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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 18/4/14 Pg. 1_Gen 18/11/05 Pg. 1 15/04/2014 20:12 Page 1

18 April 2014

COMPANY NEWS 2 Sun makes US$4 billion Mylan misses out on 2 move to gain Meda Pamplona fund takes control of Alvogen 3 Bioton benefits as sales 4 bid to snap up Ranbaxy of insulin boom Sun seeks synergies from Ranbaxy deal 5 un Pharmaceutical Industries intends to create the world’s fifth-largest generics player, Latvia’sOlainfarm sees 6 Sand India’s leading pharma company,bypaying around US$4.0 billion forits rival, upside to crisis Ranbaxy.The deal comprises US$3.2 billion of equity,and US$800 million of assumed debt. FDAcancels Hikma’sEatontown warning 7 Based on Ranbaxy contributing US$1.8 billion to the combined group’spro forma 2013 turnoverofUS$4.2 billion, the proposed all-share transaction values Ranbaxy at 2.2-times sales. Julphar strikes deal to sell MSD’sdrugs 8 The US will makeupjust under half of the combined group’sturnover, India 22% and the rest of the world 31%. Pro forma earnings before interest, tax, depreciationand amortisation MARKET NEWS 9 (EBITDA) were US$1.2 billion last year. “The combined entity will have operations in 65 countries, 47 manufacturing facilities Additional identifiers should applytoall 9 across five continents, and asignificant platform of specialty and generic products marketed GPhA questions basis for 10 globally,including 629 abbreviated newdrug applications (ANDAs),”commented Sun, adding labelling proposal that within the ANDAtotal wasapipeline of 184 filings that included “high-value first-to-files”. Spain amends rules on reference prices 11 Ranbaxy will contribute around US$500 million to the combined group’sUSturnoverof Portuguese advances 12 more than US$2 billion, and will account for two-thirds of the group’sUS$900 million sales bolster penetration in emerging markets, excluding India. Ranbaxy will also strengthen Sun’sminor presence Italyleads EU fiveonbiosimilar sales 13 in western Europe through operations in countries including France, Germanyand the UK. The boards of Sun, Ranbaxy and Ranbaxy’smajority shareholder,Daiichi Sankyo, have PRODUCT NEWS 14 approvedthe deal that will see Ranbaxy’sshareholdersreceive 0.8 Sun shares for each Ranbaxy share theyhold. Sun said this implied avalue of Rs457 per Ranbaxy share, apremium of 18% over Ratiopharm obtains Canadian damages 14 Ranbaxy’sshare price in the preceding month. Pending approvals from 75% of shareholders, as UK Herceptin patents defeated by Hospira15 well as from antitrust and other authorities, Sun anticipates closing the deal by the end of this year. Daiichi Sankyo –which will become Sun’ssecond-largest shareholder –has agreed to PTOrefuses reissue 16 indemnify Sun and Ranbaxy for certain costs that may arise from a subpoena issued by the of Copaxone patent NewJerseyAttorney’sOffice, requesting that Ranbaxy produce documents relating to its Toansa Sandoz launches its AirFluSal 17 facility in India that is the subject of aUSFood and Drug Administration (FDA) import alert. G in Norway Forfurther details of the deal, turntopage 5. Remicade suit is filed by Korea’sCelltrion 19 Endo wins appeal on 21 Opana ER injunction Francis replaces Sandoz’ George FEATURES 24 effGeorge will leave his role as head of Sandoz from 1May to succeed Kevin Buehler as US market bounces back 24 Jleader of parent companyNovartis’ Alcon ophthalmics division. He will be succeeded as as value growsbyatenth head of Sandoz by Biogen Idec’sRichard Francis, described by Novartis as “a proven pharmaceuticals and biotechnology leader” who had “held roles of increasing responsibility Unified courtrules revised 26 across several therapeutic areas in both Europe and the US overhis 13-year career” with Biogen. Francis –who most recently served as Biogen Idec’ssenior vice-president for US commercial REGULARS operations –had previously “held leadership roles across commercial and sales in Sanofiand Wyeth”, Novartis noted. As division head of Sandoz, he will join Novartis’ executive committee Pipeline Watch – Memantine 20 and will report directly to the firm’schief executive officer,Joe Jimenez. George –who joined Novartis in 2007 and became head of Sandoz at the end of 2008 –will continue to serveas Events – Our regular listing 22 amember of the committee, while Buehler,who is retiring, will “provide management and Price Watch UK – Our in-depth 23 strategic support on the Alcon business” as part of the transition. look at pricing trends in the UK George’sand Francis’ appointments “place twostrong leaders at the helm of twoleading Novartis businesses”, commented Jimenez. “These newleaders will set the direction for the People – Louw is replaced by 27 next phase of growth for our eye-care and generics businesses, twoofour core growth engines,” Wakeford at Adcock he added, insisting that George and Francis “have the vision and expertise to strengthenour market-leading positions”. G Gen 18/4/14 Pgs. 2-7_Layout 1 15/04/2014 20:12 Page 2

COMPANY NEWS

MERGERS&ACQUISITIONS STRATEGICALLIANCES/MANUFACTURING Mylan misses out on Neuland opensplant move to gain Meda to aid APIC alliance

ylan has had an undisclosed takeoveroffer for Swedish firm euland Laboratories has opened abulk-drugs manufacturing facility MMeda rejected following initial talks between the twocompanies. Nin India through acollaboration with API Corporation (APIC), a “The board has convened and decided to reject the proposal,”Meda healthcareunit of Mitsubishi Chemical Holdings. “The newfacility said in astatement. “All continued discussions between Meda and –which is located in aNeuland complexinPashamylaram, Hyderabad – Mylan have been terminated without further actions.” is the first manufacturing facility that APIC has established outside Media conjecture prior to the Swedish firm’sannouncement had of Japan,”the Indian group observed. suggested that incorporating Meda –which in 2013 reported group Pursuant to an agreement that the twofirms struck ayear ago sales ahead by 1% to SEK13.1 billion (US$2.00 billion) from speciality (Generics bulletin,22March 2013, page 3), Neuland built and will prescription and OTCbrands, as well as branded generics –within operate the facility that will makeactive pharmaceutical ingredients Mylan’soperations would have created acompanywith amarket (APIs) and intermediatesfor sale through Tokyo-based APIC. capitalisation of around US$23 billion. “This arrangement allows APIC to expand its business in Japan The US firm’sapproach fell in line with chief executive officer in atimely and cost-effective way,”commented Neuland’schairman Heather Bresch’sassertion that Mylan could conduct a“substantial and managing director,Davuluri Rama Rao, “while also helping to transaction” this year (Generics bulletin,7March 2014, page 3). raise Neuland’s profile as aquality supplier of APIs and intermediates Meda blamed lower sales of several products in the US for the to the Japanese market.” G turnoverofits Branded Generics business falling by almost atenth to SEK1.32 billion last year.Prescription Specialty Products sales IN BRIEF grewby2%toSEK8.27 billion, while OTCturnoveradvanced by 4% to SEK3.13 billion and other products added SEK396 million. PHARMANIAGA intends to build aMYR120 million (US$36.7 The Swedish group –which has just agreed to terminate joint million) manufacturingplant in Riyadh, Saudi Arabia, through ventures with Valeant in Canada, Mexico and Australia, giving it the Malaysian company’s50/50 joint venture with local company marketing rights to certain dermatology brands –generated nearly Modern Group. G two-thirds of its 2013 turnoverinwestern Europe. G

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COMPANY NEWS

MERGERS&ACQUISITIONS MERGERS&ACQUISITIONS Actavis buys Silomin Pamplona fund takes US$100mn Thai deal control of Alvogen

ctavis says it has gained a“top-fiveposition in the Thai generic rivate-equity fund Pamplona Capital Management has acquired a Apharmaceutial market” after acquiring local firm Silom Medical Pmajority stakeinAlvogen for an undisclosed sum. With headquarters Companyfor US$100 million in cash. The privately-held generics firm in NewYork and London, Pamplona manages overUS$6 billion in had “leading positions in the ophthalmic and respiratory therapeutic assets for avariety of clients, including hedge funds and pension funds. categories”, Actavis said, as well as “a strong cardiovascular franchise”. Noting that the stakewas acquired “from legacy shareholders”, Silom markets “more than 25 products in various dosage forms” Pamplona said the Luxembourg-domiciled firm’sfounder,chairman through its in-housesalesforce. A32,000 sq mmanufacturing facility and chief executive officer,Robert Wessman, would “continue to in Ayutthaya, Thailand, has an annual capacity of 660 million tablets operate the business”. “Robert is one of the leading figures in the or capsules, as well as 47 million sterile units. “Silom Medical has generics industry,and he and his team have built afirst-class business delivered year-on-year growth in revenue and profit overthe past 15 with excellent prospects for future growth,”commented Pamplona years,”Actavis noted, “most recently exceeding double-digit growth.” partner Jeremy Gelber. Actavis currently markets around 12 products through local “Alvogen,”stated former Actavis chief Wessman, “is making good distributors in Thailand, and has afurther nine registrations. Along with headway in its ambitious growth strategy,delivering double-digit revenue “opportunities to expand the core therapeuticareas of cardiovascular, and profit growth for each of the past five years. We nowhavethe ophthalmology and respiratory with complementary and novelproducts”, ideal partner to support us as we look to develop our business further.” the deal will also provide Actavis with “the potential to use Silom’s “In particular,” he continued, “we are focused on strengthening sales channels to create opportunities in newtherapeutic categories our global presence through strategic transactions, and Pamplona including oncology,women’shealth and central nervous system”. provides us with further firepower to work towards our stated ambition of becoming atop-10 global generics player.” Leading player in south-east Asia Having started out by acquiring US contract manufacturer Norwich “The acquisition of Silom Medical demonstrates our commitment Pharmaceuticals (Generics bulletin,4September 2009, page 30), to be aleading specialty pharmaceutical companyinsouth-east Asia,” Alvogen generates around half of its turnoverinNorth America. said Actavis’ chairman and chief executive officer,Paul Bisaro, adding Initially,the companyexpanded organically into newmarkets, and that the deal would “provide the combined business with an even through alliances with companies such as India’sOrchid (Generics more significant and united presence in the fast-growing Thai bulletin,28May 2010, page 3). pharmaceutical market”. More recently,the companyhas undertaken sizeable acquisitions, “Silom’sdiverse product portfolio and fully-integrated platform, such as taking amajority stakeinSouth Korea’sKunwha (Generics when combined with Actavis’ current local commercial activities and bulletin,2November 2012, page 3) and buying Romania’sLabormed world-class global generics infrastructure, will provide customers in (Generics bulletin,15February 2013, page 3). Earlier this year,the Thailand with expanded access to acombined, larger portfolio of firm folded its Asian operationsinto Lotus Pharmaceuticals, the affordable medicines,”Bisaro added. Taiwanese business in which it acquired a67% holding (Generics Furthermore, Bisaro said, Actavis’ enlarged presence in Thailand bulletin,3February 2014, page 5). –acountry in which the firm noted total pharmaceutical sales were Alvogen nowemploys 2,000 people and operates across 34 worth US$4.3 billion annually and were “poised for continued growth” – countries in North America, central and eastern Europe and the Asia- would “createafoundation for Actavis’ continued expansion across the Pacific region, with manufacturing hubs in the US, Romania and South south-east Asian region”. Korea. It has over200 products under development or pending registration, Meanwhile, Actavis has opened aregional office in Singapore “including several potential first-to-file and first-to-market opportunities”. that will serveasthe headquarters for the company’sAsia Pacific and Through apartnership with Hospira, Alvogen has started to roll Africa (APACA) region. “By centralising our regional operations in out the biosimilarmonoclonal antibody Inflectra (infliximab) in central Singapore,”Bisaro observed, “we will be better positioned to focus on and eastern Europe (Generics bulletin,7March 2014, page 23). strategies that will strengthen our growth in emerging markets across Meanwhile, its sister company, Alvotech, is developing several other south-east Asia.”Atthe same time, the firm has announced that its biological drugs. G Drug Houses of Australia (DHA) subsidiary operating in Singapore will be “transitioned to the Actavis brand”. In the UK, Actavis’ Eden Biodesign has also taken on the name MANUFACTURING of its parent company, becoming Actavis Biologics and adopting the Actavis logo. Noting that the subsidiary was“designatedasthe centre Apotex plant gets FDA alert of excellence for biologics within the Actavis group”, its chief executive officer Crawford Brown said the name change would allowitto“more he US Food and Drug Administration (FDA) has issued an import closely identify with our powerful global Actavis brand, whilst clearly Talert against Apotex’ Pharmachem facility in Bommasandra near maintaining our biologics speciality and focus within the group”. Bangalore, India. The alert covers all drugs made at the site, with the And elsewhere in Europe, Actavis has nowcompleted its deal exception of riluzole tablets, which are excluded from being detained to divest operations in sevenwestern European countries to Aurobindo without physical examination (DWPE). (Generics bulletin,3February 2014, page 1). Aurobindo said the deal Spread over1.6 hectares,Apotex’ Bangalore complexwas built would makeit“one of the leading Indian pharmaceutical companies to produce over8billion units per year,using wet and dry granulation, in Europe”. France’sArrowGénériques noted that its structure would as well as direct compression. The site produced its first abbreviated not change and that it would retain its Arrowbrand. G newdrug application(ANDA) filing in 2006. G

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COMPANY NEWS

BUSINESS STRATEGY/ANNUAL RESULTS ANNUAL RESULTS Lithalooks forward Biotonbenefits as to life as Endo unit sales of insulin boom

itha Healthcare believesthe shift in its owner from Paladin Labs rise of more than athird in sales of insulin and its derivatives Lto Endo will be “mainly positive for the group” as it restructures Aenabled Poland’sBioton to achieve agroup turnoverofPLN341 to cut costs and improve profits in the short term, before pursuing a million (US$113 million) last year.While group sales declined by medium-term strategy of reducing its dependence on imports and 16.1% as reported, theyincreased by 9.4% without apayment of of exporting from South Africa into the rest of the continent. PLN94.7 million from Actavis in the prior-year period. This was Consolidating Litha’sacquisition of Pharmaplan went only some linked to terminating an insulins sales and marketing agreement. waytocompensating for the deconsolidation of the Biovacvaccines In its domestic market, the Polish firm recorded insulin sales of business as the South African group’sturnoverfell by 27.1% to PLN104 million. In China –where Bioton distributes the SciLin and ZAR1.05 billion (US$99.8 million) last year.Without the previous Bai Lin brands through an alliance with Bayer –insulin sales reached year’sZAR172 million gain from deconsolidatingBiovac, Litha’s PLN23.1 million. Other Asian markets contributed PLN18.1 million, operating profit tumbled by four-fifths to ZAR46.9 million. while initial insulin sales in Egypt added PLN4.1 million to Bioton’s IncludingPharmaplan, sales by the Litha Pharma division climbed total turnoverfrom insulin products that advanced by 34.2% last year by 55.2% to ZAR543 million, which comprised ZAR297 million from to PLN157 million (see Figure 1). generics, ZAR145 million from original brands and ZAR102 million Bioton’santibiotics sales fell by aquarter to PLN45.6 million, from complementary medicines. But with the Pharmaplan effect evened while its turnoverfrom growth hormonesrose by 4.9% to PLN37.4 out, fourth-quarter Pharma sales fell by 5.8% to ZAR128 million on million. In August last year,the European Commission acted on a “increased competition, commoditisation of certain keygenerics and positive opinion issued by the European Medicines Agency(EMA) to the end of atender”. grant acentralised marketing authorisation to aonce-a-week form of Sales of Litha’slow-dose aspirin brand Ecotrin rose by 26.8% somatropin developed by the Polish group’sBioPartners subsidiary in to around ZAR55 million, or atenth of all Pharma sales. The Pharma partnershipwith LG (Generics bulletin,7June 2013, page 1). division also posted double-digit sales rises for the Oratane (isotretinoin) Bioton achievedanoperating profit of PLN13.1 million last year, and Dazit (desloratadine) brands picked up through Pharmaplan. G versus aPLN27.8 million loss in 2012, excluding the Actavis payment. G

Product Annual sales Change Proportion of type (PLN millions) (%) total (%) MERGERS&ACQUISITIONS Insulins 156.8 +34.2 46 Mallinckrodt to buy Questcor Antibiotics 45.6 -24.9 13 Growth hormones 37.4 +4.9 11 allinckrodt has agreed aUS$5.6 billion deal to acquire Questcor Others 101.0 +2.8 30 MPharmaceuticals, the US-based autoimmune and inflammatory diseases specialist that markets Acthar (corticotropin) injectablegel Bioton 340.9 +9.4* 100 as atreatment for conditions includingmultiple sclerosis.Last year, *excluding PLN94.7 million payment from Actavis in 2012 Questcor made an operating profit of US$440 million on aturnover that increased by 57% to US$799 million. G Figure1:Breakdown by product type of Bioton’s sales in 2013 (Source –Bioton)

18 April 2014 Issue 210 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 Meredith 46 times ayear.Annual subscriptions in Europe cost £620 (additional copies at the same address £395); Neither maythis publication be exported, distributed or Director of Subscriptions: ValDavis outside Europe £650 (£425). 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.

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4 GENERICS bulletin 18 April 2014 Gen 18/4/14 Pgs. 2-7_Layout 1 15/04/2014 20:12 Page 5

COMPANY NEWS

MERGERS&ACQUISITIONS Sun seeks synergies from Ranbaxy deal

un Pharmaceutical Industriesexpects to realise US$250 million of Annual sales Change Proportion Ssales and operating synergies by the third year after closing aUS$4.0 (Rs millions) (%) of total (%) billion takeoverofRanbaxy.These savings are to come mainly from “top-line growth, efficient procurement and supply-chain efficiencies”. US 90,862 +55 60 But the Indian companydoes not anticipateany manufacturing synergies India 35,250+19 23 from the combined entity’s47faciliites spread across five continents Rest of World 18,576 +22 12 as it concentrates on fixing compliance problems at Ranbaxy’sIndian Formulations 144,688 +40 95 facilities, including by enlisting the help of consultants. Bulk Drugs 7,486 -6 5 As the US Food and Drug Administration (FDA) has continued to find fault with Ranbaxy’smanufacturing sites and processes, the Other -7 –– latest of the firm’ssites to be made subject to aconsent decree entered Sun Pharma 152,167 +36 100 against Ranbaxy in January 2012 is its active pharmaceutical ingredients (APIs) plant in Toansa (Generics bulletin,3February 2014, page 3). Figure1:Breakdown by region and business of Sun Pharma’s turnover in Ranbaxy said the US Attorney’sOffice for the district of New calendar 2013 (Source –Sun Pharma) Jerseyissued an administrative subpoena last month seeking information Annual sales Change Proportion of “primarily related to the company’sToansa API manufacturing facility in (Rs millions) (%) total (%) India, for which aForm 483 wasissued, culminating in an import alert”. As part of the US$4.0 billion deal agreed by Ranbaxy’smajority North America 33,569 -37 32 shareholder,Daiichi Sankyo, the Japanese group –which holds a India 22,395+521 63.4% stake–has pledged to indemnify Sun and Ranbaxy for “certain Eastern Europe/CIS 16,194 +23 15 costs and expenses that may arise from the subpoena”. Africa and Middle East 10,917 +7 10 ForDaiichi, Sun’sUS$4.0 billion bid offers the Japanese group Western Europe 8,346 -14 8 an exit strategy from alargely ill-fated investment, albeit at an implied Asia-Pacific and Latin America 7,694 +3 7 selling value of Rs457 (US$7.58) per share, adiscount of almost APIs/Other 6,927 -5 7 two-fifths to the Rs737 per share that Daiichi paid six years ago (Generics bulletin,19June 2008, page 1). The Japanese firm will Ranbaxy 106,042 -13 100 become Sun’ssecond-largest shareholder with around a9%share. Under Daiichi’scontrol, Ranbaxy posted large losses, caused by not Figure2:Breakdown by region and business of Ranbaxy Laboratories’ sales in only facility remediation costs and fines, butalso foreign-currencyloans. 2013 as reported (Source –Ranbaxy) Signs that the Japanese group waslosing patience emerged last year when it started legalaction against Ranbaxy’sformer founders and He refused to be drawn on Ranbaxy’sprospects of securing 180-day shareholders, the Singh family (Generics bulletin,7June 2013, page 1). US exclusivity periods for generic Diovan(valsartan), Nexium Sun –which has ahistory of turning round struggling companies (esomeprazole) and Valcyte (valganciclovir). such as Caraco and Taro –generated three-fifths of its US$2.5 billion In their domestic market, the Indian firms would become the largest turnoverlast year from its US operations (see Figure 1). By contrast, player with close to a9%market share and 31 brands in India’stop less than athird of Ranbaxy’sUS$1.8 billion turnovercame from 300, Shanghvi pointed out. Furthermore, Ranbaxy would treble Sun’s North America as it suffered from FDAimport alerts (see Figure 2). presence in emerging markets to around US$900 million, providing Pointing out that the combined companywould boast aUS$2.0 operations with annual sales of more than US$100 million in each of billion US business (see Figure 3) –with an especially strong foothold Romania, Russia and South Africa, and giving the combined company in generic and branded dermatology –Sun’smanaging director, significant platforms in Brazil and Malaysia. Dilip Shanghvi, said the entity would have 445 approvedabbreviated Shanghvi said Sun would maintain Ranbaxy’s“hybrid business newdrug applications (ANDAs) and another 184 pendingapproval. model” of collaborating with Daiichi in certain markets. This option, he added, could fulfil Sun’sstrategic goal of building ameaningful presence in Japan (Generics bulletin,7March 2014, page 9). India Furthermore, Shanghvi added, Sun “remained excited” about the ~US$925m emerging markets alliance it formed with Merck &Cothree years ago (Generics bulletin,22April 2011, page 3). Rest of world The transaction requires court and competition authority clearances, ~US$1.30bn as well as approvalfrom 75% by value of shareholders in both Sun and Ranbaxy.Daiichi holds 63.4% of Ranbaxy’sshare capital, while the promoters of Sun have a63.7% stakeinSun Pharma. Sun said the implied value of Rs457 per Ranbaxy share offered an 18% premium to Ranbaxy’saverage share price in the 30 days preceding the offer. Shanghvi denied that the shares in Ranbaxy currently held by US Silverstreet Developers, controlled by twowholly-owned Sun ~US$2.00bn subsidiaries, amounted to abreach of insider-trading rules. Upon closing –which is anticipated by the end of this year – Ranbaxy’scurrent shareholderswill ownaround 14% of the combined Figure3:Breakdown by region of proforma sales of US$4.2 billion in 2013 by a combination of Sun Pharma and Ranbaxy.The rest of the world figureincludes company, including Daiichi’s9%stake. The Japanese group will global active pharmaceutical ingredient (API) sales to thirdparties (Source –Sun) have the right to nominate one director to Sun’sboard. G

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COMPANY NEWS

BUSINESS STRATEGY/ANNUAL RESULTS IN BRIEF ACTAVIS has struck an agreement with US contract-development Latvia’sOlainfarm and manufacturing firm Particle Sciences to develop an “unnamed complexgeneric product”. Particle –which will receive undisclosed milestone and revenue-based payments as part of the agreement – will be responsible for design, formulation and current good seesupside to crisis manufacturing practice (cGMP) supplies, while Actavis will oversee clinical testing, regulatory filings and marketing. atvia’sOlainfarm believesitmay benefit from maintaining its Loperations in the CommonwealthofIndependent States (CIS) amid CELLTRION reported turnover35% lower at KRW226 billion the current political unrest. “If the current crisis persists, it may scare (US$217 million) last year as the South Korean company’s operating offsome companies from these markets, allowing an increase in market profit almost halved to KRW99.8 billion. However, Celltrion share once the situation starts returning to normal,”insisted executive pointed out it had deferredsales of its CT-P10 rituximab biosimilar director Salvis Lapins. while it completed stability testing of clinical-trial and commercial- Russia and Ukraine account for more than half of group turnover. scale materials made in twodifferent facilities. Observing that economic sanctions did not typically affect medicines, Lapins said he anticipated Olainfarm’sturnoverinRussia stagnating SHARON BIOMEDICINE has completed the expansion of three as the firm expanded its marketing coverage of smaller cities, while manufacturing facilities following an investment of nearly Rs1.25 Ukrainian sales were running at around C0.7 million (US$1.0 million) billion (US$20.6 million).The Indian companyhas more than per month, barely half the normal level. doubled the capacity of its Dehradun formulations plant, and added Last year,Olainfarm increased its group turnoverby4%to between 30% and 50% to the capacity of twofactories at Taloja LVL54.8 million (US$108 million) as a14% sales rise in Russia to near Navi Mumbai. just overLVL20 million offset in part a45% decline in Ukraine to about LVL7.7 million due to exceptional shipments at the end of 2012. TAKEDA says it will “vigorously challenge” aLouisiana jury’s decision In its domestic market, the Latvian group increased its turnover to award punitive damages of US$6 billion against the Japanese by 70% to around LVL12.6 million, while sales in Belarus advanced company, and US$3 billion against co-defendant Eli Lilly,inadispute by 48% to about LVL3.8 million (see Figure 1). Lapins said Olainfarm overwhether the Actos (pioglitazone) diabetes drug caused apatient’s had more than quadrupled sales of tuberculosisdrugs to aWorld bladder cancer.Noting that it had wonthree previous Actos trials, Health Organization (WHO) logistics centre in the Netherlands, and Takeda stated: “This is the first [US] federal case to be tried, and had trebled its turnoverinSpain. the first in the consolidated Actos multi-districtlitigation.” “The newmarkets of Tajikistan, Turkmenistan and Kyrgyzstan – although negligible in volume –are growing very impressively,” he TORRENT PHARMACEUTICALS has receivedclearance from the said, adding that Olainfarm had started registering products in Kosovo, Competition Commission of India to acquire the Indian branded Mexico, Mongolia and Turkey. formulationsoperation of Elder Pharma.The acquired business In terms of product groups,Olainfarm barely increased its sales includes around 30 analgesic, nutraceutical, women’shealth and of finished-dose medicines to LVL41.7 million, largely due to the woundcare brands marketed in India and Nepal (Generics bulletin, exceptional shipments to Ukraine in late-2012. 10 January 2014, page 5). “The proposed combination is not likely Turnoverfrom bulk chemicals fell by 9% to LVL3.46 million, but to result in anyappreciable adverse effect on competition in India,” the group’srevenues from pharmacyretailing and wholesaling rose concluded the watchdog. by 19% to LVL7.99 million as the Latvian group raised the number of pharmaciesitoperates to 55. Silvanols –the Latvian food supplements AMERIGEN has commissioned UPM to maketwo abbreviated firm in which Olainfarm acquired amajority stakelast year –contributed newdrug application(ANDA) products at the latter’sformer Pfizer LVL1.02 million. Other operations added LVL0.62 million. facility in Bristol, Tennessee. The 10-year supply deal also allows Lapins said the greater proportion of sales from retail operations for UPM to develop and potentially supply commercial quantities had reduced the group’smargins. Earnings before interest and tax of other ANDAdrugs. (EBIT) declined by 7% to LVL11.4 million. G PARENTERAL DRUGS has started production at afacility in Ahirana Kazakhstan operated by its Punjab Formulations subsidiary.The Indian firm ~LVL2.2m has ceased production at asite in Sura, Punjab.

Others ~LVL8.2m APPLIKON BIOTECHNOLOGY has opened a facility in Guangzhou, Russia China.The Dutch firm said the Chinese site would “provide a ~LVL20.3m complete range of bioreactor systems” for both research and commercial purposes. Belarus ~LVL3.8m SIGMA PHARMACEUTICALS has expanded its wholesaling presence in Australia by acquiring local distributor Central Healthcare for A$24.5 million (US$23.0 million). Central –which has an annual Ukraine ~LVL7.7m turnoverofoverA$200 million –also owns and manages the Pharmasave pharmacyretail brand.

Latvia ~LVL12.6m AMRI has competed its US$41 million acquisition of active pharmaceutical ingredients (APIs) developer and producer Cedarburg Figure1:Breakdown by countryof Olainfarm’s turnover that increased by 4% to Pharmaceuticals (Generics bulletin,4April 2014, page 5). G LVL54.8 million in 2013 (Source –Olainfarm)

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COMPANY NEWS

BUSINESS STRATEGY/ANNUAL RESULTS MANUFACTURING Sopharma increases FDA cancels Hikma’s presence in Baltics Eatontown warning

ulgaria’sSopharma has enhanced its presence in the Baltic States, ikma has receivedaclose-out letter from the US Food and Drug Bas well as in Belarus, by increasing its holding in Latvian group HAdministration (FDA) lifting the warning letter that the firm’s Briz from 53.1% to 66.1%. Having raised the number of pharmacies solid-dose facility in Eatontown, NewJersey, receivedin2012 it owns to 91 by acquiring three chains in Belarus, medicines marketer, (Generics bulletin,9March 2012, page 4). The close-out letter –which distributor and retailer Briz nowhas an annual turnoverofaround “successfully resolves all issues raised by the FDA” –follows the C33 million (US$46 million). agency’sre-inspection of the plant in February (Generics bulletin, Last year,Sopharma increasedits group turnoverby11.0% to 21 March 2014, page 5). BGN765 million (US$540 million) as its exports sales advanced by Said Darwazah, Hikma’schief executive officer,said the firm was 15.0% to BGN248 million. “gradually re-introducing products to the US market from the In Bulgaria –where Sopharma claims to have a4%share of the Eatontown facility,adding to the products we supply from our FDA- Bulgarian pharmaceutical market by value, and a13% share by approvedfacilities in Jordan and Saudi Arabia”. volume –the group improvedits sales by 9.2% to BGN517 million. “The investment we have made to complete the remediation work, Five launches during 2013 –including amethadone oral solution, upgrade our manufacturing processes and strengthen our operations adrops formulationofthe firm’sAnalgin (metamizole) painkiller and a provides greater quality and support for our customers,” he insisted. 5% formulation of Feloran (diclofenac) gel, as well as an ampoule Having previously considered “strategic options” for its US version of Movix (meloxicam) –contributed to the turnoverrise. Generics solid-dose division in the wake of the compliance issues at Sopharma increased its operating profit by 16.5% to BGN53.0 Eatontown, Hikma recently committed to retaining and expanding the million, raising its operating margin by 0.3 percentage points to 6.9%. business, which more than doubled its turnoverlast year to US$268 Midway through last year,the Bulgarian group opened a million on strong demand for the antibiotic doxycycline. 20,000 sq mplant with an annual capacity of 4billion tablets in which “Webelieve there are an increasing number of attractive market the firm invested BGN70 million. Sopharma has also secured a opportunitiesfor our Generics business and we are investing in our grant of up to BGN3.0 million from the Bulgarian government to pipeline of oral and other non-injectable product forms, whilst continuing help it set up an ampoule-filling line. G to look for further product-acquisition opportunities,” Darwazah stated. G

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COMPANY NEWS

ANNUAL RESULTS STRATEGICALLIANCES Alkaloid advances Julphar strikes deal on domestic growth to sell MSD’s drugs

ouble-digit sales growth in its domestic market enabled Macedonia’s ulphar has secured afive-year agreement to produce, market and DAlkaloid to raise its total Pharma turnoverby4.4% to C96.9 million Jdistribute several Merck, Sharp &Dohme (MSD) brands in Bahrain, (US$135 million) last year.The Skopje-based companyimprovedits Iraq, Kuwait, Oman, Qatar and the United Arab Emirates (UAE). The domestic Pharma sales by 10.3% to C41.6 million. Including C18.4 twofirms said the deal would “enhance patients’ access to cutting- million from other businesses, Alkaloid increased its group turnover edge therapies for diabetes, asthma, allergy,pain and inflammation”, by 4.5% to C115 million (see Figure 1), while its operating profit with MSD products being made in the Middle East for the first time. improvedby3.8% to C11.6 million. G Julphar –which markets abroad range of medicines,including insulins, throughoutthe Middle East –posted aturnoverofaround Product Annual sales Change Proportion of AED1.6 billion (US$436 million) last year. G type (C millions) (%) total (%) OTC18.9 -6.1 16 Cardiovascular 18.1 +2.4 16 THIRD-QUARTER RESULTS Central nervous system 16.0 +1.5 14 Antibiotics 14.9 -1.2 13 Fluticasone fall hits Hi-Tech Bulk drugs/commodities 14.2 +25.8 12 ales of its generic rivaltoGlaxoSmithKline’sFlonase (fluticasone) Other 14.8 +15.2 13 Smore than halving to US$10.9 million contributed to Hi-Tech Pharma 96.9 +4.4 84 Pharmacal’sgenerics turnoversliding by 12% to US$47.8 million in the US firm’sfinancial third quarter ended 31 January 2014. Other 18.4 +4.6 16 Despite asurge of 58% to US$8.04 million in Hi-Tech’sbranded Alkaloid 115.3 +4.5 100 prescription sales, the group’ssales fell by 7% to US$59.9 million. Hi-Tech is the subject of aUS$640 million takeoverbid from Figure1:Breakdown by product type of Alkaloid’s sales in 2013 (Source –Alkaloid) fellowUSfirm Akorn (Generics bulletin,6September 2013, page 1). G

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MARKET NEWS

REGULATORY AFFAIRS REGULATORY AFFAIRS/BIOLOGICALDRUGS EGA and GPhA state Additional identifiers major goals for TTIP shouldapply to all

armonising regulatory processes between the European Union ny additional identifier applied to the name of biological drugs H(EU) and the US, as well as allowing advance manufacturing of Amust be independentofthe international non-proprietary name generics and biosimilars during patent-extension periods are among (INN) and be applied to all such products, not just biosimilars,the the main goals for the Transatlantic Trade and Investment Partnership chairman of the European Biosimilars Group (EBG) within the European (TTIP) set out by EU and US generics associations. Generic medicines Association (EGA) has told the World Health In ajoint letter sent to European Commissioner for Trade Karel Organization (WHO). Addressing the open session of the WHO’s58th De Gucht and US Trade Representative Michael Froman, the consultation on INNs earlier this month, EBG chairman JörgWindisch European Generic medicines Association (EGA) and US Generic said the EGA appreciated the efforts of the WHO’sINN expert committee Pharmaceutical Association (GPhA) urged both the EU and US to to establish aglobally harmonised naming system for biological drugs. “advance the regulatory convergence between the European Medicines While the European Union’ssystem of requiring either an invented Agency(EMA) and US Food and Drug Administration (FDA) by fantasy name or the substance name plus atrademark or name of the adopting the guideline or guidance for single development for marketing-authorisation holder provided “a reliable model”, Windisch biosimilarmedicines”. recognised that some countries wanted asecond levelofdifferentiation The letter claims that this would “reduce development costs of beyond the product name. up to US$200-US$300 million per product” and “avoid unnecessary “For this second levelofdifferentiation, consensus on the key and unethical duplication of clinical tests in humans”. principlesseems to have been reached,”Sandoz’ Windisch stated. The The letter also requests that TTIP negotiators “support the INN should stay the same, he said, with the additional identifying implementation of asingle development and approvalpathway for component to be applied retroactively to all biological drugs. This generic medicines”. This could be done by setting up ageneric component, he added, should not include anyaspect that identified medicines ‘cluster’ –similar to the biosimilars cluster –between the the regulatory pathway for aspecific product. It should be harmonised EMA, or national EU agencies, and the FDAtoadopt guidance on globally by the WHO’sINN office and be voluntary for regulators. the subject. The letter also calls on negotiators to “foster the “EGA welcomes this consensus, and discussed these principles mutual recognitionofgood manufacturing practice (GMP) inspections with the US Generic Pharmaceutical Association (GPhA) and the between Europe and the US” to avoid redundant inspections and International Federation of Pharmaceutical Manufacturers and free up resources for inspections outside the EU and US. Associations (IFPMA),”Windisch declared. Advanced manufacturing of generics and biosimilars during the During arecent meeting with the US Food and Drug period of supplementary protection certificates (SPCs) or patent Administration (FDA), the GPhA revealed it wasconsidering aproposal extensions should also be supported by the TTIP,the letter urges, that would “distinguish between products by attaching the company claiming that this would “help EU and US manufacturershold their name as asuffixtothe INN, without changing the INN”. ownagainst generic producers from competing markets without patent- Amgen told Generics bulletin that it backed “the overall direction extension provisions”. the WHO is taking with regard to its INN policyfor biologic Finally,the letter insists that the TTIP should “avoid harmonisation medicines”. “Amgen believesthat healthcaresystems globally must of EU and US intellectual-property regimes”, referring to the regions’ ensure all biologic medicines, including biosimilars, can be rapidly respective regimes as “divergent, butequally robust”. In particular, the and accurately identified by national regulators, healthcare providers EGA and GPhA state, “we emphatically reject the mischaracterisation and patients. Distinguishable names for all biologics will help of existing lawbyoriginators and their representativesinsupport of strengthen the accuracyoftracing via post-marketing safety monitoring their requests to ‘align’ or ‘levelup’ regulatory data protection”. G systems,”the originator stated. Speaking at the EGA’s 12th International BiosimilarMedicines Conference in London, UK, earlier this month, Professor Derek Calam said the WHO’sINN committee that he chairs had devised a REGULATORY AFFAIRS draft biological qualifier scheme that would be separate from the INN process. This voluntary scheme would consist of “a unique and random Romania backs dual notation four-letter code” that would be assigned to aspecific manufacturing octors in Romania should be free to use brand names as well as site and would be held in asecure WHO database. Dinternational non-proprietary names (INNs) when prescribing, Following consultation with industry and regulatory agencies, according to local generics industry association APMGR. Highlighting the WHO committee would aim to finalise the scheme at its next the negative effects on patient compliance caused by receiving different meeting to be held on 14-16 October,Calam explained. versions of the same drug, recently re-elected APMGR president Calam acknowledged that the WHO’sscheme may be superfluous Dragos Damian (see page 27) proposed that doctors should be able in regions such as the EU, especially when the EU Falsified Medicines to prescribe by brand names as well as by INNs. Directive brought in 2D-barcodes that would facilitate product tracing. APMGR suggested that INN prescribing had “contributed to The European Medicines Agency’s(EMA’s)Sabine Brosch told the decreased use of generic drugs”, noting that generics representing the EGA conference that 90% of all EU adverse drug reaction (ADR) 28% of the local market in 2013 compared to 36% in 2008. reports for biologicals included the brand name, butonly 22% cited Meanwhile, APMGR is also urging the Romanian government to the batch number.The agency, she said, waslooking at issues around re-evaluate its list of reimbursed drugs on the basis of health technology product- and batch-specific signal detection as it prepared to release assessments (HTAs), “to ensure the medical criteria and economic abiologicals chapter of its good pharmacovigilance practice guideline efficiencyofnew molecules”. G for public consultation during the second quarter of this year. G

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MARKET NEWS

REGULATORY AFFAIRS IN BRIEF AFRICAN countries must commit to “rigorous product quality GPhA questions basis testing, pharmacovigilance systems and regional bioequivalence centres”iftheyare to meet the “major challenge” of guaranteeing the quality and safety of generics, according to Nick Haggar, president of the European Generic medicines Association (EGA). for labelling proposal Chairing adiscussion on health and pharmaceuticals at the fifth European Union (EU) and Africa Business Forum at the start of hanges to generic labelling requirements outlined in aproposed April in Brussels, Belgium, Haggar also urged African countries CUS Food and Drug Administration (FDA) rule may lack alegal to implement the African Medicines Regulatory Harmonisation basis, according to the US Generic Pharmaceutical Association (AMRH) programme, as well as to establish an African Medicines (GPhA). The rule –which wasopened up for public comment from regulatory Agency(AMA). November last year until mid-March –would require generics firms to update safety information using the same ‘changes being effected’ BIO –the US Biotechnology Industry Organization –has (CBE) process as originators. commended the US state of Delaware for becoming the latest to The GPhA’s president and chief executive officer,Ralph Neas, pass local legislation on biosimilar substitution.Noting that the argued in aseminar hosted by the Washington LegalFoundation (WLF) bill passed by the state Senate included policies that “align with that the lawrequired the same labelling for brands and generics. BIO’sprinciples on biologicsubstitution”,the association added “Everything is predicated on sameness” under the Hatch-Waxman that this included “transparent communication on all biologic framework, Neas argued, insisting that “the FDAdoes not have the medicines dispensed in order to maintain aconsistent and complete legalauthority when the statute is so clear”. If the agencywanted to medical record”. “While the US Food and Drug Administration change the law, he suggested, it should “go to the right forum”, (FDA) oversees approvalofbiologic medicines and designation of highlighting the lawmaking role of the US Congress. interchangeability,” BIO acknowledged, “policies governing whether Furthermore, Neas stated, the FDAhad not adequately consulted one product may be substituted in place of adoctor’sprescription industry when drafting the rule. “It is incumbent upon the FDAtobe and whether apharmacistmust inform patients and doctors are inclusive and do due diligence,”Neas said, insisting that the agency covered by state law.” should have consulted with all members of the supply chain butwas instead guided almost exclusively by the opinions of trial lawyers. This EMA –the European Medicines Agency–will launch a“final round had been “extremelydisappointing”, Neas acknowledged. of targeted consultations with keystakeholders” overits draft policy AlexBrill, research fellowatthe AmericanEnterprise Institute on access to clinical trial data at the end of May.Noting that the (AEI), suggested that the rule’sgoal of creating parity between brand consultation wasmeant to “clarify and fine-tune specific aspects companies and generics firms on labelling wasalegal issue, rather and achieve the broadest possible consensus and understandingof than apublic-health concern that would fall within the agency’sremit. the policy”, the EMA said it was“committed to pursuing the The FDAhad made “no quantified estimate of the benefits of this rule” objective of full transparencyregarding clinical trial data”. The to public health, Brill stated, adding that the agencyalso had not policyisdue to be finalised by June. considered the cost implications. Recent studies have suggested that the rule could increase annual healthcare costs by around US$4 billion FDA –the US Food and Drug Administration –is moving the (Generics bulletin,14February 2014, page 9). officers and laboratories of its Center for Biologics Evaluation and Research (CBER) from Bethesda and Rockville, Maryland, FDA insists on patient benefit to the agency’sWhite Oak campus in Silver Spring, Maryland. However, the director of the FDA’sCenter for Drug Evaluation Formost offices, the move will takeplace between 25 April and and Research (CDER), Janet Woodcock, insisted that the rule would 18 May,although some operations will not move until later in the “speed the dissemination of newsafety information about generic year,between June and August. drugs to health professionals and patients”. Addressing ahearing by the US House Energy and Commerce BRAZILIAN manufacturers and importers must give local medicines Committee on 1April, Woodcock acknowledged that the rule could agencyAnvisa ayear’snotice if theyintend to withdraw products lead to “temporary differences in drug labelling” as firms updated from the market that could lead to ashortage, according to arule labels. But this was“outweighed by the benefit to public health”, she published by the agencyinApril. This, the agencyexpects, will said, “which would result from all application holders having the ability give it time to take“the necessary measures to reduce the impact to independently update drug product labelling to reflect newly-acquired on the population of the lack of adrug”. The rule relates to products information regarding important drug safety issues”. that have no local substitutes,Anvisa said. If awithdrawaldoes Furthermore, Woodcock insisted that the FDA’sauthority to extend not pose arisk of shortage, suppliers should still give the agency the CBE process to generics firms “arises from the same authority six months’ notice. under which our regulations relating to branded drug application holders and biologics license application (BLA) holders were issued”. US LEGISLATION aimed at making more transparent the process for But Neas maintainedthat it should be the FDA, rather than generics applying lists of reimbursement through maximum allowable firms, that decided whether labelling should be changed. “Generic cost (MAC) has been introduced in draft form under the title of the manufacturers only have access to the scientific and medical evidence Generic Drug Pricing Fairness Act. Such lists set alimit for the amount for their individual products, representing afraction of the market,”Neas that apharmacybenefits manager will reimburse apharmacyfor told the committee. “A generic manufacturer that unilaterally changes dispensing ageneric. One of the sponsors of the bill, Representative its label therefore does so with limited, incomplete information.” Doug Collins, noted that pharmacybenefit managers often used “Since the FDAisthe only entity that has access to all the multiple MAClists, meaning that “pharmacies of every size and information and has the expertise to evaluate and address this affiliation are faced with uncertainty about howmuch they’ll be information,”Neas argued, “it is the only body in aposition to decide reimbursed and what generic drugs are even covered”. G whether alabelling change is warranted.” G

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MARKET NEWS

MARKET RESEARCH PRICING&REIMBURSEMENT German contracts Spain amends rules save C2.85 billion on reference prices

avings to German statutory health insurance funds through rebate ncluding biological drugs in reimbursement groups and establishing Scontracts resulting from tenders increased by 36.4% to C2.85 Iaminimum reimbursement price of C1.60 (US$2.22) per pack are billion (US$3.95 billion) last year,according to an analysis conducted among the measures introduced by aroyal decree in Spain to amend by market researcher IMS Health. the country’sreference-pricing system. At pharmacyretail prices –including value-added tax –the German Royal Decree 177/2014 states that areference-price group may funds’ total gross spendingonmedicines rose by 4.8% to C34.6 billion include “one generic or biosimilar medicine”. “The existence of in 2013, IMS observed. However, the market researcher pointed out, biosimilarmedicines makes it necessary to adapt the regulation and the rebate savings and another C2.66 billion from amandatory clawback operating procedures, placing [these products] on an equal footing with on drugs not covered by rebate contracts had reduced the funds’ bill generic medicines,” the decree proclaims. by over C5.5 billion. Spain’sgeneric medicines industry association, Aeseg, recently Once almost C2billion in patient co-payments and just over C1.1 warned that biosimilars must not be subjected to the same reference- billion in mandatory pharmacydiscounts were taken into account, pricing system as small-molecule generics if potential savings of the funds’ net drugs spending had advanced by 3.3% to C26.0 billion, C1.50 billion are to be achievedby2020 (Generics bulletin,21March or three-quarters of the gross total, IMS noted. 2014, page 13). Aleading proponent of generating savings through rebate contracts, According to the decree, reference prices are determined on the the AOKgroup of 11 funds said it had raised its savings last year by basis of ex-factory prices and the number of defined daily doses more than C300 million to over C1.0 billion. Since the funds’ 12th (DDDs) per pack. The minimum reimbursement price per pack should tender round started on 1April this year,the AOKnow has under be C1.60, equivalent to 15% of the average cost per prescribed pack. contract 248 off-patent molecules or combinations with a Homogenous groups for the purpose of reference pricing no longer combined annual turnoverthrough the funds of around C5billion. have to include ageneric drug. Agroup can nowbeformed provided a “Asofthe end of February,” the AOKstressed, “the list of shortages product reimbursed under Spain’snational health service has been compiled by Germany’sfederal institute for drugs and medical devices, authorised for at least 10 years in Spain or another European Union BfArM, did not contain anymedicines covered by rebate contracts.” G (EU) member state. G

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MARKET NEWS

PRICING&REIMBURSEMENT MARKET RESEARCH Spain’s Aeseg fights Portuguese advances tenderinAndalusia bolster penetration

pharmaceutical tender process launched in the Andalusia region ortuguese sales of generics rising by around atenth in both value Aof Spain constitutesa“flagrant violation”ofSpanish law, according Pand volume terms helped the industry to capture alarger proportion to local industry association Aeseg. The association’sdirector,Angel of the country’soverall medicines market in 2013, according to data Luis Rodriguez de la Cuerda, said Aeseghad mounted alegal challenge published by local medicines agencyInfarmed. Pharmacysales to the tender,which includes drugs based on 251 active pharmaceutical increasing by 8.6% to C468 million (US$649 million) meant that ingredients (APIs) and is expected to produce annual savings of generics captured an 18.8% share of the overall medicines market, around C36.6 million (US$50.8 million). representinga2.2 percentage-point rise over2012’sfigure of 16.6%. Aeseghas previously opposed tenders in Andalusia, which is one By volume, arise of 11.9% to 68.0 million packs helped to inflate of Spain’slargest autonomous healthcare regions (Generics bulletin, the proportion of the market captured by generics by 2.9 percentage 20 May 2011, page 17). However, de la Cuerda said the latest tender – points from 25.0% in 2012 to 27.9% in 2013. And with the off-patent the fourth tender launched in the region –was different because it market expanding to constitute 62.8% of the total market in 2013 – had come after amodification of Spanish lawinJuly 2013 to compared to 60.4% in 2012 and 57.1% in 2011 –generics captured eliminate regional drug tenders. a44.4% volume share of the available market in 2013, which was The recent legislation stated that only Spain’sMinistry of Health 3.0 percentage-points higher than in the previous year. had the power to modify medicines prices, meaning that local measures affecting the price of drugs were unlawful. Although the Spanish health Prices fall by two-thirds since 2007 ministry had not taken action against the tender,delaCuerda said, Aeseg Infarmed noted that the average price of ageneric had fallen by insisted that there were “solid legalgrounds”tosuspend the tender. two-thirds between the start of 2007 and the end of 2013, with January Meanwhile, local brand industry association Farmaindustria has 2007’saverage price of C20.38 per pack comparing to afigure of also launched legalaction against the tender in Andalusia, warning C6.87 in December 2013. This waspartly achievedthrough legislation that such “opportunistic” measures could fragment Spain’snational to cut pharmaceutical prices (Generics bulletin,14October 2011, pharmaceutical market. The originator group urged the Spanish health page 1) as well as price reductions for generics through tiered pricing ministry to refer the matter to aconstitutionalcourt. G reforms (Generics bulletin,18June 2010, page 13). G Cutting through the Smoke: The Way Forward for E-cigarettes Le Méridien Hotel, London, 15th May 2014 utting through the Smoke: The WayForward forE-cigarettes is the first conference Caimed at bringing clarityto the commercial and regulatory questionsposed by the dynamic and rapidly-developing e-cigarette market. Bringing together the e-cigarette industry and manufacturers of the leading nicotine-replacement therapybrands –together with regulators, retailers, healthcareprofessionals and public-health bodies –this one-day conferencewill explain whye-cigarettes are successfully disrupting widely-held views on smoking, tobacco and nicotine use. Expert speakers from manufacturers, retailers, regulators and market researchers will provide insights and stimulate debate on one of the most important public-health topics of the moment. Organised by OTC bulletin –the business newsletter for the consumer healthcare industry – Cutting through the Smoke: The WayForward forE-cigarettes is aunique opportunity for all stakeholders and interested parties to cut through the miasma surrounding e-cigarettes, gain aclear understanding of the market and help shape the future of this growing market segment. Conference fee: £250 +VAT per delegate to include presentations, lunch and refreshments.

Organisedby To register,visit www.otc-bulletin.com or contact Natalie Cornwell on +44 1564 777 550 or [email protected]

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EGA BIOSIMILARS

IN BRIEF MARKET RESEARCH BIOSIMILAR FILGRASTIM savedhealthcaresystems in the top- five European Union (EU) markets C318 million (US$441 million) Italy leads EU five between 2008 and 2013, Sandoz’ KenWalsh told delegates to the European Generic medicines Association’s(EGA’s)12th International Biosimilar Medicines Conference in London, UK, this month. Germanyhad led the waywith savings of C113 million following on biosimilar sales rapid initial uptake, followed by Italy with C61 million and the UK with C59 million. France saved C45 million, and Spain C41 million, iosimilar sales in the five largest western European Union (EU) according to IMS Health data. “Italy wasslowtoaccept biosimilars, Bmarkets totalled US$490 million last year,according to IMS Health butnow has significant use,”Walsh observed. data. Italy accounted for around 27% –orUS$130 million –ofthat total, IMS’ Alan Sheppard told the European Generic medicines FRENCH LEGISLATION that pavesthe wayfor biosimilar Association’s(EGA’s)12th International BiosimilarMedicines substitution by pharmacists leavesseveral issues unclear,according Conference in London, UK, this month, while annual sales in France to Claude Le Pen from Paris’ DauphineUniversity.Noting that and Germanyeach exceeded US$100 million. Spain contributed US$86 statutory instruments to implement Article 47 of France’s2014 social million, and the UK US$56 million. security financing lawhad still to be published, Le Pen said the Italy and Spain, Sheppard observed, had initially shown “cultural framework by which France’smedicines agency, ANSM, wasto resistance” to biosimilars,but penetration wasnow rising strongly in drawuparépertoire-likelist of substitutable biological drugs was each country.Bycontrast, Germany’srapid initial uptakehad tailed off. unknown. Pharmacyelectronic records were likely to be inadequate France had showed steady progress, butthe UK had lagged behind. to meet the requirement that substitution wasonly practisedatthe Whereas Germany–and to alesser extent France –had established start of treatment, Le Pen argued, querying howprescribers were sizeable retail markets for biosimilars, sales in Italy and the UK were to be informed of substitution, as the legislation stipulated. Patients limited to the hospital sector,Sheppard observed. would have no incentive to accept substitution and pharmacists would Looking ahead, Sheppard suggested that Sandoz’ GP-2013 receive no compensation for the burdens placed upon them, he pointed rituximab candidate could be approvedinthe EU next year,followed out, adding that the government’ssavings expectations were “modest”. by authorisation of the firm’sGP-2017 rivaltoHumira (adalimumab) upon EU patent expiry in 2018. G MFDS –South Korea’sMinistry of Food and Drug Safety –intends this year to revise the overarching biosimilar guideline and accompanying question-and-answer document that it published in REGULATORY AFFAIRS September 2009. Noting that the MFDS had approvedlocal firm Celltrion’sRemsima (infliximab) in 2012 and Herzuma (trastuzumab) earlier this year (Generics bulletin,21March 2014, page 17), the EMA aims to update guides Ministry’sJeewonJoung said MFDS had by the end of 2013 approved eviews of three overarching biosimilars guidelines should be protocols for 15 Phase Iand eight Phase III clinical trials covering Rfinalised this year,the European Medicines Agency(EMA) has 15 biosimilarcandidates that included etanercept and rituximab. forecasted. Speaking at the European Generic medicines Association’s Nine Korean companies had submitted protocolsalong with two (EGA’s)12th International BiosimilarMedicines Conference in London, multinational players, she revealed. UK, this month, the EMA’s Iordanis Gravanis said the agencyhad largely completed its revision of the overarching quality guidelinethat covers THE EUROPEAN COMMISSION is not seeking to interfere in issues such as expression systems and comparing amino-acidsequences. individual pricing and reimbursement decisions at anational level, However, he said, the agencywas still wading through “hundreds butrather to “clarify the procedural rules of the game”, as negotiations of pages of comments” on proposed changes to the general overarching continue overrevising the TransparencyDirective,according to guideline –which defines biosimilars and outlines principlesfor Salvatore D’Acunto from the Commission’sEnterprise Directorate. biosimilarity –and to adocument on clinical and non-clinical issues. Several proposals –such as not reassessing the safety,quality of Due to some “major changes”, aplanned revision of the EMA’s efficacyofgenerics and biosimilars during pricing and reimbursement product-specific guideline on insulins waslikely to be circulated for deliberations –were “common sense”, he insisted. asecond round of consultation. G

FDA –the US Food and Drug Administration –had received22 Investigational New Drug (IND) applications for biosimilar REGULATORY AFFAIRS versions of 13 different reference products by the end of February 2014. By the same date, the agencyhad held 53 initial meetings Bridge the gap, EGA urges with biosimilar sponsors, revealed the FDA’sStevenKozlowski. Work wascontinuing on finalising four draft biosimilar guidance uropean regulators and medical societies must help to “bridge the documents the FDAhad released for consultation,headded. Einformation gaponbiosimilars” by highlighting the stringent quality, safety and efficacystandards required for approving these drugs, NICE –the UK’sNational Institute for health and Care Excellence according to Adrian vanden Hoven, director-general of the European –isconsulting stakeholders on its proposed approach to providing Generic medicines Association (EGA). advice on using biosimilars as it reviews existing guidance on Addressing around 250 delegates to the EGA’s 12th International reference products. “Wewill not do single technology appraisals Biosimilar Medicines Conference in London, UK, vanden Hovensaid of biosimilars,”NICE’sPaul Chrisp stated, adding that the health- the information gapremained “the main challenge, despite the fact that technology assessment body wastalking to the UK’sHealth and biosimilars have generated to date around 300 million patient-days Social Care Information Centre (HSCIC) about publishing a of real-world clinical experience”.Heappealed to regulators to explain report on biosimilar uptake. G their processes –especially on extrapolating indications –todoctors’ associations, which could then reassure their members. G

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PRODUCT NEWS

ANTIDEPRESSANTS IN BRIEF ACETO has through its Rising Pharmaceuticals arm launched an Ratiopharmobtains authorised generic version of Validus’ Lotensin HCT (benazepril/ hydrochlorothiazide)10mg/12.5mg, 20mg/12.5mg and 20mg/25mg tablets in the US. Aceto –which recentlyacquired fellowUSgenerics player Pack Pharmaceuticals in adeal worth US$100 million Canadian damages (Generics bulletin,4April 2014, page 3) –did not disclose financial details of the deal, nor whyithad not reached an agreement for the eva’s Ratiopharm affiliate in Canada is entitled to damages for lower 5mg/6.25mg strength. Citing IMS Health data, the firm said Tprofits lost on sales of extended-release venlafaxine between 10 the combination treatment for high blood pressure achievedUS January 2006 and 1August 2007 after it waskept offthe market by sales of approximately US$55 million in 2013. patent-linkage litigation brought by Pfizer’sWyeth. But Federal Judge Russel Zinn instructed the litigants to determine the scale of ARROW GENERIQUES has launched tramadol/paracetamol 37.5mg/ the damages themselves, based on the guidance he had given. 325mg effervescent tablets in France. The rivaltoGrünenthal’s “I am unable to finalise the quantum of damages, even taking Ixprim and Zaldiar brands is available in 20-tablet packs. abroad-axeapproach as wasrecommended by the parties,”Zinn stated. Shortly before Wyeth’sCanadian venlafaxine substance patent FDA –the US Food and Drug Administration –has issued for wasdue to expire on 10 January 2006, the originator listed the comment draft guidance on ‘immunogenicity-related considerations 2,199,778 extended-release formulation patent against its Effexor XR for the approvaloflow molecular weight heparin for newdrug antidepressant brand. applications (NDAs) and abbreviated newdrug applications (ANDAs)’. Ratiopharm –which had planned to launch when the 1,248,540 The guide includes “recommendations on meeting the requirement substance patent expired on 10 January 2006 –immediately challenged for active ingredient sameness” for ANDAs, as well as advice on the ‘778 patent, prompting legalaction from Wyeth that triggered a addressing impurities and their potential effect on immunogenicity. mandatory stay on Ratiopharm obtaining aNotice of Compliance (NOC), or marketing authorisation. In October 2006, Canada amended GLENMARK is starting human trials for its ‘GRC27864’novel its patent-linkage regulations so that generics firms did not have to molecule for treating chronic inflammatory diseases including pain. address patents added to the Patent Register after theyhad filed an The “potent, selective,orally-bioavailable inhibitor of microsomal abbreviated newdrug submission (ANDS). prostaglandinEsynthase-1 (mPGES-1)”has completed pre-clinical In August 2007, Canada’sCourt of Appeal ruled that the ‘778 and phase Ienabling studies, while aregulatory submission has been patent wasnot eligible for listing against Effexor XR. Ratiopharm filed for the first human phase Itrial with the UK’sMedicines and immediately obtained an NOC and launched in mid-September 2007. Healthcare products Regulatory Agency(MHRA). This study is Ratiopharm’sfuture sister company, Novopharm, launched due to be completed by January 2015. extended-release venlafaxine on 1December 2006 through alicensing deal with Wyeth. And in late-October 2007, Pharmascience entered GILEAD SCIENCES has filed apetition with the US Food and the market through across-licensing deal with Ratiopharm. Drug Administration (FDA) asking the agencytoreconsider its Assessing Ratiopharm’sentitlement to ‘section 8’ damages, Zinn decision to denythe originator five-year exclusivity for the twonew said Canada’svenlafaxine market between 10 January 2006 and 1 chemical entities –cobicistat and elvitegravir –inits Stribild August 2007 amounted to 362 million pills, of which generics accounted (cobicistat/elvitegravir/emtricitabine/tenofovir)antiretroviral brand. for almost 70%. Ratiopharm would have been the sole generic between 10 January and 1December 2006, when Novopharm launched, he BMJ –the UK’s British Medical Journal –has published astudy noted, at which point Ratiopharm’sprices would have fallen by 30% questioning the effectiveness of Roche’s Tamiflu (oseltamivir) and the rebate it paid would have increased from 15.0% to 46.6%. G brand. Clinical study reports analysed as part of the research “paint amuch less positive picture of oseltamivir than waspresented to regulators, policymakers, clinicians and the public”, the BMJ states, claiming that “important benefits have been over-estimated and GASTROINTESTINAL DRUGS harms under-reported”. “In particular,”itadds, “the reviewfound no compelling evidence to support claims that oseltamivir reduces Krka compensated on Nexium the risk of complications of influenza, such as pneumonia and rka has been awarded damages and legalcosts of C21.0 million hospital admission, claims that were used to justify international K(US$29.2 million) from AstraZeneca relating to an interim stockpiling of the drug.” injunction that prevented the Slovenian firm from marketing arival to Nexium (esomeprazole) in the UK between 2010 and 2011. The ACTAVIS’ bupropion extended-release 300mg tablets have had dispute had revolved around AstraZeneca’spatent EP1,020,461, covering their abbreviated newdrug application(ANDA) approvalwithdrawn the magnesium salt of esomeprazole. by the US Food and Drug Administration (FDA) after the firm Consilient Health had in 2010 obtained aUKmarketing submitted avoluntary request to the agency. The request was authorisation for esomeprazole manufactured by Krka. However, the handed in after abioequivalence study showed that the tablets were generics firms agreed not to launch before acourt ruling on infringement, not therapeutically equivalent to the reference listed drug (RLD), while AstraZeneca undertook to pay out if the injunction waslifted Valeant’sWellbutrin XL (Generics bulletin,1November 2013, (Generics bulletin,5August 2011, page 16). AstraZeneca eventually page 12). In 2012, the agencyhad found that Teva's version of the discharged the injunction against Krka and Consilient following separate product –manufactured by Impax –was not equivalent to the brand litigation with Ranbaxy (Generics bulletin,16September 2011, page 1). (Generics bulletin,19October 2012, page 1). Earlier this year,the UK’sHigh Court ruled that the firms should receive damages (Generics bulletin,14February 2014, page 16). BIOSIMILARS partnering increased by more than athird in 2013, However, Krka noted that AstraZeneca could still file an appeal against according to areport by Decision Resources Group. G the damages decision. G

14 GENERICS bulletin 18 April 2014 Gen 18/4/14 Pgs. 14-21_Layout 1 15/04/2014 20:15 Page 3

PRODUCT NEWS

CHOLESTEROL-LOWERINGDRUGS BIOLOGICALDRUGS Teva gains approval UK Herceptinpatents for Lovaza rival in US defeated by Hospira

eva has begun shipping ageneric rivaltoPronova BioPharma’s ospira has opened the door to launching abiosimilar version of Tblockbuster Lovaza (omega-3-acid ethyl esters) 1g capsules in the HGenentech’sHerceptin (trastuzumab) monoclonal antibody in the US following final approvalfrom the US Food and Drug Administration UK by obtaining invalidity decisions against twokey patents from (FDA). The Israeli firm –which is eligible for 180-day exclusivity for the High Court of England and Wales. the cholesterol-lowering agent –and ParPharmaceuticals last year While Hospira did not challenge the supplementary protection invalidated on appeal akey patent protecting Lovaza, opening the door certificate (SPC) GB04/015 –which effectively extends the UK part for the firms to launch their generic rivals. However, Par’sabbreviated of European patent EP0,590,058 until 28 July this year –the injectables newdrug application(ANDA) has yet to receive final FDAapproval. specialist brought invalidity challenges to the UK parts of twolater- US Lovaza sales were US$1.1 billion in 2013, according to IMS. expiring European patents. These were EP1,210,115, which covers a Twoyears ago, Teva and Parwere found by aDelaware district trastuzumab dosing regimen, and EP1,308,455, which protects court to have infringed twopatents protecting Lovaza –one of which compositions of trastuzumab with certain impurity profiles. subsequently expired –bysubmitting ANDAs ahead of patent expiry Both patents have been held invalid by the Opposition Division (Generics bulletin,8June 2012, page 27). Last year,however,the US of the European Patent Office (EPO), butare subject to ahearing Court of Appeals reversed this decision,ruling that Pronova’s remaining before the EPO’sTechnical Board of Appeal. US patent, 5,656,667 –which protectedLovaza until 10 April 2017 – Addressing the ‘115 dosing patent, High Court Judge Colin Birss wasinvalid as the brand had been “publicly accessible” for more noted that it covered administeringtrastuzumab every three weeks, than ayear before its patent application wasfiled. This wasonthe rather than the usual weekly dose. The dispute centred around Claim 1 basis that liquid samples of Lovaza had been provided to aUShospital of the patent, which is aSwiss-type claim to an initial loading dose for testing (Generics bulletin,20September 2013, page 19). of 8mg/kg, followed by 6mg/kg doses givenevery three weeks. Pronova –which licenses Lovaza in the US and Puerto Rico to Birss noted that the US Food and Drug Administration (FDA) GlaxoSmithKline –also has asettlement with Apotexthat permits had approvedHerceptin in September 1998 –before the ‘115 patent’s the Canadian companytolaunch arivaltoLovaza in the US from “the priority date of 27 August 1999 –atalower dose, including in first quarter of 2015”, or earlier under certain circumstances. G combination with paclitaxel that wasgiven on athree-weekly basis. “I find that the idea of athree-weekschedule for Herceptin is something which would naturally occur to askilled, butuninventive, clinician. The idea of three-weekly dosing arises because the treatment is combined with paclitaxel, which is itself three-weekly,” he stated. On reading Herceptin’sFDA-approvedlabel, the skilled clinician would learn that the half-life of trastuzumab wasdose-dependent,with a500mg dose –equivalent to just over7mg/kg in a70kg person – giving ahalf life of 12 days. “Three-weekly dosing would not be dismissed out of hand,”Birss maintained. “It wascommon ground that the skilled team –based on the FDA label and common general knowledge –would be prepared to administer adose of up to 8mg/kg,”Birss continued. “There is no basis in the specification of the ‘115 patent to support the idea that it would be inventive to select that particular three-weekly dosing regime from the other three-weekly dosing regimes that it discloses,”hestated in finding the ‘115 patent obvious. And even if the ‘115 patent had involved an inventive step, he maintained, it would have been invalid due to insufficiency. Turning to the ‘455 impurities patent, Birss accepted Hospira’s argument that the patent lacked novelty overGenentech’s‘Andya’ patent application for trastuzumab formulations that waspublished in February 1997, before the ‘455 patent’sMay 1998 priority date. The Andya application, Birss found, “makes an enabling disclosure” of aformulation with 82% native trastuzumab, and thus amaximum levelofacidic variant impurities of 18%. Therefore, several of the ‘455 patent’sclaims that described concentrations of trastuzumab with acidic variants of 18% or above lacked novelty. Furthermore, slides that Genentech had presented at a‘Waterside’ monoclonals conference in April 1996 rendered all the ‘455 patent’s claims obvious for lack of inventive step. “A composition of trastuzumab to anyspecified levelofacidic variants is technically obvious,”insisted Birss, who also granted Hospira adeclaration that five formulations of trastuzumabwith levels of acidic variants ranging between 25% and 29% did not infringe the ‘455 patent. G

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PRODUCT NEWS

BIOLOGICALDRUGS MULTIPLE-SCLEROSIS DRUGS Swissmedic accepts PTO refuses reissue bridging to EU drug of Copaxone patent

witzerland’smedicines regulatory agency, Swissmedic, will accept ylan has welcomed adecision by the US Patent and Trademark Scomparative bridging studies to justify the use of areference MOffice (PTO) to reject an application by Teva seeking the reissue product authorised in the European Union (EU), rather than in of US patent 5,800,808 covering the Israeli firm’sCopaxone (glatiramer Switzerland, for biosimilar applications. But reference products sourced acetate) brand. Noting that the PTOhad found the first claim of the from Japan and the US can only be used for supportive,rather than reissue application–which wasidentical to the only claim in the ‘808 pivotal, studies, according to an administrative order and accompanying patent –tobeindefinite, Mylan added that both claims of the reissue question-and-answer document the agencyhas published. patent were found to be unpatentable based on obviousness-type Swissmedic claims it is following the example of the European double-patenting. Medicines Agency(EMA) –and, in particular,the EMA’s draft revision Observing that the PTOhad “refused to extend patent protection to its overarching guideline–inrequiring aSwiss or EU reference on Copaxone past the patents that will expire in May 2014”, Mylan product for pivotal trials. stated that the body had “confirmed the indefiniteness for the second At least twodifferent batches should be used for bridging studies, time”. Last year,inacase that also involved Sandoz, aUSCourt of and aminimum of four batches for pivotal comparative trials, Appeals ruled that the ‘808 patent –which claims aprocess for Swissmedic states. Anon-Swiss reference product should employthe manufacturing glatiramer acetate and runs until 1September 2015 same primary container as the Swiss reference drug to avoid differences –was “indefinite” due to ambiguity in the use of the term ‘molecular in leachables, the agencyadds. weight’. This opened the door for US rivals to launch in May this If no Swiss reference product is available –and the originator year (Generics bulletin,9August 2013, page 1). declines to confirm in writing that the EU version has acomparable However, the appeals court’sdecision is to be reviewed by the formulationand production process –then applicants will not be able US Supreme Court after it granted Teva’s petition for awrit of to use Switzerland’sabridged biosimilars pathway. certiorari (Generics bulletin,4April 2014, page 1). The Israeli firm Swiss biosimilars should carry either afantasy name or the has also asked the Supreme Court to stay the appeals court’sruling international non-proprietary name (INN) followed by acompanyname. pending its review. Mylan and Sandoz have been asked for responses Pharmacysubstitution without consulting the prescriberis“not to the request. G explicitly allowed” in Switzerland, Swissmedic says, adding that there is “no legalbasis” for such switching. Unlikeinthe EU, the agencynotes, Swiss lawdoes not allow ANTIRETROVIRALS biosimilarapplications for lowmolecular weight heparins. G Patent Pool adds dolutegravir iivHealthcare has struck anew deal with the Medicines Patent BIOLOGICALDRUGS VPool that will allowgenerics firms to produce versions of the originator’s Tivicay (dolutegravir) in both adult and paediatricforms Polpharma eyes biosimilars for “countries with the highest HIV burden”. The deal comes two olpharma has struck adeal with Germany’sStrüngmann group months after the European Medicines Agency(EMA) approvedthe Pto collaborate on developing biosimilars. Noting that the agreement drug for adults and adolescents between 12 and 18 years of age, and would “speed up the work on high-quality biosimilars and open up eight months after US Food and Drug Administration (FDA) approval. the possibilities for additional development, manufacturing and global “Historically,ithas taken an average of seventonine years for commercialisation”, the Polish companysaid both partners would generic versions of newHIV treatments to reach developing countries “share the costs and risks” of developing the biosimilars, and would after introduction in industrialised nations,”the Patent Pool pointed out. “have equal rights to future products”. “By narrowing the gapbetween access to breakthrough new “This is avery important step for our company,”stated Jerzy antiretrovirals in developed versus developing countries,”stated the Starak, chairman of Polpharma’ssupervisory board. Furthermore, he Patent Pool’sexecutive director,GregPerry,“this agreement represents said, the joint venture would serveas“astarting point for possible asignificant public health achievement.”The Patent Pool would be extended cooperation with the Strüngmann group in the field of “working closely with generic manufacturers overthe next fewyears innovative biological products”. to makeitavailable to those most in need as quickly as possible”. G Polpharma noted that it had at the end of 2012 opened “Poland’s largest research and development centre at the Gdansk science and technology park”, where the firm had already begun developing ONCOLOGY DRUGS “various biosimilar products”. In late 2013, Andreas and Thomas Strüngmann struck an exclusive global licensing deal for an undisclosed biosimilar between the Prasco has authorised Evista Strüngmanns’ Santo Holding vehicle and German biotech company rasco Laboratorieshas begun shipping an authorised generic of Eli Formycon (Generics bulletin,10January 2014, page 17). PLilly’sEvista (raloxifene) 60mg tablets after striking amarketing Santo assumed development and commercialisation costs, while and distribution agreement with the US originator.The agreement Munich-based Formycon receiveda“single-digit million euro” upfront between the twofirms –for which financial details were not disclosed – fee, with further milestone payments running into “the three-digit came in response to Teva receiving final US approvalfor the first million euro range”. G generic rivals to the osteoporosis treatment last month. G

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PRODUCT NEWS

RESPIRATORY DRUGS LITIGATION Sandoz launches its Mylan sues Celgene AirFluSal in Norway on REMS restrictions

andoz has launched its AirFluSal Forspiro (fluticasone/salmeterol) ylan is seeking an injunction and “treble damages” against SrivaltoGlaxoSmithKline’sSeretide brand in Norway.Both MCelgene in the US overwhat the generics firm claims is an strengths of the respiratory treatment –50µg/250µg and 50µg/500µg “anti-competitive scheme” to use Risk Evaluation and Mitigation –havebeen launched “for the continuous treatment of patients above Strategies (REMS) as apretext for denying Mylan its requests for 12 years of age with persistent asthma or for symptomatictreatment samples of Thalomid (thalidomide) and Revlimid (lenalidomide) to of chronic obstructive pulmonary disease (COPD)”. use in bioequivalence testing. AirFluSal Forspiro has previously been launched in Denmark and Acomplaint filed in aNew Jerseydistrict court sets out Mylan’s Germany, after Sandoz receivedmarketing authorisations in several claims that Celgene has “unlawfully maintainted monopolies overits European countries (Generics bulletin,3February 2014, page 15). twolead products” by preventing generics from entering the market. The firm also has an authorisation in South Korea. “Since 2006, Celgene has made US$20.9 billion from sales of Thalomid However, Sandoz wasrecently hit by apreliminary injunctionin and Revlimid,”Mylan states, “amounts which accounted for 71% to Germanyrelated to the appearance of the AirFluSal Forspiro device 93% of Celgene’stotal yearly revenue.” (Generics bulletin,7March 2014, page 21). GlaxoSmithKline (GSK) told Generics bulletin that the injunction “prevents Sandoz from Used REMS as pretext to deny samples offering, exhibiting, advertising and selling AirFluSal Forspiro in its “Because of US Food and Drug Administration (FDA)-imposed current form”, due to Sandoz’ use of the colour purple. rigorous restrictions on the distribution of Thalomid and Revlimid, Elpen marketed its “generic” Rolenium (fluticasone/salmeterol) access to these drugs is highly restricted,”Mylan acknowledges. combination in Germanywithout purple livery,GSK noted. The Greek However, the firm notes, Celgene has “used REMS as apretext to firm –which bills its version as the first fluticasone/salmeterol hybrid prevent Mylan from acquiring the necessary samples to conduct generic for asthma and COPD –has authorisations in 27 European bioequivalence studies, even after the FDAdetermined that Mylan’s countries and boasts more than 1.5 million prescriptions filled to date. safety protocols were acceptable to conduct those studies”. Since 1March, Rolenium had also become the “exclusive rebate partner” Celgene also implemented distribution restrictions to “significantly of the German DAKand TK health insurance funds, Elpen said. G limit drug product availability”, Mylan claims, stating that it had also been unsuccessful when it had attemptedtoobtain Thalomid and Revlimid samples from wholesalers. Insisting that “Celgene’splaybook of obstructing its generic competitors by gaming the regulatory system is well-recognised”, Mylan notes that Dr Reddy’sand Lannett had previously complained of similar difficulties in obtaining Thalomid and Revlimid samples. “Celgene unjustly earns billions of dollars per year at the expense of the consumer,” Mylan states, insisting that the originator’sconduct “harms consumers by denying them the substantial benefits of lower- priced generic competition, and forces consumers and federal,state and private payors to overspend on prescriptions for these products”. Several US generics players recently settled litigation against Switzerland’sActelion overwhether the originator wasrequired to provide samples of its Tracleer (bosentan) brand for bioequivalence testing (Generics bulletin,21March 2014, page 19). G

PARKINSON’S DISEASEDRUGS Impax resubmits RytaryNDA mpax has resubmitted its newdrug application(NDA) for its Rytary I(carbidopa/levodopa) extended-release capsules to the US Food and Drug Administration (FDA). The submission process for the Parkinson’s disease treatment had been disrupted by manufacturing deficienciesatImpax’ facility in Hayward, California, which had been highlighted by an FDA warning letter almost three years ago (Generics bulletin,30June 2011, page 5), and have yet to be fully resolved. “After discussions with the FDA, the companyhas resubmitted the NDAfor Rytary providing updated safety and stabilityinformation,” Impax said, adding that the agency“will require an inspection of manufacturing facilities involved in the production of Rytary in connection with the resubmission”. G

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PRODUCT NEWS

IN BRIEF BIOLOGICALDRUGS PAR has launched potassium chloride 600mg and 750mg extended- release capsules in the US following final US Food and Drug Remicade suit is filed Administration (FDA) approvalfor its abbreviated newdrug application (ANDA). Citing IMS Health data, the US firm said the extended-release capsule formulation of the hypokalaemia treatment has annual US sales of approximately US$142 million. by Korea’s Celltrion

KERN PHARMA has widened its portfolio of generic citicoline by elltrion is seeking adeclaratory ruling from adistrict court in launching the neurological treatment in a1,000mg oral solution. The CMassachusetts, US, that would clear the wayfor it to launch arival Spanish firm –which will market the newformulation in apack to Janssen’sRemicade (infliximab) by invalidating patents protecting containing 10 sachets of 10ml –had previously offered citicoline as a the biologic brand. The South Korean firm’sRemsima version of 30ml oral solution and 500mg and 1,000mg injectableformulations. infliximab wasapprovedinSouth Korea in 2012 (Generics bulletin, 3September 2012, page 16), and in Europe ayear later (Generics LUPIN said it would in the US shortly begin shipping its substitutable bulletin,20September 2013, page 17). generic rivals to Takeda’s Actos (pioglitazone)15mg, 30mg and “Janssen holds at least three US patents –USpatents 5,919,452, 45mg tablets following final approvalfrom the US Food and 6,284,471 and 7,223,396 –that will purportedly coverRemicade beyond Drug Administration (FDA). The diabetes treatment had US sales 2014,”Celltrion’sfiling states. However, the South Korean firm is of US$236 million in 2013, according to IMS Health data. seeking adeclaratory judgement that Janssen’spatents are invalid and unenforceable, “thereby clearing the path for an affordable competitor TWI PHARMACEUTICALS has receivedfinal US Food and Drug to Janssen’sRemicade to enter the market”. Administration (FDA) approvalfor its generic equivalent of Pfizer’s “Under law, Janssen’speriod of permissible patent protection Procardia XL (nifedipine)30mg, 60mg and 90mg extended-release should have already ended,”Celltrion’sfiling states, insisting that tablets. The Taiwanese firm said it would start shipping the “Janssen has employed avariety of manipulative legaland other tactics antihypertensive –which had US branded and generic sales of to aggressively extend its multi-billion dollar patent monopoly over US$116 million in 2013, according to IMS Health data –once final Remicade throughout the world”. “Janssen and its predecessors are preparations with its US distributor had been completed. trying to improperly extend its monopoly after its initial patents expired,”Celltrion believes, claiming that the originator has “engaged BIOOUTSOURCE has launched the “first commercially available” in manipulative and deceptive practices before the US Patent and reverse-signalling apoptosis bioassay to the global biosimilars Trademark Office (USPTO) to improperly extend the length of its market. The launch completes BioOutsource’s“extensive range patent monopoly for Remicade”. of bioassays used to measure biological functions of Humira (adalimumab)and Remicade (infliximab)”, the Scottish firm said. US Remsima filing in first half of 2014 “Celltrion intends to apply for marketing approvalofRemsima HOVIONE has obtained apatent from the US Patent and Trademark in the US during the first half of 2014,”the filing reveals, adding that Office (USPTO) for the firm’s XCaps capsule-based, dry-powder the firm expects the US Food and Drug Administration (FDA) to inhaler (DPI). The inhaler has only twooperating components, approve the drug by early 2015, “assuming the approvalprocess is Hovione pointed out, “thereby achieving significant cost savings not hindered by interference from Janssen or its affiliates”. As aresult, and giving the patient unprecedented ease of use”. The firm received Celltrion expects Remsima to become “the first biosimilar of an apatent from the European Patent Office (EPO) for the device last antibody drug ever approvedinthe US”. year (Generics bulletin,20September 2013, page 21). While an at-risk launch could create “serious risks and exposure for Celltrion”,adecision to delay launching Remsima would also PROBIOMED has been told by the health ministry of Mexican be harmful to the company, it insists. “Because Celltrion expects to state Michoacán and the country’sFederal Commission for face patent-infringement allegations from Janssen, Celltrion wants Health Protection to recall all lots of its ‘rituximab-like’ cancer to start the adjudicative process,”the South Korean firm states in its treatment Kikuzubam. filing, recognising that it is on an “inevitable collision course” with the originator.Moreover, “Janssen has refused Celltrion’srequest for SYNTHON’s antibody-drug conjugate ‘SYD985’has “demonstrated alicence to its US Remicade-related patents”. unprecedentedanti-tumour activity and clearly outperformed” Roche’s “Denying Celltrion the opportunity to litigate declaratory judgement Kadcyla (trastuzumab emtansine)brand in ahead-to-head claims nowwould delay Celltrion’saccess to the judicial system for comparison, the Netherlands-based firm has reported. “Weare very about 10-12 months, and perhaps more,”the South Korean firm states. pleased with the results. When confirmed in clinicalstudies, the Meanwhile, Celltrion has filed aseparate complaint in asouthern target population for SYD985 would be significantly broader than NewYork district court seeking adeclaratory judgement overpatents that for the current therapyoption,”said Synthon. held by the Kennedy Trust for Rheumatology Research. Three patents – US patents 7,846,442, 8,298,537 and 8,383,120 –covering the use SUN PHARMA has receivedfinal US Food and Drug Administration of anti-tumour necrosis factor (TNF) alpha antibodies such as Remicade (FDA) approvalfor its generic rivals to Sanofi’s Eloxatin (oxaliplatin) alongside methotrexate are invalid, Celltrion claims, because they 50mg/10ml and 100mg/20ml vials. The Indian firm has also receiveda claim “the same invention or obvious variations of the invention tentative US approvalfor the cancer drug in the 200mg/40ml strength. Kennedy claimed in [an] earlier,now expired patent”. “Kennedy,which has no product of its own, has pursued an HEXAL has secured aGerman marketing authorisation for fentanyl aggressive licensing campaign to secure asubstantial royalty stream sublingual tablets in six strengths. The Sandoz subsidiary has also from manufacturers of anti-TNF alpha antibodies,”Celltrion claims, obtained approvalinGermanyfor rivastigmine 4.6mg and 9.5mg per adding that Kennedy “attempted to extend the enforceability period day patches, and for meropenem 1g powder for injection or infusion.G of its co-administration patents, to obtain patents which should not have been awarded, and to enforce patents that are invalid”. G

18 April 2014 GENERICS bulletin 19 Gen 18/4/14 Pgs. 14-21_Layout 1 15/04/2014 20:15 Page 8

PIPELINE WATCH Morememantine SPCs expireinApril

pril brings the expiry of supplementary protection certificates April also brings the expiry of SPCs in several EU member states A(SPCs) in Italy,Sweden and Switzerland for the Ebixa (memantine) for Pfizer’sReFacto (moroctocog alfa) recombinant anti-haemophilic brand that Merz licenses to Lundbeck. These SPCs are based on factor.“Data exclusivity for this molecule has already expired, and European patent EP0,392,059, which protects the authorised use of the expiry of these SPCs leave only Switzerland and Australiaas memantine to treat Alzheimer’sdisease. protectedmarkets,”Ark observes. Pfizer reported 2013 sales of ReFacto In the UK, Synthonsought adeclaration that the SPC wasinvalid in “developed Europe” ahead by 3% to US$386 million. or should, at best, have azero term. The Dutch firm argued that Merz Data exclusivity for Velcade (bortezomib) expires in most EU had incorrectly based its SPC application on aEuropean Union (EU) member states during April. However, Ark points out, Takeda’s centralised marketing authorisation granted in May 2002, rather than multiple myeloma and mantle-cell lymphoma treatment –which on the earlier1976 authorisation for memantine in Germany. The UK sawa32.5% US sales rise to ¥71.4 billion (US$703 million) in the Patents Court referred the case to the European Court of Justice (ECJ) nine months ended 31 December 2013 –iscovered by patent-term for aruling on what constituteda“first authorisation” under the SPC extensions around the world and will therefore not come offpatent Regulation 1768/92 (Generics bulletin,17April 2009, page 16). until 2017 in the US, 2019 in Europe and 2020 in Australia. Canada could become the first developed country to see generic bortezomib, ECJ ruling invalidated Ebixa SPC as the local patent expires in October 2015. Twoyears later,the ECJ concluded that aproduct which was Takeda’sasthma and rhinitis drug Alvesco (ciclesonide) loses placed on the market in the European Community before obtaining data exclusivity this month in Belgium, France, Germany, Italy, amarketing authorisation in accordance with Directive 65/65/EEC Luxembourg, the Netherlands, Sweden, and the UK. wasnot within the scope of the SPC regulation (Generics bulletin, “Patent and SPC protection will prevent generic entry in Europe 5August 2011, page 17). Therefore, the SPC in the UK wasinvalid. until at least 2016,”Ark says. In Canada, it notes, data exclusivity Similar proceedings in Austria, Belgium, Germany, the Netherlands for ciclesonideruns until March 2015, to be followed by atwo-year and Spain have also led to the invalidation of the SPC. However, no-marketing period and apaediatric extension, extending protection notes Ark Patent Intelligence, equivalent national patents in Hungary beyond the term of the respiratory drug’smolecule patent. G and Portugal with later expiry dates have served as the basis for memantine SPCs that run until 2015 and 2016. Data exclusivity expiries in April The advent of generic competition in several countries reduced INN Country/Region Lundbeck’sEuropean Ebixa sales by almost athird last year to DKr1.64 billion (US$305 million). Ambrisentan Turkey In the US, Forest holds memantine marketing rights under the Anidulafungin Australia Namenda brand, whose sales grewby9.4% last year to US$1.52 Artemether/Lumefantrine US billion. Forest plans to discontinue sales of immediate-release tablets Benzyl alcohol US in favour its Namenda XR extended-release version as it seeks to mitigate the impact of generic launches under the terms of patent- Bortezomib European Union litigation settlements. Those settlements permit generic entry three Ciclesonide Belgium, France, Germany, Italy, months before the expiry of US patent 5,061,703, including any Luxembourg, Netherlands, Sweden, UK extensions. The ‘703 patent expires on 11 April 2015, butForest is Doripenem Australia seeking asix-month paediatric extension that would stretch protection Ezetimibe/Simvastatin Belgium, France, Germany, Italy, to October 2015 (Generics bulletin,7March 2014, page 29). Luxembourg, Netherlands, Sweden, UK Famotidine/Ibuprofen US SPC expiries in April Febuxostat Turkey INN Country Ibritumomab tiuxetan Switzerland Micafungin Turkey CetrorelixFinland, Slovenia Mitotane European Union Memantine Italy,Sweden, Switzerland Nepafenac Canada* Moroctocog alfaAustria, Belgium, Denmark, France, Germany, PancrelipaseUS Greece, Hungary,Italy,Luxembourg, Recombinant cholera toxin European Union Netherlands, Spain, Sweden, UK Tafluprost Turkey Ranitidine Latvia Thalidomide Turkey Tirofiban Cyprus *This will be followed by ano-marketing period of twoyears during which anotice of compliance will not be granted to ageneric manufacturer.

Figure1:Molecules for which supplementaryprotection certificates (SPCs) expire Figure2:Molecules for which data exclusivity expires in certain markets during in certain markets in April 2014 (Source –Ark Patent Intelligence) April 2014 (Source –Ark Patent Intelligence)

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

20 GENERICS bulletin 18 April 2014 Gen 18/4/14 Pgs. 14-21_Layout 1 15/04/2014 20:15 Page 9

PRODUCT NEWS

DERMATOLOGY DRUGS OPIOID ANALGESICS Sandoz and Perrigo Endo wins appeal on compete on Taclonex Opana ER injunction

andoz has launched ageneric version of Leo Pharma’sTaclonex NewYork district court erred in denying Endo an injunction S(calcipotriene/betamethasone dipropionate) ointment in 60g and Apreventing Actavis and Roxane from marketing generic versions 100g tubes in the US with 180-day exclusivity.However,the generics of the originator’s Opana ER (oxymorphone) extended-release tablets, firm will face competition from an authorised generic that Perrigo has aUSappeals court has ruled. Patent-litigation settlements between introduced simultaneously through an agreement with the originator. the generics firms and the originatorthat referred to certain patents Peter Goldschmidt, Sandoz’ US head, said the firm’sTaclonex covering the branded analgesic did not grant Actavis and Roxane rival–which will be launched through apartnership with US express or implied licences to patents that were obtained later,the court contract-developer and abbreviated newdrug application(ANDA) found, overturning the earlier ruling and remanding the case back to holder Tolmar –“further broadensour strong offering of differentiated the district court for reconsideration. generic dermatology products”. Following separate settlements related to Opana ER’sUSpatents Citing IMS Health data, Sandoz said the branded version of the 5,662,933, 5,958,456 and 7,276,250, Actavis and Roxane launched psoriasis treatment had US sales of around US$96 million last year. G rivals to Opana ER three years ago. Those settlements contained a covenant not to sue for infringement against the three patents, along with a‘no implied rights’ provision that granted the generics firms ANTIBIOTICS no licence or right other than “as expressly granted herein”. Having in late 2012 obtained the US patents 8,309,122 and Apotex defeats double attack 8,329,216 –which both coverOpana ER until 4February 2023 –Endo again sued the twofirms. The originator claimed that the generics firms’ Delaware district court wasright to dismiss aUSlawsuit brought abbreviated newdrug applications (ANDAs) infringed the ‘122 and Aagainst ApotexbySenju Pharmaceutical, Kyorin Pharmaceutical ‘216 patents, and that neither firm wasentitled to implied licences to and Allerganoverare-examined gatifloxacin patent because Senju these twopatents based on the settlements. had previously asserted the same patent against the generics firm in Rejecting this and denying Endo’smotion for an injunction, the earlier litigation, aUSappeals court has ruled (Generics bulletin,1 district court had stated that stopping the twofirms from marketing October 2012, page 20). Opana ER rivals as aresult of the ‘122 and ‘216 patents was“ahighly Senju had argued that the re-examination of US patent 6,333,045 – unfair and unjust situation”.“Endo is estopped from claiming that the which discloses acombination of gatifloxacin with disodium edetate – activity of Actavis and Roxane, which has gone on for asubstantial had “createdanew cause of action”. This, the originator said, was period of time, is nowsuddenly barred because of these newpatents,” “because the re-examined patent claims are substantially different the district court insisted. from the claims in the original ‘045 patent”. However, the appeals court sided with Endo. Judge Kimberly However, the appeals court observed, “while re-examination can Moore described as “meritless” Roxane’sargument that its original makecertain changes in the patent, such changes are strictly settlement –which licensed rights to “anyUSpatent applications that circumscribed by the original patent’sdisclosure and claim scope”. “As claim priority to the Opana ER patents, including anycontinuation, aresult, are-examined patent claim cannot contain within its scope any continuation-in-part and divisional patent applications –amounted product or process which would not have infringed the original claims.” to alicence to the ‘122 and ‘216 patents. In the absence of clear proof that a“material difference” exists, “There can be no dispute that the ‘122 and ‘216 patents are not the court stated, “it can be assumed that the re-examined claims will continuations of anyofthe licensed patents,”Moore stated in amajority be asubset of the original claims”. decision, despite acknowledging that the twopatents claimed priority “Atits core, what Senju seeks is ado-over,”the court stated, to the same provisional application as the ‘250 patent. observing that the firm wasusing the re-examination process to attempt Rejecting the generics firms’ assertionsthat an implied licence to to obtain a“second bite at the apple”. But “that is exactly what claim the ‘122 and ‘216 patents existed in the settlements, Moore said the preclusion wasdesigned to prevent”, the court concluded. G appeals court could not expand the scope of the ‘impliedlicence’ doctrine. “You get what you bargain for,” Moore said, “and we will not use the implied licence doctrine to insert ourselves into that bargain MIGRAINE REMEDIES and rewrite the contract.” Vacating the district court’sdecision and remanding the case for Mylan eyes frovatriptan date further proceedings, Moore urged Actavis and Roxane to be more meticulous when striking settlement agreements. “If appellees wanted ylan says it can launch ageneric version of Endo’sFrova to market and sell their accused generic product free from anythreat M(frovatriptan) 2.5mg tablets in the US before US patent 5,464,864 of being sued …theycould have negotiated for the appropriate expires on 7November 2015. AUSdistrict court has granted Mylan’s language in the settlement and licence agreements,”she stated. G request to enforce apatent-litigation settlement overthe migraine remedy and to overturn aruling that would have blocked an earlierlaunch IN BRIEF (Generics bulletin,14February 2014, page 13). “Mylan can launch its product pursuant to the terms of the TEVA’s abbreviated newdrug application(ANDA) for generic rivals to settlement, contingent upon final US Food and Drug Administration Astellas Pharma’s Vesicare (solifenacin)5mg and 10mg tablets has (FDA) approval,”commented Mylan. Citing IMS Health data, Mylan receivedfinal approvalfrom the US Food and Drug Administration. G said frovatriptan had US sales of around US$66.4 million in 2013. G

18 April 2014 GENERICS bulletin 21 Gen 18/4/14 Pg/ 22_Layout 1 15/04/2014 20:18 Page 2

EVENTS

MAY 19-21 November 2014 20 &21-22 &23May ■ 17th IGPAAnnual Conference ■ 5th Annual Miami,USA BiosimilarsAsia This three-day event is being organised by the US Generic Pharmaceutical Association (GPhA) and is the global event of the worldwide generics industry.Itisthe Shanghai,China annual joint meeting of the Canadian, European, Japanese, South African and US Looking at strategic challenges and generics industry associations, the CGPA, EGA, JGA, NAPM and GPhA. innovations in the development of Contact:Jennifer Nguyen, GPhA.Tel:+1202 249 7127. biosimilars, this four-day event will be E-mail: [email protected]. Website: www.gphaonline.org. preceded and followed by workshops. Keytopics to be covered will include regulatory updates, clinical development 25-27 June studies as well as presentations on and intellectual-property issues. ■ 20th EGA Annual Conference demonstrating biosimilarity. Contact:IBC Asia. Madrid,Spain Contact:OxfordGlobal. Tel: +65 6508 2401. The European Generic medicines Tel: +65 657 02208. E-mail: [email protected]. E-mail: [email protected]. Association’s(EGA’s)three-day annual Website: www.biosimilarsasia.com. Website: www.biosimilarsasia-congress1.com. conference will look at topics including the 27-28 May current regulatory environment, access to medicines and implementing safety features. ■ Getting Approval of OCTOBER Contact:Lucia Romagnoli, GPAConferences. Generics in the EU &USA Tel: +44 7562 876 873. 7-9October Berlin,Germany E-mail: [email protected]. ■ CPhI Pre-Connect Conference Topics covered at this two-day conference Register onlineatwww.egagenerics.comor &CPhI Worldwide will include regulatory procedures in the www.gpaconferences.com/ega14.htm. Paris,France European Union, ANDAprocedures for CPhI Worldwide is an exhibition and approvalinthe US, the Food and Drug 26-28 June networking opportunity which will also Administration’s(FDA’s) user fee ■ CPhI China include the co-located events iCSE, P- regulation –GDUFA–and its impact, Shanghai,China MEC and Innopack. The event will be and eCTD submissions. Co-located with P-MEC, ICSE, LABWorld, preceded by the Pre-Connect Conference Contact:Concept Heidelberg. InnoPack and BioPh, this three-day trade taking place in the same location. Tel: +49 6221 8444 0. showwill provide an insight into the latest Contact:UBM Information. E-mail: [email protected]. industry trends with over2,200 exhibitors. Website: www.gmp-compliance.org. Tel: +44 207 921 8039. Contact:UBM. E-mail: [email protected]. Tel: +31 204 099 544. Website: www.cphi.com JUNE E-mail: [email protected]. Website: www.cphi.com/china. 3-4June 13-15 October 11th TOPRA Annual ■ GPhA CMC Workshop JULY ■ Maryland, USA Symposium This two-day workshop hosted by the US 24-25 July Brussels,Belgium Organised by The Organisation for Generic Pharmaceutical Association ■ Legal &RegulatorySummit (GPhA) will provide information on Professionals in Regulatory Affairs (TOPRA) chemistry,manufacturing and controls on Generic Drugs in conjunction with Belgium’sFederal (CMC) regulatory requirements. New Yo rk,USA Agencyfor Medicines and Health Products Contact:GPhA. Looking at the legaland regulatory (FAMHP), this event will covercurrent Tel: +1 202 249 7100. changes affecting the industry,this two- and forthcoming regulatory issues. day conference will coverissues including E-mail: [email protected]. Contact:TOPRA. Website: www.gphaonline.org. 180-day generic market exclusivity,user Tel: +44 207 510 2560. fees and biosimilars strategies. E-mail: [email protected]. 23-24 June Contact:American ConferenceInstitute. Website: www.topra.org. Tel: +1 212 352 3220. ■ EuroPLX 55 E-mail: [email protected]. 27-29 October Vienna, Austria Website: www.americanconference.com. ■ GPhA Fall Technical This meeting provides aforum for Conference business-development decision makers to SEPTEMBER discuss and negotiate collaborative Maryland, USA agreements, in-licensing, marketing and 25-26 September This three-day GPhA conference will distribution of patented medicines, look at the current regulatory and generics, biosimilars, OTCproducts, ■ 2nd Annual Biosimilars Asia technical issues and their impact on the medical devices and food supplements. Singapore generics industry. Contact:Raucon. This two-day meeting will discuss topics Contact:GPhA. Tel: +49 6222 9807 0. including emerging markets, commercialising Tel: +1 202 249 7127. E-mail: [email protected]. biosimilars, manufacturing and clinical E-mail: [email protected]. Website: www.europlx.com. trials. The conference will include case Website: www.gphaonline.org.

22 GENERICS bulletin 18 April 2014 Gen 18/4/14 Pg. 23_Layout 1 15/04/2014 20:16 Page 3

PRICE WATCH ...... UK CategoryMthrows up winners and losers

uts in the pharmacyreimbursement prices of generic medicines Cfrom the start of this month are intended to save the UK around AvAmilerageAve£ AmilDrug DrugTariffTariff MinimumAmi Min £ 1010 £120 million (US$200 million) annually.The country’sDepartment of Health (DoH) and the body representing pharmacy, the Pharmaceutical 88 Services Negotiating Committee (PSNC), have agreed areduction of £10 million per month, which will be savedbyadjusting reimbursement 66 prices for medicines in category Mofthe Drug Tariff(Generics 4 bulletin,4April 2014, page 10). Price (£) 4 We asked WaveData to takeacloser look at the winners and losers at an individual product levelinthe government’sattempts to keep 22 margins in line with an overall goal. Four category Mproducts were 0 selected that were found historically to have offered the best and worst 0 Jul 05 Jul 07 Jul 11 Jul 13 deals to independent pharmacists and dispensing doctors in percentage Mar 04Nov 04 Mar 06Nov 06 Mar 08Nov 08Jul 08Mar 10Nov 10 Mar 12Nov 12 Mar 14 and cash terms. Based on average trade and Drug Tariffprices, 28-tablet packs of amiloride 5mg provided a1,613% loss; while for 100-tablet Figure1:Lowest and average trade prices, compared with Drug Traiff packs of mebeverine 135mg, the loss amounted to £12.19per pack. reimbursement prices, for 28-tablet packs of amiloride 5mg (Source –WaveData) Similarly,pharmacists have enjoyed an 87% gain from dispensing Av
erage Drug
Tariff 
Minimum 100-tablet packs of dispersibleaspirin 75mg; and £39.27 from 30-  3.5 tablet packs of modafinil 200mg. 3.0 Charles Joynson, WaveData’smanaging director,pointed out prices  for the amiloride product had “gone well offthe scale” since October  2.5 2013, “forcing pharmacists to lose 1,613% of the Drug Tariffprice each 2.0 time theydispense aprescription”(see Figure 1). The DoH, he adds,  1.5 has “come to the rescue” with monthly concessionaryprices of Price (£) £20.62 in the December to February period and £19.55 last month. 1.0  0.5 Bounce around in amost extraordinaryway 0 The aspirin product, meanwhile, has seen its Drug Tariffprice            Jul 05 Jul 11 “bounce around in amost extraordinary way”, while its average and Mar 04Nov 04 Mar 06Nov 06Jul 07Mar 08Nov 08 Jul 08Mar 10Nov 10 Mar 12Nov 12 Jul 13Mar 14

minimum prices have “remained relatively stable (see Figure 2). Figure2:Lowest and average trade prices, compared with Drug Traiffreimbursement “Pharmacists could have made an 87% –£2.50 –profit for each pack prices, for 100-tablet packs of dispersible aspirin 75mg (Source –WaveData) dispensed in March,”Joynson adds. Three historical price “bounces” have been experienced by the AvMeberage Ave £ DrugMeb DrugTariff Tariff MebMinMinimum £ 1820 mebeverine product,heobserves, with the Drug Tariff“attempting to 1618 keep ahead of changes” (see Figure 3). This wasachievedsuccessfully 16 14 in 2008, butwas less effective in 2011 and nowagain in 2014. Despite 14 12 prices that exceeded the Drug Tarifffor most of 2011, price concessions 12 were only granted of £7.52 in April and £9.25 in October.More 1010 88

recently,prices started rising last October and aprice concessionof Price (£) £6.20 wasgranted in November 2013. This has since risen to £18.00 66 in March –when some firms were listing the product as being in 44 short supply –asthe product’saverage trade price has risen to £16.62. 22 0 Since its launch in 2011, there has been agradual average-price slide 0

for the modafinil product (see Figure 4). Meanwhile, the Drug Tariff Jul 05 Jul 07 Jul 13 Mar 04Nov 04 Mar 06Nov 06 Mar 08Nov 08Jul 08Mar 10Nov 10Jul 11Mar 12Nov 12 Mar 14 price wassteady at £105.15 until June 2013, when it begantorise. “The Drug Tariffprice rose by £11.09between November 2013 and Figure3:Lowest and average trade prices, compared with Drug Traiffreimbursement prices, for 100-tablet packs of mebeverine 135mg (Source –WaveData) March 2014,”points out Joynson, “whilst the product’saverage price fell by £2.80 overthe same period, giving an average pharmacyprofit ModafinilAverageAve£ DrugModafinilTa Drugriff Tariff MinimumModafinil Min £ in March of £39.27.” But then at the beginning of April, he adds, the 140140 Drug Tariffwas adjusted dramatically downward by nearly £44 to 120120 £78.75 “leaving pharmacists with apotential loss of £4.66.” G 100100 80 WANT MORE LIKE THIS? 80 6060

Long-term product price trends or other price analyses are available. Price (£) Please specify the product and period of time you would liketo 4040 investigate and email your request to [email protected]. 2020 ■ Forfurther information see www.bppi.co.uk. 00 Alternatively,contact Charles Joynson at Aug 12 Oct 12 Dec 12 Feb 13 Apr 13 Jun 13 Aug 13 Oct 13 Dec 13 Feb 14 Apr 14 WaveData Limited, UK. Tel: +44 (0)1702 425125. E-mail: [email protected]. Figure4:Lowest and average trade prices, compared with Drug Traiffreimbursement prices, for 30-tablet packs of modafinil 200mg (Source –WaveData)

18 April 2014 GENERICS bulletin 23 Gen 18/4/14 Pgs. 24-25_Layout 1 15/04/2014 20:17 Page 2

MARKET RESEARCH US market bounces back as value growsbyatenth

n2013, turnoverfrom generics rising by almost a An increase of nearly Brand Annual sales Change Market tenth helped the overall US prescriptionmarket to (US$ millions) (%) share(%) atenth in US generics Irecoverfrom adownturn in the previous year that sales in 2013 had represented the first annual decline since records Abilify 6,545 +14.7 2.0 began. Arise of 9% in unbranded generics sales to Nexium 6,181 +5.1 1.9 contributed to the US$56.7 billion helped to drive overall growth of 3.2% Humira 5,566 +24.2 1.7 to US$329 billion in 2013, in contrast to the 1.0% country’stotal Crestor 5,372 +8.4 1.6 decline seen last year (Generics bulletin,22March Cymbalta 5,278 +14.5 1.6 2013, page 24). Brand sales edged up by 1.9% to prescription market Advair Diskus 5,185 +8.0 1.6 US$232 billion. By volume, the total number of growing by 3.2%, prescriptions advanced by 1.4% to 4.21 billion in 2013. Enbrel 4,711 +12.0 1.4 “US market growth is rebounding,”observed Doug Remicade 4,115 +7.2 1.3 reversing 2012’s Long, vice-president of industry relations at IMS Health, Copaxone 3,711 +5.6 1.1 decline. David as he presented the US market data during the 2014 Neulasta 3,588 +4.4 1.1 annual meeting of the US Generic Pharmaceutical Top 1050,251 +10.6 15.3 Wallace reports. Association (GPhA). Long forecasted acompound Others 279,008 –84.7 annual growth rate (CAGR) for the prescription market of between 1% and 4% between 2013 and US pharma market 329,259 +3.2 100.0 2017, with overall sales reaching US$350 billion. Figure3:Sales of the best-selling prescription pharmaceutical Generics turnoveradvancing by 9% wastosome brands in the US in 2013 (Source –IMS Health) extent drivenby“price increasesand drug shortages, in part caused by generic good manufacturing practice that could be, buthad not been, dispensed as generics. (GMP) issues”, Long observed, such as the exit of Ben While certain brands were opened up to generic Venue from the injectables market after parent company competition in 2013, the value of expiries did not match Boehringer Ingelheim concluded that it would taketoo that seen in 2012, commonly cited as the edge of the much time and investment to address manufacturing ‘patent cliff’ faced by generics firms. problems (Generics bulletin,18October 2013, page 3). At the start of the year,Mallinckrodt introduced a Value sales of US$56.7 billion gave generics a rivaltoJohnson &Johnson’sConcerta (methylphenidate) 22.1% share of the overall prescriptionpharmaceutical with 180-day exclusivity (Generics bulletin,11January market –once branded generics were disaggregated 2013, page 1). And later in the year Teva benefitted between generics and brands –thus continuing the from similar exclusivity for its generic version of annual trend of increased penetration. By volume, the Merck &Co’sTemodar (temozolomide), although the proportion of the market enjoyed by generics rose by Israeli firm had to compete with an authorisedgeneric more than twopercentage points to 83.1% (see Figure 1). from Sandoz (Generics bulletin,6September 2013, The ‘generic efficiencyrate’ –referring to the page 19). proportion of eligible prescriptions that were substituted Actavis launched arivaltoEndo’sblockbuster with ageneric –of95.1% still provided “some avoidable Lidoderm (lidocaine) 5% patch in September (Generics cost opportunity”, Long observed, citing US$11.9 bulletin,20September 2013, page 7), while several billion of avoidable costs from 85 million prescriptions generics players introduced rivals to Cymbalta

Brands
 Generics
 40 35.2 US Dollars (%) Prescriptions dispensed (%) 35  100 2013-2019 exposure: US$94 billion 30 14.2%

14.8%  16.8% 18.1% 80 21.0% 22.1%  25  21.5

%) 19.2 19.5 18.4 e( 60 20 18.0 67.9%

 70.5%  16.5 74.0% 76.7% 80.7% 83.1% 15 12.2

85.8%  81.9%

40 83.2% 85.2% 10.6 Sales (US$ billions)  79.0% 77.9% 9.4 10

Market shar  5.4  20 5 32.1% 29.5% 26.0% 23.3% 19.3% 16.9% 0 0 2008 2009 2010 2011 2012 2013 2008 2009 2010 2011 2012 2013 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019               
   Figure1:Value and volume shares of the US prescription market enjoyed by Figure2:Annual sales value of US drugs –excluding biologicals –that were, or generics and brands between 2008 and 2013, with branded generics will be, exposed to generic competition in the years between 2009 and 2019 ‘disaggregated’ between the two (Source –IMS Health) (Source –IMS Health)

24 GENERICS bulletin 18 April 2014 Gen 18/4/14 Pgs. 24-25_Layout 1 15/04/2014 20:17 Page 3

MARKET RESEARCH

(duloxetine) capsules –which had brand sales of US$5.3 with a7.4% rise translating to additional sales of around billion in 2013 –atthe end of the year upon patent US$700 million. And by volume, Apotexgained 40.4 expiry (Generics bulletin,10January 2014, page 16). million prescriptions, more than doubling its figure Between 2013 and 2019, Long forecasted, non- from the previous year. biological US brands with acumulative annual value Cumulative sales among the top 10 firms by value of US$94 billion would lose exclusivity (see Figure 2). growing by 7.6% to US$34.1 billion –and among the However, if Teva’s Copaxone (glatiramer acetate) top 20 by 8.0% to US$43.7 billion –suggested that faced competition in 2014, Long noted, the individual the overall generics market growth of 9.0% was figure for 2014 would rise from US$19.2 billion to being drivenbygains from smaller firms. nearly US$23 billion. Meanwhile, 2018’speak of Meanwhile, in volume terms, the top 10 firms US$19.5 billion waslargely linked with aforecasted increased the combined number of prescriptions loss of exclusivity for Pfizer’sLyrica (pregabalin). dispensed with their generics by 3.6% to 2.10 billion, while the top 20 sawtheir cumulative figure rise by Small molecules will ‘dryup’ 4.7% to 2.79 billion. In total, 3.38 billion prescriptions “Generic opportunities are abundant in the near- were dispensed as an unbranded generic, representing term for orals,”Long observed, although small-molecule a4.9% increase over2012’sfigure. opportunitieswould “start to dry up mid-decade”. Looking ahead, Long predicted that key However, Long predicted, this downturn would be offset developments in the US would include resolving the at least in part by opportunities to compete with uncertaintyoverwhether Copaxone would face generic biological drugs. As Figure 3shows, biological drugs competition from May (see page 16). US Food and such as Humira (adalimumab), Enbrel (etanercept), Drug Administration (FDA) guidance on biosimilars – Remicade (infliximab) and Neulasta (pegfilgrastim) are including naming conventions –was also expected in increasingly dominating the list of best-selling US the near future, as well as potential OTCswitches for pharmaceutical brands. brands such as Pfizer’sLipitor (atorvastatin). Ranking firms in order of their US unbranded Long also pointed to the significant impact of generics sales, IMS found that four companies –Teva, industry consolidation,including among purchasers. Mylan, Actavis and Sandoz –continued to lead the way This included Walgreens’ investment in Alliance Boots by both value and volume. Their rankings remained (Generics bulletin,29June 2012, page 3), the generics “Generic opportunities unchanged since 2012, with Teva maintaining its lead purchasing joint venture between Cardinal and CVS in both lists despite a5.2% value slide (see Figure 4) Caremark(Generics bulletin,10January 2014, page 3) are abundant in and avolume increase of just 0.3% (see Figure 5). and the takeoverofCelesio by McKesson (Generics In absoluteterms, Mylan gained the most by value, bulletin,3February 2014, page 5). G the near-termfor orals,”Long observed, Annual sales Change Share Prescriptions Change Share (US$ millions) (%) (%) (millions) (%) (%) although small-molecule Teva 6,903 -5.2 12.2 Teva 493 +0.3 14.6 opportunities would Mylan 6,599 +7.4 11.6 Mylan 366 -5.5 10.8 “starttodry up Actavis 6,319 +4.0 11.1 Actavis 258 -9.4 7.6 Sandoz 4,301 +1.8 7.6 Sandoz 208 +4.5 6.2 mid-decade”. ParPharma 2,390 +7.4 4.2 Lupin 175 +9.2 5.2 Sun Pharma 2,150 +37.1 3.8 Qualitest (Endo) 171 +17.1 5.0 Dr Reddy’s1,431 +39.5 2.5 Amneal 138 +10.6 4.1 Lupin 1,425 +46.1 2.5 Zydus Cadila 103 +17.1 3.0 Greenstone (Pfizer) 1,318 +12.2 2.3 Sun Pharma 96 +25.0 2.8 Perrigo 1,229 +25.9 2.2 Aurobindo 96 +32.7 2.8 Top 1034,063 +7.6 60.1 Top 102,104 +3.6 62.2 Apotex1,227 +24.8 2.2 Dr Reddy’s93+12.6 2.7 Hospira 1,182 +4.5 2.1 Greenstone (Pfizer) 85 -2.6 2.5 Mallinckrodt 1,082 +57.7 1.9 Mallinckrodt 82 -2.7 2.4 Roxane (Boehringer)999 -17.6 1.8 Apotex80+102.6 2.3 APP (Fresenius Kabi) 922 -8.2 1.6 Camber (Hetero) 69 +14.3 2.0 Amneal 912 +59.1 1.6 Roxane (Boehringer) 63 -0.4 1.9 Qualitest (Endo) 879 +22.3 1.6 Ranbaxy (Daiichi Sankyo) 61 -25.0 1.8 Glenmark 872 +25.0 1.5 Internatl Labs 51 -1.0 1.5 Sanofi849 -10.0 1.5 Wockhardt 50 +28.8 1.5 Impax 700 -17.7 1.2 Northstar 48 +15.8 1.4 Top 2043,686 +8.0 77.1 Top 202,785 +4.7 82.3 Total US market 56,692 +9.0 100 Total US market 3,384 +4.9 100

Figure4:Top 20 US generics companies in 2013 by the Figure5:Top 20 US generics companies in the 2013 by the value of their unbrandedgenerics turnover in the US (Source – number of prescriptions dispensed in the US with their unbranded IMS Health) generics (Source –IMS Health)

18 April 2014 GENERICS bulletin 25 Gen 18/4/14 Pg. 26_Layout 1 15/04/2014 20:17 Page 2

INTELLECTUAL PROPERTY Unified courtrules revised

As aEuropean Unified fter a40-year gestation period, the birth of a harm” to each litigant and the balance of convenience. Unified Patent Court (UPC) in Europe is within But there wasa“general consensus” that amicus briefs Patent Courtnears A sight, albeit at adelivery date that has yet to be were inappropriate due to fear of delays to cases and reality,Aidan Fry determined. The first European Union (EU) member suspicions of allied interests. states have started to ratify the UPC agreement entered Outlining keytopics of concern for the generics looks at the debate into just overayear ago, and preparations for the court industry during the EGA’s LegalAffairs Forum, Duncan to start operating are well underway. Curley–director of lawfirm Innovate Legal–questioned around the rules on The preparatory committee charged with laying the what wasmeant by the rules’ requirement that applicants howitwill operate. groundwork for the UPC has cited the “end of 2015 at for injunctions provide “reasonable evidence to satisfy the earliest” as aprospective date for the court to start the court with asufficient degree of certainty” that determining the infringement and validity of patents, the patent wasvalid and infringement wasimminent. including unitary patents that will have effect in 25 “Perhaps this test is leaning towards the German signatory member states and will co-exist with current approach, where the courts generally prefer the validity and future European patents, as well as with national of apatent to have been tested –such as in European patents (Generics bulletin,4April 2014, page 9). Patent Office (EPO) opposition proceedings –before Unitary patents and associated supplementary granting apreliminary injunction,”heobserved. protection certificates (SPCs) will be enforced or By contrast, Curleynoted, the rules’ instruction to invalidated through asingle court action before the UPC. weigh up the interests of the parties “suggests aUK- However, during atransitional period, patent holders type approach to preliminary injunctions, which in will be able to opt out of participating in favour of pharma cases almost always means that the interestsof maintaining European or national patents. the incumbent patentee will prevail”. While the Council of the European Union recently Discussing bifurcation, Curleysaid Rule 37 in the declared that “the missing piece” for creating the UPC 16th draft provided little guidance, despite requests for wasinplace, following acompromise agreement on clarification from several interest groups. recognising judgements (Generics bulletin,21March Rule 37(4) states that UPC judges may stay 2014, page 1), much of the detailed work to lay down infringement proceedings pending afinal decision in regulationsfor the court has still to be completed. arevocation procedure, “and shall stay the infringement That task has fallen in large part to aseven-member proceedings where there is ahigh likelihood that the committee created twoyears ago to draft the UPC’s relevant claims of the patent or patents will be held to rules of procedure. be invalid on anyground by the final decision in the revocation procedure”. Issues on injunctions and bifurcation Acknowledging industry concerns that patent Discussing the recently-released 16th draft rules challengers could be subjected to measures based on of procedure during the European Generic medicines infringement findings before their invalidity arguments Association’s(EGA’s)10th LegalAffairs Forum, the had been heard, Mooneynoted industry suggestions preparatory committee’schairman, Kevin Mooney, said that the “high likelihood” test should be replaced by at least one public hearing on the draft would be held a“reasonable likelihood”or“sound prospects” of an this summer.Heacknowledged that the generics industry invalidity finding. had several concerns,including those around languages, “There is some support for a‘reasonable likelihood’ injunctions and bifurcation of infringement and validity test, butthe ‘high likelihood’ test should be retained proceedings, as well as around the opt-out provisions. for acompulsory stay pending the validity decision,” Describing the issue of languages as a“severe Mooneystated. Pointing out that his committee had political problem”, Mooneysaid there were differing proposed that courts should give reasons for bifurcating views on whether the plaintiff, defendant or member specific cases, he said there wasa“general consensus state in which the regional or local divison waslocated that bifurcation will be limited in practice”. should dictate which languages were used in proceedings. Opt-out provisions under Rule 5dictate that all “This matter is for the UPC’spreparatory committee designations of apatent must be opted out and that to decide,”headded. anyopt-out also covers supplementary protection Turning to provisional relief, Rooneyacknowledged certificates (SPCs) that refer to that patent. “There is the generics industry’sconcern that Rules 190 and considerable support for an opt-out fee at an 191 on orders to produce evidence and information ‘administrative reimbursement’ level,”Mooneysaid, were “too wide and open to abuse”. adding that such fees should reflect the work involved. Rule 211 covered provisional measures such as Curleyhighlighted that Rule 5(7) rendered injunctions, he noted. The rules committee –comprising ineffective anyopt-out application if arevocation action judges and lawyers from France, Germany, the had already been filed with the UPC. Forgenerics firms Netherlands and the UK –was of the viewthat the UPC that acted quickly,hesuggested, this presented “a should look at patent validity before granting injunctions, one-time central knockout opportunity”. he said. “There should be some requirement of urgency,” The rules around opting out are set to be key, Mooneyadded, recognising that different courts across especially giventhe risk to originatorsofhaving their Europe treated the imminence of threat differently. patent invalidated by asingle UPC ruling. As Mylan’s Furthermore, he added, the rules of procedure Fiona Bor observed: “Opting out is thought likely to be required the court to takeinto account the “potential the default position for most pharma patent holders.” G

26 GENERICS bulletin 18 April 2014 Gen 18/4/14 Pg. 27_Layout 1 15/04/2014 20:18 Page 3

PEOPLE

APPOINTMENTS RESIGNATIONS/APPOINTMENTS Nornholdshoulders Louwisreplaced by dual role with Impax WakefordatAdcock

mpax Laboratories has amalgamated its quality and manufacturing dcock Ingram’schief executive officer of eight years, Jonathan Ioperations into asingle division entitled “technical operations”, ALouw,has stepped down from the role with immediate effect “to which will be led by Jeffrey Nornhold as senior vice-president. In pursue other interests”, the South African firm has announced. He his newposition, Nornhold will be responsible for overseeing Impax’ has been replaced by Kevin Wakeford,53, who joins the firm from manufacturing, supply-chain,quality and technical operations. He has majority shareholder Bidvest, having most recently served as chief since March 2011 served as head of quality with the US firm, having executive officer of its traveland aviation business. previously worked for Actavis in asimilar role. “The board decided that strong business skills are what is required “Jeffhas done an outstanding job of building ahighly skilled to lead Adcock’srecovery and growth into the future,”said the South internal quality organisation,”said Impax’ president and chief executive African firm’schairman Brian Joffe, who also recently joined the firm officer,Larry Hsu. “Webelieve Jeffisthe ideal person to manage from Bidvest after Adcock’sboard of directorsousted former chairman this newstructure.” Khotso Mokhele (Generics bulletin,7March 2014, page 31). “Kevin’s Meanwhile, head of global operations Mark Fitch has announced broad experience in anumber of fields and his entrepreneurial spirit plans to retire,but will continue to work temporarily alongside stand him in good stead to lead the company,”headded. Nornhold to “ensure asmooth transition”. Having also joined Impax three years ago, Fitch had worked closely with Nornhold in his role Hall remains as deputy overseeing manufacturing and quality. Adcock’schief financial officer Andy Hall would continue to This included resolving good manufacturing practice (GMP) serveasdeputy chief executive officer –having taken on those problems at the firm’sHayward facility that last year received12 responsibilities following Louw’sresignation –to“ably support” Form 483 observations (Generics bulletin,8March 2013, page 9), Wakeford in his newrole, Joffe noted. further to awarning letter from the US Food and Drug Administration Departing chef executive officer Louw joined Adcock from former (FDA) in 2011 (Generics bulletin,30June 2011, page 5). G parent group Tiger Brands in 2003, before eventually rising to lead the companythree years later (Generics bulletin,17March 2006, page 23). His departure comes shortly after Chilean firm CFR APPOINTMENTS Pharmaceuticals failed in its bid to acquire amajority stakeinthe South African firm, as well as recent preliminary results that showed Damian retains APMGR role Adcock’sturnoverduring its financial quarter ended 31 March 2014 had shown “no improvement” compared to the prior-year period ragos Damian –chief executive officer of Ranbaxy’sRomanian (Generics bulletin,4April 2014, page 2). “The companythanks Dsubsidiary Terapia Ranbaxy –has been re-elected as president Jonathan for his contribution overthe years and wishes him well with and chairman of local generics manufacturersassociation APMGR. his future endeavours,”Adcock stated. Damian has served as the association’spresident since it wasestablished Meanwhile, the South African firm has appointed three non- five years ago. executive directorstoits board following an extraordinary general Meanwhile, APMGR has elected Amelia Dinu –managing director meeting of the firm’sshareholders. These are Anna Mokgokong, of B. Braun Medical Romania –toits board of directors. Along with co-founder and executive chairperson of Community Investment Damian, she joins aboard consisting of Cristina Garlasu of Dr Reddy’s, Holdings; Lindsay Ralphs,chief executive officer of Bidvest; and Zentiva’s Simona Cocos,and SteffenWagner of Sandoz. G Roshan Morar,who serves as managing director of Morar Inc. G

IN BRIEF IN BRIEF TRIS PHARMA has named Stephen Kovary as vice-president of IGI has appointed former West-Ward executive Damian Finio to operations. Before joining the US-based drug-delivery specialist, its board and as chairman of the firm’saudit committee. Michael Kovary held senior positions at firms including Abbott, Bristol-Myers Hemric resigned from the board at the start of April, while IGI’s Squibb, Daiichi Sankyo, Lannett and Purdue. He takes overthe chairperson and director, Joyce Erony,has decided not to run for operations role from Rajul Parikh. G re-election at the firm’sannual meeting in May. G

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