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Bulletin Publishing Group is a division of OTC Publications Ltd Registered Office: 4 Poplar Road, Dorridge, Solihull B93 8DB, UK. Registered in England No 2765878 Gen 19-9-14 Pg. 1_Gen 18/11/05 Pg. 1 17/09/2014 17:16 Page 1
19 September 2014
COMPANY NEWS 3 FDA’s Purple Book lists Sun’sRanbaxy deal has ‘adverse effect’ 3 Bioton sees decline in its keycountries 4 Aspen keeps it focus on anticoagulants 5 Pharmstandardrises despite 6 US biologics exclusivity OTCspin-off Cipla snaps up twofacilities forRs1bn 7 Latvia’sOlainfarm will target Mongolia 8 ‘Purple Book’ listing exclusivity expiry dates and other details of approvedUS Abiological drugs, along with any biosimilar and interchangeable counterparts, has been launched by the US Food and Drug Administration (FDA). This should “enable auser to MARKET NEWS 9 see whether aparticular biological product has been determined by the FDAtobebiosimilar to or interchangeable with areference biological product,”the agency explained. Launches save the US nearlyUS$140bn 9 Likethe ‘Orange Book’ for small-molecule drugs, the Purple Book wasan“easy-to- Luxembourg lays out 10 remember nickname” that offered a“similarly user-friendly term” for the biologics list, which substitution initiative had previously been mooted by industry as apotentiallyuseful resource for biosimilars EGA urges amending WHO 11 manufacturers (Generics bulletin,7March 2014, page 16). However, unlikethe Orange Book, INN proposals the Purple Book –comprising twoseparate lists of biological drugs approvedbythe FDA’s Center for Drug Evaluation and research(CDER) and Center for Biologics Evaluation and PRODUCT NEWS 12 Research (CBER) –does not currentlycontain patent information. “The lists include the date abiological product waslicensed,”the FDAnoted, as well as Te va overturns UK 12 the date that anyreference-product exclusivity –including paediatricexclusivity –will expire. patent forSymbicort “The Purple Book will also enable auser to see whether abiological product licensed under Te va launches arival to Canadian Cipralex 14 section 351(k) of the Public Health Service Act has been determined by FDAtobebiosimilar US courtlifts bar on rivals to Precedex 15 to or interchangeable with areference biological product,”the agencypointed out, noting that Prosonix applies for 16 biosimilarand interchangeable biologics would be listed under the related reference product. fluticasone in the EU At present, exclusivity expiry dates are listed only for Granix (tbo-filgrastim), Neupogen FDAgives answers on ‘rescue’ inhalers 17 (filgrastim) and Perjeta (pertuzumab). “Asresources permit, these lists will be updated periodically when FDAlicenses a Sandoz cuts term of 19 biological product,”the agencystated, as well as when it makes adetermination regarding the Remodulin protection date of first licensure for abiological product (Generics bulletin,5September 2014, page 13). Cipla’sinhalers reach Germany 21 The FDAhas also published aquestion-and-answer document offering further background and Sweden information on the Purple Book. G FEATURES 24
Four forces compel firms to 24 Commissionclears insulin glargine consider alternativemodels li Lilly and its partner Boehringer Ingelheim have obtained amarketing authorisation from Adverse forces are compelling Europe’s Ethe European Commission for Abasria (insulin glargine), the first insulin product approved generics players to reassesstheir operating through the European Union’sbiosimilars pathway.The Commission’sclearance of the rival models. Anew report from The Boston Consulting Group suggests some options, to Sanofi’sLantus brand follows apositive opinion issued by the European Medicines Agency as Aidan Fry outlines. (EMA) at the end of June this year (Generics bulletin,11July 2014, page 1). “Studies have shown Abasria to have acomparable quality,safety and efficacyprofile to REGULARS Lantus,”the EMA stated in recommending approvalof the biosimilar treatment for diabetes mellitus in adults, adolescents and children aged twoyears and above.Lilly and Boehringer said their “comprehensive clinical-data programme” included Phase III trials in patients with Pipeline Watch – Cetuximab and 18 type 1and type 2diabetes, as well as pharmacokinetic and pharmacodynamic studies. panitumumab Pointing out that the basal insulin had the same amino-acid sequence as Lantus, the two Paragraph IV Watch – Prolensa 20 partners said their insulin glargine would be manufactured by Lilly and would be available in pre- Events – Our regular listing 22 filled pens and cartridges for reusable pens. Noting that the Abasria brand name wasnot approvedin Price Watch UK – Our in-depth 23 certain regions, the partners are “targetting aglobal trade name” for their insulin glargine product. look at pricing trends in the UK Lilly –which is engaged in patent litigation overLantus in the US –recently filed an People – Tiefenbacher builds 27 invalidation action overtwo patents covering Lantus devices in the UK. Western Europe foundation for future accounted for C421 million (US$544 million),and the US C1.99 billion, of Sanofi’sglobal Lantus sales of C3.01 billion in the first half of this year. G Leading developer of anti-infectives for multi-drug resistant bacteria
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COMPANY NEWS
ANNUAL RESULTS MERGERS&ACQUISITIONS Price increases help Sun’s Ranbaxy deal Lannett leap ahead has ‘adverseeffect’
rice increases for products in Lannett’stwo largest therapeutic un Pharma’sproposed US$4.0 billion takeoverofRanbaxy “is Pareas –levothyroxine in thyroid deficiencytreatments and digoxin Slikely to have an appreciable adverse effect on competition”, in cardiovascular drugs –helped the US companytoraise its turnover according to the Competition Commission of India (CCI), which is by more than four-fifths to US$274 million in its financial year inviting comments and objections –with supporting documents – ended 30 June 2014. from affected parties by 25 September. Combined, the twotherapeuticareas made up around three-fifths Having demanded that the twofirms publish details of the merger of group sales. Levothyroxine sales jumped by just overthree-quarters (Generics bulletin,5September 2014, page 12), the CCI reached a to US$102 million, while digoxin sales made up the bulk, or US$54.7 prima facie opinion that the merger could be anti-competitive. million, of cardiovascular turnoverthat soared by 140% to US$62.1 According to the published details of the proposed merger,the million. Other than obesity drugs –the only category in which turnover deal to “create the fifth-largest global specialty generics company” slid –gallstone treatments were the only product group that did not would give the combined entity an Indian market share of approximately experience adouble- or treble-digit sales rise (see Figure 1). 9.2% –Sun contributing 5.35%, and Ranbaxy 3.87% –that would be Digoxin –which the firm distributes under licence from Jerome around 2.8 percentage-points higher than their nearest rival, Abbott. Stevens –was recently the subject of asubpoena receivedbyLannett “The parties have acombined presence in 18 therapeuticareas, following an investigation by the Connecticut attorney-general into 127 therapeutic groups and 246 molecules,” the disclosure reveals. Of price-fixing (Generics bulletin,8August 2014, page 22). “Our product those 246 molecules, the twofirms have shortlisted 37 for which they pricing decisions are made independently by the company,”Lannett’s hold an Indian market share of greater than 15%. That list includes president and chief executive officer,Arthur Bedrosian, told investors. dominant market shares for tamsulosin/tolterodine and rosuvastatin/ During its most recent quarter,Lannett receivedan“unexpected” ezetimibe combinations, as well as more than half the local market final US Food and Drug Administration (FDA) approvalfor diazepam for terlipressin.Two of the molecules on the list –atorvastatin and oral concentrate5mg/ml, as well as nods for codeine sulphate 15mg, losartan –fall under the Indian government’snational list of essential 30mg and 60mg tablets and oxycodone 5mg capsules. medicines (NLEM) that are subject to price controls. These approvals left 23 abbreviated newdrug applications “There are manylarge international and domestic pharma (ANDAs) pendingwith the FDA, of which four contain paragraph IV companies that compete with the parties in the market and will continue challenges including for arivaltoImpax’ Zomig (zolmitriptan) nasal to exercise competitive constraints on the combined entity post the spray (Generics bulletin,8August 2014, page 25). In addition, the transaction,”the twofirms claim in their disclosure. Ranbaxy,it US firm has apipeline of 45 ANDAs or newdrug applications (NDAs) acknowledges, “has been facing regulatory and growth challenges”. in development, including an NDAfor an oxycodone oral solution. “The merger between Sun and Ranbaxy would not foreclose the Lannett has also just bolstered its portfolio by acquiring ANDAs upstream market for active pharmaceutical ingredients (APIs) or the for estradiol tablets and selegiline capsules from an unnamed vendor, downstream market for formulations,”theyinsist, noting that the deal and has struck separate distribution agreements for zidovudine tablets would also give Sun Ranbaxy’s46.8% holding in Hyderabad-based and an authorised generic of Symplmed’sAceon (perindopril biotech firm Zenotech. G erbumine) tablets. Bedrosian stated that recent merger and acquisition discussions with a“number of parties” had not been fruitful,but the companycontinued to search for adeal in a“tax-favourable jurisdiction”. MANUFACTURING Even including aUS$20.1 million charge linked to extending its contract with JSP last year,Lannett’soperating profit more than Galenicum acquiresafactory quadrupled to US$88.1 million. G alenicum is acquiring aproductionplant located near Madrid, Therapeutic Annual sales Change Proportion GSpain, from Merck, Sharp &Dohme for an undisclosed price. The category (US$ millions) (%) of total (%) Spanish companysaid the deal would help it to produce the pipeline of products it wasdeveloping, to continue growing organically and to Thyroid deficiency102.2 +76 37 maintain “absolute independence”. The Spanish companyintends to Cardiovascular 62.1 +140 23 invest C10 million (US$13 million) in modernising the 24,000 sq m Pain management 27.2 +28 10 facility to give it an annual capacity of 2.0 billion tablets, 20 million Migraine 14.5 +168 5 liquid-filled bottles and 43 million tubes of cream. Antibiotics 13.6 +48 5 Buying the factory in San Augustín de Guadalix via its affiliate SAG Manufacturing would, Galenicum said, allowittooptimise its production Glaucoma 12.0 +87 4 capacity and gain greater control overmanufacturing processes. Gout 10.8 +113 4 The Barcelona-based firm –which has offices in Madrid, as well Gallstone 6.6 +8 2 as in Brazil, Chile, Peru, Malta, China and India –recently completed Obesity 4.0 -15 1 adevelopment process for the antibiotic tigecycline using “substantial Other 20.7 +129 8 innovations” in lyophilisation.Galenicum has also secured clearance Lannett 273.8 +81 100 to conduct bioequivalence studies for the thrombocytosis treatment anagrelide and for the Parkinson’s disease drug rasagiline. It intends Figure1:Breakdown by therapeutic categoryofLannett’s sales in its financial to start decentralised marketing-authorisation procedures for both year ended 30 June 2014 (Source –Lannett) products once data-exclusivity periods expire. G
19 September 2014 GENERICS bulletin 3 Gen 19-9-14 Pgs. 3-9_Layout 1 17/09/2014 17:22 Page 4
COMPANY NEWS
STRATEGICALLIANCES FIRST-HALF RESULTS Lupin suppliesMerck Biotonsees decline in emerging markets in its key countries
upin will work with Merck Serono to develop, manufacture and eclines in sales in its keymarkets including Australia, China, Lmarket arange of “affordable, high-quality medicines” in emerging DIndia, Italy and Russia caused Poland’sBioton to report a5.9% fall markets under the provisions of a“long-term strategic partnership” to PlZ157 million (US$48.4 million) in group turnoverinthe first struck between the twofirms. half of this year.But pre-tax profit rose by 68.8% to PlZ7.82 million. “Through this partnership, Merck Serono will expand its overall TurnoverinIndia declined by 29.4% to PlZ6.80 million, whilst portfolio in core therapeuticareas in selected countries in Latin sales in Italy and China slipped more sharply,each falling by overa America, Asia, Central and Eastern Europe and Africa,”the German third to PlZ11.0 million and PlZ5.50 million respectively.InRussia – firm said, adding that this covered “major markets” such as Brazil, where Bioton had recently struck adeal with local firm Biotec to Mexico, Indonesia and the Philippines. Last year,Merck Serono – produce, distribute and market insulin brands (Generics bulletin,11 the biopharmaceuticals arm of Germany’sMerck KGaA –had July 2014, page 24) –sales fell by 6.4% to PlZ13.9 million and sales in emerging markets of almost C1.8 billion (US$2.3 billion). Australian turnoverdecreased by 5.4% to PlZ14.0 million. However, Under the terms of their alliance, Lupin will develop products, sales in South Korea climbed by 73.5% to PlZ8.44 million and in provide product dossiers and supply finished-dose formulations to Thailand turnoverimprovedby5.3% to PlZ7.22 million. Merck Serono, which will hold marketing authorisations and capitalise The Polish firm’stotal domestic sales dropped by 8.3% to PlZ50.2 on its local distribution networks. Noting that the agreement primarily million (see Figure 1). Meanwhile, its gross profit margin advanced covered cardiovascular and diabetes treatments in emerging markets, by 2.5 percentage points to 44.6%. G Lupin said the twowould also supply to Africa drugs in additional therapeutic areas, “reflecting local healthcare needs, such as the Country First-half sales Change Proportion availability of antibiotics”. (PlZ millions) (%) of total (%) Poland 50.2 -8.3 32 Cover up to 20 launches Australia 14.0 -5.4 9 Lupin said the agreement –which “builds on an establishedworking Russia 13.9 -6.4 9 relationship between the twocompanies” –could add “up to 20” new Italy 11.0 -37.1 7 products to Merck’sGeneral Medicines portfolio in emerging markets. The first launches are slated for 2016. Financial details of the agreement South Korea 8.4 +73.5 5 were not disclosed, although Lupin said it would receive an upfront Thailand 7.2 +5.3 5 payment from Merck Serono, along with milestone-based licensing fees. India 6.8 -29.4 4 Earlier this year,Lupin expanded its footprint in emerging markets China 5.5 -36.0 4 after acquiring Mexican ophthalmics specialist Laboratorios Grin for Others 39.5 +14.2 25 an undisclosed sum (Generics bulletin,4April 2014, page 3). The Indian firm has also in 2014 boughtDutch drug delivery specialist Bioton 156.5 -5.9 100 Nanomi, and allied with Japan’sYoshindo to develop biosimilars for Figure 1:Breakdownby country of Bioton’s salesin the first half of 2014 the local market. G (Source –Bioton)
19 September 2014 Issue 218 published 20 times ayear – twice monthly, except and areprotected by copyright, trademark and other laws. monthlyinJuly, August, December and January, and Editor: Aidan Fry Subscription enquiries: As left, or delivered by air mail – and afreeweeklyemail [email protected] Deputy Editor: David Wallace newsflash News@Genericsbulletin published 46 Assistant Editor: Liudmila Kotko times ayear.Individual annual subscriptions in Europe Te rms &Conditions: No partofthis publication maybe copied, reproduced, stored in aretrieval system, distributed cost £620 (additional copies at the same address Business Reporter: Dean Rudge or transmitted by anymeans, including electronic,mechanical, Production Controller: Debi Minal £395); outside Europe £650 (£425). photocopying or recording, without the prior written Production Editor: Jenna Meredith The 20 Generics bulletin newsletters arenow available permission of the publisher,orunder the terms and conditions as adigital edition, Generics bulletin-i,for either of aGlobal Site Licence or of alicence issued by the Copyright Director of Subscriptions: ValDavis Licensing Agency (CLA) in London, UK, or rights bodies in Apple or Android mobile devices at acost of £895. Group Sales Manager: Anisa Shan other countries that have reciprocal agreements with the CLA. This subscription includes News@Genericsbulletin. Awards Manager: Natalie Cornwell Neither maythis publication be exported, distributed or Managing Director: MikeRice Acombined annual subscription to Generics bulletin circulated by anymeans outside the staff who work at the (hard-copynewsletter plus weekly email newsflash)and address to which it is sent by the publisher without the prior written permission of the publisher. Editorial enquiries: GENERICS bulletin, Generics bulletin-i (digital edition)costs £1,095. 4Poplar Road, Dorridge,Solihull, While due carehas been taken to ensurethe accuracy of Single hard-copynewsletters cost £50 each. Subscription information contained in this publication, the publisher makes West Midlands B93 8DB, UK. rates maybeadjusted to coverany period and can be no claim that it is free of errorand disclaims anyliability Website: www.generics-bulletin.com backdated. Subscriptions mayonlybecancelled at expiry. whatsoeverfor anydecisions or actions taken as aresult Te l: +44 (0)1564 777550 Fax: +44 (0)1564 777524 of its contents. Corporate subscriptions: Global Site Licences are E-mail: [email protected] ® available to companies.These provide in-house electronic ©OTC Publications Ltd.All rights reserved. Generics bulletin Advertising enquiries: is registered as atrademark in the European Community. access forstaff to Generics bulletin or Generics As above,[email protected] bulletin-i and [email protected] ask for ISSN 1742-0784. SUBSCRIPTIONS aquotation. Such licences aresupplied strictlyonthe Companyregistered in England No 2765878. Individual subscriptions: A GENERICS bulletin condition that both publications arethe intellectual Printed by Warwick Printing CompanyLimited, annual subscription includes this hard-copynewsletter property of the copyright holder,OTC Publications Ltd, Leamington Spa CV31 1QD, UK.
4 GENERICS bulletin 19 September 2014 Gen 19-9-14 Pgs. 3-9_Layout 1 17/09/2014 17:22 Page 5
COMPANY NEWS
BUSINESS STRATEGY/ANNUAL RESULTS Aspen keepsits focus on anticoagulants
spen Pharmacare says it remains focused on expanding its global Region Annual sales Change Proportion Aanticoagulants presence, as it seeks to realise “newand important (ZAR millions) (%) of total (%) growth drivers” from the raft of “significant” acquisitions it has completed overthe last 12 months. Europe/CIS 7,200 +419 24 “There are opportunities to grow, particularly in emerging Latin America 3,485 +122 12 markets,”the South African firm said of the Arixtra (fondaparinux) Rest of world 1,745 +181 6 and Fraxiparine (nadroparin) deep-vein thrombosis (DVT) injectable International 12,430+248 42 brands that it last year bought for £700 million (US$1.14 billion) from GlaxoSmithKline (GSK), along with arelated manufacturing plant Asia-Pacific 8,799 +14 30 in Notre-Dame-de-Bondeville (NDB), France (Generics bulletin, South Africa 7,451 +1 25 28 June 2013, page 5). Sub-Saharan Africa 2,753 +30 9 Furthermore, “once unconstrained supply of active pharmaceutical ingredients (APIs)” is secured, Aspen plans to extend the number of Eliminations -1,918 +31 -6 territories where its fractionated heparin Orgaran (danaparoid) Aspen 29,515 +53 100 brand is marketed. Orgaran wasone of 11 brands acquired in aUS$1.0 billion tie-up with Merck &Colast year,which also included Merck’s Figure1:Breakdown by region of Aspen’s sales in its financial year ended API business in the Netherlands that Aspen operates under the Aspen 30 June 2014 (Source –Aspen) Oss and Aspen API names (Generics bulletin,12July 2013, page 3). Aproject to tackle supply limitations of danaparoid was arange of infant-nutrition brands from Nestlé (Generics bulletin,3 “progressing positively”, the firm said, along with abid to lower the May 2013, page 2) –caused total Latin American sales to jump by 122% cost of producing all three DVTtreatments by increasing production to ZAR3.49 billion. Brazilian sales fell by 4% to ZAR788 million. of finished-dose formulations at the NDB site, which joined Aspen in Aspen’soperations in the rest of the world also experienced a April this year.“Additional capacity [at NDB] is being added with the triple-digit sales climb, soaring by 181% to ZAR1.75 billion on the construction of an entirely newproductionarea,”the firm revealed, back of “increased exposure to the US”. adding that its under-construction sterile facility in Port Elizabeth, South The bulk of Aspen’sAsia-Pacific turnoverthat rose by 14% to Africa, would also be used to supply the GSK brands once operational. ZAR8.80 billion came from Australia and NewZealand, where sales However, Aspen commented, “significant activity” had been increased by just overatenth to ZAR7.88 billion. Former GSK necessary at the Oss and NDB sites due to the current condition of brands added ZAR635 million to turnover, while nutritional sales their operations. At Oss, “improvements to the safety profile of the were oversix times higher at ZAR904 million. site were receiving urgent attention”, Aspen noted. In Australia, Aspen said it would move away from co-marketed and licensed products in order to focus on its ownhigher-margin Sold US Arixtra rights to Mylan brands, while the South African firm also noted that its Noble Park Meanwhile, Aspen has just agreed to sell US sales, marketing and and Baulkham Hills facilities were both scheduled to be divested intellectual-property rights for Arixtra –aswell as an authorised overthe next 12 months. generic –toMylan in adeal worth US$300 million (see page 19). The rest of Asia-Pacific turnovercame from Asia, where Japan That deal formed apart of Aspen’sgreater strategy to trim its and the Philippines together made up just overhalf of regional sales pipeline of products that are unlikely to “achieve medium-term growth that rose by 63% to ZAR923 million. “Over athird of growth was for stakeholders”,such as its agreement to divest its Herron OTC organic,”Aspen commented. range to Perrigo in Australia and NewZealand for US$51 million In the South African firm’sdomestic market, acombination of earlier this year (Generics bulletin,21March 2014, page 19). lower antiretroviral prices and volumes –along with the “inexplicable In total, acquisitions of ZAR19.8billion overthe last 12 months trend” of lower tender sales “givengrowing patient numbers” –caused helped the firm to increase its sales by 53% to ZAR29.5billion in its turnovertovirtually stall at ZAR7.45 billion. This wasinspite of financial year ended 30 June 2014. And as aresult, Aspen’sInternational private-sector pharmaceutical and consumer sales that both climbed region –comprising Europe and the Commonwealth of Independent by around atenth –9%and 12% –toZAR4.75 billion and ZAR1.31 States (CIS), Latin America and the rest of the world –comfortably billion respectively.“Aspen has remained the largest supplier of tablets became the firm’slargest by sales, as International turnovermore and capsules to the public sector under the recently awarded oral-solid than trebled to ZAR12.4 billion (see Figure 1). dose tender,” the firm pointed out, adding that the expansion of its fine In Europe and the CIS –where Aspen has from 1January chemicals facility in Cape Town was“proceeding”. introduced a“specialised sales and marketing team” comprised of 400 West Africa accounted for 56% of Aspen’sSub-Saharan Africa personnel in 18 countries –turnoverwas more than five times higher turnoverthat rose by 30% to ZAR2.75 billion. East Africa made up at ZAR7.20 billion. Eastern Europe and the CIS made up ZAR1.07 just overathird, while Southern African sales amounted to just under billion of that total, against ZAR75 million in the prior-year period, atenth of turnover. “[The region] is likely to continue to delivergood while Western European sales more than trebled to ZAR2.88 billion. organic growth, provided socio-political influencesdonot interfere Just overaquarter of sales came from European API and finished-dose unduly,” the South African firm said, noting it wasreviewing potential contract-manufacturing turnover, which wasaround seven-and-a-half opportunitiesfor expansion. times higher at ZAR3.24 billion. Those increased sales sawAspen’soperating profit increase by 47% Meanwhile, “good performances” in Mexico and Venezuela to ZAR7.42 billion, of which 78% wasgenerated outside of South resulting from the Merck acquisitions pushed Spanish Latin American Africa. But the firm’soperating margin dipped by just under a pharmaceutical sales up by 57% to ZAR1.18 billion, as aZAR1.52 billion percentage-point to 25.2% as Aspen incurred transaction costs of contribution from infant-milk formula products –gained from buying ZAR339 million. G
19 September 2014 GENERICS bulletin 5 Gen 19-9-14 Pgs. 3-9_Layout 1 17/09/2014 17:22 Page 6
COMPANY NEWS
ANNUAL RESULTS FIRST-HALF RESULTS Pack and Rising aid Pharmstandardrises Aceto’spharma sales despite OTC spin-off
aunching five generics through its Rising Pharmaceuticals arm, harmstandard’sturnoveredged ahead by 2% to RUR17.2 billion Lcombined with atwo-month contribution from US generics specialist P(US$467 million) in the first half of this year as higher prescription- Pack Pharmaceuticals, helped Aceto to increase sales through its Human drug sales and supplies to the Russian firm’srecently spun-off Health business by 23.6% to US$160 million during its financial year OTCPharm affiliate more than offset lower sales of OTCbrands and ended 30 June 2014. Of those five launches, three came in the fourth products distributed for third parties. quarter alone, with the introduction of an authorised generic to Validus’ Prescription turnoverahead by 4% to RUR3.04 billion included Lotensin HCT (benazepril hydrochloride/hydrochlorothiazide) quickly sales of the best-selling products Phosphogliv(glycyrrhizic acid), followed by Aceto shippinggeneric rivals to Pfizer’sDiflucan Combilipen (lidocaine)and Octolipen (alpha-lipoic acid) that increased (fluconazole) and Daiichi Sankyo’sEvoxac (cevimeline). by 39.2% to RUR731 million, by 14.6% to RUR326 million and by Rising’sHuman Health sales grewbyUS$15.1 million, while Pack 24.5% to RUR167 million respectively.Doxorubicin made afirst-time contributed US$8.1 million. Having tied up its US$100 million move contribution of RUR29.5 million. for the latter barely amonth after the deal wasfirst announced earlier Following the spin-offofOTCPharm from 1April (Generics bulletin,7March 2014, page 8), Pharmstandard’sown OTCsales Business Annual sales Change Gross margin fell by 45% to RUR3.64 billion, reducing its total Pharmaceutical Segment (US$ millions) (%) (%) turnoverby23% to RUR12.3 billion. But supplying rawmaterials Pharma Ingredients 176 -4.6 20.8 and finished products to OTCPharm generated first-time revenues Performance Chemicals 174 -6.3 17.1 of RUR3.60 billion (see Figure 1). Human Health 160 +23.6 30.3 Reduksin hit third-party sales Aceto 510 +2.1 22.5 Meanwhile, sales of third-party products that amounted to over two-fifths of the company’stotal turnoverdropped by 12% to Figure 1:Breakdownby businesssegment ofAceto’s sales and gross margin in RUR5.20 billion. Pharmstandard attributed this decline largely to sales its financialyear ended30June 2014 (Source –Aceto) of Reduksin (sibutramine)falling by 65% to RUR508 million. The this year (Generics bulletin,4April 2014, page 3), Aceto has more firm said it had suspended distribution of the obesity treatment after than doubled its pipeline of abbreviated newdrug applications (ANDAs) the Russian Ministry of Health enforced alist of medicines and to around 90, and has also made aforay into branded generics. pharmaceutical substances subjected to the special controls. “Aceto has made significant progress toward becoming amore Astronger contribution from third-party products helped Human Health-orientated company,”Aceto’schief executive officer, Pharmstandard’soperating profit to rise by 29% to RUR5.36 billion. Sal Guccione, commented, pointing out that the company’sthree Alongside recent agreements to produce Novartis’ Tasigna business segments nowmade roughly equal contributions to turnover. (nilotinib)and Merck-Serono’sRebif (interferon-beta-1a) in Russia, “[Four years ago] Human Health accounted for only 14% [of group the companyinJuly acquired a20% stakeinbiotech developer Biocad sales] and Performance Chemicals almost half,”hestated. (Generics bulletin,6June 2014, page 5). G As can be seen from Figure 1, turnovergrowth in the year to June waslimited to just 2.1% –moving ahead to US$510 million –asAceto’s First-half sales Change Proportion Performance Chemicals and Pharma Ingredients segments both suffered (RUR millions) (%) of total (%) single-digit slips. Responding to investors, Guccione said the firm had “no plans at this point” to sell its Performance Chemicals division. “We Third-party products 5,202 -12 30 likethe cash flowthat business provides,”henoted, adding that any OTC3,637 -45 21 further acquisitions would bolster the firm’sHuman Health arm. Prescription 3,037 +4 18 Stronger gross profits across all three business segments more Drug substances 466 -9 3 than offset the effect of Aceto almost doubling its research and Pharmaceuticals 12,342 -23 72 development investment to US$5.22 million, as the firm’soperating profit increased by 28.6% to US$44.3 million. OTCPharma supplies 3,596 –21 In its current financial year ending June 2015, Guccione said the Other 1,286 +38 8 firm wastargetting double-digit sales growth through the scheduled Pharmstandard 17,224 +2 100 launch of afurther 11 generics –two of which would be first-to-market – and afull-year contribution from Pack. Furthermore, he added, Aceto Figure 1:Breakdownby businesssegment ofPharmstandard’s salesin the first would raise its research and development spending to US$9.0 million. G half of 2014 (Source–Pharmstandard) IN BRIEF IN BRIEF
SCINOPHARM said generics projects accounted for more than WATSONS DRUGSTORES in the Philippines has introduced a three-quarters of group sales that fell by 11% to NT$2.25 billion ‘Buy Generics and Save’campaign that includes grouping its (US$74.5 million) in the first half of this year.Contract research generics offers from partners in adedicated counter within its and manufacturing made up 23% of sales. The Taiwanese bulk-drugs pharmacyunits. The retailer said it wasworking with generics specialist’soperating profit halved to NT$395 million. G partners including Pharex, Ritemed and Unilab. G
6 GENERICS bulletin 19 September 2014 Gen 19-9-14 Pgs. 3-9_Layout 1 17/09/2014 17:22 Page 7
COMPANY NEWS
FIRST-HALF RESULTS MANUFACTURING Oncology launches Ciplasnaps up two bolster Veropharm facilities for Rs1bn
aunching newstrengths and dosage forms of oncology drugs ipla is spending Rs1.01 billion (US$16.8 million) to acquire – Lincluding Gistamel (imatinib), Maverex(vinorelbine) and Tautax Cthrough its Medispray Laboratories subsidiary –two manufacturing (docetaxel) helped Veropharm to increase its prescription-drug sales by facilities in India from twoOkasa companies controlledbyrelatives 9.2% to RUR1.96 billion (US$53.0 million) in the first half of this year. of the Indian firm’sowner-operators. “A significant portion of the Sales of Veropharm’sfivebest-selling prescription brands –Tautax [facilities’] capacities are [already] dedicated to the manufacture of plus Amigrenin (sumatriptan), Cerepro (choline alfoscerate), Geptor Cipla’sproducts,”Cipla stated, promising “operational synergies”. (ademetionine) and Irunine (itraconazole) –amounted to RUR948 Almost three-quarters –orRs719 million –ofthat total wasspent million, or 35.3% of the Russian firm’stotal turnover, which rose on Okasa Pharma’sfacility in Satara, Maharashtra, while the remaining by 12.4% to RUR2.69 billion. Rs290 million wasspent on Okasa Private’splant located in Goa. Meanwhile, the Russian firm’sOTC sales climbed by 5.2% to The deal for the twoplants is the latest in Cipla’sdrive to expand RUR404 million. Over three-fifths of that total came from Xilen its operations inorganically,which has included buying monoclonal (xylometazoline). Other operationsadded RUR329 million to the antibody developer Mabpharm and acquiring majority stakes in firms in group’stotal turnover. Veropharm’soperating profit fell by 10.8% Yemen and Sri Lanka (Generics bulletin,11July 2014, page 2). to RUR584 million. Building “organisational capability” including manufacturing The Russian companyachieved96.6% of its turnoverinits domestic capacity is one of five priorities identified by Cipla for its financial market, with exports contributing the other 3.4%. During the period, year ending March 2015. Managing director and chief executive officer Veropharm registered eight products, includingfour antineoplastic agents, Subhanu Saxena said the companywould strengthen its position in in the Commonwealth of Independent States (CIS) and Mongolia. India and South Africa –having bought out its Medpro marketing Russia’sgovernment commissiononmonitoring foreign investments partner in the latter –while it established“afront-end presence in recently approvedVeropharm’sUS$650 million takeoverbyAbbott select international markets”. (Generics bulletin,11July 2014, page 1). According to the Commission, Such sales and marketing front ends, Saxena said, would support the deal also includes another US$250 million that will be invested pipeline launches including respiratory drugs in Europe (see page 21). in constructing production facilities. G Cipla also plans to invest in development and to simplify its business. G
19 September 2014 GENERICS bulletin 7 Gen 19-9-14 Pgs. 3-9_Layout 1 17/09/2014 17:22 Page 8
COMPANY NEWS
MANUFACTURING/FIRST-HALF RESULTS BUSINESS STRATEGY/FIRST-HALF RESULTS Siegfried completes Latvia’sOlainfarm its Chinesefacility willtarget Mongolia
iegfried has finished building an active pharmaceutical ingredient lainfarmintends to start selling its products inMongolia by the end S(API) facility in Nantong, China, and is nowperforming validation Oof this year. The Latviancompanyalso plans to beginmarketing runs on the equipmentithas installed ahead of commercial production the portfolio of its Silvanols subsidiary –thefood-supplements firm that will start early next year.The Swiss group says the Chinese site in whichOlainfarmraised its stake to 70.9% lastyear (Generics will give it “300 cubic metres of cost-competitive capacity”. bulletin,28 June2013,page 8) –in its “traditionalmarkets”. An API facility in Zofingen, Switzerland, that is being constructed Mongolia wasamong 12 countries in whichthecompanysecured to the same design to streamline product transfers is scheduled to open atotal of 27 productapprovalsduring the firsthalf ofthis year,with in mid-2015, “replacing several older buildings that can no longer Kosovo, Poland and Romania among the others.The firm alsohas be run efficiently”. The group has also expanded its spray-drying marketing authorisationspending approval incountriesincluding capacity at its site in Pennsville, US. Bosnia&Herzegovina and Turkey. The Swiss group’sturnovertumbled by 16.0% to SFr165 million At present, Russia and Ukraineaccount for around halfof (US$181 million) in the first half of this year as its sales of finished- Olainfarm’s groupturnover,while afurther fifth comes fromthe dose Drug Products slid by 37.2% to SFr38.7 million. “This wasdue Latviangroup’s domestic market. mainly to the fact that several customers were less successfulwith Thegroupovercametheupheavalin Russia and Ukraineto post their tender business compared to the previous year,” the firm stated. afirst-half41% turnover increaseto C48.6million(US$62.9 million) Positive volume developments could not prevent a6.4% decline on higher sales in Poland. Olainfarm quadrupleditssales in Ukraine, in active pharmaceutical ingredients(APIs) turnovertoSFr126 million, almost trebled turnover intheNetherlands and doubleditssales in of which 43% came from controlledsubstances and 57% from Uzbekistan. But currencydevaluation cut its turnover inKazakhstan. exclusive-synthesis projects. Tight cost controls helped to lift the Aslightlystrongergrossmargin helped the Latvian group to group’soperating profit by 6.9% to SFr16.6 million. improveitsearningsbefore interestandtax(EBIT) by 79% to C11.3 Having bought California’sAlliance Medical Products (AMP) two million.However, in lightof the “tense relationsbetween Russia and years ago, Siegfried said it waslooking for further sterile-filling Ukraine”, Olainfarm tookaprovision on all receivables outstanding acquisitions in Europe or on the east coast of the US. G from these countries as of 30 June. G
8 GENERICS bulletin 19 September 2014 Gen 19-9-14 Pgs. 3-9_Layout 1 17/09/2014 17:22 Page 9
MARKET NEWS
PRICING&REIMBURSEMENT MARKET RESEARCH Spectrum seeks bids Launchessave the as Barmer hands out US nearly US$140bn
eading German health insurance fund group SpectrumK has enerics that came to the US market during 2013 savedthe country’s Llaunched its largest generics tender to date by inviting offers to Ghealthcaresystem US$140 billion last year,according to an analysis supply 195 active ingredients or combinations with combined annual conducted by IMS Health for the US Generic Pharmaceutical sales through the group of 70 funds of around C400 million (US$517 Association (GPhA). Coupled with US$98 billion from generics that million). In total, the 70 funds insure around 8million Germans. were on the market before 2013, total savings generated by the industry The 195 ingredients covered by SpectrumK’s12th tender round amounted to US$239 billion last year,anincrease of 14%, or US$30 are divided into 278 bidding lots. Forjust over100 of the lots, the billion, overthe US$209 billion achievedin2012 (see Figure 1). group of funds intends to strikedeals with three suppliers. All of the Athird of the US$239 billion total savings last year came from other lots will be awarded on an exclusive basis. nervous system drugs, while cardiovascular treatments generated almost Interested parties have until 16 October to submit bids. Most of aquarter of the total. Metabolic drugs accounted for 14% of the figure, the supply contracts will begin on 1January 2015 and run for twoyears, while anti-infectivesproduced 7% of the savings. although deals for 60 lots will start on 1February 2015. According to the GPhA’s sixth annual drug savings report, generics Meanwhile, one of Germany’slargest funds, Barmer-GEK, has have savedthe US healthcaresystem close to US$1.5 trillion over just awarded supply contracts in its sixth tender round, which covers the past decade. 138 molecules or combinations –divided into 146 bidding lots –with The savings were calculated on the basis of the average ex- annual sales through the fund of C414 million. For41lots, the fund manufacturer brand price during the final year of patent protection. They awarded exclusive contracts, while it has appointed up to three suppliers represent the difference between the cost of the generics and the amount for the other 105 lots. Contracts will begin on 1November and will theywould have cost if theyhad been sold at the average brand price. run until the end of 2016. Generics had played a“keyrole in the downturn of rising health Among the winners of exclusive supply contracts were: Aurobindo costs” in the US, the GPhA stated, pointing out that the country’s for quinapril/hydrochlorothiazideand valaciclovir; Mylan for baclofen Congressional Budget Office had recently forecasted that Medicare and lorazepam; and Neuraxpharm for amitriptyline and zolmitriptan. spending would drop by US$49 billion –less than 1% –between Hexal secured exclusive deals for alfacalcidol,benazepril/ 2015 and 2024, while Medicaid spending would drop by US$40 hydrochlorothiazide, calcitriol and hydrocortisone,while sister firm billion –around 1% –overthe same period. 1A Pharma got acontract for piretanide.The Teva/Ratiopharm bidding “This track record of savings is unparalleled,”said GPhA president consortium wassuccessful with bids to supply on an exclusive basis and chief executive officer Ralph Neas, adding that “the savings will alprazolam, bromocriptine, clonidine and diazepam, as well as growsubstantially as we enter the era of biosimilars, the next frontier erythromycin, lormetazepam, perindopril/indapamide and propafenone. of generic industry innovation”. Barmer-GEK awarded exclusive contracts for Sanofi’sZentiva to “With FDA’sfirst acceptance of the application for afiling of a supply fexofenadine, flupirtine, ramipril/piretanide and sulfasalazine, biosimilartherapythis year” –Sandoz’ filgrastim (Generics bulletin, while Zentiva teamed up with Stada’sAliud to secure adeal for 8August 2014, page 1) –“the next decade promises to showmajor formoterol. Aliud gained an exclusive contract for cefixime. cost savings from biosimilars,”the US association stated, “with the potential to reach more than US$250 billion over10years according Multiple partners strengthen compliance to Express Scripts.” Pointing out that it had awarded only just overaquarter of the lots Pointing out that the timing of the IMS study coincided with the exclusively,Barmer-GEK said “the multiple-partner model opens up 30th anniversary of the Hatch-Waxman Act that wassigned into law alternativesfor doctors, pharmacists and patients, and also strengthens in September 1984, Neas said the regulatory framework introduced by therapeutic compliance”. Furthermore, having several drugs from which the Act had “yielded hundreds of unprecedented medical breakthroughs to choose had “positive effects on availability”. by rewarding innovation, and trillions of dollars in savings from Meanwhile, the IKK Classic fund –Germany’ssixth-largest with encouraging competition”. G 3.6 million members –has awarded 369 supply contracts for drugs with annual sales through the fund of C347 million. The tender covered 165 moleculesorcombinations,divided into 204 bidding lots, with 239 250 two-year contracts to start on 1January 2015. While it favoured the 209 193 multiple-partnermodel, relatively lowvolumes in some cases led the 200 fund to award around one in five contracts on an exclusive basis. 173 Noting that 49 of the 81 bidding firms and consortia had secured 156 at least one contract, IKK Classic said 42% of its contracts were 150 130 divided between Germany’stop-three generics players: Hexal/Sandoz, 111 92 100 82 Teva/Ratiopharm and Stada/Aliud. 74 According to official figures unveiled by the country’sministry Savings (US$ billions) of health, savings achievedthrough tenders organised by statutory 50 health insurance funds in Germanyincreased by around 15% to C1.5 billion in the first half of this year.Nevertheless, the funds’ total 0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 medicines spending increased by 8.9%, which the ministry attributed to “providing newinnovative medicines” and to the expiry at the end Figure1:Annual US savings generated through using generics between 2004 of last year of amandatory 16% clawback on patented drugs. G and 2013 (Source –IMS/GPhA)
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MARKET NEWS
MARKET RESEARCH GENERIC SUBSTITUTION French figures show Luxembourglays out ‘worrying’ sales drop substitution initiative
rench sales of generics fell by 11% in value and 4.6% in volume uxembourgisaiming to save around C2million (US$2.58 million) Fin July 2014, according to figures that have just been published Lannually by introducing generic substitution for statins and proton- by local generic industry association Gemme. pump inhibitors (PPIs) from 1October,according to plans set out by This “worrying drop” represented “the market’smost significant the country’shealth minister,Lydia Mutsch. At the same time, apublic fall in volume since the introduction of the tierspayant contre information campaign will be launched explaining the initiative and génériques scheme”, which allows patients to be instantly reimbursed for outlining the benefits of generic substitution. their prescription at the point of dispensing only if theyaccept ageneric “Contrary to other European countries, Luxembourghas opted for (Generics bulletin,14September 2012, page 11). amoderate approach, initiallylimiting itself to twoproduct groups Moreover, the association noted, the rate of generic substitution for substitution,”the country’sMinistry of Health explained, adding for eligible prescriptions had fallen to 75.1%, which Gemme said was that the substitution framework would involvethe Ministry defining the lowest figure since the start of the year.“This confirms the alist of eligible medicines. Patients will be able to opt for amore downward trend seen in the first quarter”, the associationstated expensive alternative butwill have to pay the difference. (Generics bulletin,16May 2014, page 14), renewing its call for Noting that generic statins and PPIs were on average around 30% government measures to encouragegreater prescriptionwithin the cheaper than their branded equivalents in Luxembourg, the Ministry country’s répertoire of substitutablegenerics, including apublic said the twoproduct groups accounted for around atenth of total information campaign. spending by local health insurer CNS. An initial evaluation of the Meanwhile, an order published in France’s Official Journal has substitution initiative will be conducted at the end of 2015. from the start of September set French suppliers of generics alimit Meanwhile, apublic information campaign has been launched on customer rebates or discounts of no more than 40% of the pre-tax featuring the slogan “whychoose generic medicines?”. Emphasising ex-factory price of the productssupplied. Forproducts that are subject the equivalent quality and efficacyaswell as the lower cost of generics to areference price –or tarif forfaitairederesponsabilité (TFR) – compared to brands, the campaign’sposters showimages of two rebates or other “commercial advantages” must not exceed 40% of identical capsules, bottles of water or loavesofbread, with vastly the relevant pre-tax ex-factory price. G different prices. Internet advertising will also support the campaign. G
REGULATORY AFFAIRS Romanian body urges action
oncrete measures to support Romania’sgenerics industry should Cbe introduced by the country’sgovernment, according to local generics industry association APMGR. While the association welcomed the recognition of the value of Romania’spharmaceutical industry in acompetitiveness strategy unveiled by the country’sEconomics Ministry,APMGR said this should be accompanied by adifferential calculation for generics firms of the pharmaceutical clawback tax. Furthermore, APMGR said Romanian doctors should prescribe medicines by brand name rather than by international nonproprietary name (INN) to ensure that patients receive the specific products prescribed bydoctors. Curbing “excessive discounts” would also remove barrierstoaccess for generics in pharmacies, APMGR suggested. G
REGULATORY AFFAIRS FDA guides on corresponding equests for guidance on designing bioequivalence studies, for Rreviewing bioequivalence clinical protocols and for meetings prior to submitting abbreviated newdrug applications (ANDAs) will be excluded from target dates for the US Food and Drug Administration (FDA) to respond to controlled correspondence, according to adraft guidance that the agencyhas released for comment. Under acommitment letter on implementing the 2012 Generic Drug User Fee Amendments (GDUFA), the FDAhas pledged in its fiscal year starting October 2014 to respond to 70% of controlled correspondence within four months from submission. G
10 GENERICS bulletin 19 September 2014 Gen 19-9-14 Pgs. 10-12_Layout 1 17/09/2014 17:17 Page 3
MARKET NEWS
IN BRIEF REGULATORY AFFAIRS BOGIN,the Dutch generics industry association, has launched a social-media promotional campaign by opening aYouTube EGA urges amending channel and creating its ownentry on Wikipedia. The first video posted on Bogin’sYouTube channel shows adiscussion between the association’schairman, Martin Favié, and Dutch member of parliament Linda Voortman. Meanwhile, Bogin’sWikipedia entry WHO INN proposals provides information about generics and biosimilars. roposals by the World Health Organization (WHO) to introduce TGA –Australia’s Therapeutic Goods Administration –isencouraging Pavoluntary qualifier for biological drugs in addition to their generics manufacturerstoparticipate in the International Generic international non-proprietary names (INNs) could be improved, Drug Regulators Pilot (IGDRP) collaboration on evaluating generic according to the European Generic medicines Association (EGA). drug applications (Generics bulletin,5September 2014, page 13). The proposals –onwhich comments have been solicited bythe “The objective of the pilot is to confirm that the sharing of this WHO until 19 September (Generics bulletin,8August 2014, page information can facilitate the marketing-authorisation process by 25) –involveafour-letter code assigned at random to biological active the participating non-European Economic Area (EEA) regulators,” substances manufactured at specific sites. The WHO intends the scheme the agencynoted, adding that decentralised applications in Europe to be self-funding through asingle fee per application. would be “submitted concomitantlytothe TGA”. Addressing apre-conference meeting of the International Conference of Drug Regulatory Authorities(ICDRA) in Rio, Brazil, UNITE,which claims to be the UK’s“biggest union”, is demanding Suzette Kox–the EGA’s senior director of scientific affairs and an exemption forthe UK’sNational Health Service (NHS) from coordinator of the European Biosimilars Group –urged removing links certain provisions of the Transatlantic Trade and Investment between the qualifier code and the biologic’smanufacturing site, as well Partnership (TTIP) between the European Union (EU) and US. The as taking steps to avoid confusing the qualifier with the product’sINN. union objects to provisions that would grant US firms, or companies “EGA appreciates the WHO’sINN secretariat’sefforts in putting with US investors, “the power to sue the government if it attempted forward aproposal to avoid the proliferation of separate and distinct to takeprivatised health services back into public ownership”. naming schemes for biologicals by individual regulatory authorities Urging UK Prime Minister David Cameron to “use his veto to around the world,”Kox acknowledged. exempt the NHS”, Unite warned that the TTIP deal could “make “Unique product names –inaddition to, and separate from the NHS privatisation irreversible by giving the profits of corporations INN –are the best solution,” she said, adding that this would help precedence overnational lawmakers”. to clearly identify biological products, to track and trace biologics, and to ensure unambiguousprescriptions. PRIME THERAPEUTICS –aUSpharmacybenefits manager that Moreover, the EGA “welcomes the keyprinciples” of the biologic “serves more than 25 million people” –has submitted comments qualifier proposal, Koxsaid. These included having aqualifier that supporting citizen petitions filed by Novartis and the US Generic wasseparate and distinct from the INN; that wasapplicable to all Pharmaceutical Association (GPhA). The petitions urge the US Food biologics, not just biosimilars; that wasapplicable retroactively; that and Drug Administration (FDA) to apply the same non-proprietary wasvoluntary for regulatory agencies; and that wasadministered name to biosimilars and their reference products. and operated by the WHO’sINN secretariat. However, Koxsaid the EGA did not support linking the qualifier GERMAN REGIONS should agree targets forbiosimilars uptake, with manufacturing sites. This would “divorce the product from its Jens Spahn, parliamentary healthcare spokesperson for the CDU/CSU marketing-authorisation holder,who is solely legally responsible”, parties, told ameeting of the country’sgenerics industry association, she pointed out, adding that the qualifier scheme would be unworkable Pro Generika. Highlighting similar targets in Bremen, Saxonyand in the case of contract-manufacturing and licensing agreements. Westphalia-Lippe, Pro Generika’smanaging director,Bork Bretthauer, said biosimilars should not be subject to tenders based solely on Doctors prescribe biologics by brand name price and urged insurance funds to end supply contracts for original “Most quality issues arise at the product level, which would not biologics once biosimilarversions entered the market. According to be covered by the biologicqualifier system,”Kox said, adding that market researcher Insight Health, biosimilars and generics accounted doctors prescribed biologic drugs by brand name, “not active substances for 68.9% of all prescriptions through Germany’sstatutory health produced at aspecific manufacturing site”. insurance funds in the first half of this year.This represented a Among other measures opposed by the EGA wasincluding the rise of 0.3 percentage points. qualifier on the same line as the INN. This was“contradictory with the proposal”. The association also queried the proposed use of the AUSTRALIA’S PHARMACY GUILD has advised its members that term ‘biosimilars’ for all follow-on biologics, regardless of the approval an 80% generic substitution rate is “average”.According to financial standards. “Biosimilar stands for specific regulatory standards, always benchmarks included in afactsheet released by the community requiring an extensive comparability exercise,”Kox said. pharmacybody,asubstitution rate above 85% is “excellent”, while a Moreover, she urged, the qualifier should not be used for rate below73% suggests apharmacyis“underperforming”, because prescribing purposes. “A four-letter code will be very difficult to generics offer “greaterprofit margins” than brands. memorise for doctors and patients,”Kox pointed out, suggesting that random codes could “add to confusionand the likelihood of misreading ISPE –the International Society for Pharmaceutical Engineering – or mistranscription, and lead to possible medication errors”.The has based its drug-shortages prevention plan around six themes: qualifier should be linked to the companyname, the EGA urged. Corporate quality culture, robust quality systems, metrics, business- “EGA reiterates its request to fully user-test the biologic qualifier continuity planning, communication with authorities and building proposal with all relevant stakeholders –physicians, pharmacists, capability.ISPE will unveil details of its plan during its annual patients and payers –before moving to the next steps,”Kox stated. meeting that will be held on 12-15 October in Las Vegas, US. G The industry association said it was“looking forward to contributing to further discussions.” G
19 September 2014 GENERICS bulletin 11 Gen 19-9-14 Pgs. 10-12_Layout 1 17/09/2014 17:17 Page 4
PRODUCT NEWS
LITIGATION/HORMONE REPLACEMENTTHERAPIES RESPIRATORY DRUGS FTC takes action on Teva overturns UK US AndroGel delays patent for Symbicort
errigo and Teva have been sued by the US Federal Trade eva says it has taken a“big step” towards rolling out its DuoResp PCommission (FTC), along with US originator AbbVie and its partner TSpiromax (formoterol/budesonide) combination in Europe after Besins Healthcare, for allegedly conspiring to delay the US launch of the UK’sPatents Court found that apatent protecting AstraZeneca’s generic rivals to AbbVie’sAndroGel (testosterone) 1% gel blockbuster. Symbicort original wasobvious. The UK part of European patent According to acomplaint filed in aPennsylvania district court, EP1,085,877 covers acombination of formoterol and budesonide as AbbVie effectively paid Perrigo and Teva –the latter in the form of asingle-inhaler maintenance and relief treatment. adeal for an authorised generic to AbbVie’sblockbuster TriCor “AstraZeneca’scase is that the idea for having treatment for (fenofibrate) –todrop their challengestoUSpatent 6,503,894 asthma for both maintenance and relief by means of asingle inhaler, protecting the AndroGel brand until August 2020. This allowed the as set out in the patent, is noveland wasnot obvious at the priority originator to not only extend its monopoly on the product, butalso gave date for the patent in June 1998,”Judge Philip Sales summarised. AbbVie the time needed to switch patients to areformulated 1.62% But Sales ruled that reading aprior-art patent from 1993 in light of version, the FTC maintained. common general knowledge in June 1998 rendered the ‘877 patent “The FTC is acting today to stop anticompetitive conduct by obvious. “The relevant skilled person at that date would have regarded it AbbVie, Besins Healthcare, Teva [and Perrigo] which has forced as obvious to pursue the particular approach of combining adose of consumers to overpay hundredsofmillions,”the Commission’s formoterol with an inhaled corticosteroid (ICS) such as budesonide for Chairwoman, Edith Ramirez, proclaimed. The agreements, according both maintenanceand relief therapywith areasonable or fair expectation to the FTC, violated section 5(a) of the FTC Act amounting to “unfair of succeeding in securing effective treatment of asthma,”hestated. or deceptive acts or practices in or affecting commerce”. By June 1998, he continued, formoterol’sfast onset waswell In 2011, AbbVie filed separate patent-infringement lawsuits against known, making the drug “an obvious candidate” for relief therapy. And Perrigo and Teva after receiving 505(b)(2) hybrid newdrug applications using long-acting beta-antagonists (LABAs) such as formoterol in (NDAs) containingparagraph IV challenges asserting that generic maintenance therapyalong with an ICS wasalso well established. testosterone gels manufactured by the firms would not infringe the Noting that AstraZeneca wascurrently appealing against the ‘894 patent. This wasonthe basis that the ‘narrow’ ‘894 patent only European Patent Office’s(EPO’s) decision to revoke the’877 patent covered the use of aspecific penetration enhancer used to speed the after Teva had brought opposition proceedings, Sales also refused the delivery of testosterone –isopropyl myristate –whereas Perrigo’sand originator’s bid to amend the patent because changes such as inserting Teva’s versions contained isostearic acid and isopropyl palmitate. specific dosage regimes would amount to adding matter to the patent. Nevertheless, the suits triggered an automatic 30-month stay of Teva pointed out that it had already had twoother European final US Food and Drug Administration (FDA) approval. These suits patents covering the formoterol/budesonide combinations –EP0,613,371 were a“sham” and “baseless”, according to the FTC, as “Perrigo’sand and EP1,014,993 –revoked before the EPO and Norwegian courts. G Teva’s products were clearly outside the literalscope of the ‘894 patent”. “Even with no realistic chance of winning the lawsuits,”the FTC asserted, “the 30-month stays were of tremendous value to ANTIBIOTICS AbbVie because theyblocked entry of Teva’s and Perrigo’sproducts and gave…time to shift sales away from AndroGel 1% to AndroGel Mylan gets Venus’ meropenem 1.62%.”Teva’s and Perrigo’sNDAsreceived final FDAapprovalin February 2012 and January 2013 respectively. enus Remedies has entered into anon-exclusive agreement that However, the generics firms agreed to drop litigation in return Vallows Mylan to market its meropenem products in Denmark, for settlement agreements guaranteeing them specified US launch Finland and Sweden. The five-year deal for the antibioticthat Venus dates for their testosterone gels. As part of its settlement, Teva was manufactures at its facility in Baddi, India, follows asimilar marketing also giventhe rights to an authorised generic of AbbVie’sblockbuster tie-up it struck last year with Mylan for the French market (Generics TriCor (fenofibrate). “While asweetheart deal for Teva,the TriCor bulletin,6September 2013, page 22). authorised deal cannot be explained as an independent business deal The Indian companyalso recently obtained its first marketing from [AbbVie’s] perspective,” the FTC insisted. Details of Perrigo’s authorisation in Switzerland for gemcitabine, which is to be launched settlement were redacted in the FTC’scomplaint, although the toward the end of this year though local partner Swiss Pharma Commission noted that the US firm’sdecision to settle had been driven (Generics bulletin 5September 2014, page 19). G by the “competitive position” it found itself in. “Overall, the anticompetitive conduct blocked competition IN BRIEF from both Teva’s and Perrigo’slower-cost substitutes for brand- name AndroGel and preserved AbbVie’smonopoly for a BRECKENRIDGE PHARMACEUTICAL has been sued by Novartis substantial period of time,”the commission concluded. in aDelaware district court overfour US patents protecting Novartis’ Calling for “equitable relief as the court finds necessary”, the FTC Zortress (everolimus)0.25mg, 0.5mg and 0.75mg tablets. The US also requested that the generics firms and AbbVie be “permanently generics specialistclaims all four unexpired patents listed against the enjoined from engaging in similar and related conduct in the future”. brand are invalid and/or would not be infringed by its generic version Perrigo’stestosterone gel 1.0% wasrecently givenan‘AB’ of the immunosuppressant. Along with its manufacturing partner, therapeutic equivalence rating by the FDAthat will allowthe hormone Natco, Breckenridge believesitisthe only companythat qualifies treatment to be substituted for the brand (Generics bulletin,8August for 180-day generic market exclusivity. G 2014, page 20). G
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PRODUCT NEWS
ANTIDEPRESSANTS GENITOURINARYDRUGS Teva launches arival US overturns ruling to Canadian Cipralex on Lysteda patents
eva has launched aCanadian rivaltoLundbeck’sCipralex US district court waswrong to find that Actavis’ generic rivals to T(escitalopram) following expiry of Canadian patent 1,339,452 AFerring’sLysteda (tranexamic acid) 650mg tablets infringed three protecting the antidepressant. Citing IMS data, the Israeli firm noted of the originator’s patents, the US Court of Appeals has ruled. that the brand had annual sales of around US$260 million in Canada. Actavis’ abbreviated newdrug application(ANDA) wasearlier Health Canada also lists versions by Apotexand Sandoz. this year deemed to have infringed US patents 7,947,739, 8,022,106 Apotexwas previously made to hand overC$1.71 million (US$1.55 and 8,273,795 (Generics bulletin,14February 2014, page 16). The million) in profits it made on escitalopram exports after afederal judge court ordered Actavis to stop selling its version and told the US Food rejected allegations of invalidity and found that the Canadian firm had and Drug Administration (FDA) to reset the approvaldate of the firm’s infringed the ‘452 patent (Generics bulletin,5April 2013, page 13). ANDAtopatent expiry in March 2025. Meanwhile, Teva has begun shipping the first US generic version But the appeals court found that data extrapolated from Actavis’ of Bristol-Myers Squibb’sBaraclude (entecavir) 0.5mg and 1mg finished-dose products were shown to be “outside the scope of the tablets with 180-day exclusivity,after the US Food and Drug asserted claims” of the patents, which coverspecified dissolution rates Administration (FDA) granted the Israeli firm final approvalfor its of the active ingredient in water.However,the Court of Appeals abbreviated newdrug application(ANDA). sided with the district court in rejecting Actavis’ assertion that the Earlier this year,the US Court of Appeals upheld aUSdistrict patents were obvious in light of prior art. court’s2013 decision that found the originator’s sole compound patent Having receivedfinal FDAapprovalfor the first US generic rivals to for the hepatitis Btreatment invalid on the grounds of obviousness Lysteda in late 2012, Actavis launched ‘at risk’ early last year with (Generics bulletin,20June 2014, page 15). litigation against Ferring still pending (Generics bulletin,11January With its launch, Teva has entered the market almost ayear before 2013, page 18). Ferring licensed an authorised generic to Prasco. the expiry of that patent –USpatent 5,206,244 –on21August 2015, In aseparate ruling, the appeals court affirmed the district court’s including six months of paediatric exclusivity.The twostrengths of prior decision that an amendment to an ANDAfiled by Apotexto Baraclude had US sales of around US$328 million for the 12-months include aspecification on dissolution rates rendered moot the Swiss- ended June 2014, according to IMS Health data. G based originator’s infringement claims. G
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PRODUCT NEWS
IN BRIEF SEDATIVES SANDOZ has introduced ageneric version of Eisai’s Dacogen (decitabine)injectable myelodysplasiatreatment in the US. The US courtlifts bar on 50mg/20ml single-dose vials were developed by InnoPharma, which licensed US sales and marketing rights to Sandoz. Citing IMS Health data for the 12 months to April 2014, the twopartners said Dacogen had annual US sales of US$251 million. Dr Reddy’scurrently markets rivals to Precedex ageneric rivaltothe oncology brand. ylan and Parcan resume distributing US rivals to Hospira’s DAIICHI SANKYO will expand its generics portfolio in Japan by MPrecedex(dexmedetomidine) after aMaryland district court lifted introducing an authorised generic of its own Cravit (levofloxacin) atemporary restraining order suspending aUSFood and Drug antibiotic brand. The firm will offer levofloxacin 250mg and 500mg Administration (FDA) decision to approve the generic sedativesbased tablets, as well as 10% granules, through its Espha generics on alabelling ‘carve-out’. subsidiary once it obtains entries on the country’sprice list. Granting asummary judgement in favour of the generics firms and the FDA, the court found that the agencyhad acted lawfully in approving WOCKHARDT said it could expect to receive ‘fast-track’ US Food the abbreviated newdrug applications (ANDAs), despite claims by and Drug Administration (FDA) approvals for twoofits novel Hospira that amethod-of-use patent should prevent such approvals. anti-infectives–WCK-2349 and WCK-771 –after the agency Hospira had recently convinced the court to issue the restraining granted them qualified infectious disease product (QIDP) status, the order after the FDAapprovedgeneric 200µg/2ml versions that were “first instance” for an Indian company. “These drugs will be entering launched immediately by Mylan and Par(Generics bulletin,5 global Phase III clinical trials early next year,” noted Wockhardt. September 2014, page 19). The agencyhad determined that it should be able to approve ANDAs that contained a‘section viii’ statement ANSM –France’smedicines agency–has added to the country’s and omitted labelling disclosing amethod of use that wasprotected répertoire of generic equivalents interchangeability groups for by Hospira’sUSpatent 6,716,867 covering intensive-care unit sedation. prolonged-release oxycodone tablets in eight strengths. Three versions But Hospira had argued that ANDAs with section viii statements from Acino –named Oxarutis, Oxyquales and Oxyredit – should not be approvedifthe statement overlapped with the brand’s accompanyEGLabo’sprolonged-release oxycodone tablets in 5mg, use code as published in the FDA’sOrange Book. 10mg, 15mg, 20mg, 30mg, 40mg, 60mg and 80mg strengths. Judge George Jarrod Hazel found that the FDAhad “on several occasions approvedsection viii ANDAs for broad, general indications MALLINCKRODT has agreed to return all US licensing rights to the that may partially overlap with aprotected method of use, so long as any osteoarthritis treatments Pennsaid (diclofenac)1.5% and 2% topical express references to the protected use are omitted from the labelling”. solutions to NuvoResearch under the terms of asettlement agreement The agency’sdecision was“entirely consistent with the FDA’s reached between the twofirms that resolves all pending litigation. established practice of approving generic drugs and therefore did not The US analgesics specialist will also pay NuvoUS$10 million. effect achange to settled law”, Hazel found. “Indeed, this is exactly the practice the FDAfollowed in its handling of the approvalofgeneric PHARMAC –New Zealand’sPharmaceutical Management Agency– repaglinide, generic tramadol and generic oxandrolone”. has published adata sheet advising local doctors of the differences in particle size between Teva’s Qvar (beclomethasone dipropionate) Law requires focus on label 50µg and 100µg per dose inhalers and other beclomethasone inhalers. Observing that “Hospira’sargument boils down to what doctors Noting that Qvar –which has been listed in NewZealand’s may do with generic Precedex”, Hazel said the FDAwas “not obligated pharmaceutical schedule from 1September –was “designed to deliver to consider howthe product might be used by physicians beyond the smaller particles of beclomethasone dipropionate compared with approvedlabelling”. Instead, he said, “the lawrequires afocus other brands”, Pharmac also observed that Teva’s inhaler was“not only on the label”. “Because the ANDA’slabel does not disclose directlyinterchangeable” with other brands. the protected intensive-care unit sedation use,”Hazel found, “the FDAreasonably concluded that authorisation to approve the TWO FIRMS –Mylan and Sagent –havebegun shipping US rivals ANDAs section viii statements wasappropriate.” to Roche’s Boniva (ibandronate sodium)3mg/3ml injectable after Hospira has filed an appeal, although the court rejected the firm’s receiving final US Food and Drug Administration (FDA) approval. request to immediately stay the latest ruling pendingthis process. Local sales of the treatment for osteoporosis in postmenopausal “The court is not satisfied that Hospira will suffer irreperable harm women were approximately US$18 million for the 12 months ended absent astay,” Hazel stated, noting that while the earlier restraining July 2014, according to IMS Health data. Indian player Emcure order had been issued partly on the basis that “98.4% of Hospira’s Pharmaceuticals also recently gained aUSnod for the drug. US branded sales are of Precedex”, the court had since learned that this wasnevertheless “a relatively small portion of its overall company”. VENUS REMEDIES has reached an agreement with Teva to develop But Mylan and Par, Hazel reasoned, would “suffer continued harm and market a“blockbuster” lung-cancer treatment in Canada. The if theywere forced to continue to turn away customers”. Moreover, undisclosed product wasunder patent until 2016, the Indian firm said, he added, “the public interest would not be served by astay”. and had annual sales in Canada of approximately US$75-100 million. Sandoz also intends to appeal against the ruling, claiming that it Under the terms of the agreement, Venus will develop and manufacture would be “significantly harmed because its right to be the exclusive the drug, and will assist Teva with securing regulatory approval. generic on the market beginning January 2015 would be lost”. A settlement agreement with Hospira allows the Novartis subsidiary to LANNETT said it expected to launch “shortly” its generic rivalto launch aUSrivaltoPrecedexfrom 26 December this year (Generics Lehigh Valley’s oxycodone 100mg/5ml oral solution following final bulletin,10January 2014, page 23). US approval. Citing IMS Health data, the US firm said the analgesic Citing data from IMS Health, Parsaid annual US sales of Precedex had annual US sales of US$43 million at average wholesale prices. G –which Hospira markets under alicensing deal with Orion –were around US$156 million. G
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PRODUCT NEWS
RESPIRATORY DRUGS IN BRIEF FDA –the US Food and Drug Administration –must grant Depomed’s Prosonix applies for Gralise (gabapentin)tablets seven-year orphan drug exclusivity for the managementofpostherpeticneuralgia following the US firm’sfavourable ruling against the agencyinaColumbia district court. Actavis wasrecently thwarted in its bid to introduce the first fluticasone in the EU US generic rivals to Gralise after NewJerseydistrict judge Joel Pisano ruled the firm’sabbreviated newdrug application(ANDA) K-based respiratory specialist Prosonix has submitted amarketing infringed all sevenpatents protecting the analgesic until 2024 Uauthorisation application for its PSX1001 inhaler –arivalto (Generics bulletin,5September 2014, page 23). GlaxoSmithKline’sFlixotide Evohaler (fluticasone propionate) –tothe UK’sMedicines and Healthcare products Regulatory Agency(MHRA). MASTERS SPECIALTY PHARMA has struck an agreement with Having validated the submission, the UK agencyisacting as the Apotexaffiliate ApoPharma to distribute the latter’s Ferriprox reference member state (RMS) for Prosonix’filing under Europe’s (deferiprone)500mg tablets in three South Asian countries. The decentralised procedure, as well as for aduplicate submission made UK-based company–which specialises in supplying drugs to countries on behalf of the UK’sfirm’sinternationalmarketing partner,Mylan. “where an unmet need exists” –has gained rights to distribute the “Our marketing authorisation application for PSX1001 is the first treatment for iron overload in India, Pakistan and Sri Lanka. of our product pipeline to be reviewed under European Union (EU) regulatory guidelines that allowthe potential approvalofgeneric inhaled AKORN’S Hi-Tech Pharmacal has receivedfinal US Food and Drug products based on in vitro data alone,”stated Prosonix’ chief executive Administration (FDA) approvalfor its generic version of Allergan’s officer and co-founder,David Hipkiss. Zymaxid (gatifloxacin)0.5% ophthalmic solution. Last year,Lupin Declining to disclose which concerned member states (CMS) introduced the first generic rivalafter aUSdistrict court found a would be involved in the decentralised procedure, Hipkiss told keypatent protecting the bacterial conjunctivitis treatment obvious Generics bulletin that the MHRA washighly respected for its expertise in light of prior art (Generics bulletin,18October 2013, page 14). in the respiratory field. The decentralised procedure route offered defined timelines for areviewand approvalprocess which could lead to TIANYIN PHARMACEUTICALS’ Jiangchuan Macrolide (JCM) therapeutically equivalent, fully substitutable alternativestoFlixotide. active pharmaceutical ingredient (API) business has begun the Prosonix’ application, he revealed, wasfor the same three 50µg, application process for an Indian import certificate, following a 125µg and 250µg strengths as the Flixotide Evohaler original, while “surge in orders” from Indian API consumers for JCM’s extensive scientific advice the companyhad obtained had made clear azithromycin API products and intermediates. that the metered-dose delivery device must be essentially similar to GlaxoSmithKline’sEvohaler device. Discussing Prosonix’ design and LEE’S PHARMACEUTICAL –aHong Kong-based biopharmaceutical colour choice for its inhaler,Hipkiss said the firm had been watching company–has reached an agreement with Abiogen Pharma to closely recent European litigation overtrade livery. distribute the Italianfirm’srange of Thorens Cholecalciferol Hipkiss also said Prosonix’ regulatory approach wasconsistent (vitamin D)products, includingoral drops, oral solutionand solution with recently-updated Global Initiative for Asthma (GINA) management for injection,inmainland China, Hong Kong, Macau and Taiwan. and prescribing guidelines, which stress the importance of net cost when making population-leveldecisions about preferred options for treating MYLAN has receivedfinal US Food and Drug Administration (FDA) asthma. “Webelieve these guidelines are set to dominate the approvalfor its generic version of Endo’s Frova (frovatriptan) reimbursement and payer agenda for the foreseeable future,”hestated. 2.5mg tablets. Earlier this year,aUSdistrict court granted Mylan’s Under the global licensing agreement that Prosonix struck with request to enforce apatent-litigation settlement, which allowed the Mylan earlier this year (Generics bulletin,2May 2014, page 13), the US firm to launch its rivals to the migraine treatment ahead of US US firm has marketing rights to PSX1001–aswell as to the similar patent 5,464,864 expiring on 7November 2015 (Generics bulletin, PSX1050 rivaltoGlaxoSmithKline’sFlovent (fluticasone) in the US – 18 April 2014, page 21). in the EU, Iceland, Liechtenstein, Norway and Switzerland, as well as in Turkey,Russia, the CommonwealthofIndependent States (CIS), LUPIN has signed an agreement with Salix Pharmaceuticals to market India, Japan, Australia, NewZealand, Canada and the US. and distribute the US firm’s Zaxine (rifaximin)550mg tablets and Hipkiss said he was“happywith progress” on the PSX1050 US Relistor (methylnaltrexone bromide)subcutaneous injectable development programme with Mylan. The UK-based company’s gastroenterology treatments in Canada. The agreement includes development of its PSX2005 generic version of GlaxoSmithKline’s access to future dosage forms, strengths and indications of the drugs, Seretide (fluticasone/salmeterol) combination in three strengths was along with an option to market other gastroenterology products in “on track”, while it wasmaking good progress on atriple combination Salix’ Canadian pipeline pursuant to Health Canada approval. Salix of an inhaled corticosteroid (ICS), long-acting beta-antagonist (LABA) will receive an undisclosed upfront payment from the Indian firm, and long-acting muscarinic antagonist (LAMA) using the firm’s in addition to pre-commercial and sales milestone payments. proprietaryMulti-Component Particles (MCP) technology(Generics bulletin,4October 2013, page 24). NEOS THERAPEUTICS has reached asettlement agreement with Earlier this year,Prosonix reported “encouraging data” from Shire granting Neos access to the originator’sUSpatent 6,913,768, Phase II clinical studies for its PSX1002 drug-only formulation of along with reissued US patents RE42,096 and RE41,148. This will glycopyrronium bromide –the LAMA in Novartis’ Seebri Breezhaler – allowNeos to manufacture and market its NT-0202 candidate for as apressured metered-dose inhaler for chronic obstructive pulmonary an extended-release, orally-disintegrating tablet (ODT) formulation disease (Generics bulletin,3February 2014, page 12). of Shire’s Adderall (amphetamine salts)that wasfiled under the The Oxford-based firm also has twoother respiratory programmes 505(b)(2) hybrid newdrug application(NDA) pathway.Under the underway with an undisclosed European partner –PX1439, arivalto agreement, which settles all pending litigation between the twofirms, GlaxoSmithKline’sSerevent (salmeterol); and PX1442, which targets Neos will pay Shire sales-based royalties until patent expiry. G Boehringer Ingelheim’s Spiriva (tiotropium bromide). G
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PRODUCT NEWS
HYPERPARATHYROIDISMDRUGS RESPIRATORY DRUGS Aceto pays US$8.2m FDA gives answers for three Par ANDAs on ‘rescue’ inhalers
ceto has struck adeal worth US$8.2 million to acquire through ivals to ‘rescue’ inhalers containing albuterol or levalbuterol –such Aits Rising Pharmaceuticals arm three soft-gel capsule abbreviated Ras Teva’s ProAir HFA(albuterol) –are not required to add further newdrug applications (ANDAs) from fellowUSgenerics player Par: safety-related labelling statements regarding their interchangeability, doxercalciferol, paricalcitol and dutasteride. according to aUSFood and Drug Administration (FDA) response to The first twodrugs –for treating excessive secretion of parathyroid acitizen petition filed by the director of Teva’s Life Cycle Initiatives, hormones –would, Aceto said, be “important additions to Rising’s Michael Nicholas. “The adequacyoflabelling would be assessed Vitamin Dofferings which also include ergocalciferol capsules”. during the normal course of the abbreviated newdrug application Dutasteride, meanwhile, is indicated for the treatment of benign (ANDA) review,”proclaimed director of the FDA’sCenter for Drug prostatic hyperplasia.The valuation of the deal includes “upfront, Evaluation and Research (CDER), Janet Woodcock. milestone, development and other deal costs”. Furthermore, Woodcock stated, the FDAdid not intend to impose Of the three drugs, Aceto noted, only paricalcitol had thus far auniversal requirementthat all metered-dose inhalers (MDIs) contain receivedfinal US Food and Drug Administration (FDA) approval, with adose-counter if this would mean limiting patients’ options. alaunch scheduled for the first half of 2015. The other twoANDAs The petition had also called for the FDAtorefrain from approving have been filed with the US agency, with anticipated approvaldates generic MDIs that had not through “clinical-use studies” proventhe of late 2014 for doxercalciferol and late 2015 for dutasteride, according “accuracy, ruggedness, and reliability” of the dose counter,aswell as to Aceto. No launch dates were forecasted. inhalers that had not shown acomparable risk of actuator clogging. Paricalcitol and dutasterideare expected to have “multiple generic On clinical-use studies, the FDAstated that, while it “generally competitors” at launch, while Aceto noted that twofirms already agreed”, an alternative approach could be used if it satisfied “the offered generic doxercalciferol in the US. requirementsofthe applicable statutes and regulations”. According to IMS Health data cited by Aceto, annual US sales of However, the agencydisagreed with Nicholas’ request regarding generic doxercalciferol capsules are approximately US$50 million, tests to demonstrate the comparable risk of the actuator clogging, noting while Aceto’sdutasteride and paricalcitol would compete for ashare that it would not implement acategorical requirement for “in vivo of branded markets that were worth US$500 million and US$100 performance data under avariety of cleaning methodologies, million per year respectively. G including under real-world-use conditions”. G
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PIPELINE WATCH SPC protection ends for two monoclonals eptember brings the expiry of supplementaryprotection certificates applications were rejected by authorities in Austria, Germanyand S(SPCs) for twomonoclonal antibodies (mAbs) –Merck Serono’s Switzerland, while an application waswithdrawn in the UK. Erbitux (cetuximab) and Amgen’sVectibix (panitumumab) –inseveral Furthermore, SPC applications for panitumumab combinations with of Europe’slargest markets. Each of the SPCs references European other cancer drugs such as cisplatin, irinotecan or paclitaxel were patent EP0,667,165, which covers combinations of monoclonal rejected by national intellectual-property offices, or were withdrawn. antibodies that bind to the extracellular domain of human epidermal However, Ark cautions, the European panitumumab molecule growth-factor receptor with an antineoplastic agent. patent EP0,979,246 runs until 5May 2018, and SPCs linked to that Even though the ‘165 patent refers to combination products, it patent extend protection for Vectibix until December 2022 in countries formed the basis of several SPCs relating to the single active ingredient such as France, Germany, Italy,Spain and the UK. In anycase, European cetuximab that were granted in Belgium, France, Greece and Italy,as Union (EU) data exclusivity precludes marketing-authorisation well as Luxembourg, Spain, Sweden and Switzerland (see Figure 1). applications for biosimilar versions of Vectibix until December 2017. Ark Patent Intelligence observes that SPCs for cetuximab in As Figure 2shows, September brings the end of 10-year data combination with irinotecan were applied for in several European exclusivity terms awarded in several EU member states for Eli Lilly’s countries, butwere granted only in Greece and Luxembourg. Other chemotherapyagent Alimta (pemetrexed), which is used in combination countries objected that the marketing authorisation on which the SPC with cisplatin to treat malignant pleural mesothelioma and locally applications had been based wasfor cetuximab alone. advanced or metastatic non-small-cell lung cancer.Earlier this year, “Inconsistencies amongst the European countries’ decisions on Actavis wonaUKHigh Court ruling that its version would not whether to grant SPCs for drug combinations reflect the disharmony infringe Lilly’svitamin-dosage regimen patent in France, Italy,Spain in interpreting SPC legislation in each country,” Ark maintains. or the UK (Generics bulletin,6June 2014, page 17). The ruling Merck Serono’sErbitux brand presented an attractive target for opened the door for Actavis to introduce its alternative salt form biosimilardevelopers. The German group reported European Erbitux when SPCs linked to the European pemetrexedcompound patent sales 3.5% higher at C130 million (US$168 million) in the second EP0,432,677 expire in December 2015. quarter of this year,with emerging markets such as China and Latin September also brings the expiry of 10-year protection awarded America contributing C62.9 million and the rest of the world C36.5 in the EU for The Medicines Company’sAngiox (bivalirudin). G million to abrand total in the three-month period ahead by 6.5% to C229 million. These figures exclude North America, where Eli Lilly – the owner of Erbitux’ developer,ImClone –markets the oncology drug Data exclusivity expiries in September through an alliance with Bristol-Myers Squibb (BMS). In the second INN Country/Region quarter of 2014, BMS reported Erbitux sales of US$186 million. In the same three-monthperiod, Amgen’sVectibix achievedsales Babesia canis/Babesiarossi European Union of US$36 million in the US –where the Food and Drug Administration Bepotastine US (FDA) approvedthe panitumumab brand for use in combination with Bivalirudin European Union the Folfox (leucovorin/5-fluorouracil/oxaliplatin) chemotherapy Firocoxib European Union regimen in patients with metastatic colorectal cancer –and US$96 Hexylaminolevulinic acid Belgium, France,Germany, Italy, million in non-US markets. Luxembourg, Netherlands, Belgium, France, Greece, Italy and Luxembourggranted SPCs Sweden, UK for panitumumab based on the European ‘165 patent, butsimilar Human papillomavirus proteins European Union Insulin glulisine European Union SPC expiries in September Lercanidipine Switzerland INN Country Mavacoxib Turkey Natalizumab Canada Cetuximab Belgium, France, Greece, Italy, Luxembourg, Spain, Sweden, Switzerland Nilotinib Canada* PemetrexedEuropean Union Cetuximab/Irinotecan Greece, Luxembourg Pralatrexate US Leuprorelin Luxembourg Ranelic Acid European Union Panitumumab Belgium, France, Italy,Luxembourg, Rivaroxaban Canada*,Turkey Spain Telavancin US Rosiglitazone Austria, Denmark, France, Germany, Tigecycline Canada Greece, Hungary,Ireland, Luxembourg, Varenicline European Union Norway,Portugal, Slovenia, Sweden, *This will be followed by ano-marketing period of twoyears during which anotice of Switzerland, UK compliance will not be granted to ageneric manufacturer.
Figure1:Molecules for which supplementaryprotection certificates (SPCs) expire Figure2:Molecules for which data exclusivity expires in key markets during in key markets during September 2014 (Source –Ark Patent Intelligence) September 2014 (Source –Ark Patent Intelligence)
This monthly update of keypatent, SPC and data exclusivity data is extracted from Ark Patent Intelligence Expiry Database. Covering 50 countries and over1,600 INNs, Ark Expiry Database contains watertight data teamed with the ultimate in generic launch analysis. Forfurther information, visit www.arkpatentintelligence.com, or contact: Europe: +44 870 879 0081. North America: +1 704 665 1986. Or e-mail: [email protected].
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PRODUCT NEWS
CARDIOVASCULAR DRUGS CARDIOVASCULAR DRUGS Aspen sells to Mylan Sandoz cuts termof US rights for Arixtra Remodulinprotection
ylan has agreed to pay Aspen up to US$300 million for US sales, andoz may be able to market an alternative to United Therapeutics’ Mmarketing and intellectual-property rights to Arixtra (fondaparinux SRemodulin (treprostinil sodium) from October 2017 after New sodium) and an authorised generic of the deep-vein thrombosis JerseyDistrict Judge Peter Sheridan found that Sandoz’ generic did treatment. The US firm is already selling the brand locally through not infringe aUSpatent protecting the intravenous cardiovascular an interim distribution agreement with Aspen, while its Mylan treatment until 2029. Institutional unit will assume marketing of the authorisedgeneric Sheridan ruled that United had failed to prove that Sandoz’ generic from Apotexbythe end of this year. version of the treatment for pulmonary arterial hypertension would Aspen will supply the injectable brand and authorised generic to induce infringement by physicians of US patent 7,999,007, which Mylan, subject to certain terms and conditions. Of the US$300 million expires on 29 March 2029 and covers methods of selectively killing price, US$225 million will be paid upon completion after antitrust gram-negative bacteria via buffer solutions. Sandoz, he found, had clearance, while US$75 million is dependent on certain undisclosed successfully carved out from its labelling the use of aspecific sterile conditions. Citing IMS Health data for the 12 months ended June diluent that wascovered by the ‘007 patent. 2014, Mylan said Arixtra and its authorised generic had annual US Sandoz argued successfully that it had carved out from its proposed sales of US$18.8 million and US$95.3 million respectively. product label anyuses covered by the ‘007 patent, and the patent did Aspen paid GlaxoSmithKline £700 million (US$1.14 billion) for not coverits proposed instruction to use the generic intravenous global rights to the Arixtra and Fraxiparine/Fraxodi (nadroparin) brands formulation diluted with sterile water or 0.9% sodium chloride. Sheridan in adeal that also included aFrench manufacturing site (Generics denied United’sclaim that warnings of bloodstream infectionsin bulletin,10January 2014, page 7). Sandoz’ labelling would have actively induced physicians to prescribe Dr Reddy’shas since July 2011 held the only US approvalfor a the patented diluent for Flolan (epoprostenol). generic version of Arixtra. The Indian firm’sdevelopment partner, Alchemia, said Reddy’shad captured almost athird of the US Infringed ‘117 patent fondaparinux market by volume in the three months ended 30 June However, Sheridan said Sandoz’ abbreviated newdrug application 2014, compared to 64% for Apotexand 4% for GlaxoSmithKline. G (ANDA) for 1mg/ml, 2.5mg/mland 5mg/ml strengths infringed –under the doctrine of equivalents –USpatent 6,765,117, which expires on 24 October 2017. Noting that Sandoz’ generic contained bulk treprostinil supplied by Alphora Research, he said the para-methoxybenzyl (PMB) group used in Alphora’sprocess “performs substantially the same function,insubstantially the same way, with substantially the same result” as agroup defined in the ‘117 patent. Sheridan also rejected Sandoz’ invalidity attacks on both patents. Earlier this year,the NewJerseycourt dismissed adispute overanother Remodulin patent after Sandoz dropped its challenge to US patent 5,153,222, which expires on 6October this year. United said it wasconsidering an appeal against the district court’s non-infringement finding on the ‘007 patent. G
HORMONE REPLACEMENTTHERAPIES Endo has authorised Fortesta ndo has begun shipping through its Qualitest generics arm an Eauthorised generic of the US firm’sown Fortesta (testosterone) 10mg/0.5g gel, the “first and only” generic 2% topical testosterone gel marketed in the US to treat hypogonadism. “Weexpect this launch will create the opportunity to maximise the value of our Fortesta franchise while also enhancingthe commercial partnershipopportunitiesbetween our branded and generics business segments,”commented Endo’spresident and chief executive officer, RajivDeSilva. Sales of the treatment for hypogonadism in adult males –which Endo acquired from ProStrakanin2009 –more than doubled to US$65.9 million in 2013. Last year,Actavis triggered apatent-infringement lawsuit after submitting an abbreviated newdrug application(ANDA) containing paragraph IV challenges against US patents 6,319,913 and 6,579,865 that protect Fortesta until November 2018 (Generics bulletin,8March 2013, page 19). The trial will be heard in February 2015. G
19 September 2014 GENERICS bulletin 19 Gen 19-9-14 Pgs. 14-21_Layout 1 17/09/2014 17:18 Page 8
PARAGRAPH IV WATCH Prolensa presents acomplicated picture
hen monitoring litigation surrounding Paragraph IV patent Wchallenges, it is tempting to regard each challenge as if it were KEY DETAILS: PROLENSA asingle court case for the sakeofsimplicity.Inthe end, challenges Brand: Prolensa often boil down to adecision in asingle case after actions are consolidated or certain legalissues are resolved along the way. In the Active ingredient: bromfenac sodium early stages of litigation, however, cases can proliferate, complicating Delivery form: 0.07% ophthalmic solution the task of tracking case developments. This complexity is exemplified by the challenges to Bausch & Brand owner: Bausch &Lomb (Valeant) Lomb’sProlensa (bromfenac sodium) ophthalmic solution for post- operative inflammation and ocular pain. Although there are only two First paragraph IV 26 July 2013 known abbreviated newabbreviated newdrug applications (ANDAs) filing submitted to FDA: containing paragraph IV patent challenges for generic versions of Known paragraph IV Lupin, Metrics/Coastal Prolensa solution (see Figure 1), at present theyhavegiven rise to filers: six different cases in twoseparate courts. The US Food and Drug Administration (FDA) reports that the US Patents at issue – 8,129,431 –11September 2025 first ANDAwith aparagraph IV certification for ageneric version 8,669,290 –16January 2024 of Prolensa wassubmitted in July 2013. In December 2013, Valeant’s 8,754,131 –16January 2024 Bausch &Lomb receivednotification of Lupin’sparagraph IV District court locations: NewJersey challenge to US patent 8,129,431, which wasthe only patent then Eastern District of North Carolina listed for Prolensa in the FDA’sOrange Book. As expected, in January 2014, Bausch &Lomb and Senju –the assignee of the Litigation references: Senju et al. vs Lupin Ltd et al. – patent –filed an infringement suit against Lupin in aNew Jersey (NewJersey) 1:14-cv-00667 district court, triggering a30-month stay on final ANDAapproval. Senju et al. vs Lupin Ltd et al. – Then in March 2014, the US Patent and Trademark Office (USPTO) 1:14-cv-04149 issued US patent 8,669,290, which wassubsequently listed against Senju et al vs Lupin Ltd et al – Prolensa in the Orange Book. In June 2014, Bausch &Lomb and 1:14-cv-05144 Senju sued Lupin for infringement of that patent. And at around the Senju et al vs Metrics Inc et al – same time, the USPTOissued athird Prolensa patent, US patent 1:14-cv-03962 8,754,131, which the FDAduly listed in its Orange Book. In August Senju et al vs Metrics Inc et al – 2014, Bausch &Lomb and its Japanese partner filed athird suit 1:14-cv-04964 against Lupin, alleging infringement of the ‘131 patent. (E District, North Carolina) Senju et al vs Metrics Inc et al – The story for the second known filer of an ANDAfor ageneric 4:14-cv-00141 version of Prolensa is somewhat different. In June 2014, just days after the third Prolensa patent –the ‘131 patent –issued, Bausch & Figure1:Paragraph IV challenges to Bausch &Lomb’s Prolensa (bromfenac Lomb and Senju filed apatent-infringement suit in the NewJersey sodium) ophthalmic solution in the US (Source –Thomson Reuters) court against Metrics, Coastal and parent group Mayne Pharma, alleging infringement of all three Prolensa patents. “The complaint, 180 PATENT 180 160 CHALLENGES however, makes no mention of Metrics’ paragraph IV notice letter,” 156 observes Thomson Reuters, which compiles adatabase of paragraph 160 150 IV certifications and associated litigation (see Figure 2). 140 117 One week after the suit wasfiled, Bausch &Lomb receiveda 120 paragraph IV notice letter from Metrics concerning an ANDAfor bromfenac solution. Consequently,inAugust 2014, the originator 100 90
81 74 filed anew suit against Metrics and its affiliate Coastal in the New 80 69 Jerseycourt, alleging infringement of the same patents. To complicate 60 53 matters further,the same parties filed asubstantially identical suit the 40
next day in adistrict court for the Eastern District of North Carolina. Number of patent challenges Thomson Reuters believesthis wasaprotective measure, in case Metrics 20 contests the jurisdiction of the NewJerseycourt. And in late-July, 0 Metrics petitioned the USPTOfor inter partes reviews of the ‘431 and Par Teva Lupin
‘290 patents on the basis of prior-art patents and printed publications. Actavis Mylan Sandoz Apotex As Generics bulletin went to press, all six court cases remained Sun Pharma Dr Reddy’s Aurobindo pending and none had been consolidated, so anyobserver must followall Figure2:Numbers of compounds subject to patent challenges by company,as six –and the inter partes reviews –tokeep fully abreast of the matter. G recorded by Thomson Reuters to 30 June 2014 (Source –Thomson Reuters)
Thomson Reuters draws on strategic intelligence and competitive analysis information on the US generics industry to create Newport Premium™,the criticalproduct-targeting and global business-development system from the industry authority on the global generics market. Forfurther details contact Benjamin Burck, Thomson Reuters API Intelligence, 215 Commercial Street, Portland, Maine 04101, USA. Tel: +1 207 808 7977. Fax: +1 207 871 9800. E-mail: [email protected]. Website: scientific.thomsonreuters.com/newport.
20 GENERICS bulletin 19 September 2014 Gen 19-9-14 Pgs. 14-21_Layout 1 17/09/2014 17:18 Page 9
PRODUCT NEWS
GASTROINTESTINAL DRUGS RESPIRATORY DRUGS Petition urges FDA Cipla’s inhalers reach to end Nexium delay Germany and Sweden
he US Food and Drug Administration (FDA) should waive ipla has introduced its salmeterol/fluticasone metered-dose inhalers TRanbaxy’sright to launch the first US generic rivaltoAstraZeneca’s Cin Germanyand Sweden. In Germany, the Indian companyis US$6 billion Nexium (esomeprazole) brand with 180-day exclusivity, marketing its 25µg/125µg and 25µg/250µg pressurised metered-dose unless the agencyisprepared to immediately approve the Indian firm’s inhalers (pMDIs) under the Serroflo brand name with launch list prices pending abbreviated newdrug application(ANDA), Connecticut of C53.59 (US$70.48) and C71.66 respectively for a120-dose unit. attorneygeneral George Jepsen has argued in acitizen petition. In Sweden, the combination asthma drug is called Salmeterol/Fluticasone Under the terms of a2008 agreement,Ranbaxy agreed to drop Cipla. Cipla already markets the combination as Duohal in Croatia. all litigation with AstraZeneca in return for the rights to launch the Launches of both strengths in the Czech Republic and Slovakia first rivaltoNexium on 27 May 2014, with 180-day generic market will followunder the Fullhale brand name once the companyhas exclusivity (Generics bulletin,2May 2008, page 11). secured local regulatory and reimbursement approvals. Numerous manufacturing issues –which have resulted in the FDA Cipla will promote the inhalers in the Czech Republic and Slovakia halting US shipments of active pharmaceutical ingredients(APIs) through its ownsalesforce, managed by the company’scommercial from four of Ranbaxy’s Indian manufacturing facilities under the head. Distribution of the respiratory drugs will be handled through provisions of a2012 consent decree (Generics bulletin,3February acommercialcollaboration Cipla has just struck with S&D Pharma, 2014, page 3) –havesince held up Ranbaxy’sbid to gain full approval which forms part of the UK-based London Pharma &Chemicals Group. for its ANDA, and have caused that launch date to lapse. The Indian “Weare excited to partner with S&D Pharma and believe that this firm did, however, recently receive final FDAapprovalfor the first US collaboration will enable us to drive access in the Czech Republic and rivaltoNovartis’ Diovan(valsartan) blockbuster through its Ohm Slovakia across therapyareas in the coming years,”stated Frank Pieters, Laboratories subsidiary (Generics bulletin,11July 2014, page 19). head of Cipla Europe. The Indian firm said the deal would allowit Having delayed generic entry by six years, the 2008 deal “further “to focus on its core therapyareas, while S&D Pharma will be the compounded unfairness to consumers”, according to Jepsen, because keypartner for generics”. it contained an agreement whereby Ranbaxy manufactured esomeprazole Using Sweden as the reference member state (RMS) for ahybrid active pharmaceutical agreement (API) –and later finished-dose application through Europe’sdecentralised procedure, Cipla –through formulations–tosell to the originator for “a substantial profit”. regulatory affairs specialist ELC Group –secured marketing approvals “Ranbaxy and AstraZeneca should be competing –instead, they for the fixed-dose 25µg/125µg and 25µg/250µg combinations in the are working together to defeat competitionand harm consumers,” Czech Republic, Germany, Greece, Iceland, Luxembourgand Slovakia. Jepsen maintained. The application waswithdrawn from concerned member state (CMS) However, according to Jepsen, Ranbaxy had agreed to relinquish Poland during the clock-stop period. first-to-file rights to certain ANDAs –including “upon publically Using Seretide Evohaler 25µg/250µg as the reference product and available information and belief” its esomeprazole ANDA–ifitfailed extrapolating to the lower strength, Cipla and ELC submitted three to meet certain requirements within its consent decree by 30 September pivotal pharmacokinetic studies in healthyvolunteers, as well as a 2014. “AsofAugust 2014, Ranbaxy has not launched ageneric pharmacodynamic study “to support the safety of salmeterol”. [esomeprazole] product, althoughitclaims it has met all of the The first pharmacokinetic trial wasatwo-way,single-dose, milestones set forth in the consent decree,”heasserted. crossoverbioequivalence study without an active charcoal blockade Describing the 2008 agreement as an example of a“systemic to evaluate total systemic safety of both active ingredients. Asecond problem” within the industry whereby branded and generic firms had two-treatment, four-period, single-dose crossoverstudy assessed “rigged the system…to delay entry of generic drugs for as long as bioequivalence using an aero chamber and volumatic spacer.Athird, theypossibly can”, Jepsen called on the FDAtorelinquish Ranbaxy’s similar bioequivalence study evaluated similarity in lung-disposition exclusivity,and authorise “otherwise approvable ANDAs”. G in support of the efficacyofsalmeterol. Sweden’smedicines agency, Läkemedelsverket,said the firm’s newpMDI device –using norflurane as the propellant –delivered flow rates of 30-60 litres per minute, which wassimilar to the reference product’s in vitro performance. Cipla’sdevice is indicated for adults and children aged 12 years and older. Noting that around 30 million Europeans aged under 45 years suffered from asthma, Cipla said half of the continent’sasthma patients had “sub-optimalcontrol”. Through patient-engagement programmes, the firm is aiming to raise awareness of its “cost-efficient option”, while the firm also sponsored asymposium on “device and drug dilemmas”during the European RespiratoryCongress held in Munich, Germany, earlier this month. “Over the next 12-18 months, we will see aseries of launches throughoutEurope as we knowthere is acommon need for high-quality, affordable, reliable and thus sustainable therapyalternatives,”Cipla said. The Indian companyiscurrently rolling out an ipratropium metered-dose inhaler in the UK and amometasone nasal spray in the Netherlands (Generics bulletin,5September 2014, page 3). G
19 September 2014 GENERICS bulletin 21 Gen 19-9-14 Pg. 22_Layout 1 17/09/2014 17:18 Page 2
EVENTS
OCTOBER 19-21 November 2014 6&7-9October ■ 17th IGPAAnnual Conference ■ CPhI Pre-Connect Conference Miami,USA &CPhI Worldwide This three-day event is being organised by the US Generic Pharmaceutical Association (GPhA) and is the global event of the worldwide generics industry.Itisthe Paris,France annual joint meeting of the Canadian, European, Japanese, South African and US CPhI Worldwide is an exhibition and generics industry associations, the CGPA, EGA, JGA, NAPM and GPhA. Topics covered networking opportunity which will also will include market trends, regulatory developments and intellectual property.There will include the co-located events iCSE, P-MEC be speakers from companies such as Actavis, Hospira, Mylan, Sandoz and Teva,along and Innopack. The event will be preceded with opportunities to network. by the Pre-Connect Conference taking Contact:Jennifer Nguyen, GPhA.Tel:+1202 249 7127. place in the same location. E-mail: [email protected]. Website: www.gphaonline.org. Contact:UBM Information. Tel: +44 207 921 8039. E-mail: [email protected]. NOVEMBER agreements, in-licensing, marketing and Website: www.cphi.com. distribution of patented medicines, generics, 4-7November biosimilars, OTCproducts, medical devices 13-15 October ■ 9th Generics Asia and food supplements. ■ 11th TOPRA Annual Singapore Contact:Raucon. Tel: +49 6222 9807 0. This is afour-day conference which will look Symposium E-mail: [email protected]. Brussels,Belgium at topics including strategic partnerships, Website: www.europlx.com. marketing, the challenges of biosimilars Arranged by The Organisation for and opportunities in supergenerics. Quote Professionals in Regulatory Affairs (TOPRA) code P46253GB for a15% discount on DECEMBER and Belgium’sFederal Agencyfor Medicines registration rates. and Health Products (FAMHP), this event 2-4December will coverregulatory issues. Contact:IBC Asia. Tel: +65 6508 2401. ■ CPhI &P-MEC India Contact:TOPRA. E-mail: [email protected]. Mumbai,India Tel: +44 207 510 2560. Website: www.generics-asia.com. This is athree-day exhibition and E-mail: [email protected]. Website: www.topra.org. networking event which will also provide 5-7November technical and educational seminars. 27-29 October ■ 17th APIC/CEFIC Contact:UBM. Conference on APIs Tel: +31 2040 99544. ■ GPhA Fall Technical E-mail: [email protected]. Conference Vienna, Austria Website: www.cphi.com. Maryland, USA This conference will look at regulatory This three-day GPhA conference will look at developments and updates. There will be JANUARY the current regulatory and technical issues speakers from UK and US authorities as and their impact on the generics industry. well as Swissmedic and companies such 21 January as Hovione and Pfizer. Contact:GPhA. ■ 8th EGA Pharmacovigilance Tel: +1 202 249 7127. Contact:Concept Heidelberg. Discussion Forum E-mail: [email protected]. Tel: +49 6221 84 440. London, UK Website: www.gphaonline.org. E-mail: [email protected]. Website: www.api-conference.org. This European Generic medicines Association (EGA) event will takethe 11-12 November form of adiscussion forum and look at ■ 3rdAnnual World Biosimilar topics including legislation. Congress Europe Contact:Lucia Romagnoli, GPAConferences. Tel: +44 7562 876 873. Geneva, Switzerland Cocktail Reception & E-mail: [email protected]. Covering the latest developments in the Register onlineatwww.egagenerics.comor Awards Presentation biosimilarsmarket, this two-day event will www.gpaconferences.com. Tu esday7th October 2014 include keynote presentations as well as case studies and interactive discussion formats. 22-23 January Sheraton Paris Airport Contact:Terrapinn. ■ 14th EGA Regulatory& Hotel &Conference Centre Tel: +44 207 092 1000. E-mail: [email protected]. Scientific Affairs Conference Sponsor,Attend Website: www.terrapinn.com. London, UK Find out moreat This two-day conference will followthe 17-18 November EGA’s Pharmacovigilance Forum. Both www.generics-bulletin.com events are at the same venue in London. ■ EuroPLX 56 Contact:Lucia Romagnoli, GPAConferences. Alternatively, contact Nice,France [email protected] Tel: +44 7562 876 873. This meeting provides aforum for or [email protected] E-mail: [email protected]. or call +44 (0)1564 777550 business-development decision makers to Register onlineatwww.egagenerics.comor discuss and negotiate collaborative www.gpaconferences.com.
22 GENERICS bulletin 19 September 2014 Gen 19-9-14 Pg. 23_Layout 1 17/09/2014 17:19 Page 3
PRICE WATCH ...... UK Valsartan prices put Drug Tarifftothe test
rices for the three strengthsofvalsartan capsules have all featured 40mgAv04 mgerage 2882 avg£vga £ 40mgDrug04 mg 2882 DrugTagruD riffTTaaririffffff 40mg4£4Minimum04 mg 2882 minnmi £nmi £ Pon the Department of Health’smonthly list of price concessions Concession Brand 16 40mg04 mg 2882 NCSOSOCN DiovanD oi nva 40mg04 mg 2882 ListiL PricecePrist every month since June, and have once again appeared in September £16.00 among the exceptions to the Drug Tariffofpharmacyreimbursement £14.0014 prices. The latest concessionary prices are alittle lower than last £12.0012
month, butare still nevertheless several times greater than those £10.0010
contained in the Drug Tariff, which would otherwise apply. £8.008 The price concession for the 28-capsule packs of the 40mg strength, 6 Price (£) £6.00 for example, is £8.45 (US$13.64) in September.This compares with £4.004 £8.50 in August, butismore than five-times the Drug Tariffprice of 2 £1.61. Similarly,the price concessions in September for the 80mg and £2.00 160mg strengths are £10.80 and £10.90 respectively.InAugust, the £0.000 comparable concessions were £11.15 and £11.30, considerably more Oct 11Dec 11Feb 12Apr 12Jun 12Aug 12Oct 12Dec 12Feb 13Apr 13Jun 13Aug 13Oct 13Dec 13Feb 14Apr 14Jun 14Aug 14 than the equivalent Drug Tariffreimbursement prices of £2.21 and £2.47. Limited supplies, rather than shortages, and higher prices of Figure1:Lowest and average trade prices, compared with brand, Drug Tariffand valasartan capsules in recent months makeaninteresting case study. concessionaryprices, for 28-capsule packs of valsartan 40mg (Source –WaveData) All of the recognisable trends have been apparent: only the prices 80mgAv08mgerage 2882 avgavg £ £ 80mgDrug08mg 2882Ta DrugDruriffg TariffTTaariffff 80mgMinimum08mg 2882 minmin £ £ Brand of certain presentations of the ingredient have been affected enough 16 80mgConcession08mg 2882 NCSONCSO DiovanD oivan 80mg08mg 2882 ListiL Pricest Price to receive aprice concession; less affected presentations of the same £16.00 14 ingredient have experienced a‘halo’ effect of higher prices, either as £14.00 12 aresult of switching between products or enterprising suppliers trying £12.00 10 to cash in; and the Department almost certainly has failed to pitch its £10.00 8 concessionary prices at levels to prevent pharmacylosses. £8.00
Price (£) £6.006
Concessionaryprices fail to prevent losses £4.004
Figure 1illustrates the third of these very well. While the average £2.002 trade price of 28-capsule packs of valsartan 40mg rose from £5.61 £0.000 in June to £9.14 in August, the price concession granted by the Department oscillated between £8.50 and £9.28. Pharmacists made Oct 11Dec 11Feb 12Apr 12Jun 12Aug 12Oct 12Dec 12Feb 13Apr 13Jun 13Aug 13Oct 13Dec 13Feb 14Apr 14Jun 14Aug 14 an average dispensing profit on each product of nearly £3 in June, Figure2:Lowest and average trade prices, compared with brand, Drug Tariffand aprofit of £0.85 in July and aloss of £0.64 in August. Theyfared a concessionaryprices, for 28-capsule packs of valsartan 80mg (Source –WaveData) little better with the 80mg strength in Figure 2, although an average dispensing profit of £0.19 in July wasaclose call. Similarly,the average 320mgAv023 eragemg 2882 a avgvg £ 320mgDrug023 mgTa2 2882 riffD Drugrug TTaaririffffff 320mgMinimum023 mg 2882 mi minn £ DiovanDBrandoi van 3 320mg023 mg 2882 ListiL st Pri Pricece dispensing profit for the 160mg strength wasprecisely £0.02 in August. £25.0025 Meanwhile, the average prices of 28-tablet packs of valsartan 320mg and seven-tablet packs of valsartan 40mg have also drifted £20.0020 upwards in recent months. At no time, however, have theylooked like exceeding their Drug Tariffequivalents (see Figure 3). £15.0015 Arguably,this is because these tablet forms are in category A £10.0010 of the Drug Tariff, based on the list prices of Actavis and Teva as Price (£) well as the twoleading wholesalers. The capsule forms, in contrast, £5.005 are in category M, based on actual prices in the marketplace.
Whereas the Drug Tariffprice of valsartan 40mg in 28 capsules £0.000 was£1.61 in August, it was£2.65 for just seventablets. Similarly, the Drug Tariffprice of the 320mg tablets was£12.91, which was Oct 11Dec 11Feb 12Apr 12Jun 12Aug 12Oct 12Dec 12Feb 13Apr 13Jun 13Aug 13Oct 13Dec 13Feb 14Apr 14Jun 14Aug 14 totally out of step with the lower capsule strengths. Figure3:Lowest and average trade prices, compared with brand and Drug Tariff Valsartan products in combination have seen little or no price effect reimbursement prices, for 28-tablet packs of valsartan 320mg (Source –WaveData) whatsoever. As Figure 4shows, the minimum, average and category M avga1Avvg erage£ DrugD£gru TTaaririfTafffff£riff18.41£ 4.8 1 minMinimumnmi £ Drug Tariffprices for 28-tablet packs of valsartan 160mg with £20.0020
hydrochlorothiazide 12.5mg have bumped along at between about £18.0018 £1.50 and £3.00 for some time. G £16.0016 £14.0014 12 WANT MORE LIKE THIS? £12.00 £10.0010
Long-term product price trends or other price analyses are available. £8.008 Price (£) 6 Please specify the product and period of time you would liketo £6.00 4 investigate and email your request to [email protected]. £4.00 £2.002 ■ Forfurther information see www.bppi.co.uk. £0.000 Alternatively,contact Charles Joynson at Jun 13 WaveData Limited, UK. Tel: +44 (0)1702 425125. Oct 11Dec 11Feb 12Apr 12Jun 12Aug 12Oct 12Dec 12Feb 13Apr 13 Aug 13Oct 13Dec 13Feb 14Apr 14Jun 14Aug 14 E-mail:[email protected]. Figure4:Lowest and average trade prices, compared with Drug Tariffprices, for 28- tablet packs of valsartan 160mg/hydrochlorothiazide 12.5mg (Source –WaveData)
19 September 2014 GENERICS bulletin 23 Gen 19-9-14 Pgs. 24-25_Layout 1 17/09/2014 17:23 Page 2
BUSINESS STRATEGY Four forces compel firms to consider alternativemodels
Adverse forces are golden age for Europe’sgenerics industry appears mergers and acquisitions; and barriers to the growth to have come to an end. Having picked the low- of the generics sector’smarket share. compelling Europe’s Ahanging fruit of major solid-dose patent expiries, “The impact of disruption – which is turning some generics players to companies nowface more challenging pipelines and segments of the generics business into commodities – disruptive forces that will compel them to adjust their has been particularly acute in the US$80 billion market reassess their business models, according to Ewald Kreid, apartner for off-patent drugs in Europe,”the report observes. and managing director of the Vienna office of The “Although conventional wisdom holds that the European operating models. Boston Consulting Group. generics market faces ableak outlook, our work reveals Anew reportfrom “Anindustry that has been thriving, attracting amore complexreality,” the study adds, highlighting capital and talented people, is nowatacrossroads,” opportunitiesfor generics firms to learn from business The Boston Consulting Kreid told Generics bulletin.“Generics companies are models employed in other commoditised industries. Group suggests no longer participating in avery attractive industry,” Discussing the first of the four forces, pricing he argued, stressing the need for firms to identify pressure, Kreid observed: “Generic-drug prices in Europe some options, as strategies that would confer acompetitive advantage. are headed in only one direction – down.”Taking the Outlining research contained in the ‘Transforming example of Europe’slargest market, Germany, he Aidan Fryoutlines. Europe’sGenerics Industry’ report that he co-authored contrasted the gradual decline to 30% of the brand price with colleague Martin Reeves, Kreid said between 2005 for captopril after generic entry in 1995 with the day-one and 2011 aglobal sample of 18 publicly-traded generics launch by 17 entrants of generic atorvastatin in May firms posted an average total shareholder return of 15%. 2012 that led to an instant 92% discount to the brand. This compared to just 3% for 35 other pharma firms. Atorvastatin’sinstant price erosion, he pointed out, had But in the 2011 to 2014 period, the generics been achievedbefore the lipid-lowering blockbuster was sample’sreturn dropped to 12%, half of the 24% enjoyed subjected to tenders that had broadly halved generics by non-genericsfirms. “Three generics players showed prices in Germanysince their introduction in 2007. anegative shareholders’ return,”Kreid pointed out. Countries such as the Netherlands and Norway had Similarly,the median return on capital for eight used similar mechanisms to reduce prices, Kreid noted, leading US and European generics companies fell from while discount competition wasalso fierce in southern 7.5% in 2011 to 6.7% in 2013. “Atthese levels, returns European markets that linked generics prices to those are not covering the industry’s estimated cost of capital of the original. And with most European counties of around 9%,”hecommented. employing international reference-pricing, reductions According to the report – for which Boston in one market quickly translated to cuts elsewhere. Consulting conducted interviews with more than 20 Meanwhile, generics suppliers were coming under industry executivesand experts, analysed data for the increasing pressure from the second force, increasingly top six European markets and developed financial powerful distributors and pharmacychains that could projections to 2020 for generics industry sectors – these use their buying power to demand discounts on already financial declines reflect“four powerful forces” that are depressed list prices. “The top-fivedistributors hold disrupting the industry: unprecedentedpressure on more than 90% market share in France and Germany, prices; increasingly powerful distributors and pharmacy and close to 80% in the UK and Poland,”Kreid noted. chains; arelatively fragmented industry,despite recent But while generics companies’ keycustomers had
Market share, 2012 (%) Projected market share, 2020 (%) 100 100
30 80 49 80 50 61
60 80 77 60
57 40 40 48 42 20 38 20 19 21 13 1 1 3 2 8 0 0 Volume Value Profits* Volume Value Profits*
Biosimilars Standard generics *EBITDA Specialty generics Figure1:Actual and projected European market shares in 2012 and 2020 by volume and value sales and earnings beforeinterest, tax, depreciation and amortisation (EBITDA) for standardgenerics, specialty generics and biosimilars (Source -Boston Consulting)
24 GENERICS bulletin 19 September 2014 Gen 19-9-14 Pgs. 24-25_Layout 1 17/09/2014 17:23 Page 3
BUSINESS STRATEGY
consolidated, thereby increasing their buying power, “The challenges facing the generics industry are Europe’sgenerics industry remained fragmented. “Only hardly unique,”hepointed out. “Commoditisation and twoplayers –Teva and Sandoz – are among the top- price erosion have buffeted manyindustries – airlines, five players in France, Germanyand the UK,”Kreid textiles, chemicals, steel and cement to name afew.” pointed out, noting that the prevalence of local players One option, he outlined, wastoembrace had limited the combined share of the top-fiveplayers in commoditisation by focusing on streamlining the supply Italy,Poland and Spain to barely half of the market. chain and eliminating costs. Forexample, plastics Furthermore, originators had become skilled in producer Indorama had become aleading polyethylene erecting barriers to generic penetration, such as through producer by consolidating, simplifying its business and flexible pricing arrangements. As aresult, originators maximising the utilisation rates of its assets. And low- still controlled more than aquarter of the off-patent cost airlines had stripped out costs by offering direct market in Poland, around half in Germanyand the UK, connections rather than using hubs, operating standard three-fifths in France, two-thirds in Spain and three- fleets to achieve economies of scale in maintenance, quarters in Italy. and shifting to online booking and check-in. Generics companies’ vulnerability to these four Kreid said similar options open to generics firms forces depended on what sort of productstheyoffered, included rationalising portfolios to focus on the most Kreid commented. The report divides the industry into profitable stock-keeping units, reducing complexity by three main segments – standard generics, typically dedicating production sites to specific products and presented in oral solid forms, that can be branded or technologies, harmonising regulatory filings and adopting unbranded; specialtygenerics with more complex uniform packaging. Industry could also followairlines formulationssuch as inhalable products, eyedrops, in adopting dynamic pricing models that reflected real- “By 2020, we expect topical treatments, transdermal patches and certain time shifts in demand and movesbycompetitors. injectable therapies; and biosimilars with “success Rethinking firms’ manufacturing footprint–asthe that about 70% of factors that are closer to ame-too pharma model”. textiles industry had done – was another option. For Boston Consulting estimatesthat in 2012 standard example, he said, it might be most efficient to source industry profits in the generics accounted for 61% of industry value sales in bulk drugs in Asia buttoformulate and package drugs top-six European Europe – and four-fifths of volume sales – but only 49% in the market in which theywould be sold. Industry of earnings before interest,tax, depreciation and consolidation could eliminate excess capacity,raise markets will come amortisation (EBITDA). Branded and unbranded utilisation rates and create economies of scale, he added. standard generics contributed equally to the earnings, Even in the highly commoditised steel industry, from specialty generics even though unbranded generics made up 38 percentage producers had found profitable niches such as products and biosimilars” points of the value sales, and branded generics 23 points. for the gasand oil industries, Kreid continued, drawing As can be seen from Figure 1, specialty generics parallelswith pharma niches such as specific therapeutic generated 38% of value sales on about half that volume categories. And the example of Samsung in the percentage.Furthermore, theycontributed almost half smartphones sector – inwhich the South Korean group of the industry’sEBITDA, with biosimilarsadding 3% had captured twice the market share of Apple – had of profits on just 1% of sales. shown that starting as aclone and then adding unique features could yield high customer satisfaction. Less than one thirdofprofits “The generics industry has plenty of room to “Weproject that by 2020 standard generics will innovate,”Kreid insisted, pointingtofixed-dose account for less than one-third of industry profits, down combinations, slow-release formulations and pre-filled from about half in 2012,”the report states, adding that syringes as examples. However, he acknowledged, firms theywill represent nearly four-fifths of the market by would have to work hard to persuade payers to reward volume, butonly half by value as prices slide further. such advances through premium prices. Kreid acknowledged that generics companies were “Today it is not typical for generics companies to investing to overcome development, production and provide services on top of their products,”hestated. intellectual-property barriers as the pipeline of patent Cement makers, he noted, had vertically integrated into expirations shifted from the primary-care to the specialist distribution by supplying ready-mixcement directly sector.Two-thirds of drugs losing patent protection to construction sites. Likewise, generics companies between 2014 and 2020 would be specialtydrugs or could strikedeals with distributors and retailers, such biologics, he highlighted. as exclusive supply contracts for own-label ranges. “By 2020, we expect that about 70% of industry Partnerships and outsourcing offered options for profits in the top-six European markets will come from responding quickly to market needs and for shrinking specialty generics and biosimilars,”hestated. While balance sheets to improve returns on investment, Kreid originatorswould use lifecycle-management strategies continued. And as electronics giant IBM had done with to protect their brands after patent expiry,generics firms personal computers, generics companies needed to would erode originators’ market share that currently recognise when theycould not compete and pull out. stood at around 55% for standard generics, 65% for Recognising that adapting strategies and practices specialty generics and at least 85% for biologics. would be most difficult for the industry’scurrent Manyexecutivesinterviewed for the report had incumbents, Kreid recommended looking to other recognised that current success factors – proactive industries such as patented pharma to recruit fresh talent pipeline management, patent-challenge capabilities, as larger players looked to compete in several industry agility and speed to market, and lowsourcing, production sectors simultaneously.“The ability to deploydifferent and distribution costs – would not guarantee future strategies, tactics and skills simultaneously in different success. So Kreid proposed looking for lessons from markets and regions is one that most players are only other industries that had faced commoditisation. beginning to develop,”heasserted. G
19 September 2014 GENERICS bulletin 25 Partnerships Grow Businesses
Showcase your business Aposting on theSourceGenerics websitewill showcase your generics business opportunities to potential partners around theworld (free-of-charge* to Generics bulletin subscribers)
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Find out how SourceGenerics can help you find the right partners to grow your business by contacting Deborah Wilkes, Director of Source Publishing Limited by telephone on +44 121 314 8757 or by email at [email protected]
* Subscribers to Generics bulletin can post up to fi ve business opportunities on the SourceGenerics website free-of-charge for a year. i n association with Shorter periods can be arranged, depending on your needs. Confi dential listings are subject to a small fee. To take advantage of this off er, contact Deborah Wilkes by phoning +44 121 314 8757 or sending an email to [email protected].
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PEOPLE
MANAGEMENT RESHUFFLES EUROPEANCOMMISSION Tiefenbacher builds Polish Commissioner foundation for future willoverseepharma
nthe course of amajor reorganisation of its senior management, olish deputy prime minister Elzbieta Bienkowska is set to take IAlfred ETiefenbacher (AET) has appointed Kim Kleinert as its chief Presponsibility for pharmaceuticals and medical devices across financial officer.Moreover, Dr Nicolas Boege,former head of licensing, the European Union (EU) after she wasasked to lead the European has movedinto the position of chief commercial officer,replacing Commission’sDirectorate-General (DG) Internal Market, Industry, Carol vonGersdorff,who has left the German group (Generics Entrepreneurship and Small and Medium Enterprises. bulletin,5September 2014, page 31). One of several Commissioner-designates revealed by European “Asjoint managing director,von Gersdorffcontributed considerably Commission president-elect Jean-Claude Juncker, Bienkowska will to AET’sgrowth and success in the past 12 years,”the group said. The oversee pharmaceuticals, including the European Medicines Agency firm’smanagement quartet is completed by chief technology officer Dr (EMA). Her appointment comes as three Commission units –D5 Hans-Martin Schwarm and chief executive officer Dieter Schoenfeld. covering medicines authorisations and the EMA, D6 that is responsible “Weare constantly adjusting tomarket changes and improving for the quality,safety and efficacyofmedical products, and B2 for our services to assure our continuous success. As part of this process, health technology and cosmetics–transfer across to her remit from it wasinevitable to takethese steps,”Schoenfeld stated. G DG Health and Consumers. In aletter outlining Bienkowska’smission, Juncker said combining most of the responsibilities held by the current DGs Enterprise and INDUSTRY ASSOCIATIONS Market would help her achieve goals that include raising industry’s proportion of the EU’sgross domestic product (GDP) to 20% by 2020. Leaders take stage at IGPA DG Health and Food Safety will be the responsibility of former Lithuanian health minister Vytenis Andriukaitis.Denmark’s eaders from Actavis, Hospira, Momenta, Mylan, Sandoz and Teva Margrethe Vestager will head the Commission’sDGCompetition, Lwill share the stage during an ‘executivesunplugged’ panel discussion while DG Trade will be led by Sweden’s Cecilia Malmström. at the 17th annual conference of the International Generic Pharmaceutical Provided the Parliament givesits consent, the newCommission’s Alliance (IGPA) being held in KeyBiscayne, US, on 19-21 November.G five-year term will start on 1November 2014. G
19 September 2014 GENERICS bulletin 27 Do you know what your Generics bulletin print generics competitors are doing and thinking?
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