1/11/13 Pgs. 20-21_Layout 1 30/10/2013 19:45 Page 2

BUSINESS STRATEGY Stada sets greatstoreby lureofeastern promise

European company mid the generics industry’sdrive towards  Serbia Germany globalisation, Stada Arzneimittel has remained C33.8m C154.7m Stada is looking Aalargely regional player.Having abandoned its +40% -7% eastwards towards attempts to build ameaningful presence in the US, the companygenerated more than 96% of its total turnover Asia and the in the first half of this year from its operationsinEurope Others and the Commonwealth of Independent States (CIS). C123.6m Commonwealth of Over recent years, the German group has been Russia C76.7m Independent States working to reduce its dependence on its domestic market, +16% and especially on aGerman generics arena that has seen UK (CIS) for growth. its value diminished markedly by the advent of health C4.2m -8% insurance fund tenders around six years ago. As can be Italy Aidan Fryreports. France seen from Figure 1, Germanyaccounted for aquarter C74.2m C40.9m +24% of Stada’sfirst-half Generics sales. Similarly,the firm’s +17% Spain operations in Germany–generics and branded products C46.8m Belgium –made up just under aquarter of group sales that grew -14% C67.6m, -1% by atenth to C974 million (US$1.34 billion). Figure1:Breakdown by countryofStada Generics’ sales that rose Stada’sstrategy for reducing its domestic by 6% to C618 million in the first half of 2013 (Source –Stada) dependence has centred on twomain elements. Firstly, the firm has invested in expanding its Branded Products from the start of this year.Through acombination of business segment, both by driving organic growth of its Pymepharco and its existing operation in Vietnam, Stada OTCand prescription brands, and through acquisitions. expects the country to account for around four-fifths Secondly,the group has used acquisitions to expand of its turnoverinthe region this year (see Figure 2). eastwards into the CIS and Asia-Pacific regions. Citing IMS Health data for 2012, Choo said Stada While the German group has had asizeable Vietnam and Pymepharmco had acombined market presence in the CIS region for most of the past decade – share of around 2.5%, ranking them fourth in Vietnam’s it bought Russia’sNizhpharm in 2005 (Generics C1.65 billion pharmaceuticals market, just behind the bulletin,19November 2004, page 1) –Stada’spush largest local player,DHG Pharma. into Asia-Pacific markets has been more recent. Addressing the group’sannual general meeting YanChoo, Stada’svice-president for its Asia region, earlier this year (Generics bulletin,28June 2013, noted that the group’sactivities in the region had, to page 7), executive chairman Hartmut Retzlaffsaid Stada date, focused on aselect number of countries. Last year, would use its manufacturing facilities in Vietnam as Vietnam accounted for 58% of Stada’stotal Asian sales “regional production hubs” and as low-cost sources for of C25 million, with China contributing 14%, Thailand exports to Europe. The group, he added, wasseeking 10%, the Philippines 8%, and other markets 9%. acquisition targets in south-east Asia as it looked to fill For2013, Stada anticipates its Asia-Pacific turnover in “white spots” on its map that ranged “from countries more than doubling to over C60 million as it fully that border Vietnam, all the waytoSouth America”. incorporates its Vietnamese affiliate, Pymepharmco, Countries targetted for expansion include Myanmar,

Others Retail Hospital Reimbursement 3% Vietnam -Stada 

 
 Market size Philippines (C millions) 4% 23% Thailand Russia 67% 20% 13% 15,300 4% China 7% Ukraine 83% 17% 2,931

Kazakhstan 55% 35% 10% 1,350

Serbia 37% 15% 48% 550

Bosnia- 32% 24% 44% – Herzegovina Vietnam -Pymepharco 59%

Figure2:Breakdown by countryofStada’s forecasted Asia- Figure3:Proportions of selected EasternEuropean and CIS countries represented by the retail, hospital Pacific sales of at least C60 million in 2013 (Source –Stada) and reimbursement sectors (Source –Stada/IMS Health)

20 GENERICS bulletin 1November 2013 Gen 1/11/13 Pgs. 20-21_Layout 1 30/10/2013 19:45 Page 3

BUSINESS STRATEGY

to which the Vietnamese plants currently export around expenditure in the Philippines and Vietnam, that figure 20 products for marketing by alocal agent (Generics was75% in Thailand. bulletin,5April 2013, page 5). In alliance with that Stada, he said, would run country operations as agent, Stada has secured apermit to build the country’s individual profit centres while exploring synergies “first private pharmaceutical factory”. The German between them. The companycurrently has its ownsales group is ramping up its local sales and marketing and marketing set-ups in China and Hong Kong, the activities in expectation of holding 50 local marketing- Philippines, Thailand and Vietnam. authorisation approvals by the end of this year. “Newventures to be considered overthe next two Hong Kong-based Choo said the low-cost to three years, besides Myanmar,are Indonesia and Vietnamese manufacturing base had opened up Japan,”Choo revealed, noting the relatively lowlevel opportunitiestoexport to nearby countries such as of generic penetration in Japan. Myanmar,Laos and Cambodia. The group’sfour Manyofthe same considerations –demographic Vietnamese plants produce not only oral solid-dose trends favouring quality generics –are driving Stada’s products, butalso syrups, soft-gel capsules and expansion in Eastern Europe and CIS countries. injectables for both retail and hospital channels, and Dmitry Efimov, who leads Stada’sCIS operations, have in part been certified for good manufacturing noted that the German group had followed up its 2005 practice (GMP) by European Union (EU) regulators. purchase of Nizhpharm by acquiring Serbia’sHemofarm Stada’smanufacturing site in Beijing, China, has been ayear later (Generics bulletin,18August 2006, page 1). GMP audited by local authorities. Hemofarm’sfacility in Obinsk, Russia, now contributes to aregional production network that also Zone IV stability suits MENA region includes plants in NizhnyNovgorod, Russia; Dubovac, By ensuring that its dossiers and products fulfilled Sabac and Vrsac, Serbia; Banja Luka, Bosnia; and all Association of South-East Asia Nations (ASEAN) Podgorica, Montenegro. Having last year divested two requirements–including Zone IV stabilitydata –Stada Russian sites to improve its cost structure (Generics wasnot only ready for regulatory and trade harmonisation bulletin,1October 2012, page 3), the region’splants in the region, Choo maintained. It wasalso prepared have acombined annual capacity of almost 9.5 billion to supply drugs to the Middle East and North Africa tablets, 460 million capsules and 390 million (MENA) region, where Stada had recently set up a suppositories, as well as over90million packs of logistics and distribution hub in Dubai (Generics ointments, creams and gels, nearly 50 million bottles bulletin,5April 2013, page 5). of syrup and 14.6 million packs of solution. Choo identified niche opportunities within the Stada has more than 1,100 sales representativesin generics sector,such as supplying Halal-compliant drugs Eastern Europe and CIS countries, operating either “New ventures to be to MENAmarkets and Asian countries with large Muslim through its ownorrepresentative offices. Efimov considered over the populations, such as Indonesia and Malaysia. In general, observed that local salesforces were tailored to market he said, Stada would look to capitalise on the group’s conditions that varied considerably.For example, he next twotothree years, German heritage and reputation for quality at affordable said, the retail sector represented two-thirds of Russia’s besides Myanmar,are prices. The firm’spricing strategy,heoutlined, would C15.3 billion pharmaceutical market, butless than a aim to “establish Stada in the ‘premium’ generics segment third of sales in Bosnia-Herzegovina (see Figure 3). Indonesia and Japan” within avery crowded market” by setting prices above Two-thirds of Stada’stotal turnoverinthe region – those of local and regional players. ahead by 28% to C292 million in the first half of this Highlighting the demographic trends that suggested year –came from Russia with C194 million (see Figure 4). sustained growth in demand for high-quality generics Discussing conditions in the C15.3 billion Russian throughoutthe Asia-Pacific region, Choo cautioned pharma market, Efimovsaid double-digit growth was that it wasvital not to adopt the same strategy in all being drivenbyprice increases as volumes had slipped markets. Forexample, he pointed out, while government back slightly in 2012. By volume, branded and unbranded spending accounted for only around athird of medicines generics made up nearly nine-tenths of the market. Stada’sstrategy for capitalising on forecasted 10% market growth through to 2017 wasbased on offering Kazakhstan C9.3m a“well-balanced portfolio” of generics and branded +38% products under the strong Hemofarm and Nizhpharm Others/exports corporate brands, Efimovoutlined. Last year,56% of C25.1m +30% Stada’sRussian sales came from its Branded Products Bosnia- segment, and 44% from Generics. Herzegovina The firm’stop-fiveRussian generics were diclofenac C6.7m with annual sales of C14 million, enalapril with C12 +13% Ukraine million, glycerin with C10 million, indapamide with C17.0m C9million and amoxicillin with C8million. +30% Among its leading Russian brands, Stada’sSnup Russia (xylometazoline) decongestant spray is growing strongly, C194.2m with sales of C11.6 million in the first half of 2013, +30% Serbia compared to C17 million in all of 2012. Stada has also C40.3m +29% been bolstering its Russian brands portfolio through acquisitions, such as of haemostatic Tranexam (tranexamic acid) tablets and ampoules (Generics Figure4:Breakdown by countryofStada’s group sales in EasternEurope and the CIS totalling C292 million in the first bulletin,6April 2012, page 5). It is also paying C131 half of 2013 (Source –Stada) million for the Aqualor sea-water brand (see page 15). G

1November 2013 GENERICS bulletin 21 NEW

Essential Business Development Tools For The OTC Industry. Designed by Deborah Wilkes, co-founder and former Editor &Publisher of OTC bulletin

OTCToolbox DealsDatabase Asearchable database that captures Analyse significantdeals involvingthe OTCindustry worldwideinaformatthatisquick thepast… andeasy foryou to explore

News, News Extras, Briefings Deliver andReports Aportfolio of publications that keepsyou informedabout thefuture keydevelopments affecting theOTC industry worldwide

SourceOTC Ashowcasefor newbusiness opportunities that allows you to target the right people anddevelopthe right partnerships to grow your OTC Think Inside The Box business at theglobal,regionalor www.OTCToolbox.com locallevel

ToolboxA4leaflet-.indd 1 21/05/2013 10:54 Gen 1/11/13 Pg. 23_Layout 1 30/10/2013 19:45 Page 3

PEOPLE

APPOINTMENTS APPOINTMENTS Alvogenadds Alkins Polpharma’s Glinka as Drysdale departs leadsMylanEurope

ormer Teva and Glades executive Darren Alkins has become ylan has appointed Jacek Glinka as president of its operations Fpresident of Alvogen America.Asamember of the generics Min Europe, effective from 2December.The former Polpharma specialist’smanagement board, Alkins is responsible for the firm’s executive –who will report to Mylan’schief operating officer, Hal activities in both North and South America. Alkins takes overfrom the Korman –will takeoverfrom Enrico Baroncia.Less than ayear former chief executive officer of Alvogen America, Doug Drysdale, after he took up the position, Baroncia has left to join Recordati as who has left the company“to pursue other opportunities”. Drysdale general manager of the Italian group’sdomestic operation (Generics had led the firm’sactivities in the Americas since late-2010. bulletin,18October 2013, page 27). “With more than 25 years of commercial experience in both branded Glinka served as Polpharma’schief executive officer in twostints, and generic pharmaceuticals, Darren’ssuccessful history driving key from 2003 to 2006, and then between 2009 and 2013. Mylan pointed organisational initiatives, expertise and leadershipwill help lead Alvogen out he had overseen the Polish group exceeding an annual turnover into our next phase of growth,”commented Alvogen’schairman and of US$1 billion, achievedinpart through acquisitions, including chief executive officer,Robert Wessman. those of PolfaWarsawand Bioton’santibiotics division in Poland, Having started his career with Bristol-Myers Squibb, Alkins served and of Chimpharm in Kazakhstan. as senior vice-president of corporate development at Stiefel Laboratories, and then in 2006 became president of Stiefel’sGlades generics subsidiary Led Polpharma’s expansion in the US (Generics bulletin,21April 2006, page 19). “Glinka led the transformation of Polpharma from asmall local He then spent almost four years at Teva as vice-president of player into aleading pharmaceutical companyincentral and eastern business development and alliance management, before he joined drug- Europe, the Caucasus and central Asia,”Mylan commented. development specialist Osmotica as executive vice-president. G Under his leadership, the US firm added, Polpharmahad integrated Russia’sAkrihin and expanded into countries including Azerbaijan, Uzbekistan and Vietnam. “I have been following Mylan closely for some time,”Glinka APPOINTMENTS stated, “and believe its massive global scale, vertical integration, broad product portfolio and unwavering commitment to quality are true Mallinckrodt reinforces team differentiators in the highly competitive and diverse European market.” allinckrodt has added three members to its senior management With Glinka’sdeparture, Polpharma’smanagement board is headed Mteam as the US analgesicsspecialistfocuses on “growing its by chairman Jerzy Starak. It includes former Watson executive Francois core business as aspecialty pharmaceutical company”, following its Menard as vice-president for global research and development, as spin-offfrom Covidien earlier this year. well as former Sandoz executive Hannes Teissl, who is responsible Hugh O’Neill has joined as president of Specialty Pharmaceuticals. for the Polish group’sbiopharmaceuticals and contract manufacturing He previously held several positions at Sanofi, includingvice-president operations, and for marketing and business development for the Polish of commercial excellence and president of SanofiCanada. group’sFine Chemicals business unit. Former head of global health and healthcare industriesatthe World Business development and strategic sourcing is the responsibility Economic Forum, Gary Phillips,has become Mallinckrodt’schief of Bozenna Kozakiewicz, while Rajmund Martyniuk oversees global strategy officer with responsibility for portfolio management, business commercial operations. G development, licensing, market analytics and alliance management. Mario Saltarelli has joined from Shire as chief science officer. He leads Mallinckrodt’srecently-consolidated functions of research APPOINTMENTS and development, medical affairs and regulatory affairs. G Farrington joins ChemAgis IN BRIEF errigo has hired Harold Farrington as director of sales for SIMCERE has appointed Jingwu Zang to become the Chinese PChemAgis –the US firm’sactive pharmaceutical ingredient (API) firm’schief scientific officer.Zang had previously held positions in division –inNorth America.Former SST Corporation executive neurosciences and research and development at GlaxoSmithKline. G Farrington will be responsible for leading sales and operationsfrom ChemAgis’ Mountain Lakes, NewJerseylocation. G

Finding information is easy these days But finding GOOD information is just as tough as ever That’s why OTC bulletin is Essential Reading Visit www.OTC-bulletin.com

1November 2013 GENERICS bulletin 23