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29 June 2012

COMPANY NEWS 2 Eli Lillyinvests in China’sNovast Labs 2 EU is ready to accept Walgreens will ownAlliance Boots stake 3 India’sJBsees sales decline by atenth 4 Paladin closes in on stakeinSA’sLitha 5 global biosimilars data Sumatriptan raises Russia’sVeropharm 6 Exports and oncologyare 7 drivers forNatco uropean Union (EU) authorities will accept biosimilar applications based on reference Jubilant rejoices as generics leapahead 8 Eproducts sourced from outside the EU after “reconsidering their approach” to biosimilars in the light of increasing globalisation, according to European Commissioner MARKET NEWS 9 forHealth and Consumer Policy,John Dalli. “After careful analysis of the scientific and regulatory elements, the European Commission will revise its interpretation” of existing European legislation governing biosimilars,Dalli told GPhA hails passage 9 the 18th Annual European Generic medicines Association (EGA) conference held in Malta of user-fee package this month. Developing biosimilars had become “an increasingly global business”, Dalli said, French body blames doctors 10 butheadmitted that current EU rules “do not fully match this natural and positive trend”. forrate slide By changing its interpretation of existing legislation, Dalli said, the Commission would Irish price cuts will save C10mn in 2012 11 be able to alter its approach “without alengthylegislative process”. Instead, changes to the EGA warns of threat from API shortages 12 EU's overarching biosimilars guidelineare likely to be needed. “These details are currently Commission invites market-access data 13 under further discussion by our experts,”Dalli stated. However, he emphasised that protecting Belgian body boasts price ‘breakthrough’ 14 public health was“uppermost in our minds” and insisted that it would be essential to ensure that reference products from outside the EU were comparable. PRODUCT NEWS 15 Earlier this year,Nils Behrndt –deputy head of cabinet at the European Commission’s Directorate-General for health and consumer protection (DG Sanco) –had told the EGA’s EMA finalises guides fordeveloping mAbs 15 10th international symposium on biosimilarmedicines that the EU was“keen” to consider Three firms infringe US Hectorol patent 16 global reference products (Generics bulletin,4May 2012, page 11). Mylan to enter earlywith 17 The EGA’s senior director of scientific affairs, Suzette Kox, called Dalli’scomments a US Provigil deal “major and far-reaching regulatory breakthrough”. Meanwhile,she indicated, firms had also Size of Sun’stablets is cited by Osmotica 18 receivedwritten confirmation from the US Food and Drug Administration (FDA) that European Celltrion’sCT- P13 matchesRemicade 19 reference productscould be used in clinical comparative trials for biosimilars in the US. G Aspen addresses SA tenofovir shortages 21 FEATURES 24 Teva triumphs on US Copaxone Fresenius has emerging aim 24 NewYork district judge has ruled that all asserted claims of patents protecting Teva’s but fears biosimilar risks ACopaxone (glatiramer acetate)blockbuster up to 1September 2015 are valid, enforceable and infringed by the generic versions being developed by alliances of Sandoz with Momenta REGULARS and Mylan with Natco. Judge Barbara Jones announced her ruling on 22 June in asingle paragraph. She gave Pipeline Watch – Infanrix 20 no explanation, butstated: “The full opinion of the court’sfindings of fact and conclusionsof Events – Our regular listing 22 lawwill followimmediately after the parties have had the opportunity to reviewitinorder to Price Watch UK – Our regular 23 request redactions of anyproprietary information it may contain.” look at pricing trends in the UK Teva said the ruling should prevent the US Food and Drug Administration (FDA) approving People – Codexis grabs Nicols 27 anygenerics of the multiple sclerosis treatment –for which Teva reported US sales up by 22% to of Albemarle as head US$2.8 billion last year –until sevenpatents listed in the agency’sOrange Book expired on 24 May 2014. Furthermore, the Israeli firm believed, Jones’ decision enjoined Sandoz/Momenta COMPANY DATA NOWAVAILABLE and Mylan/Natco from selling their products until anon-Orange Book process patent expires Charts and data from the comprehensive on 1September 2015. Responding to Jones’ decision, Mylan and Natco expressed their reviewofleading generics players published disappointment. “Wefully intend to evaluate our options for an appeal once the court’sfull in the 8June 2012 issue of Generics bulletin opinion becomes available,”theystated. Momenta also said it intended to appeal. are nowavailable as aPDF file. Fordetails The ruling came days after Teva unveiled positive results from aPhase III clinical trial contact: [email protected]. into adouble-strength 40mg/1ml formulation of Copaxone that is administered three times per week, rather than daily. G Gen 29_6_12 Pgs.2-9_Layout 1 28/06/2012 07:10 Page 2

COMPANY NEWS

MANUFACTURING STRATEGICALLIANCES Aurobindo is to sell Eli Lilly invests in intermediates plant China’s Novast Labs

urobindo Pharma intends to divest its Indian ‘Unit X’ intermediates li Lilly has invested US$20 million in Chinese generics firm Novast Afacility in Cuddalore, Tamilnadu. The Indian firm is currently ELaboratories as part of adeal that the brand companyexpects to conducting apostal ballot of shareholdersand expects to report the “greatly enhance its efforts to build aportfolio of Lilly-branded generic outcome on 20 July. medicines in China”. Novast may also ultimately provide local Having set up the “small plant” in 2002 to makeselected manufacturing capabilities for newLilly brands, noted the originator, intermediates, Aurobindo said it had not “upgraded or expanded which already held astakeinthe Chinese firm. capacity” at the plant due to local constraints. “It has become unviable Novast will increase the manufacturing capacity of its site in to manufacture those fewintermediates as against directly procuring Nantong “overthe next several years”, whilst Lilly will provide from others,”the Indian companystated. Operations at the Cuddalore “technical support to enhance quality standards”. Only part of the site have been suspended. G additional capacity would be used for Lilly products, the firms stated. Novast and Lilly have drawn up an “initial list of medicines across multiple therapeutic areas” to be manufactured at the Nantong plant DISTRIBUTION once the expansion is complete. G DHL opens centreinMumbai IN BRIEF HL Supply Chain has opened alife sciences and healthcare ALKALOID’s manufacturing facility for solid pharmaceutical forms Ddistribution centre in Mumbai, India. Housed within anewly- such as hard gelatine capsules has receivedacertificate of good constructed 56,000 sq mwarehouse, the centre offers services including manufacturing practice (GMP) complianceafter passing an order-management, storage and distribution. inspection by the Bulgarian Drug Agency. The Macedonian company “Wehavethe capabilities to distribute to wholesalers, pharmacists said the certification would enable it to continue registering and and hospitals from our newcentre in Mumbai,”stated the firm’schief marketing drugs in the European Union (EU). G operating officer in India, Vikas Anand. G

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COMPANY NEWS

MERGERS&ACQUISITIONS MERGERS&ACQUISITIONS German Dermapharm Walgreens will own gets most of Axicorp Alliance Boots stake

kincare specialist Dermapharmhas acquired an 85% holding in algreens is to create “the world’slargest purchaser of prescription SfellowGerman companyAxicorp for an undisclosed fee. The Wdrugs” –including more than US$6 billion per year spent on combined firm will offer arange of generic, OTCand parallel-import generics –bypaying US$6.7 billion in cash and shares for a45% stake products that will generate an annual turnoverofover C400 million in the privately-owned European wholesaler and retailer Alliance Boots. (US$510 million). Axicorp will contribute almost half of that total. The US drugstore giant has also taken an option –which it can Between 2008 and 2011, generics and parallel imports supplier exercise in approximately three years’ time –toacquire the remaining Axicorp formed part of India’sBiocon group. But Biocon last year sold 55% stakefor afurther US$9.5 billion in cash, shares and assumption the business back to amanagement buy-out team, having taken back of Alliance Boots’ debt. local marketing rights to the biosimilar insulins and insulin analogues Subject to regulatory approvals, Walgreens expects to complete that it wasdeveloping through anow-defunct alliance with Pfizer its initial investment in Alliance Boots by 1September 2012. The (Generics bulletin,6May 2011, page 3). partnershipwill create “the global leader” in pharmacy-based retailing Dermapharm and Axicorp said the transaction –which was with over11,000 stores in 12 countries. brokered by Munich-based Ferber &Co–would allowthem to realise Alliance Boots will contribute around 3,330 stores and a synergies through close collaboration on “key projects” while they wholesaling network comprising 370 distribution centres delivering to worked towards full integration. Stressing that Friedrichsdorf-based more than 170,000 pharmacies, doctors’ surgeries, hospitals and health Axicorp would not lose anyofits almost 300 employees as aresult of centres in 21 countries. Alliance Boots also offers its ownAlmus range the deal, the firm’schief executive officer and managing shareholder, of generics in five countries –France, Italy,Portugal, Spain and the UK. Dirk Ullrich –who will continue to head the business –insisted the By 2016, Walgreens expects to achieve procurement and retailing transaction represented “an exciting opportunity jointly to accelerate synergies of US$1 billion as the management teams work towards our core strategies and advance with our European roll-out”. “full integration in approximately three years’ time”. Group turnover The combined companyclaims it will possess a“unique platform in 2016 would be greater than US$130 billion, producing earnings for growth” throughout Europe, with “distribution and manufacturing before interest and tax (EBIT) of US$8.5-US$9 billion and an operating capabilities in agrowing number of European markets”. cash flowofaround US$7 billion, Walgreens said. Family-owned Dermapharm wasfounded in 1991 with afocus on Giventhe “complementary geographic footprints”ofWalgreens dermatology and allergy products. It has since developed into an and Alliance Boots, there were no plans for job reductions at either umbrella group that includes generics suppliers Acis and Mibe, as well companyasaresult of the transaction, the twofirms insisted. Walgreens as oncology specialist Cancernova. G would maintain its existing headquarters in Deerfield, Illinois, while Alliance Boots remained “committed” to its current support offices across Europe, including its operational headquarters in Nottingham, UK. MERGERS&ACQUISITIONS Walgreens’ president and chief executive officer,Gregory Wasson, insisted that by collaborating the twofirms would be “ideally positioned Watson holds Actavis meeting to expand our customer offerings in our existing markets, and to become the health and wellbeing partner of choice in emerging markets”. round 25 employees from each of Watson and Actavis met in the In the year ended 31 May 2012, Walgreens posted aturnoverof AUS on 17-19 June to start formal planning to merge the two US$73 billion. The US-based group has around 8,300 outlets across firms. The companies expect to complete Watson’s C4.5 billion (US$5.6 the US, Guam and Puerto Rico. billion) acquisition of Actavis during the fourth quarter of this year. Speaking as Alliance Boots posted group sales up by 12.5% to Having recently created aglobal integration management office £25.4 billion (US$39.5 billion) for the year ended 31 March 2012 under the leadershipofMarc Lehnen (Generics bulletin,18May –comprising £7.67 billion from health and beauty retailing, £16.8 2012, page 24), Watson hosted the meeting near its headquarters in billion from wholesaling, and the remainder from joint ventures and Parsippany, NewJersey. It focused on “defining the strategies necessary minority holdings –Alliance Boots’ executive chairman, Stefano Pessina, to combine our commercial operations,human resources, finance, legal had insisted that big deals in Europe were no longer possible. If the and information-technology teams to ensure that these functions are companywanted to be truly global, he said, it needed to gain scale prepared for the first day of operation as acombined organisation”. in the Americas and Asia through partnerships and mergers. “Wewill then move into more tactical planning, based on the Following closure of the initial deal, the owners of Alliance Boots strategies defined in the first series of meetings,”the twofirms stated. –the private-equity firm KohlbergKravis Roberts (KKR) and Alliance Subsequent integration meetings will focus “more directly on specific Santé Participations, acompanyindirectlyowned by Pessina –will segments within each company”, such as research and development, hold around 10% of Walgreens’ shares. KKR and Alliance Santé paid business development and particular commercial regions. G £11.1 billion to takeAlliance Boots private in 2007. G

IN BRIEF IN BRIEF AMGEN has completed its acquisition of more than 99% of the shares MEDICHEM said its 8,800 sq mactive pharmaceutical ingredients of privately-held Turkish injectables specialist Mustafa Nevzat (APIs) facility in Hal Far, Malta, had passed an inspection by the (MN) Pharmaceuticals.The US$700 million deal wasannounced US Food and Drug Administration (FDA) with no ‘Form 483’ twomonths ago (Generics bulletin,4May 2012, page 3). G observations. The plant started operating in 2005. G

29 June 2012 GENERICS bulletin 3 Gen 29/6/12 Pgs.2-9_Layout 1 27/06/2012 19:55 Page 4

COMPANY NEWS

ANNUAL RESULTS ANNUAL RESULTS Lansoprazolehelps India’s JB sees sales Chemiphar advance decline by atenth

igher sales of the proton-pump inhibitor lansoprazole and elling its OTCbusiness in Russia and the Commonwealthof Hcontributions from recently-launched products helped Nippon SIndependent States (CIS) last year led sales by India’sJBChemicals Chemiphar to achieve its goal of registering double-digit growth in &Pharmaceuticals to drop by atenth to Rs8.02 billion (US$145 million) generics sales during the Japanese firm’sfinancial year ended 31 March in its financial year ended 31 March 2012. Calling the divested 2012. Total generics turnoverahead by 10.7% to ¥20.1 billion (US$251 operations –for which Johnson &Johnson paid Rs9.39 billion (Generics million) included lansoprazole sales that advanced by 9.4% to ¥1.50 bulletin,10June 2011, page 10) –a“significant part of the company’s billion, offsetting lower sales of pravastatin and voglibose. business”, JB also noted that its pre-tax profits had more than halved Turnoverfrom Chemiphar’sbest-selling generic, amlodipine, grew to Rs829 million following the transaction. That figure excluded an by 6.5% to ¥2.86 billion. Amlodipine equated to atenth of group sales exceptional gain of Rs7.61 billion from selling the OTCbusiness in that increased by 4.2% to ¥28.5 billion as “fierce competition” depressed Russia and the CIS. turnoverfrom the firm’s‘core brands’ such as Uralyt (potassium citrate) Nevertheless, JB said it wasgaining “good traction” in export and Soleton (zaltoprofen) by 6.5% to ¥5.75 billion (see Figure 1). markets such as Africa, Asia, Australia, Europe and the Middle East, The firm’sgenerics growth wasdrivenbysales to pharmacies as the company’ssales outside of India grewbymore than athird. increasing by 13.8% and accounting for two-thirds of the company’s Focusing on contract-manufacturing would enable the firm to “build total generics turnover. asustainable revenue stream with acontinued focus on niche branded generics” in its export markets, whilst JB also said it wasbuilding Achieved double-digitgenerics growth up its prescription salesforce in Russia and the CIS. While the Japanese firm missed its annual target of raising group Meanwhile, the firm said it had been “encouraged by success in turnoverby6.4% to ¥29.1 billion, it achievedits “top priority” of the US” –where sales almost doubled during the year –and planned to recording double-digit generics growth (Generics bulletin,1November file between eight and 10 abbreviated newdrug applications (ANDAs) 2011, page 4). Chemiphar also exceeded its expectations by improving annually.But domestic formulations sales that rose by 18% remained its operating profit by 46.2% to ¥2.92 billion as it sold more generics “the growth driverfor the business” as the companyplaced greater that it developed itself rather than purchased from third parties. The firm focus on smaller cities and rural areas, JB observed. G cut its research and development spending by 4.7% to ¥1.79 billion. In its current financial year ending on 31 March 2013, Chemiphar plans to invest ¥2.20 billion in research and development, an increase of 6.9%. The firm expects to improve its operating profit by almost a fifth to ¥3.50 billion. Group turnoverisset to rise by 12.2% to ¥32.0 billion, drivenbya21.6% growth in generics sales to ¥24.4 billion. Launches this month of losartan, paroxetine and zolpidem –as well as of pioglitazone as both standard and orally-disintegrating tablets –will help to fuel the generics uplift, as will introducing anastrozole, mosapride and olopatadine in December. In the longer term, Chemiphar intends to expand into other Asian countries, including China, to offset slowing growth in its domestic market. The Japanese companyplans to offer both pharmaceutical and diagnostic products. By its financial year ending March 2015, Chemiphar wants to achieve agroup turnoverof¥40 billion, three- quarters of which will come from its domestic generics business. G

Annual sales Change Proportion (¥ millions) (%) of total (%) Amlodipine 2,864 +6.5 10 Lansoprazole 1,496 +9.4 5 Pravastatin 1,347 -1.1 5 Voglibose 1,086 -5.4 4 Others13,290 +14.8 47 Generics 20,083 +10.7 70 Core Brands 5,746 -6.5 20 Others 2,684 -12.6 10 Nippon Chemiphar 28,513 +4.2 100

Figure1:Breakdown of sales by Nippon Chemiphar in its financial year ended 31 March 2012 (Source –Nippon Chemiphar)

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COMPANY NEWS

BUSINESS STRATEGY MERGERS&ACQUISITIONS JHP launches division Paladincloses in on to market injectables stakeinSA’sLitha

terile injectables specialist JHP Pharmaceuticals has introduced anada’sPaladin Labs’ plan to takealeading minority stakeinSouth S“a range of products in avariety of therapeutic areas” in the US CAfrica’sLitha Healthcare has movedastep closer to completion after launching its dedicated JHP Generics division amid ongoing after the deal wasapprovedbyLitha’sshareholders. injectables shortages. The NewJersey-based firm –which already The R590 million (US$70.0 million) transaction –which was markets brands such as Aplisol (tuberculin), Brevital (methohexital) announced in late-February (Generics bulletin,9March 2012, page 4) and Dantrium (dantrolene), and operates acontract-manufacturing –isexpected to close on 2July,provided South Africa’sCompanies business –said its generics business wasinitially offering 13 acute-care and Intellectual Property Commission (CIPC) approves. stock-keeping units (SKUs) in areas such as anaesthetics, anti- The complexdeal will see Paladin first acquire the 55.01%ofits infectives, gastroenterology and women’shealth. South African affiliate Pharmaplan that it does not already own. Litha Launching the generics division waspart of astrategy to “expand will then takeownership of Pharmaplan and merge it with its own the business through the establishment of additional growth platforms”, Pharma division. Former Pharmaplan head Dr Gert Hooglandwill take JHP stated, adding that its generics business had “a strong pipeline the helm at the merged operation. with several newproducts launchingthroughout the course of 2013 and Litha will takeownership of Pharmaplan in exchange for R125 beyond”. The firm –which has just started an US$8 million laboratory million in cash and an issue of more than 169 million shares worth expansion at its sterilesfacility in Rochester,Michigan –said these R465 million. This will result in Paladin holding a44.52% stakein launches would “contribute towards addressingmarket shortages in Litha, which it will seek to raise to 49.09% through an offer to Litha’s the acute care and oncology segments”. G minority shareholders. Noting that Pharmaplan had “an enviable market position in the private specialist and niche generics markets”, Litha’schief executive MERGERS&ACQUISITIONS officer,Selwyn Kahanovitz, said the partnership with Paladin would “be akey driverinincreasing deal flowand future product acquisition”. Merging Pharmaplan’sportfolio with Litha’sproducts would CeteroassumesPRACS name complement the South African firm’sgenerics and OTCbusinesses, roubled US contract research organisation (CRO) Cetero Research Kahanovitz added, while the companywould also gain access to research Thas been renamed PRACS Institute after its takeoverbyaninvestor and development pipelines that would improve its ability to expand group led by Freeport Financial.The investors have brought in former into newmarkets including biogenerics. Cetero employee James Carlson as chief executive officer of PRACS Boosted by acquisitions of companies including South African Institute, which will be based in Fargo, North Dakota. John Pottier has generics player GoldexHealthcare, Litha increased its turnoverby joined from Worldwide Clinical Trials as executive vice-president almost two-fifths to R1.75 billion last year (Generics bulletin,6 of business development. April 2012, page 4). Cetero had sought authorisation for restructuring through a Paladin’sinterim president and chief executive officer,Mark ‘Chapter 11’ filing with aUSbankruptcycourt. This came after the US Beaudet, said the Canadian firm would become “a formidable Food and Drug Administration (FDA) ordered it to re-conduct or audit competitor for the long run on the African continent”. G several studies due to issues with timekeeping and preparation of samples (Generics bulletin,4May 2012, page 3). G BUSINESS STRATEGY ANNUAL RESULTS InnoPharma secures funding Indoco sees exports expand S-based sterile products specialist InnoPharma has secured US$8 Umillion in funding to support its development pipeline of generic trong demand for ophthalmic drugs such as latanoprost helped and innovative injectable and ophthalmic drugs. SIndia’sIndoco Remedies to raise its sales from formulations exports The NewJerseyfirm’spresident and chief executive officer, by 31.0% to Rs1.86 billion (US$32.5 million) in its financial year Navneet Puri, said the loan facility from Comerica Bank and NXT ended 31 March 2012. Exports to ‘regulated markets’ rose by 34.5% to Capital Venture Finance provided “the financial flexibility to support Rs1.50 billion, while sales to ‘emerging markets’ grewby18.1% to the company’scontinued growth and to accelerate advancement of key Rs360 million. These latter sales made up athird of group turnover products in our development programme”. that advanced by 16.9% to Rs5.60 billion. InnoPharma’spipeline includes “small molecules with solubility Exports of active pharmaceutical ingredients (APIs) rose by 9.1% and stability challenges, as well as difficult-to-produce and difficult-to- to Rs163 million as Indoco struck amarketing and distribution deal characterise polypeptides and carbohydrates”. The privately-held with DSM (Generics bulletin,17February 2012, page 21). The Indian company’sresearch and development centre in Piscataway, NewJersey, firm’sdomestic API sales shot up by 31.0% to Rs193 million, while can handle potent and cytotoxic molecules. turnoverfrom Indian formulations wasatenth higher at Rs3.38 billion Having secured its first approvalfrom the US Food and Drug as the companylaunched acardiology and diabetology division. Administration (FDA) in early 2010 with ageneric version of Pfizer’s Indoco –which has alliances with firms including Aspen and Corvert (ibutilide fumarate)cardiovascular drug, InnoPharma last year Watson –saw higher staffand finance costs reduce its pre-tax profit secured FDAclearance for products including injectable forms of by almost atenth to Rs513 million. G levetiracetam and olanzapine. G

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COMPANY NEWS

ANNUAL RESULTS ANNUAL RESULTS Exports carry Ipca Sumatriptan raises to a24% sales rise Russia’s Veropharm

37% leap in export sales enabled Ipca Laboratories to report a24% lmost doubling its sales of the migraine drug Amigrenin Aadvance in group turnovertoRs23.4 billion (US$422 million) in A(sumatriptan)helped Russia’sVeropharm to raise its group turnover the Indian company’sfinancial year ended 31 March 2012. Turnover by 17.7% to RUR6.35 billion (US$195 million) last year. from Ipca’sexports “to over110 countries” amounted to Rs14.0 billion, Amigrenin became the firm’sfourth-largest Prescription brand or three-fifths of the firm’stotal sales. with sales ahead by 91.9% to about RUR250 million. It accounted for Having last year secured clearance from the UK’sMedicines and 5.6% of Prescription turnoverthat rose by 18.4% to RUR4.46 billion. Healthcare products Regulatory Agency(MHRA) for its oral solids Veropharm’stop-fivePrescription brands made up aquarter of facility in Pithampur,Madhya Pradesh (Generics bulletin,8April group turnoverwith combined sales of RUR1.58 billion. Cerepro 2011, page 10), Ipca increasedits formulations export sales by 44% (choline alfosterate) led the waywith a30.1% sales rise to around RUR425 million, although Irunine (itraconaozle) closed the gapwith Business Annual sales Change Proportion 51.8% growth to approximately RUR375 million. Geptor (ademetionine) (Rs millions) (%) of total (%) and Doxorubicin-Lens together contributed about RUR530 million. Exports 9,961 +44 43 During 2011, the Russian companyintroduced a75ml version India 7,534 +8 32 of doxorubicin 2mg/ml, along with newdosages of epoetin beta, Formulations 17,496+26 75 fludarabine, mycophenolate mofetil and zoledronic acid. The firm also introduced the Bergolak (cabergoline), Mielastra (filgrastim), Exports 4,058 +22 17 Osteover(calcitonin) and Vero-Netilmicin brands. India 1,439 -1 6 Sales of Xilen (xylometazoline) up by almost afifth lay behind APIs 5,497 +15 23 Veropharm’sOTC turnoverrising by 15.6% to RUR815 million. Sales Other 430 –2of adhesive bandages and cosmetics increasedby19.3% to RUR1.05 Ipca 23,423 +24 100 billion, butthe firm’sturnoverfrom ‘traditional’ drugs such as dexamethasone slumped by 41.3% to RUR29 million. The Russian firm Figure1:Breakdown by business and region of Ipca Laboratories’ sales in its generated all but2.4% of its group turnoverinits domestic market. financial year ended 31 March 2012 (Source –Ipca) Adecline of just overtwo percentage points in Prescription gross to Rs9.96 billion. The Indian firm’sdomestic formulations sales rose margin to 69.3% dragged down the group margin by 1.5 points to 68.1% by 8% to Rs7.53 billion as its total turnoverfrom finished-dose products (see Figure 1). But Veropharm improvedits operating profit by 23% improvedby26% to Rs17.5 billion (see Figure 1). to RUR1.87 billion and its pre-tax profit by athird to RUR1.95 billion. G Total turnoverfrom Ipca’sactive pharmaceutical ingredients (APIs) increased by 15% to Rs5.50 billion, even including a1%domestic dip Product Annual sales Change Gross to Rs1.44 billion. API exports rose by 22% to Rs4.06 billion after the segment (RUR millions) (%) margin (%) Indian group incorporated bulk-drug producer Tonira Pharma. Prescription 4,455 +18.4 69.3 Midway through its financial year,Ipca strengthenedits contract- OTC815 +15.6 73.8 manufacturing operations by paying £4.60 million (US$7.10 million) for Traditional drugs 29 -41.3 43.7 the UK’sOnyxScientific (Generics bulletin,2September 2011, page 8). Bandages/Cosmetics 1,049 +19.3 59.4 Ipca’searnings before interest, tax, depreciation and amortisation (EBITDA) improvedby37% to Rs5.13 billion. The firm’sEBIT – Veropharm 6,348 +17.7 68.1 excluding aRs527 million exchange-rate loss –advanced by 40.3% Figure1:Breakdown by product segment of Veropharm’s sales and gross margin to Rs4.58 billion. G in 2011 (Source –Veropharm)

29 June 2012 Issue 174 Subscription enquiries: Asubscription to Te rms &Conditions: No partofthis publication may GENERICS bulletin includes the hard-copy be copied, reproduced, stored in aretrieval system, Editor: Aidan Fry newsletter published 20 times ayear –twice distributed or transmitted by anymeans, including Assistant Editor: David Wallace monthlyexcept monthlyinJuly, August, December electronic,mechanical, photocopying or recording, without Assistant Editor: Matt Stewart and January–and the weeklyelectronic newsflash the prior written permission of the publisher,orunder the Associate Editor: Deborah Wilkes News@Genericsbulletin published 46 times a terms of alicence issued by the Copyright Licensing year.Annual subscriptions in Europe cost £560 Agency (CLA) in London, UK, or rights bodies in other Production Controller: Debi Minal (additional copyatthe same address £345); outside countries that have reciprocal agreements with the CLA. Subscriptions and Europe £590 (£375). Single copies cost £50 each. Marketing Manager: ValDavis Enquiries as left, or [email protected]. Neither maythis publication be exported, distributed or EditorialDirector: MikeRice circulated by anymeans outside the staff who work at the Advertising enquiries: Editorial enquiries: GENERICS bulletin, address to which it is sent by the publisher without the As left, or [email protected] prior written permission of the publisher. 4Poplar Road, Dorridge,Solihull, West Midlands B93 8DB, UK. Printed by Warwick Printing CompanyLimited, While due carehas been taken to ensurethe accuracy of Leamington Spa CV31 1QD, UK. Website: www.generics-bulletin.com information contained in this publication, the publisher Te l: +44 (0)1564 777550 ©OTC Publications Ltd. All rights reserved. makes no claim that it is free of errorand disclaims any Fax: +44 (0)1564 777524 ISSN 1742-0784 liability whatsoeverfor anydecisions or actions taken as a E-mail: [email protected] Companyregistered in England No 2765878. result of its contents.

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COMPANY NEWS

FIRST-QUARTERRESULTS ANNUAL RESULTS Grindeks’ sales rise Exports and oncology despite fall in APIs aredrivers for Natco

alling sales of active pharmaceutical ingredients(APIs) failed to 37% increase in export sales helped Natco Pharma to raise its group Fprevent Grindeks from growing in the first quarter of 2012, as the Aturnoverby15% to Rs5.56 billion (US$100 million) in its financial Latvian company’sturnoveradvanced by 13.9% to LTL15.9 million year ended 31 March 2012. With sales of Rs1.83 billion, exports (US$28.7million). This came despite API sales slipping by 6.5% accounted for athird of the Indian firm’stotal. to LTL1.45 million. Grindeks blamed the API slide on customers Introducing the breast-cancerdrug anastrozole in the US and shifting deliveries to the second half of the year. launching its Bendit (bendamustine) leukaemia treatment in India at a Meanwhile, sales of final dosage-forms grewby16.4% to 92% discount to Astellas’Treanda original helped to raise Natco’ssales LTL14.5 million, with the majority of these sales coming from Russia, of oncology drugs by 22% to Rs1.48 billion. the Commonwealth of Independent States (CIS) and Georgia. Turnover Hyderabad-based Natco recently created headlines around the world from these three markets rose by 18.3% to LTL12.3 million, whilst the by securing acompulsory licence in India to produce an alternative to Baltic states and Europe contributed the remainder with combined Bayer’sNexavar (sorafenib) brand for treating liverand kidneycancer sales that rose by 6.8% to LTL2.19 million. (Generics bulletin,23March 2012, page 17). Last year,the Indian Having completed “essential work on product portfolio assessment” firm struck adeal to acquire three oncology monoclonal antibodies in the first quarter –after making a“top priority” expanding its range –bevacizumab, rituximab and trastuzumab –aswell as the autoimmune for 2012 (Generics bulletin,23March 2012, page 8) –Grindeks said treatment etanercept from Mabxience, the biosimilars division of it nowhad “a clear vision of product development for the next 10 Chemo Lugano (Generics bulletin,1November 2011, page 12). years”. The companyisinvesting atotal of LTL1.28 million in a However, Natco has just suffered asetback in its attempts to bring manufacturing unit for ethanol-based gels and ointments in Riga, Latvia, arivaltoTeva’s Copaxone (glatiramer acetate) to the US market through that will help to extend the firm’sproduct range, whilst it is also an alliance with Mylan (see front page). developing four APIs to add to the 22 currently offered by the firm. Natco’stotal formulations sales climbed by 22% to Rs2.82 billion, The Latvian company’sbulk-drug portfolio includes oxytocin, while its turnoverfrom active pharmaceutical ingredients (APIs) shot tegafur and zopiclone, while its keyexport markets for APIs are up by 40% to Rs1.48 billion. The Indian companyincreased its pre- Germany, Japan, the Netherlands and the US. G tax profit by 22% to Rs795 million. G

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COMPANY NEWS

ANNUAL RESULTS IN BRIEF CHENGDU SHENGNUO has passed an inspection of its bulk Jubilant rejoices as peptides facility by the US Food and Drug Administration (FDA) with no ‘Form 483’ observations. Shenguo is collaborating with its exclusive regulatory and sales agent, ChemWerth, to develop 10 peptide active pharmaceutical ingredients (APIs), including bivalirudin, generics leap ahead eptifibatide and exenatide.

ore than doubling sales through its Generics business unit on CFR PHARMACEUTICALS –the Chilean branded generics and M“newlaunches, better pricing and demand for current niche injectables supplier –said acquiring Canada’s Uman Pharma products” enabled Jubilant Life Sciences to increase its group turnover helped it to increase its turnoverby15.4% to US$122 million in the by 24% to Rs42.8 billion (US$768 million) in the Indian firm’sfinancial first quarter of this year.The Chilean firm’sdomestic sales rose by year ended 31 March 2012. That total wassplit almost equally between 5.9% to US$33.7 million, while its turnoverinPeru increased by Jubilant’sPharmaceuticals and Life Science Ingredientsdivisions. 12.2% to US$25.5 million. Sales in Argentina advanced by 13.9% “With about 50% assets outside India, Jubilant is nowtruly to US$23.2 million. The Chilean company–which is spending transformed into aglobal life sciences company,”stated the firm. US$20.8 million on a50.0% stakeinIndian injectables specialist Generics sales shot up by 161% to Rs5.37 billion as Jubilant Stellence Pharmscience –said selling, general and administrative started supplies to Japan. As of 31 March 2012, the firm held approval expenses up by athird to US$70.3 million had halved its pre-tax for 19 of the 48 abbreviated newdrug applications (ANDAs) it had profit to US$15.7 million. filed in the US, while all butfour of the 35 dossiers it has submitted in the European Union (EU) have been approved. At present, the HOVIONE raised its turnoverinthe year ended March 2012 by 24% Generics unit markets 11 products in the US and nine in Europe. to US$180 million, marking its “sixth consecutive year of sales growth”. “The Generics business commanded better margins due to The Portuguese active pharmaceutical ingredients (APIs) firm said it leadership positions in niche products,”stated Jubilant, which claims to had passed several facility inspections during the 12-month period be aleading supplier of meclizine, methylprednisoloneand terazosin. as it took steps to “strengthen its ability to serveinnovators and Active pharmaceutical ingredients (APIs) sales ahead by athird to consolidate its leadership in off-patent contrast agents”. to Rs4.48 billion were “drivenbynew launches in sartans, donepezil in the US and olanzapine in Europe”. Adding irbesartan and valsartan IND-SWIFT LABORATORIES increased its turnoverby36.3% to to its bulk-drugs portfolio increased utilisation of the sartans facility Rs14.3 billion (US$250 million) in its financial year ended 31 that the Indian companycommissioned in its previous financial year. March 2012.Evenwith staffcosts 43.0% higher at Rs286 million, As of March 2012, Jubilant had submitted 58 drug master files (DMF) the Indian company–which recently struck adeal with Wockhardt in the US, and had made 29 similar filings in the EU. to market atorvastatin tablets in the UK –improvedits earnings Turnoverfrom contract manufacturing –such as for sterile before interest and tax (EBIT) by 20.8% to Rs1.72 billion. Ind-Swift injectables –climbed by 17% to Rs6.21 billion (see Figure 1). Sales recently raised Rs96.6million (US$1.69 million) to expand its through Jubilant’sSpecialty Pharma allergy and radiopharmaceuticals Indian facilities in Derabassi, Jammu and Mohali. unit rose by aquarter to Rs3.11 billion, while the Drug Discovery & Development Solutions division increased its turnoverby16% to Rs2.44 DSM SINOCHEM has officially opened afacility in YuShu, China, billion. The small Healthcare unit added Rs140 million to total turnover that produces the betalactam intermediate 6-APA. The partners had by the Pharmaceuticals division that climbed by 41% to Rs21.8 billion. begun constructing the plant to makethe keyintermediate for semi- Greater vertical integration and astronger product mix gave the synthetic penicillins in 2010. The Netherlands’ DSM Anti-Infectives Generics unit an earnings before interest, tax, depreciation and and China’sSinochem formed a50/50 joint venture last year. amortisation (EBITDA) margin of around 27%, helping to lift the Pharmaceuticals margin by 16 percentage points to 26.7%. The group’s OLAINFARM said acquiring pharmacies in its domestic market, Latvia, EBITDAmargin strengthened by 4.4 points to 20.9%, butJubilant’s towards the end of 2011 contributed LTL1.6 million (US$3.02 million) pre-tax profit halved to Rs1.14 billion due to Rs3.49 billion of exceptional to the firm’ssales in the first three months of this year.This helped items. These included Rs200 million for discontinuingcertain generic quadruple its domestic turnovertooverLTL2 million and contributed development projects and aRs1.50 billion goodwill-impairment charge to an overall sales rise of 48% to LTL12.1 million. Olainfarm as the group’sclinical-trials business, Jubilant Clinsys, struggled. G acquired 30 pharmacies in its domestic market last year by purchasing local firms Ilmas Aptiekas and Juko99(Generics bulletin,18 November 2011, page 14) as well as four other retailers (Generics Annual sales Change Proportion bulletin,13January 2012, page 10). The firm plans to rebrand all of (Rs millions) (%) of total (%) these outlets under the name ‘LVAptieka’, and aims to increase Contract Manufacturing 6,210 +17 15 its number of pharmacies to between 50 and 60 by the end of 2012. Generics 5,370 +161 13 APIs 4,480 +33 10 VETTER –the German contract manufacturer –isbuilding afilling Specialty Pharma 3,110 +25 7 line for pre-filled syringes at its facility in Ravensburg, Germany. The line will be able to handle batches of up to one million units per day. Development Solutions 2,440 +16 6 Healthcare140 +17 – AANJANEYALIFECARE said it had increased its turnoverby49.9% Pharmaceuticals 21,750 +41 51 to Rs4.80 billion (US$84.2 million) in its financial year ended March Life Science Ingredients 21,030 +11 49 2012. The bulk-drugs and finished-dose supplier –which recently acquired fellowIndian firm ApexDrugs &Intermediates (Generics Jubilant Life Sciences 42,780 +24 100 bulletin,17February 2012, page 5) –improvedits pre-tax profit Figure1:Breakdown of Jubilant Life Sciences’ sales –rounded to the nearest by 15.4% to Rs630 million. G Rs10 milion –inits financial year ended 31 March 2012 (Source –Jubilant)

8 GENERICS bulletin 29 June 2012 Gen 29/6/12 Pgs.2-9_Layout 1 27/06/2012 19:55 Page 9

MARKET NEWS

MARKET RESEARCH REGULATORY AFFAIRS CGPAcites savings GPhA hails passage of C$8bn for Canada of user-fee package

ore than C$8 billion (US$7.75 billion) wassaved from Canada’s final version of legislation setting out aframework governing Mhealthcarespending in 2011 through using generics, according Auser fees for generics and biosimilars in the US has been approved to IMS data cited by the Canadian Generic Pharmaceutical Association by Congress. The agreed final text is acompromise between versions (CGPA). “Generic prescriptionmedicines were dispensed to fill more of the legislation recentlypassed by the country’sSenate and House than 60% of all prescriptions in Canada, yet accounted for less than of Representatives(Generics bulletin,8June 2012, page 14). 25% of the C$22 billion Canadians spent on prescription drugs in 2011,” Applauding the House and Senate for the “remarkable effort and the association pointed out. bipartisancooperation theyhaveshown throughout this process”, the The figures showed that generics provided “excellent value for US Generic Pharmaceutical Association’s(GPhA’s)president and Canadians”, said the CGPA’spresident, Jim Keon. The average price chief executive officer,Ralph Neas, called on President Barack of abrand-name prescriptioninCanada wasC$73.76, he observed, Obama to “quickly sign the user-fee legislation into law”. whilst for ageneric prescription the figure wasC$25.04. As generics Under the Food and Drug Administration Safety and Innovation firms invested in the research, development and litigation necessary Act (FDASIA), industry will pay US$299 million in small-molecule to bring newgenerics to market, Keon insisted, Canada should take user fees annually for five years from 1October 2012, with the “the next step” of ensuring the sustainability of drug-benefit plans figure adjusted for inflation each year.Neas said this would give by increasing the use of generics. the FDA’sOffice of Generic Drugs (OGD) additional resources and Forevery percentage-point increase in generic drug utilisation would “ensure all participants in the US generic drug system –whether in Canada, Keon noted, Canadians savedanadditional C$262 million. US or foreign-based –comply with our country’sstrict quality Meanwhile, private sector payers savedC$140 million with each 1% standards”. Aportion of the user-fee income is to be dedicated to increase. If the country’sgeneric dispensing rate in 2011 had matched helping the FDAinspect overseas facilities more regularly. that of the US –where generics filled 80% of prescriptions –Canada Aseparate set of tariffs covers fees payable to the FDAbyfirms could have saveduptoanadditional C$3 billion, Keon pointed out. that are developing and seeking approvalfor biosimilardrugs. However, the CGPAwarned that Canada’ssavings could be “wiped Commending Congress for “addressing in the user-fee legislation out” by European Union (EU) proposals to prolong market exclusivity the unintended consequences of the 30-month forfeiture provision as part of atrade agreement. The associationclaims the deal would in the Medicare Modernization Act of 2003”, the GPhA also noted add C$2.8 billion to annual drug costs and delay generic entry by an that measures included in the legislation to “prevent abuse of the FDA’s average of 3.5 years (Generics bulletin,4March 2011, page 16). citizen petition process” would “greatly improve the safety of our Meanwhile, the CGPAhas welcomed plans to construct asecond nation’sdrug supply and expedite consumer access to generic drugs”. bridge between Windsor,Ontario and the US city of Detroit, Michigan However, the association acknowledged that some of the elements as “a critical step forward in ensuring faster and more reliable border it had backed –such as language passed by the Senate regarding crossings” that would improve the speed at which Canadian products restricted-accessdrugs, as well as proposals for increasing the can enter the US. G security of the drug supply chain –had not been included in the final legislation. Nevertheless, the GPhA said it was“encouraged by the progress made on these important issues”. PRICING&REIMBURSEMENT Among the proposed amendments that were omitted from the final act wasamove by Senator JeffBingaman that would have allowed anygenerics firm that successfully challengedapatent to launch SpectrumK starts next tender immediately with sole or shared exclusivity,regardless of whether it pectrumK, the group of 84 health insurance funds that coveraround held first-to-file status (Generics bulletin,9December 2011, page 19). S9million Germans, says it will publish in early August its fourth Also left out wasabid to stop originators using risk evaluation and tender round in the European Union’s Official Journal.Supply contracts mitigation strategies (REMS) to block access to the product samples for around 40 “newactive ingredients” –aswell as for anymolecules that were needed during generic development projects. G excluded from earlier tenders on economic grounds –will start on 1 January next year.Atotal of 131 contracts awarded during SpectrumK’s third round –which covered 56 active ingredients –began on 1May INTELLECTUAL PROPERTY this year (Generics bulletin,23March 2012, page 11). Meanwhile, Stada claims it was“very successful” in the second Chinese can overide patents round of tenders run by the Barmer-GEK fund that insures about 8.5 million Germans. The German firm said it had secured 13 of the 64 hina has overhauled its patent laws to allowits domestic companies exclusive supply contracts starting on 1August. Cto makegenerics of patented medicines under compulsory licences. Torrent’sHeumann/Heunet operation ranked second with nine The newlegislation provides for granting such licences in national exclusive supply contracts, followed by Mylan Dura and the Sandoz emergencies and extraordinary circumstances, or when such amove group, each with seven. Aurobindo and Sanofi’sWinthrop each secured would be in the public interest. deals to supply five active ingredients to the fund on an exclusive basis. The move by China’sState Intellectual-Property Office comes Teva/Ratiopharm wonthree awards from Barmer-GEK, as did within weeks of Indian authorities having granted acompulsory licence local player Aristo Pharma. Sweden’sBluefish and Krka’sTad Pharma to local firm Natco. The Indian companysaid it could supply arival were both successful with bids for twomolecules.Eight companies of Bayer’sNexavar (sorafenib) cancer drug at a97% discount to secured contracts to supply asingle molecule. G the original (Generics bulletin,23March 2012, page 17). G

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MARKET NEWS

FREE-TRADE AGREEMENTS GENERIC SUBSTITUTION Canadawelcomes French body blames TPP talks invitation doctors for rate slide

formal invitation receivedbyCanada to join negotiations on aTrans- rench doctors marking prescriptions as ‘non-substitutable’ are APacific Partnership (TPP) free-trade agreement has been welcomed Fresponsible for the country’s generic substitution rate falling to a by the Canadian Generic Pharmaceutical Association (CGPA). Noting “newlow”of67.7% of eligible prescriptions in March 2012, according that the Asia-Pacific region was“an important source of pharmaceutical to France’sgenerics industry association, Gemme. This compared to inputs and other rawmaterials for Canadian-made generic medicines”, around 76% of eligible prescriptions being substituted for ageneric the CGPAadded that the region wasalso “an important export market towards the end of 2008, the associationpointed out. for Canadian generic pharmaceutical manufacturers and presents On average, more than afifth –22% –ofprescriptionsbyFrench enormous potential for export growth”. general practitioners (GPs) were marked as non-substitutable, Gemme However, the CGPAemphasised that its support for Canadian said, citing astudy of 200 GPs carried out by local market researcher participation in the TPP negotiations “does not represent support for BVAinMarch. The figure wasevenhigher for GPs over55years all proposals that have or may be made”. Some intellectual-property old and with alarge patient base, the study found. provisions proposed in the negotiations “would create significant However, French health insurer CNAM said that its ownstudy – delays in the ability of Canadian generic pharmaceutical companies covering 12,000prescriptionsand more than 8,000 pharmaciesacross to develop, manufacture and export newgeneric drugs to TPP member France –had concluded that just 4.2% of prescriptions were marked countries”, the association pointed out. as non-substitutable. The figure varied depending on the molecules prescribed, CNAM noted, with the figure falling as lowas0.8% for No need for moreintellectual-property provisions ibuprofen prescriptions butrising as high as 12.6% for clopidogrel. “Canada’sintellectual-property regime for pharmaceuticals exceeds Of those prescriptions that consisted of more than one substitutable international standards and goes farbeyond the provisions available product, CNAM said, prescriptions which had each line marked as in most TPP countries,”the CGPAinsisted, adding that no new non-substitutable –suggesting a“systematic use” of the mechanism intellectual-property provisions for pharmaceuticals should therefore by doctors –accounted for just 2.6%. be required by Canada to conclude aTPP agreement. “CGPAlooks Nevertheless, Gemme insisted that action must be taken to address forward to working with the government of Canada to ensure the final the problem. The association repeated its call on the French authorities text of the TPP will not create barriers for Canada’sgeneric to launch an information campaign to overcome prejudices and pharmaceutical manufacturers,”the association concluded. misconceptions about generics (Generics bulletin,3October 2011, Last year,Fabiana Jorge of consultants MFJ International warned page 10). Gemme also wants France’sgovernment to encouragemore that adraft text for the TPP “benefits almost entirely the originator prescribing within the répertoire of generic equivalents and restrict industry at the expense of the generics industry and consumers” doctors’ ability to mark prescriptions as non-substitutable. “The (Generics bulletin,18November 2011, page 19). G authorities and CNAM cannot wait anylonger before adopting effective, rapid and fair measures,”Gemme insisted. CNAM admitted that its target of achieving an average substitution rate of 85% for eligible prescriptions by the end of 2012 –recently REGULATORY AFFAIRS agreed with French pharmacist unions –was “ambitious”. Nevertheless, it maintained that the goal wasachievable with the combined effort FDA will shelve old ANDAS of doctors, pharmacists and health insurers. bbreviated newdrug applications (ANDAs) pendingapprovalthat “Drastic price cuts” recently applied to generics –which Gemme Athe US Food and Drug Administration (FDA) has found to be last year labelled as “too high, unfair and unequal” (Generics bulletin, incomplete –and on which the ANDAapplicant has not corresponded 18 November 2011, page 1) –had put at risk French and European with the agencysince 8July 1991 –will be considered withdrawn, production, the association warned. Furthermore, the price reductions unless the applicant informs the FDAinwriting by 13 August that had “not resolved the fundamentalproblem: the insufficiencyof it intends to pursue approval. prescriptions within the répertoire and the excessive use of marking According to anotice that wasrecently published in the US prescriptions as non-substitutable”. Federal Register,the FDAhas identified 364 such inactive ANDAs. In 2011, France’sgenerics market suffered a3%drop in volume Manyofthese are for older antibiotics. G sales to 614 million, whilst value sales grewbyjust 3% to C2.65 billion. Gemme attributed the first annual volume decline since market formation in 1999 to the falling generic substitution rate (Generics bulletin, BIOSIMILARS/REGULATORYAFFAIRS 17 February 2012, page 13). Meanwhile, acampaign launched by French pharmacygroup EvoluPharm is aiming to rebuild consumer confidence in generics in EMA advice requests double the wake of areport by France’sAcademy of Medicine earlier this he number of requests for scientific advice on biosimilars that the year.This had suggested certain generics were “far from equivalent” to TEuropean Medicines Agency(EMA) receivedlast year more than their reference products (Generics bulletin,9March 2012, page 13). doubled to 31, according to the agency’s2011 annual report. The EvoluPharm’scampaign involves sending 600,000 information corresponding number in 2010 was15. The EMA receivedthree leaflets with the title “Don’tfrown at generics –theyare the future of initial-evaluation applications for biosimilars in 2011, having been our health!” to 2,000 of the group’spharmacies. Anine-point guide asked to assess just one dossier for a‘similar biological product’ in explains the nature of generics as well as touching on issues of each of the preceding twoyears. G bioequivalence, quality and pricing. G

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MARKET NEWS

MARKET RESEARCH PRICING&REIMBURSEMENT Brazilian penetration Irish price cuts will breaks 25% barrier save C10mn in 2012

ne in four medicines sold in Brazil between January and March reland expects to save C10 million (US$12.6 million) in 2012 and O2012 wasageneric after unit sales rose by almost aquarter, IC20 million on an annual basis through interim price cuts for off- according to data published by the country’smedicines agency, Anvisa. patent brands agreed between the country’sHealth Service Executive Calling the penetration figure of 25.4% “a historicallandmark”, Brazil’s (HSE) and the Irish Pharmaceutical Healthcare Association(IPHA). generics industry association, Pró Genéricos, predicted that generic Upon market entry of the first generic equivalent, an off-patent penetration could reach 30% by the end of 2012 after local patents brand will immediately have its price reduced by 30%. Previously – expired for products such as ziprasidone and sirolimus. under an agreement that expired at the start of March –the initial price Pró Genéricos also noted that sales in the first quarter had increased cut had been just 20% followed by afurther 15% cut after 22 months. in value by more than athird to R$2.4 billion (US$1.22 billion), or Forthose products that had already undergone a20% cut under the old 23.5% of the Brazilian medicines market by value. Generics prices scheme, butwere still waiting for the subsequentreduction, the were on average 52% less than the equivalent brands, the association Department of Health (DoH) said an immediate 10% cut would apply. claimed, with this figure rising to 85% for certain products. The latest price cuts had been accepted “in advance of further However, Pró Genéricos insisted that generic penetration could discussions with IPHA which are expected to delivermore significant have been even higher if products had been registered more quickly. savings to the Irish patient and taxpayer”, according to the DoH. Claiming that the number of generics registered in Brazil last year Earlier this year,the DoH said introducing reference-pricing and had grown by almost athird, the association’spresident, Odnir Finotti, generic substitution in 2012 would enable Ireland to save C30 million said more generics could have been sold if the delay in registering by 2014 (Generics bulletin,13January 2012, page 16). Under products had been shorter.Hetherefore urged Anvisa to prioritise proposals published last year,Irish pharmacists would be allowed to reviewing rivals to brands that had no generic competition. substitute medicines designated as interchangeable within the same Meanwhile, Finotti pointed out, the profile of Brazil’stop ten reference-price group, with reference prices set at the lowest available generics by volume waschanging. Analgesics and antibioticswere from all potential suppliers.The HSE also plans to save around C10 beginning to makeway for treatments of more complexconditions, such million annually through further price cuts for generics, on top of as erectile dysfunction, hypertension and high cholesterol, he stated. G reductionsimplemented in August 2011. G

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18TH EGA CONFERENCE

PRICING&REIMBURSEMENT FALSIFIEDMEDICINES Industrymust make EGA warns of threat case moreforcefully from API shortages

urope’sgenerics industry has not been aggressive enough in warning ncertainty overEuropean measures that will from 2July 2013 Ethat pricing pressures and regulatory burdens are threateningthe Urequire countries outside of the European Union (EU) to supervise sustainability of companies that supply half of the continent’smedicines, and authorise exports to the region of active pharmaceutical ingredients according to apanel of leading industry executives. (APIs) could threaten European API supplies,according to the European Speaking during around table that concluded the 18th annual Generic medicines Association’s(EGA’s)senior manager for quality conference of the European Generic medicines Association (EGA), and regulatory affairs, Julie Maréchal-Jamil. Mylan’spresident for Europe, the Middle East and Africa, Didier Barret, Certain countries outside the EU had not yet made clear howthey insisted that “industry does not value its power at the levelitshould intended to address the API export requirements, which are being do”. He wasbacked up Sandoz’ commercial head for western Europe, implemented as part of Directive 2011/62/EU on falsified medicines, Nick Haggar,who said industry’svoice had not been “strong or Maréchal-Jamil told the 18th Annual EGA conference held in Malta. coherent enough” in making the case against tenders and price cuts These countries included China, India, South Korea, Taiwan and Turkey. rather than for initiativestoincrease volume. “Getting India and China on board is essential,”Maréchal-Jamil insisted, pointing out that half of existing marketing authorisations Falsified medicines rules ill-conceived held by EGA members referred only to API suppliers outside the EU. Stada’schief production and development officer,AxelMüller, If these marketing authorisations had to be altered to include an EU- highlighted the cost to industry of implementing ill-conceived regulatory based API supplier,the total cost would come to around C10 million requirementssuch as the European Union’sfalsified medicines directive. (US$12.6million), she stated. Furthermore, no EU-based API supplier Emile Loof –who leads Teva’s Pharmachemie business in the would be available in half of these cases, suggesting that it would Netherlands –said anti-counterfeiting measures and “increasingly takebetween 12 and 18 months to reactivate existing EU capacity. stringent regulatory requirements” were endangering firms’ ability to Stada’schief production and development officer,AxelMüller, control their cost of goods. Having already largely lost control of voiced concern overpossible shortages as aresult of the measures, reimbursement prices, he proposed that industry should push to get drugs suggesting that the industry needed a‘plan B’ in the event that India delisted to relieve the cost pressure. At retail prices of afew euros, most did not comply with the directive’s requirements. However, Maréchal- Europeans could afford to pay for generics themselves, he suggested. G Jamil noted, the timelines for implementing the directive were included within the legislation and would be difficult to alter. European Commissioner for Health and Consumer Policy, John Dalli, said he was“fully aware that parts of industry” –including EGA MARKET RESEARCH members –“are worried that keythird countries such as India or China will not be ready in time to comply with these rules and that this could Returns will requirepatience lead to supply shortages”. However, he insisted the Commission was iosimilar developers may have to wait 15 years or more to see a “very sensitive to this aspect and determined to avoid shortages”. Breturn on their investment, an industry consultant warned delegates “In order to achieve compliance, we need to closely cooperate with to the 18th annual conference of the European Generic medicines the third countries,”heinsisted. G Association (EGA). Frances Cloud, managing director of Pharmacloud, said afinancial model she had developed suggested that industry leader and pioneer Sandoz would have to wait until 2019 for areturn on the MANUFACTURING biosimilarinvestments it had started making in the mid-1990s. Cloud’smodel is based on several assumptions, includingSandoz having spent C250 million (US$312 million) on researchand East African firms seek input development to bring its first three biosimilars –Omnitrope (somatropin), ast African pharmaceutical firms are seeking investment to develop Binocrit (epoetin alfa) and Zarzio (filgrastim) –tomarket. It also Emanufacturing in the region, according to Nazeem Mohamed, includes the impact of anticipated European launches of the monoclonal director of the Federation of East AfricanPharmaceutical Manufactuers antibody (mAb) rituximab, along with pegfilgrastim, in 2015. (FEAPM). Addressing the 18th Annual European Generic medicines Predicting that the size of the European biosimilars market could Association (EGA) conference held in Malta in June, Mohamed told treble to around C1billion by 2017, Cloud presented twovisions of delegates that the region’smanufacturers “would rather get your howbiosimilar mAb markets could develop. technical expertise than your money” as theysought to improve quality Forclinician-led indications requiring extensive marketing support, standards and enhance efficiency. biosimilar mAbs would slowly capture athird of the market by volume, Noting that the combined pharmaceutical markets of Kenya, she forecasted. Discounts would start at 30% to the brand, butwould Tanzania and Uganda were worth around US$1.61billion –including reach 65% by the time the fifth biosimilar entered the market. “Early medical devices and diagnostic equipment –Mohamed said FEAPM entrants will achieve high operating margins and arapid return on had set agoal of raising the proportion of East Africa’s medicines that their investments,”predicted Cloud, “but late entrants and companies were manufactured locally from 20% to 50% overthe next 10 years. with apoor quality image are likely to struggle”. Investors could expect “higher returns than in the west”, he promised. In tender markets, the price of rapid penetration would be discounts Meanwhile, Rich DiCicco, chairman of Harvest Moon of up to 80% of the pre-competition brand price. “The first market entrants Pharmaceuticals, said sub-Saharan Africa offered opportunities for will makeareasonable –albeit declining –return,”Cloud predicted. companies that could offer ‘generic plus’ products that were locally “Late market entrants will only achieve lowornoprofitability.” G manufactured and were unavailable on the black market. G

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18TH EGA CONFERENCE

IN BRIEF PRICING&REIMBURSEMENT MALTA’S GOVERNMENT has approvedreduced fees for the country’s medicines authority to act as reference member state (RMS) in Commission invites decentralised and mutual-recognition marketing-authorisation procedures. “It is hoped that the change in fees will bring about a larger interest by applicants to submit applications to Malta as RMS,” stated the authority.Malta has been acting as an RMS since 2007 market-access data and has led assessment of products including ibuprofen, metformin and ramipril. Speaking at the 18th annual conference of the European ata indicating the cost of delaying the market entry of generics in Generic medicines Association (EGA) in Malta, the authority’schief Dthe European Union (EU) could help the European Commission executive officer,Patricia Vella Bonanno, urged companies to include to negotiate ashorter time limit for pricing and reimbursement Malta as aconcerned member state (CMS) in procedures. Registering decisions, according to Salvatore D’Acunto, head of unit at the more products in Malta would help to alleviate drug shortages, she said. European Commission’sDirectorate-General for Enterprise. Earlier this year,the Commission proposed cutting the duration of national pricing SUBMITTING DATA for a medicines database being compiled by and reimbursement decisions to amaximum of just 30 days for generic the European Medicines Agency(EMA) will cost 30 of the EGA’s medicines from 180 days at present as part of revisions to the EU’s direct-member companies around C13 million (US$16 million).For transparencydirective (Generics bulletin,9March 2012, page 1). the largest firms with up to 25,000marketing authorisations in the Addressing the 18th Annual European Generic medicines European Union (EU), implementing the requirements of Article Association (EGA) conference recently in Malta, D’Acunto urged 57 of pending pharmacovigilance legislation would cost more than companies to submit data indicating the cost of delays to market entry. C2million each, the EGA’s regulatory affairs director,Beata This would be useful when negotiating the 30-day limit with individual Stepniewska, told delegates to the association’sannual conference. member states, he insisted, acknowledging that implementing the The deadline for submitting data is 2July 2012. revisions aimed at accelerating market access was“not something that has been easy” as it might require national reforms. INDUSTRY should work towards developing a“more sustainable Some member states were “not reacting very positively” to the model” for implementing tenders,according to Professor Steven transparencydirective revisions,D’Acunto noted, observingthat the Simoens from Leuven’sCatholic university.Simoens told the 18th Commission had encountered particularopposition from Austria and annual EGA conference that “tendering is not going to go away”, so Luxembourg. The proposed revisions also include more effective industry should ensure: there wasa“solid legalframework”; contracts remedies for appealing reimbursement decisions, as well as an obligation were awarded in atransparentmanner; multiple firms receivedsupply for member states to provide reports on pricing and reimbursement deals for each molecule; contractsran for between six months and a decisions every six months. year; and that products not subject to tender contracts could still be Whilst 2012 would be a“transitional year” for the transparency dispensed, albeit on less favourable terms. Simoens also insisted directive,D’Acunto suggested “the transitional year might be more that there was“no economic rationale” to link the prices of generics important than the final year”. At best, the revised directive would not to those of their reference brands, as this allowed originators to enter into force before the end of 2014, D’Acunto stated, acknowledging maketactical pricing movestohinder competition. “I don’tknow that this wasanoptimisticestimate and the process could last until 2016. of anyother industry that allows your biggest competitor to set When the proposed transparencydirective revisions were announced your price,”hepointed out. earlier this year,the EGA’s director-general,GregPerry,called the proposals “an opportunity to implement certainkey recommendations FRANCE needs to conduct a nationwide study into the extent to of the pharmaceutical-sector inquiry”. which doctors mark prescriptions ‘non-substitutable’, according to Under the Commission’sproposals,member states will have to Laure Lechertier from health insurance group Mutualité Française. designate abody entrusted with the powers to takerapid measures, Speaking at the EGA’s annual conference in Malta, Lechertier pointed including awarding damages and imposing penalty payments. They out that the French generics industry association, Gemme, believed will also have regularly to report their decisionsaswell as the time more than afifth of prescriptions were marketed as non-substitutable, involved, and notify the Commission of draft pricing and reimbursement buthealth insurer CNAM put the figure at barely 4% (see page 10). measures “to facilitate compliance from the beginning”. The proposals also state: “Intellectual property rights should not FIXED DISPENSING FEES for pharmacists rather than price-linked interfere with pricing and reimbursement procedures, as is already the distribution margins are essential if authorities are to preserve case for marketing authorisation procedures.”Furthermore, the pharmacists’ support for pro-generic policies, according to John Chave Commission proposes that “elements already assessed in the framework from the Pharmaceutical Group of the European Union (PGEU). of the marketing authorisation process –quality,safety and efficacy, Representing Europe’spharmacists’ associations during the EGA’s including bioequivalence –may not be reassessed in the framework annual conference, Chave said ongoing generic price cuts threatened to of pricing and reimbursement procedures.” G push pharmaciststoavoid generic substitution for economic reasons. Chave also urged governments that were considering whether to implement tenders to assess the costs of administering such systems. INTELLECTUAL PROPERTY/MANUFACTURING TENDERS are “pure evil” in light of the shortages theycreate and EU needs pre-SPC production the loss of competition theycause, according to Warwick Smith, director-general of the British Generic MedicinesAssociation llowing generics firms to manufacture commercial quantities (BGMA). Smith told delegates to the 18th annual EGA conference Afor export during the term of the originator’s patent-extending that allowing industry only “a minimal margin to survive”would supplementary protection certificate (SPC) would create “a level not fund development of complexproducts such as biosimilars playing field” for European Union (EU) companies to compete in a and respiratory drugs. G global market, according to Edda Eggertsdottir,president of the European Generic medicines Association (EGA). G

29 June 2012 GENERICS bulletin 13 Gen 29/6/12 Pgs.10-14_Layout 1 27/06/2012 19:57 Page 6

MARKET NEWS

DRUG SHORTAGES PRICING&REIMBURSEMENT FDA actions blamed Belgian body boasts for shortages in US price ‘breakthrough’

rug shortagesinthe US have been caused in part by “over-aggressive irms supplying antibiotics and antimycotics to the Belgian market Dand excessive regulatory action” taken by the US Food and Fwill be able to more closely match competitors prices to secure Drug Administration (FDA), according to areport from the US House entry into designated low-priced substitution groups, following the of Representatives’ committee on oversight and government reform. government’sacceptance of changes advocated by local industry Claiming that “FDAregulatory activity has effectively shut down 30% association FeBelGen to the country’sso-called ‘automatic INN’ system. of the total manufacturing capacity at four of America’s largest Calling the latest development a“breakthrough”, FeBelGen said producers of generic injectablemedications: Bedford Laboratories, allowing firms to match the lowest prices would “increase the number Hospira, Sandoz and Teva”, the report said the agencyhad “failed to of companies that are able to supply the market”, as well as leading ensure that ongoing enforcement is conducted in amanner that does to fewer shortages and a“more sustainable market dynamic”. Previously, not create unnecessary shortages”. FeBelGen said, companies submitting prices had been forced to take Of the 219 drugs placed on aUSshortages list, the report stated, a“shot in the dark” without knowing whether their prices would more than half –oratleast 128 –were produced by “at least one qualify for automatic substitution. facility undergoing FDAremediation”. Furthermore, “among shuttered From 1May,pharmacists have treated Belgian prescriptions for manufacturing lines that occurred overthe twoprevious years, the antibiotics or antimycotics as substitutable regardless of whether the committee’sreviewdid not find anyinstances where the shutdown doctor has prescribedbyinternational non-proprietary name (INN) wasassociated with reports of drugs harming consumers”, the report or brand name (Generics bulletin,13January 2012, page 16). An stated, warning that the damage inflicted by the FDA’sdecisions “may equivalent product from adesignated group of low-priced medicines extend well beyond the current drug shortage crisis”. is dispensed, provided that it matches the active ingredient, strength, “When problems that do not pose an immediate threat to public dosage form and pack size of the prescribedproduct. Each group of safety are detected,”the report observed, “directing facilities to make low-priced medicines has amaximum price set at 5% more than the targeted improvements under close supervision of the FDAcan be lowest-price product in the group. And every group must contain at amore appropriateresponse than actions that lead companies to shut least three products, even if some exceed the 5% threshold. down manufacturing lines.”Iturged the agencytoadopt a“common Noting that the details of howthe newmechanism would function sense regulatory approach” that considered the impact its activities were still being discussed, FeBelGen said firms would be able to reduce were having on shortages. their prices before each low-cost group wasestablished. Earlier this Other factors influencing the shortages included increasing market year,FeBelGen claimed that introducing the automatic INN system concentration, group purchasing contracts, and asmall number of would produce annual savings of C2.6 million (Generics bulletin, generic injectables suppliers, the report acknowledged. G 9March 2012, page 12). G

ANTI-COUNTERFEITINGMEASURES MANUFACTURING EU committee rejects ACTA Australia must manufacture he European Parliament should reject adraft multinational Anti- ustralia should adopt public policies that favour pharmaceutical TCounterfeiting Trade Agreement (ACTA), according to the Amanufacturing in the face of competition from Asia, according to parliament’sInternational Trade Committee. Voting 19-12 against Hospira’sAsia-Pacific president, TimOldham. Addressing the country’s ACTA,the committeejoins four other European Parliament committees Prime Minister,Julia Gillard, at an economic forum in Brisbane, Oldham that have recommended rejecting the proposals. Aparliamentary debate highlighted the “intense competition coming from countries such on ACTA is scheduled for 3July,tobefollowed by avote on 4July. as India, which can produce the same medicines for less”. Non-governmental organisations (NGOs) including Médecins Sans Generics manufacturing in Australia delivered “significant health Frontières and Oxfam also recently criticised the European Commission and economic benefits to the Australian public” ,Oldham said, adding for failing to address fundamental problems with the ACTA proposals that “other countries in the region look to Australia for its high production (Generics bulletin,6April 2012, page 12). The NGOs highlighted standards, innovation and quality assurance”. Gillard should ensure that a“lack of accountability or transparency”, adding that ACTA should Australia had “appropriately balanced intellectual property” and “efficient be rejected due to its impact on access to medicines. G access to export markets, particularly within Asia”, Oldham urged. G

MARKET RESEARCH REGULATORY AFFAIRS SA market increases by 13% Variations text open for input outh Africa’sprivate generics market grewby12.6% in value to nterestedparties have until 15 July to comment on apublic consultation SR6.7 billion (US$791 million) in the year ended March 2012, Ijust released by the European Commission ahead of aplanned revision according to IMS data. Generics captured more than athird of the of guidelines addressing variations to marketing authorisations. The country’sprescription market, which advanced by 6.4% to R18.4 billion. update of the guidelines is required, in part, by the effects of implementing In volume terms, generics sales grewby6.3% to 5.1 billion units. G newpharmacovigilance legislation from next month. G

14 GENERICS bulletin 29 June 2012 Gen 29/6/12 Pgs.15-21_Layout 1 27/06/2012 19:58 Page 3

PRODUCT NEWS

ATTENTIONDEFICIT HYPERACTIVITY DISORDER DRUGS BIOSIMILARS Actavis is first with EMA finalises guides US Adderall XR rival for developing mAbs

ctavis has started shipping the first US rivaltoShire’sAdderall XR wo keyguidelines for companies developing biosimilar monoclonal A(amphetaminesalts) capsules after the generics firm received Tantibodies (mAbs) have been finalised by the European Medicines US Food and Drug Administration (FDA) approvalfor its version of Agency(EMA). Both guidelines were adopted by the agency’s the attention deficit hyperactivity disorder treatment in six strengths. committee for human medicinal products (CHMP) at the end of May, However, the originator insisted it would “remain competitive in the and come into effect on 1December this year. Adderall XR marketplace” through authorised generics of the brand Aguideline on non-clinical and clinical issues associatedwith already marketed by Impax and Teva.Citing IMS Health data, Actavis biosimilarmAbs aims to “establish general principles” on demonstrating claimed Adderall XR and its equivalents had US sales of around comparability through a“stepwise approach”. It covers in vitro studies US$1.99 billion in the year ended March 2012. as well as in vivo trials in animals and humans, plus pharmacovigilance At the same time as the FDAapprovedActavis’ 5mg, 10mg, 15mg, requirements(Generics bulletin,3December 2010, page 1). 20mg, 25mg and 30mg capsules, it also responded to acitizen petition “Extrapolation of clinical efficacyand safety data to other filed by Shire requesting that the agencyapply more stringent indications of the reference mAb, not specifically studied during the bioequivalence requirements to generic versions of Adderall XR. These clinical development of the biosimilar mAb, is possible based on the included subjecting generics to several partial area-under-the- results of the overall evidence provided from the comparability exercise concentration-time-curve(AUC) measurements to establish equivalence and with adequate justification,”the guideline states, noting that this with the brand between several different time intervals. would be “more challenging” where the reference mAb is authorised Whilst the agencysaid it would not grant Shire’sspecific requests as both an immunomodulator and an oncology antibody.The guide for the agencytorequire several partial AUCmeasurements, the FDA also says biosimilar applicants may need to “go beyond routine said it would require generic versions of Adderall XR to demonstrate two pharmacovigilance” by performing post-authorisation safety studies. partial AUCparameters when establishing bioequivalence. This was The second guideline on immunogenicity assessment of mAbs for because the formulation contained both immediate-release and delayed- in vivo clinical use is aimed at products at “the marketing authorisation release components and wasdesigned to achieve both rapid onset of application stage”. It addresses issues such as selecting appropriate activity and sustained activity throughout the day,the agencyexplained. G assays, assessing neutralising capacity and risk management. G

29 June 2012 GENERICS bulletin 15 Gen 29/6/12 Pgs.15-21_Layout 1 27/06/2012 19:58 Page 4

PRODUCT NEWS

OSTEOPOROSIS DRUGS METABOLICDRUGS EPO revokesRoche’s Three firms infringe Boniva ‘041 patent US Hectorolpatent

he European Patent Office’s(EPO’s) board of appeal has revoked nchen, Roxane and Sandoz induced infringement of US patent TRoche’sEuropean patent EP1,506,041 following an oral hearing. A5,602,116 by filing abbreviated newdrug applications (ANDAs) Following opposition proceedings brought by several generics for rivals to Sanofi’sHectorol (doxercalciferol) treatment for companies including Gedeon Richter,Mylan, Synthon and Teva,the hyperparathyroidism, according to aDelaware district court. Furthermore, EPO revokedthe ‘041 patent for added matter.Teva responded Judge Gregory Sleet ruled, the ‘116 patent –which expires on 11 quickly,launching ibandronate 150mg tablets in the UK with list February 2014 –was not invalid due to lack of utility or obviousness. prices that are 30% belowthose of Roche’sBonviva. Sleet said the ANDAs induced infringement of akey claim in the Roche had applied for the patent in 2003 and had been granted ‘116 patent because their proposed labels instructed physicians “to it in 2007 with the title of ‘Ibandronic acid for the treatment and perform each element of the patented method detailed in claim 7”. prevention of osteoporosis’.According to patent-intelligence expert “The court is not persuaded by the defendants’ assertion that GenericsWeb, the ‘041 patent could –ifunchallenged –havebarred ‘lower[ing] and maintain[ing] lowered blood concentrations of competition to Roche’sonce-monthlyBoniva/Bonviva 150mg parathyroid hormone without alower incidence of hypercalcemia’ tablets until May 2023. Supplementary protection certificates (SPCs) constitutes anon-infringing use,”Sleet stated. linked to Roche’sibandronate molecule patent EP0,252,504 expired Addressing arguments brought by Anchen and Roxane that their in several major European markets in June last year (Generics doxercalciferol capsules had “a substantial non-infringing use” for bulletin,30June 2011, page 23). stage 3and 4chronic kidneydisease, Sleet said this wasa“secondary In the US, Apotexand Mylan recently launched ibandronate and markedly under-developed defence”. It wasinsufficient to overcome 150mg tablets at risk after the US Court of Appeals refused to grant “the preponderance of the evidence” that the generic labels would induce Roche atemporary restraining order and injunction (Generics bulletin, infringement of apatented use in treating secondary hyperparathyroidism. 6April 2012, page 14). Watson said it would launch “in the second Sandoz’ANDAfiling wasfor injectabledoxercalciferol. “Sandoz’ quarter” of this year,while Indian firms Dr Reddy’sand Orchid now proposed products can only be used for the treatment covered in also hold marketing authorisations for 150mg tablets. G claim 7,”remarked Sleet in finding contributory infringement. G

CHOLESTEROL-LOWERINGDRUGS BIOSIMILARS Simvastatins pass French test Pharmacists seek substitution imvastatin 20mg generic tablets are as safe and effective as Merck’s harmacists in the US “should be able automatically to substitute SZocor and Sanofi’sLodales brands, astudy by French health Pbiosimilarinterchangeable products” to generate cost savings, insurer CNAM has concluded. Having launched its two-year study of according to aletter sent by three industry associations to the US 100,000 patients amid public debate oversafety and efficacyofgenerics, Food and Drug Administration (FDA) as the agencyfinalises draft CNAM said it had chosen simvastatin because it wasone of France’s biosimilarguidances. “Wesupport the development of an FDA-compiled most widely-used anti-cholesterol drugs. In 2011, the country reimbursed interchangeability reference list, something similar to the current Orange nearly six million packs of the 20mg strength at avalue of C88 million Book for generics”, said the American Pharmacists Association (APhA), (US$111 million). “There are no differences in efficacybetween the National Association of Chain Drug Stores (NACDS) and the National branded and generic simvastatin 20mg in terms of preventing serious Community Pharmacists Association (NCPA). Theyoppose “mandating cardiovascular events and deaths,”CNAMstated. G the use of unique international non-proprietary names (INNs)”. G

ONCOLOGY DRUGS Pfizer offers US cytarabine fizer has added cytarabine to its portfolio of injectable oncology Pgenerics in the US. Through its Established Products business unit, the originator has introduced the leukaemia drug as 100mg/5ml and 2g/20ml single-dose vials, as well as 500mg/25ml multi-dose vials and 1g/50ml pharmacybulk packages. G

IN BRIEF BRECKENRIDGE has startedshipping rivastigmine capsules equivalent to Novartis’ Exelon in the US after it reached apatent- litigation settlement with the originator.India’sAlembic is supplying the Alzheimer’sdisease drug. G

16 GENERICS bulletin 29 June 2012 Gen 29/6/12 Pgs.15-21_Layout 1 27/06/2012 19:58 Page 5

PRODUCT NEWS

BIOSIMILARS NARCOLEPSYDRUGS NZ plans sole supply Mylan to enter early for Sandoz’ filgrastim with US Provigildeal

andoz’ Zarzio (filgrastim) 300µg and 480µg pre-filled syringes may ylan will be able to launch modafinil 100mg and 200mg tablets Sbe awarded sole subsidised supply status in NewZealand from 1 Min the US from 10 August 2012 after settling litigation over September 2012 until 31 December 2015, according to proposals by the Teva’s US$1.2 billion Provigil brand for improving wakefulness. country’spharmaceutical management agency, Pharmac. As well as Earlier this year,the US Food and Drug Administration (FDA) being the sole subsidised filgrastim in these presentations, Sandoz’ awarded Teva 180-day exclusivity –running until 26 September 2012 – version would also be awarded hospital supply status from 1January for ageneric version of the brand, which is marketed by the Israeli 2013 until 31 December 2015. The agencyisseeking feedback by 10 firm’sown Cephalon affiliate (Generics bulletin,20April 2012, page 15). July on the proposals, which it expects to “result in significant savings”. Teva had filed its abbreviated newdrug application(ANDA) containing Under the terms of the proposals, packs of five Zarzio syringes aparagraph IV certification before acquiring Cephalon. would be reimbursed at NZ$540 (US$431) for the 300µg/0.5ml strength Having initially sued the FDAoverits decision to award Teva and NZ$864 for the 480µg/0.5ml syringes. The same presentations of exclusivity,Mylan said it had now“resolved all disputes with Teva Roche’sNeupogen pre-filled syringes would be delisted from 1January stemming from the litigation” through the settlement, the financial terms 2013, butthe brand company’s300µg Neupogen vials and Neulastim of which were not disclosed. The agreement is subject to reviewbythe (pegfilgrastim) 6mg pre-filled syringes would remain listed. US Department of Justice and the Federal Trade Commission (FTC). Noting that Sandoz’ 300µg Zarzio vials were still in development, Parlaunched modafinil tablets at the start of April, having gained Pharmac said this version of the granulocyte colony-stimulating factor rights to an authorised generic as acondition of the FTC approving Teva’s (G-CSF) would be listed once it had been registered in NewZealand. takeoverofCephalon (Generics bulletin,14October 2011, page 11). The agencyadded that the proposed supply arrangements for Sandoz’ Mylan also recently settled US patent litigation overTeva’s Nuvigil filgrastim would be wider than at present because it would include (armodafinil) tablets with adeal that allows Mylan to launch under non-cancer indications as well as cancer-related use. G licence from June 2016 (Generics bulletin,4May 2012, page 1). G

MUSCLE RELAXANTS ONCOLOGY DRUGS Apotex survives on tizanidine Mylan gets EU zoledronic acid potexcan continue marketing tizanidine capsules in the US after ylan has receivedapositive opinion from the European Medicines Athe US Court of Appeals affirmed without comment alower MAgency’s(EMA’s)committee for human medicinal products court’sfinding that US patent 6,455,557 wasinvalid for lack of (CHMP) recommending it should be granted amarketing authorisation enablement. Acorda Therapeutics –the owner of the Zanaflexmuscle for zoledronic acid 4mg/5ml concentratefor solution for infusion. relaxant –had brought the appeal against aNew Jerseydistrict court’s Meda receivedapositive opinion for its ‘hybrid’ Zyclara (imiquimod) ruling on the ‘557 patent, which has an expiry date of 28 November 3.75% cream for treating actinic keratosis. 2021 (Generics bulletin,16September 2011, page 16). Recently,Medac wasgranted apositive CHMP opinion for a Acorda responded to Apotex’ US approvaland launch of tizanidine zoledronic acid solution and concentrate, whilst Synthon has completed 2mg, 4mg and 6mg capsules in early February this year by licensing “multiple decentralised procedures” for similar products (Generics an authorised generic to Watson (Generics bulletin,17February 2012, bulletin,8June 2012, page 22). page 22). Prior to the NewJerseycourt’sdecision, annual US sales Meanwhile, the CHMP has recommended restricting the use of of Zanaflexcapsules and tablets were around US$45 million. G tolperisone after concluding that its benefits only outweighed its risks when used as an oral formulation to treat adults with post-stroke spasticity.Italso recommended that doctors should not prescribe trimetazidine for patients with tinnitus, vertigo or vision disturbance, BIOSIMILARS Finox poised to file for r-FSH following areviewinitiated by the French agency, ANSM. G inox Biotech plans to file soon for biosimilar approvalofits Afolia ANALGESICS/ALZHEIMER’SDISEASE DRUGS Frecombinant follicule stimulating hormone (r-FSH). The Swiss companysaid a410-patient, Phase III clinical trial had “met its primary endpoint” and had “demonstrated clinical and statistical equivalence Teva UK offers rivaltoDifflam to the reference product, Gonal-f”. eva UK has launched arivaltoMeda’sDifflam (benzydamine) “Submission of the registration dossier to the European health T0.15% oromucosal spray.Using amarketing authorisation held authorities is expected by the fourth quarter of 2012,”stated chief by Focus Pharmaceuticals, Teva has introduced its Oroeze locally- executive officer Anjan Selz. Finox has agreed a‘special protocol acting analgesic and inflammatory agent with aretail price of £3.50 assessment’ with the US Food and Drug Administration (FDA) to (US$5.48) for a30ml pack. This representsa3.6% discount to Meda’s conduct apivotal Phase III study for Afolia, which is delivered through non-prescription original. Teva UK has also introduced arivalto single-use, disposable injector pens. Selz told Generics bulletin Novartis’ Exelon (rivastigmine) capsules, with list prices for the that Finox wascurrently identifying marketing partners in Europe, Alzheimer’sdisease treatment of £18.29 for 28 capsules, and £36.58 the US and elsewhere, buthad not yet finalised anydeals. G for a56-count pack, representing a45% discount to the original. G

29 June 2012 GENERICS bulletin 17 Gen 29/6/12 Pgs.15-21_Layout 1 27/06/2012 19:58 Page 6

PRODUCT NEWS

MULTIPLE SCLEROSISDRUGS ANTIDEPRESSANTS UK removes block on Size of Sun’s tablets former Teva lawyer is cited by Osmotica

nin-house patent attorneywho previously worked for Teva may un Pharma’sUSabbreviated newdrug application(ANDA) for Aact on behalf of her current employer,Mylan, in UK litigation S225mg extended-release venlafaxine tablets should be rejected by overher former employer’sCopaxone (glatiramer acetate)brand, the the US Food and Drug Administration (FDA) if the Indian firm’stablets Court of Appeal has ruled. Removing an injunction put in place by are “considerably larger than the tablet size of the reference-listed the High Court, the appeals court dismissed Teva’s argument that drug”, Effexor XR, according to Osmotica. The brand companyhas confidential information the attorneymay have learned about Copaxone filed acitizen petition with the FDAasking it to refuse approvalofthe whilst employed by the Israeli firm may influence –evensubconsciously ANDAdue to “safety and efficacyconcerns posed by alarge tablet”. –her strategy and conduct on behalf of Mylan. Noting that Sun’sexisting 150mg venlafaxine extended-release Although the attorneywas not concerned with, and claimed to tablet is “considerably larger” than Osmotica’sversion, the brand have no knowledge of, anyCopaxone litigation whilst working for companysaid Sun’sANDAnotification letter had indicated that the Teva,the Israeli firm said she had been exposed to discussion of such generics firm planned to use “the same technology for the 225mg litigation overthe UK version of European patent EP0,762,888 strength that it used for the other tablet strengths”. If Sun’s225mg through being copied on e-mails containing confidential information. tablet were proportional to the firm’s150mg tablet, Osmotica claimed, the higher strength tablet would weigh more than 1g in total and be Confidential information was peripheral more than 24mm long and 9mm thick. In comparison, Osmotica’s But appeals court judge Sir Robin Jacob stated that “the alleged version weighs 595mg and is just over11mm in diameter. confidential information wasatmost peripheraltothe Copaxone “Patients frequently have difficulty swallowing large tablets”, litigation”. Teva’s conduct overthe matter had suggested there was Osmotica argued, adding that this caused a“potential safety problem”. no “real risk” that the information would be disclosed, he maintained. Furthermore, “patients are less likely to comply with their medication Agreeing that the injunction should be lifted, Lord Justice Etherton regimens if the medication is difficult to swallow”, the firm added. said the High Court judge’s“mere suspicion” that the attorney’s Osmotica had previously filed citizen petitions with the FDAinan memory of the information may “unconsciously” influence her conduct attempt to block venlafaxine ANDAs filed by Sun (Generics bulletin, fell “well short of satisfying the burden on Teva to prove areal risk 12 February 2010, page 14) butthese failed to prevent the Indian firm that the information would be used or disclosed”. Lord Justice Ward from launching37.5mg, 75mg and 150mg extended-release tablets also concurred that Mylan’sappeal should be allowed. G in 2010 (Generics bulletin,3September 2010, page 18). G

PARKINSON’S DISEASEDRUGS ANTIRETROVIRALS Three cleared on US ropinirole Mylan debuts European ARV hree companies –DrReddy’s, Sandoz and Watson –secured ylan has launched its first antiretroviral (ARV) drug in Europe Tapprovals from the US Food and Drug Administration (FDA) to Mwith the introduction of ageneric version of GlaxoSmithKline’s launch rivals to GlaxoSmithKline’sRequip XL (ropinirole) 2mg, 4mg, Epivir (lamivudine) 150mg and 300mg tablets in Italy and the UK. 6mg, 8mg and 12mg extended-release tablets immediately upon US Thecompanysaid lamivudine tablets had annual sales of around patent 5,422,123 expiring on 6June. However, theyface competition C12.5 million (US$15.7 million) in Italy and around C3.4 million in from Actavis, which had introduced its version around three weeks the UK during the year ended March 2012. before patent expiry (Generics bulletin,8June 2012, page 25). Annual Meanwhile, Mylan will enjoy180-day exclusivity in the US for US sales of the Requip XL Parkinson’s disease brand are just under its alternative to Viiv’s Ziagen (abacavir) 300mg tablets following US$60 million. approvalfor the antiretroviral immediately upon US patent 5,034,394 Four years ago, Mylan, Par, Roxane and Teva secured FDAapproval expiring on 18 June. Mylan had challenged US patent 6,294,540 –which for ropinirole immediate-release tablets, having carved out anow-expired expires on 14 November 2018 –but wasnot sued within the 45-day method-of-usepatent (Generics bulletin,16May 2008, page 15). G windowthat would have resulted in a30-month stay on approval. G

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PRODUCT NEWS

ALLERGYREMEDIES BIOSIMILARS Apotex works round Celltrion’s CT-P13 US Nasonexpatent matches Remicade

potex’ proposed generic version of Merck &Co’sNasonex elltrion’sCT-P13 biosimilar candidate has “an efficacyand safety A(mometasonefuroate) allergy remedy does not infringe keyclaims Cprofile” comparable to that of Johnson &Johnson/Merck’s of US patent 6,127,353, NewJerseydistrict Judge Peter Sheridan Remicade (infliximab) in rheumatoid arthritis patients, according to has ruled. However, the Canadian firm failed in its invalidity attacks the results of an international Phase III clinical study presented at the against the ‘353 patent, for which paediatric exclusivity expires on 2012 meeting of the European League Against Rheumatism (EULAR). 3April 2018. Similar extensions to twoother US patents listed against The firm also presented positive Phase Iresults for the monoclonal Nasonexend on 27 July 2014. antibody (mAb) as atreatment for ankylosing spondylitis. On infringement, Apotexasserted that the active pharmaceutical The South Korean company’s‘Planetra’ randomised, double-blind ingredient (API) in its nasal spray wasnon-infringing, because it was Phase III trial compared the clinical efficacyand overall safety of mometasone furoate anhydrous, rather than the monohydrate form CT-P13 versus Remicade in around 600 patients with active rheumatoid described in the ‘353 patent. But Merck insisted that the anhydrate arthritis. Celltrion said the study had used 125 centres in 19 countries. in Apotex’ generic converted to monohydrate after it wasmade, but Participating patients were administered 3mg/kg infusionsofeither before the drug’stwo-year expiration date. CT-P13 or Remicade on arandomised basis in addition to methotrexate Sheridan ruled that Merck had failed to meet its burden of proof and folic acid. The primary endpoint wasthe proportion of patients to showthrough x-ray particle diffraction that samples of Apotex’ generic at 30 weeks achieving a20% improvement in the American College contained the monohydrate form, not least because shaking or of Rheumatology (ACR) index, which measures clinical efficacy ‘vortexing’ the samples fundamentally changed their formulation. using criteria such as incidences of tender or swollen joints. A15% However, Sheridan rejected Apotex’ argument that the ‘353 patent margin wasused to determine the equivalence of the twotreatments. wasinvalid because it wasanticipatedbythe expired US patent “Atweek 30, ACR20 response rates were 60.9% for CT-P13 versus 4,472,393 covering anhydrous mometasonefuroate. He also turned 58.6% for infliximab in the intent-to-treat population,”the international down the generics firm’sobviousness attack in light of prior art, research team told the EULAR meeting. Celltrion’sversion also maintaining that askilled person would not have been motivated to outscored Remicade in terms of ACR20 response in the per-protocol develop anasal spray using mometasone furoate. G population, and wasahead when measured using 50% and 70% ACR indices. Adverse events considered by the investigators to be related to the study treatment were generally slightly lower for CT-P13, although tuberculosis wasreported in three patients who received the biosimilar candidate, compared to just one for Remicade. The Phase Itrial compared the pharmacokinetic profiles of CT-P13 and Remicade in around 250 patients with ankylosing spondylitis. As well as finding equivalent pharmacokinetic profiles such as area under the concentration-time curveoveradosing interval (AUCτ), the 30-week study also suggested that “CT-P13 waswell-tolerated, with an efficacy and safety profile comparable to that of infliximab up to week 30”. Celltrion noted that the 30-week trial duration had been approved by the European Medicines Agency(EMA), which recently validated the South Korean firm’smarketing-authorisation application for CT-P13 (Generics bulletin,20April 2012, page 17). Hospira holds marketing rights in the European Union, the US, Canada, Australia and NewZealand under the terms of adeal agreed with Celltrion three years ago (Generics bulletin,16October 2009, page 13). In Russia and four other CommonwealthofIndependent States (CIS) countries, Egis holds exclusive rights, while the Hungarian firm has semi-exclusive rights in 12 central and eastern European markets (Generics bulletin,5March 2010, page 18). Celltrion also has regional biosimilartie-ups with companies including Turkey’s Abdi Ibrahim and Jordan’sHikma. Johnson &Johnson reported 2011 sales of Remicade –which is also indicated for psoriatic arthritis, adult and paediatric Crohn’sdisease, ulcerative colitis and plaque psoriasis –that rose by 19.1% to US$5.49 billion. Three-fifths of that total wasachievedinthe US. G

IN BRIEF SANDOZ has announced a“precautionary recall” of 10 lots of its Introvale (levonorgestrel/ethinylestradiol)oral contraceptivein the US due to apackaging error. G

29 June 2012 GENERICS bulletin 19 Gen 29/6/12 Pgs.15-21_Layout 1 27/06/2012 19:58 Page 8

PIPELINE WATCH Infanrix expiryshows complexity of SPCs ate June brings the loss of supplementary protection certificate in turn referred the case to the European Court of Justice (ECJ). L(SPC) exclusivity in Italy for GlaxoSmithKline’smultivalent vaccine Having interpreted Article 3(a) of the European Union’s(EU’s) Infanrix (DTPa-IPV/Hib vaccine). However, similar SPCs remained just SPC Regulation 469/2009 –which requires that, to qualify for a applications in Austria, Belgium, Denmark, Germany, the Netherlands monopoly extension, aproduct be protected by abasic patent –the and the UK, so theynever entered into force (see Figure 1). ECJ ruled SPCs could only be granted to products solely containing Even though Infanrix represents asignificant commercial active ingredients specified in the claims of the basic patent (Generics opportunity –global brand sales declined by 2% to £690 million bulletin,9December 2011, page 15). (US$1.09billion) last year due to a7%reverse to £403 million in According to patent intelligence expert GenericsWeb –which Europe amid price cuts –developing such acomplexvaccine is beyond compiles adatabase of SPC, data exclusivity and patent expiries –the the scope of manygenerics players. But Infanrix’ equally complex ECJ’s‘Medeva’ruling could render invalid up to athird of SPCs for intellectual-property landscape has ensured it has been the focus of combination products (Generics bulletin,6April 2012, page 24). industry attention for other reasons. In terms of data exclusivity (see Figure 2), June brings the expiry of In April 2009, GlaxoSmithKline’spartner,Medeva,filed five SPC 10-year protection in most EU member states for Pegasys (peginterferon applications for several vaccines, referencing the basic patent alfa-2a), Roche’sblockbuster hepatitis treatment, which achievedglobal EP1,666,057. It supported these filings by referencing marketing sales of SFr1.44 billion (US$1.52 billion) last year,including SFr297 authorisations for different DTPa-IPV/Hib vaccines, butthe UK’s million in western Europe. However, GenericsWeb points out, “patent intellectual property office (IPO) rejected the applications. Medeva protection extending beyond exclusivity in all major territories remains appealed against the IPO’sdecision to aUKCourt of Appeal, which aconstraining factor for the launch of generic peginterferon alfa-2a”. Sales of Pegasys are expected to increase due to the recent launches of twonovelhepatitis Ctherapies that are indicated as triple Data exclusivity expiries in June therapies in combination with peginterferon and ribavirin –Merck INN Country/Region &Co’sVictrelis (boceprevir) and Vertex’sIncivek(telaprevir), which is also marketed by Janssen-Cilag as Incivo. Abatacept Canada Among potential generic-development targets (see Figure 3), the Ambrisentan US US Food and Drug Administration’s(FDA’s) approvalinMarch 2012 Cefovecin Turkey of Omontys (peginesatide)from Affymax and Takeda –including a Drotrecogin alfa(activated) Switzerland preservative-free version of the anaemia treatment –has led to the Entecavir Turkey listing of several patents in the FDA’sOrange Book. G Eprosartan/hydrochlorothiazide Switzerland Exenatide Australia SPC expiries in June Fondaparinux sodium Switzerland Glimepiride/rosiglitazone Turkey INN Country Lapatinib Australia Carbidopa/melevodopa Italy Natalizumab Turkey Cefdinir Austria Oseltamivir European Union Desirudin Spain Peginterferon alfa-2a European Union Rimonabant Turkey Dibotermin alfaAustria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Figure2:Molecules for which data exclusivity expires in certain markets during Luxembourg, Netherlands, Norway, June 2012 (Source –GenericsWeb) Spain, Sweden, Switzerland, UK Molecules in the spotlight DTPa-IPV/Hib Vaccine Austria*, Belgium*, Denmark*, Germany*, Italy,Netherlands*, UK* INN Event Lepirudin Switzerland Florbetapir First US Orange Book patents listed following FDAapprovalofAmyvid on 6April 2012 Levofloxacin Spain Peginesatide First US Orange Book patents listed following Olanzapine Switzerland FDAapprovalofOmontys &Omontys Preservative Penciclovir Cyprus Free on 27 March 2012 Pramipexole Spain Remestemcel-L First Canadian patent listed in Patent Register Topotecan Cyprus following Health Canada approvalofProchymal on 22 May 2012 *indicates that the SPC remained an application at expiry,sonever entered into force

Figure3:Molecules in the spotlight, based on recent regulatoryorlitigation Figure1:Molecules for which supplementaryprotection certificates (SPCs) events (Source –GenericsWeb) expireincertain markets during June 2012 (Source –GenericsWeb)

Want more? This data is extracted from the monthly update for Pipeline Scope, an online intelligence tool that provides fast access to reliable information on keypatent, SPC and data-protection expiries, covering 44 countries and over1,500 INNs. Forfurther information, visit www.genericsweb.com, or contact: Europe: +44 870 879 0081 North America: +1 704 665 1986 Or e-mail: [email protected]

20 GENERICS bulletin 29 June 2012 Gen 29/6/12 Pgs.15-21_Layout 1 27/06/2012 19:58 Page 9

PRODUCT NEWS

IN BRIEF ANTIRETROVIRALS PERRIGO will be able to sell ageneric version of Stiefel’s Olux-E (clobetasol propionate)0.05% foam in the US from 1February 2013, Aspen addresses SA or earlierunder certaincircumstances, after the generics firm settled patent litigation with the GlaxoSmithKline subsidiary.Inconjunction with Cobrek Pharmaceuticals, Perrigo submitted the first abbreviated newdrug application(ANDA) containing aparagraph IV certification tenofovir shortages against the US$40 million brand, and so will be entitled to 180-day exclusivity.The firm has already receivedtentative US Food and spen has “met and exceeded, both in timing and required quantity” Drug Administration (FDA) approvalfor its version. Aits obligations to supply tenofovir in South Africa under astate tender contract, the companyhas confirmed in response to reported WATSON is claiming victory in aUSlawsuit overAllergan’s shortages of the antiretroviral (ARV). Sanctura XR (trospium)extended-release capsules after aUS Noting that it wasrequired to supply 70% of tenofovir volumes Court of Appeals confirmed an earlier district court ruling that all awarded in the South African tender –which beganon1January 2011 five patents listed against the brand in the US Food and Drug (Generics bulletin,14January 2011, page 22) –Aspen said it had Administration’s(FDA’s) Orange Book were invalid. The generics supplied 2.4 million packs of the product between March and May firm’sabbreviated newdrug application(ANDA) for arivaltothe 2012, which was400,000 more than its contractualrequirement. And urology drug is still pending FDAapproval. The litigation also in June, the firm said, it had supplied1.2 million packs “which exceeds involved Sandoz and Perrigo’sPaddock. Sanctura XR had US the entire tenofovir public-sector requirement for the month”. sales of around US$66 million in the year ended April 2012. Watson Aspen declined to comment on media reports that fellowSouth has also filed an ANDAwith aparagraph IV challenge to US African firm SonkePharmaceuticals had wonthe remaining 30% of the patent 6,673,838, which protects Pfizer’s Pristiq (desvenlafaxine) tenofovir tender buthad been unable to increase its production to meet 50mg and 100mg extended-release tablets until 11 February 2022. demand for the product. However, the firm confirmed that it had been The ANDAissubject to a30-month stay on FDAapprovalrunning “advised by the National Department of Health that it is needed to over- until 29 August 2015. Watson believesitmay be entitled to 180- supply on its contractual commitment because the supplier required to day exclusivity. supply the other 30% of the tenofovir tender is unable to do so”. Furthermore, Aspen noted it had already “stepped in and supplied ARROW has launched candesartan 4mg, 8mg, 16mg and 32mg three other ARVmedicines, where other suppliers had experienced tablets in France. The Watson subsidiary said its version of supply constraints”. These included lamivudine and stavudine tablets. G AstraZeneca’s Atacand wasinthe process of being included in the country’s répertoire of generic equivalents. Local rivals to the antihypertensive are also marketed by Actavis, EG Labo, Mylan, ANALGESICS Sandoz and Teva.Inthe UK, Arrowhas launched lercanidipine 10mg and 20mg tablets that are equivalent to Recordati’sZanidip. Germany ponders opioid move ALPHAPHARM,DrReddy’sand ParPharmaceutical have failed to pioid analgesics should be exempted from automatic generic overturn aruling upholding the validity of twoUSpatents protecting Osubstitution by German pharmacists, according to aparliamentary Treximet (sumatriptan/naproxen). The US Court of Appeals for committee. But patients’ organisation Deutsche Schmerzliga–which the Federal Circuit upheld last year’sruling by aTexas district court had petitioned for the exemption, citing side effects and the need for in favour of Pozen (Generics bulletin,2September 2011, page 21). individual dosing –fears that the German parliament, the Bundestag, will merely open the door to general exemptions from substitution. AARTI DRUGS has had its European Certificates of Suitability (CEPs) Aproposed amendment to Germany’smedicines lawwould allow for the active pharmaceutical ingredients(APIs) diclofenac and health insurance funds and the German pharmacists’ association, the metformin suspended by the European Directorate for the Quality DAV, to agree not to substitute certain medicines. But Deutsche of Medicines and Healthcare(EDQM). The manufacturer has also Schmerzligaisdemanding aclear statement that all opioid analgesics been removedfrom CEPs for ciprofloxacin and zolpidem. are exempt from automatic substitution. G

ROXANE has launched authorised generic versions of parent company Boehringer Ingelheim’s Viramune (nevirapine)inthe US. Roxane’s ANTIHYPERTENSIVES version is available as 200mg tablets and a50mg/5ml suspension. France and Spain reject SPC TOLMAR has receivedUSFood and Drug Administration (FDA) approvalfor its adapalene 0.3% topical gel. oehringer Ingelheim cannot extend patent protection for a Bcombination of telmisartan and hydrochlorothiazide via a TEVA has launched ageneric version of Eli Lilly’s Symbyax supplementary protection certificate (SPC) based on European patent (olanzapine/fluoxetine)capsules in the US. The Israeli firm’sversion EP0,502,314, courts in France and Spain have ruled. The combination of the antidepressant –which has annual US sales of around US$82 –which forms the basis of the originator’s Micardis Plus brand –was million –isavailable in 6mg/25mg, 12mg/25mg,6mg/50mg and not eligible for an SPC because the ‘314 patent did not claim the 12mg/50mg strengths. telmisartan/hydrochlorothiazide combination, despite disclosing hydrochlorothiazide in alist of additional compounds that could be MICRO LABS has receivedtentative US Food and Drug used in combination with telmisartan. Administration (FDA) approvalfor its version of Bristol-Myers The decisions followthe European Court of Justice’s(ECJ’s) ruling Squibb’s Sustiva (efavirenz)600mg tablets through the President’s last year that SPCs can only be granted to products containing solely EmergencyPlan for AIDS Relief (PEPFAR). G active ingredients that are specified in the claims of abasic patent (Generics bulletin,9December 2011, page 15). G

29 June 2012 GENERICS bulletin 21 Gen 29/6/12 Pg.22_Layout 1 27/06/2012 19:59 Page 2

EVENTS

JULY 24-25 September 15-17 October ■ Biosimilarsand Biobetters ■ Branded Generics 17-19 July London, UK Strategy Asia ■ 5th Product and Pipeline Looking at the regulatory challenges Singapore Enhancement for Generics involved in biologics, together with This event will look at all aspects of the WashingtonDC, USA competition and marketing, this event will generics landscape, including regulatory Keytopics to be covered at this three-day also include case studies and provide up to issues, marketing, and strategic developments. date information on topics such as clinical conference will include Food and Drug Contact:IBC Asia. Administration (FDA)proposals on trials and emerging markets. Tel: +65 6508 2482. biosimilarsdevelopment and user fees, Contact:SMi Group. E-mail: [email protected]. business strategy,portfolio management and Tel: +44 870 9090 711. Website: www.generics-asia.com. patent issues. There will be speakers from E-mail: [email protected]. Amneal Pharmaceuticals and the US Website: www.smi-online.co.uk. 29-30 October Federal Trade Commission. ■ PharMeet Contact:Marcus Evans Conferences. OCTOBER Lisbon, Portugal Tel: +1 312 540 3000 ext.6625. This two-day event is designed to offer E-mail: [email protected]. 1-3October Website: www.marcusevans.com. delegates the opportunity to network as well ■ GPhA/FDA Fall Technical as the chance to strikelicensing deals for a SEPTEMBER Conference wide range of products, including biosimilars. Maryland, USA Contact: PharMeet. 10-12 September With presentations from US FDA Tel: +34 91 637 0660. ■ Business of Biosimilars representatives, this three-day meeting of the E-mail: [email protected]. Website: www.pharmeet.com. and Generic Drugs US Generic Pharmaceutical Association (GPhA) will look at legaldevelopments as Boston, USA well as current regulatory and technical issues. NOVEMBER The aim of this well-established event is to Contact:GPhA. give drug-development and market-access Tel: +1 202 249 7100. 5-6November executivesthe tools to compete and maximise E-mail: [email protected]. ■ EuroPLX 50 pipeline profitabilityintoday’sglobal Website: www.gphaonline.org. Sorrento, Italy environment. There will be speakers from This two-day meeting provides aforum firms includingMylan and Pfizer. 8October for firms to discuss licensing,marketing Contact:IIR USA. ■ CPhI Pre-Connect Conference and distribution opportunities for patented Tel: +1 646 895 7327. drugs, generics, biosimilars, OTC E-mail: [email protected]. Madrid,Spain Website: www.biosimilarsevent.com. Taking place the day before CPhI Worldwide, medicines and nutraceuticals. this event will provide information on Contact:Raucon. 11-13 September strategies in pharmaceutical development, Tel: +49 6222 9807 0. manufacturing and partnering. E-mail: [email protected]. ■ World Biosimilars Congress Website: www.europlx.com. London, UK Contact:UBM Information. Tel: +44 207 921 8039. 7-9November Issues covered at this three-day event will E-mail: [email protected] include pharmacovigilance and Website: www.cphi.com. ■ 15th APIC/CEFIC European biomanufacturing. The meeting will look at Conference on APIs the global regulatory landscape and there 9-11 October Budapest, Hungary will be presentations by executivesfrom ■ CPhI Worldwide firms includingAmgen and Glenmark. Discussing the latest developments in the Madrid,Spain areas of GMP and regulatory compliance, Contact:Terrapinn. this event will include presentations from Tel: +44 207 092 1186. This three-day exhibition and networking E-mail: [email protected]. opportunity will also include the co-located speakers from the US FDA, the European Website: www.terrapinn.com. events iCSE, P-MEC and Innopack. Medicines Agency, and industry associations. Contact:UBM Information. Contact:Concept Heidelberg. 18-20 September Tel: +44 207 921 8039. Tel: +49 6221 84 440. E-mail: [email protected]. E-mail: [email protected]. ■ Generics &Biosimilars Website: www.cphi.com. Website: www.concept-heidelberg.com. Istanbul,Turkey With 25 speakers from 15 countries – including representativesfrom keyemerging 4-6December 2012 markets such as Russia, Ukraine and Turkey, ■ 15th IGPAAnnual Conference and the regulated markets of the European Kyoto, Japan Union and US –CPhI’sconference will This three-day conference is being organised by the Japanese Generic provide information on the latest in product Medicines Association (JGA) and is the global event of the worldwide generics industry. developments, partnerships and strategies. It is the annual joint meeting of the Canadian,European, Indian, Japanese, South African Contact:UBM Conferences. and US generics industry associations, the CGPA, EGA, IPA, JGA, NAPM and GPhA. Tel: +44 207 921 8039. Contact:Japan Generic Medicines Association. Tel: +81 33279 1890. E-mail: [email protected]. E-mail: [email protected]. Register onlineatwww.congre.co.jp/igpa2012. Website: www.cphi-generics.com.

22 GENERICS bulletin 29 June 2012 Gen 29_6_12 Pg.23_Layout 1 28/06/2012 07:16 Page 3

PRICE WATCH ...... UK Ranbaxy makesrunning on esomeprazole

ith patent expiries coming thick and fast this year –Teva UK Esomeprazole Olanzapine Wclaims to have executed 10 ‘day-one’ launches immediately upon 25 Valsartan/ Valsartan patent expiry out of atotal of 21 introductions it has made to date in hydrochlorothiazide 2012 –WaveData wasasked to look at which products were currently 20 the subject of the most sales activity. 15

Not surprisingly,perhaps, atorvastatin 20mg and 40mg came top of (£) the pile as twoofthe most recent, and probably most important,ofthe 10 newmarket entrants. Having covered last month the initial launch Price period of atorvastatin from 8May onwards (Generics bulletin,18May 5 2012, page 21), it is too early,however,todrawany further conclusions. Just behind the twostrengths of cholesterol-lowerer,agroup of 0 four product lines wasidentified by WaveData which were not only 11 11 1 11 12 12 12 12 12 v1 recent launches,but had also been promoted more heavily than other Sep Oct No Dec Jan Feb Mar Apr May products. All four –28-tablet packs each of esomeprazole 40mg, Figure1:Average price declines for four recently-launched categoryMproducts olanzapine 10mg and valsartan/hydrochlorothiazide 160mg/12.5mg; that have been generating high volumes of price offers (Source –WaveData) and 28-capsule packs of valsartan 80mg –havepharmacyreimbursement prices that are in category Mofthe Drug Tariff. This means that Arrow Ranbaxy Sandoz Teva pharmacists are reimbursed at arate that is based on actual prices in 25 the marketplace. The declines in average price for all four products 20 since generic launch are shown in Figure 1. WaveData’smanaging director,Charles Joynson, remarks that the 15 esomeprazole product wasinteresting as it had been heavily advertised (£) after launch, mainly by Ranbaxy via short-line wholesalers. Looking

Price 10 at Figure 2, Ranbaxy also offered the cheapest price in eight out of the months monitored, observes Joynson, noting that Ranbaxy was 5 supplying Actavis for at least apart of the period studied. Ranbaxy launched the UK’sfirst generic esomeprazole alternative 0 11 11 1 11 12 12 12 12 12 12 to AstraZeneca’sNexium –which had UK sales of £60 million (US$94 v1 Jan Jun million) in the year ended June 2011 –shortly after it convinced the Sep Oct No Dec Feb Mar Apr May Patents Court of England and Wales that the esomeprazole it intended Figure2:Price declines by manufacturer from launch for 28-tablet packs of to import did not infringe AstraZeneca’spatent EP1,020,461 (Generics esomeprazole 40mg (Source –WaveData) bulletin,16September 2011, page 1). The ruling followed one by the Arrow Ranbaxy Sandoz Teva European Patent Office’sOpposition Division that overturned both the 35 ‘461 and EP1,020,460 patents for lack of an inventive step (Generics 30 bulletin,30June 2011, page 17). 25

The launch price for Ranbaxy’sesomeprazole 40mg was£17.99, offers which offered only a29% discount on the trade price of £25.19 for 20 the Nexium equivalent. This represented aprice premium compared price

of 15 with other relatively important generics, atrend that has continued until today,when the average price in the marketplace still offers only a 10

50% discount on the brand. Number 5 Price offers for Ranbaxy’sproduct (see Figure 3) came mainly 0 through short-line wholesalers likeDEGroup, Forte Direct and 11 11 1 11 12 12 12 12 12 12 v1 Mawdsley’s. Teva,onthe other hand, concentrated on full-line Sep Oct No Dec Jan Feb Mar Apr May Jun wholesalers likeAAH and Phoenix. “Asthe full-line wholesalersare nationwide, whereas the short-liners are regional, the outcome is likely to Figure3:Promotional activity by manufacturer from launch –measured by price offers –for 28-tablet packs of esomeprazole 40mg (Source –WaveData) be greater volume sales for Teva than for Ranbaxy,” comments Joynson. “Because of the greater distribution effort made by Ranbaxy,” he Arrow adds, “there wasmore promotional activity for esomeprazole than for Teva the other three products. Overall, Ranbaxy’s ‘share of voice’ during the launch period for esomeprazole 40mg was59% (see Figure 4). G

WANT MORE LIKE THIS? Sandoz Long-term product price trends or other price analyses are available. Please specify the product and period of time you would liketo investigate and email your request to [email protected]. ■ Forfurther information see www.bppi.co.uk. Ranbaxy Alternatively,contact Charles Joynson at WaveData Limited, UK. Tel: +44 (0)1702 425125. E-mail: [email protected]. Figure4:Shareofvoice within total promotional activity by different manufacturers from launch of 28-tablet packs of esomeprazole 40mg (Source –WaveData)

29 June 2012 GENERICS bulletin 23 Gen 29/6/12 Pgs.24-25_Layout 1 27/06/2012 20:08 Page 2

BUSINESS STRATEGY Fresenius has emerging aim but fears biosimilar risks

Broadening its aving achievedaturnoverofalmost C4.0 billion (US$5.0 billion) last year,Fresenius Kabi is Asia-Pacific footprint in emerging Hgunning for C5.5 billion by 2015. The German C702m Europe +18% C1,826m markets rather than hospital products specialisthas abroad growth strategy +7% across all four of its product segments –intravenous investing in biosimilars (IV) generic drugs, clinical nutrition,infusion solutions and medical devices –and its geographic regions. But is key to Fresenius Latin emerging markets in the Asia-Pacific, Africa and America/ Latin America regions are aparticular point of focus. Africa Kabi’sstrategy for C434m Deputy chairman Mats Henriksson –who at the +8% growing its generic end of this year will takeoverasexecutive chairman from Rainer Baule (Generics bulletin,13January 2012, injectables business. page 31) –said the proportion of the company’sturnover Aidan Fryreports. generated in the Asia-Pacific, Africa and Latin America regions would rise from 29% last year to 35-40% in 2015. Reaching the upper end of that range, he said, North America C1,002m would depend on finding attractiveacquisition targets. +3% The 40% target implies a2015 turnoverfrom emerging markets of C2.2 billion. Last year,Fresenius Figure1:Breakdown by region of Fresenius Kabi’s sales that Kabi’scombined sales in these regions were C1.14 increased by 8% to C3.96 billion in 2011 (Source –Fresenius Kabi) billion – C702 million in Asia-Pacific and C434 million the segment’s C1.44 billion turnoverwas achievedin in Latin America/Africa –which equated to 29% of total North America. By contrast, the region accounted for turnoverthat rose by 8% to C3.96 billion (see Figure 1). barely aquarter of the company’stotal turnover, and IV Drugs wasFresenius Kabi’slargest product represented 39% of the global market for injectable segment last year with an 8% sales rise to C1.44 billion, generics, excluding enoxaparin. aided by injectable drug shortages in the US. Turnover Europe makes up nearly half of the global generic by the Clinical Nutrition segment increasedby9%to injectables market, butthe region accounted for only C1.15 billion, while sales by the company’sInfusion just overafifth –orabout C300 million –ofFresenius Therapysolutions and colloids unit advanced by 6% to Kabi’sIVDrugs sales last year.This wasinsignificant C895 million (Generics bulletin,9March 2012, page 3). part because of the German group’sstrong anti- Medical Devices and Transfusion Technologies wasby infectivesand oncology positions in its domestic market, farFresenius Kabi’ssmallest product segment with where the firm had maximised the impact of recent sales ahead by 9% to C477 million (see Figure 2). launches of cancer treatments such as oxaliplatin and “The companywill continue to benefit from two topotecan by formulating infusion bags for individual major global trends: the outstanding growth in emerging- patients at its five compoundingcentres in Germany. market healthcare spending; and the increasing demand Fresenius Kabi’sIVDrugs segment derived16% for high-quality intravenous generic drugs in light of of its turnoverlast year –approximately C230 million – numerous patent expirations and healthcarebudget from emerging markets, predominantly in the Asia- constraints in the western world,’’ insisted Fresenius’ Pacific region. While this proportion waslargely in line group chief executive officer,Mark Schneider.However, with the global generic injectables market, it wasfar the firm’smedium-term forecast –which requires lower than the 29% of the company’soverall turnover increasing its earnings before interest and tax (EBIT) that wasobtained from these markets. from C803 million last year to at least C1.0 billion by “Wehaveasignificant growth opportunity in the 2015 –does not include asignificant impact from European Union and Asia-Pacific, where Fresenius biosimilars, as the company’smanagement believes Kabi’s[injectables] market share is still relatively low,” market uncertainties preclude making major investments. commented John Ducker,regional president for North With compound annual growth rates (CAGRs) America. The success of the Clinical Nutrition and overthe past five years of 16% for sales and 23% for Medical Devices segments in these regions would provide EBIT,Fresenius Kabi’stargets may appear eminently aplatform from which to target hospitals, he added. achievable. However, those CAGRs were achievedin In China, for example, IV Drugs accounted for just part through major acquisitions, not least the purchases 9% of the company’slocal turnoverofC364 million of Indian oncology specialist Dabur Pharma and US last year,assales in the firm’sthird-largest market were injectables companyAPP four years ago (Generics dominated by around C275 million from Clinical bulletin,19September 2008, page 5). Nutrition. With state health insurance nowcovering Acquiring APP in 2008 gave global scale to most of China’spopulation, Fresenius Kabi believes Fresenius Kabi’sIVDrugs segment, butitalso made the there is great potential to expand its local injectables business heavily dependent on the US and Canadian portfolio beyond its strong position with propofol. markets. Last year,63%, or just over C900 million, of Similarly,the German companysees opportunities

24 GENERICS bulletin 29 June 2012 Gen 29/6/12 Pgs.24-25_Layout 1 27/06/2012 20:08 Page 3

BUSINESS STRATEGY

to build upon its propofol franchise elsewhere in the remarked. Such abroad offering, he added, wascrucial Asia-Pacific region, while its successful compounding to competing effectively in public and private tenders. business in Australia and NewZealand could serveas Citing 2011 IMS Health data, Ducker said the global aplatform from which to create scale in fast-growing small-molecule injectables market that Fresenius Kabi local oncology markets. While India –through the wastargeting wasvalued at C9.8 billion. That figure Dabur Pharma acquisition four years ago (Generics excluded enoxaparin –which was“more likeabiologic bulletin,2May 2008, page 3) –isamajor hub for drug” –aswell as Japan due to its “particular entry developing and producing oncology generics, Fresenius barriers”. Fresenius Kabi controlled atenth of the market, Kabi acknowledges that it has yet to “capture the ranking it joint second with Sandoz behind Hospira. opportunity in India’sintravenous generics sector” by Pointing out that the IMS data showed the top-five marketing locally not only cancer therapies, butalso generic players controlling barely two-fifths of the anaesthetics, anti-infectivesand critical-caredrugs. global market, Ducker said there wasconsiderable In Latin America alone, where the firm’stotal sales scope for Fresenius Kabi to participate in anticipated rose by atenth last year to C312 million, Fresenius Kabi consolidation in the fragmented sector. claims to be among the top-three generic injectables Through initiativessuch as safety labelling, unique players in Argentina and Chile. However, it perceives doses, pre-filled syringes, dual-chambered bags and potential to capitalise on its reputation as ahigh-quality bundling oncology drugs with nutrition services, European supplier –albeit with alocal manufacturing Fresenius Kabi is seeking to differentiate its generics base –tostrengthen its position in Brazil, Colombia, portfolio. Vertical integration –such as through running Mexico and Peru, as well to expand into other markets. its ownplantations in India to source rawmaterials for “Ecuador and Costa Rica are the next targets for us,” botanically-derivedoncology molecules such as stated Marc Crouton, who oversees the region along irinotecan and paclitaxel –and economies of scale will with Africa and western and southern Europe. Crouton ensure acompetitive cost of goods, the companybelieves. “You can expect to see added that the firm’sstrong presence in Argentina Noting that several companieshad established US our geographic and could provide abase from which to push into Uruguay, sales and marketing operations to sell drugs sourced while its oncology compounding businesses in Argentina, from Asia, Ducker was“not convinced that it is the right portfolio expansion in Brazil and Chile could benefit from synergies with model, because these companies have to share what is Europe and Asia-Pacific the group’sparenteral nutrition operations. already ageneric margin among multiple partners”. In emerging markets that have an established local Acknowledging that the firm’sUSinjectablessales fuelling our growth, with industry,Fresenius Kabi intends to makeacquisitions had benefitted of late from shortages of keydrugs such to become “an insider”, with local manufacturing that as gemcitabine and propofol, Ducker recognised that aparticular focus on can respond quickly to spikes in demand and that appeals Fresenius Kabi had not been immune from such issues. emerging markets” to governments by bringingtechnology and creating Earlier this year,the firm wasissued with awarning jobs. In countries with less-established local industry, letter due to deficiencies at its facility in Grand the companyplans to takeback marketing rights from Island, NewYork (Generics bulletin,9March 2012, local distributors and to roll out its global portfolio. page 3). However, he insisted the issues highlighted in the letter were “manageable” and could be Plans to launch US range globally resolved without shutting down the plant. “Aswemove forward,”Ducker stated, “you can Ducker is in no hurry to rush into US biosimilar expect to see our geographic and portfolio expansion investments in light of the ongoing uncertainty over in Europe and Asia-Pacific fuelling our growth, with clinical studies, interchangeability and post-marketing aparticular focus on emerging markets. We are active requirements. “I don’texpect to see biosimilars in the in 145 countries, butwecertainly do not sell our full US market in anymeaningful waybefore 2016 or 2017, portfolio everywhere.”Registering the firm’sextensive and Ibelieve monoclonal antibodies will not arrive US portfolio of injectable generics in global markets before 2020,”hestated. G would generate organic growth, he maintained. Noting that manyofthe countries that the IV Drugs business wastargeting had relatively high patient co- payments –and were thus “very susceptible to generic Infusion Therapy Clinical Nutrition C895m C1,154m penetration” –Ducker said Fresenius Kabi was +6% +9% developing generic dossiers with aviewtomeeting the requirements of regulators around the world. “Weare not treating China as an afterthought,”heinsisted. Around aquarter of the 110 generics development projects that Fresenius Kabi currentlyhas underway are targeted at emerging markets, with just overathird aimed at Europe and two-fifths at the US. Viewed by therapeutic category,oncology drugs account for 36% of the projects and critical-caredrugs 23%, while anti- Medical Devices/ infectivesand anaesthetics/analgesicseach makeup Intravenous Drugs Transfusion about afifth. Fresenius Kabi had no immediate plans C1,438m Technologies +8% to expand beyond injectables into other steriledrugs, C477m such as ophthalmics, Ducker revealed. +9% Fresenius Kabi’sglobal roster of injectable molecules Figure2:Breakdown by product segment of Fresenius Kabi’s already almost matched those of Sandoz and Teva,and sales that increased by 8% to C3.96 billion in 2011 (Source – wasslightly larger than Hospira’sportfolio, Ducker Fresenius Kabi)

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PEOPLE

INDUSTRY ASSOCIATIONS APPOINTMENTS Innes becomes chair Codexis grabsNicols of Britishassociation of Albemarle as head

he British Generic ManufacturersAssociation (BGMA) has ndustrial enzymes specialist Codexis has appointed John Nicols as Tappointed Kim Innes to serveasits chair for atwo-year period. Iits president and chief executive officer.Nicols spent more than 20 Innes –who is commercial director of Teva UK’sgenerics unit –replaces years at Albemarle, most recently as the chemical company’ssenior Actavis’ Michael Cann,who will act as BGMA vice-chairfor ayear. vice-president of strategic development and catalysts. Nicols takes Praising the progress made by Cann overthe past twoyears, Innes – overatCodexis from interim chief executive officer Peter Strumph, who chaired the BGMA between 2008 and 2010 –said the association who had stepped in after Alan Shaw resigned earlier this year would “continue to focus on our three core objectivesofincreasing (Generics bulletin,23March 2012, page 27). patient access to medicines, maintaining market efficiencyand providing Shortly after Nicols’ appointment, Brian Dowd resigned as economic sustainability for the industry”. It was“crucial we do not Codexis’ interim chief financial officer,vice-president and controller. undermine the uniquely successful competitive market we have in the Nicols said he and the firm’sboard would continue searching for a UK by acontinued downward pressure on pricing”, she added. G permanent chief financial officer. G

APPOINTMENTS APPOINTMENTS Siegfried recruits Roche man MSF gets new head of access iegfried has recruited Roche’shead of technical development for édecins Sans Frontières (MSF) has appointed Dr Manica Ssmall molecules, Dr René Imwinkelried,tolead its research and MBalasegaram to takeoverasexecutive director of its Access development activities from 1September.Hewill takeoverfrom Campaign from mid-August following the departure of Dr Tido von Dr Wolfgang Wienand,who will focus on corporate strategy and Schoen-Angerer at the end of May after almost six years in the role. acquisitions –aswell as on legalaffairs and intellectual-property The Access Campaign’sdeputy director, Daniel Berman,will serveas management –asamember of the Swiss group’sexecutive committee. G interim executive director until Balasegaram assumes the position. Balasegaram –who will be based in Geneva,Switzerland –is currently head of the Leishmaniasis Clinical Program for Drugs for Neglected Diseases Initiative (DNDi). He previously worked on various MSF medical projects as well as for the group’sManson research unit. He wasalso on the board of MSF Switzerland. G

IN BRIEF STRIDES ARCOLAB’s executive director, Venkat Iyer,has stepped down from his role to “fully focus” on his duties as chief executive officer of the firm’sAgila Specialties division.

WATSON has appointed Bob Candea to become executive director of sales operations for the firm’sUSBrands division. Candea has previously held senior leadershiproles at Duramed, Endo and Teva.

NATCO PHARMA has promoted RajeevNannapaneni to the role of vice-chairman and chief executive officer of the Indian company.

INNOPHARMA has appointed John Deighan as chief financial officer.Deighan has 20 years of experience in corporate finance, having most recently served as chief financial officer of Eagle Pharma.

AESICA has promoted Ian Lafferty from chief technical officer to site director of its formulation development facility in Nottingham, UK. He will “oversee the continued growth of the site and the increased interest in high-potencyand biological formulations”.

ONYX SCIENTIFIC has appointed Brian Jolly as director of European business development for the contract manufacturer.

ADCOCK INGRAM has made former AstraZeneca employee Professor Mattias Haus anon-executive director of the South Africancompany. G

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