16 June 2017

COMPANY NEWS 2 Biosimilar notice may Vivimed’s API site in Spain 2 cleared by FDA Zydus’ Baddi facility 2 overcomes Form 483s precede approval in US Xantis Pharma buys Russia’s Alsi Pharma 3 Takeover deal values AMRI near US$1bn 3 iosimilar applicants in theUSmay provide the statutory 180-day noticeofcommercial Reddy’s eyes profits 4 Bmarketing before they obtain approval from the US Food and Drug Administration from its bio portfolio (FDA), the US Supreme Court has stated in aunanimous decision favouring Sandoz MARKET NEWS 5 over Amgen.Furthermore, the requirement in the US Biologics Price Competition and Innovation Act (BPCIA) for biosimilar sponsors to provide the reference-brand owner Savings of US$253bn 5 with their application and manufacturing information “is not enforceable by an injunction are registered in US under federal law”, but may be so under state competition law. UPC operationdateispushed into 2018 5 Sandozand Amgen haddisagreed overthe meaning of Section 262(l)(8)(A) in theBPCIA, BGMAresponds to EMA’s Brexit guide 6 which states that abiosimilarapplicant “shall provide notice to the reference-product sponsor Brand body calls for 6 not later than 180 days before the date of the first commercial marketing of the biological product biosimilarlabelshift licensedunder subsection (k)”. TheFederal Court of Appeals hadsided with Amgeninfinding that this meant the 180-day notice could only be given after the biosimilar had been approved by AAM report warns of REMS abuse scale 7 the FDA, and had granted an injunction that delayed Sandoz’ launch of its Zarxio(filgrastim-sndz) Tevaand Aliud top latest AOKtender 7 rival to Amgen’s Neupogen (Generics bulletin,7August 2015, page 1). House drops REMS from user-fees bill 8 But the Supreme Courtoverturnedthat finding. “Because the phrase‘of the biological product licensed undersubsection (k)’modifies ‘commercial marketing’ rather than ‘notice’,” it stated, PRODUCT NEWS 9 “‘commercial marketing’ is the point in time by which the biosimilar must be licensed.” HadCongress intendedtomaketwo timing requirements –FDA approval andnotice180 days Coherus pegfilgrastim 9 before launch –“it presumably would have done so expressly” as elsewhere in the BPCIA. knocked back by FDA Addressing whether providing the application and manufacturing information was obligatory WHO splits antibiotics 9 and enforceable by injunction, the Supreme Court said the Court of Appeals had reached the into three categories right conclusion, but on flawed reasoning. The remedy provided by Section 262(l)(9)(C) of the EMA adds infliximab to CHMP review list 10 BPCIA –allowing the originator to bring an immediate declaratory-judgementaction for artificial US bevacizumab and 10 infringement –“excludes all other federal remedies, including injunctive relief”, found the Supreme trastuzumab date set Court, which ordered the Court of Appeals to rule on whether failure to provide information was “unlawful” under Californian competition law. G UACTurges denialof 13 Xtandi patent in India Zydus’ rival to Lialdareceives US approval 13 Stada acquisition threshold is cut FEATURES 14 he private-equity backed vehicle proposing to take control of Stada will now seeits offer Inhalers and biosimilars star Tsucceedifatleast 67.5% of all of the German firm’s sharesare tendered by 22 June 2017, in Orion’s future firmament after lowering the minimum acceptance threshold for the offer and extending by two weeks Rivals both to leading respiratory inhaler the offer’s acceptance period. In April,Stada voicedits support for a C66.00(US$74.21) per brands and to major biological therapies share takeover offertabled by Bain Capital and Cinven’s Nidda Healthcare Holding that valued are central to Orion’s plans as the Finnish the German group at around C5.32 billion (Generics bulletin,14April 2017, page 1). The Nidda firm prepares for its next century. vehicle set an initial acceptance period with a minimum threshold of 75% of shares ending on Aidan Fry reports. 8June (Generics bulletin,5May 2017, page 3). Stada –which has postponed until 30 August the firm’s annual general meeting in light REGULARS of the offer –insisted all other offer conditions would remain unchanged. “The executive board and supervisory board will continue to recommend to the shareholders Events – Our regular listing 8 of Stada to accept the offer as it is in the best interest of the company and its stakeholders,” Price Watch UK – Our regular listing 12 Stada commented. “The executive board and supervisory board also think that the total compensation People – Mylan hits back over 16 of C66.00 per Stada share continues to adequately reflect the enterprise value and represents controversy on Coury the financially most attractive offer.”Although Nidda’s offer has been endorsed by Stada, China’s Issue No.313 ShanghaiPharmaceuticals lastmonth admittedaninterestinacquiring Stada,but denied submitting an offer (Generics bulletin,26May 2017, page 3). G COMPANY News

MANUFACTURING/ANNUAL RESULTS MANUFACTURING/ANNUAL RESULTS Vivimed’s API site in Zydus’ Baddi facility Spain cleared by FDA overcomes Form483s

ivimed Labs has announcedthatits active pharmaceutical ingredient ydus Cadila says it has successfully remedied deficiencies at the V(API) facility in Sant Celoni, Spain, recently passed aUSFood and ZIndian firm’s finished-dose formulations manufacturing facilityin Drug Administration (FDA) inspection with zero ‘Form 483’ observations. Baddi, Himachal Pradesh, after the facility was issued with an In abid to “growits presence in the US finished-dosageformulation establishment inspection report from the US Food and Drug business segment”, the Indian firm recently entered into ajoint venture Administration (FDA). In March, the US agency served Zydus’ plant with Strides Shasun, which acquired a50% stake in Vivimed’s with three ‘Form 483’ observations following apre-approval inspection businesses in India and Singapore (Generics bulletin,26May 2017, “for aspecific product” carried out between21Februaryand 1March page 5). The companiesthroughthe venture will own Vivimed’s Indian (Generics bulletin,10March 2017, page 5). Triggered by news of the establishment inspection report, Zydus Business Annual sales Change EBIT simultaneously announced that it had received FDA approval for segment (Rsmillions) (%) margin (%) mirtazapine 15mg, 30mg and 45mg orally-disintegrating tablets that Pharmaceuticals 10,104 +3.7 14.3 will be produced at the Baddi facility. Shortly beforehand, Zydus described as “significant” an FDA Specialty Chemicals 4,515 +21.6 48.1 approval for levofloxacin 500mg/20ml and 750mg/30ml injectables, Other 81 – – as this was “the beginning of the approval process” for filings made Vivimed 14,700 +8.4 20.1 from the firm’s key manufacturing facility in Moraiya, Ahmedabad, that was officially cleared by the FDA following an inspection in February Figure 1: Breakdown by business segment of Vivimed Labs’ sales and earnings (Generics bulletin,24February 2017, page 3). The site had previously before interest and tax (EBIT) margin in its financial year ended 31 March 2017 (Source –Vivimed) been subject to awarning letter since the end of 2015. Zydus revealed that it had received more than 10 abbreviated new FDA-approved formulationsfacilityinAlathur,Tamil Nadu, and will drug application (ANDA) approvals and filed over 45 applications house Vivimed’s current portfolio of abbreviated new drug applications during its financial year ended 31 March 2017, as the firm posted (ANDAs) in Singapore. The deal closed on 31 May. total turnover flat at Rs96.3 billion (US$1.49 billion). In Vivimed’s financial year ended 31 March 2017, the firm’s “The company’s formulations business in the US clocked sales groupturnoverroseby8.4% to Rs14.7 billion (US$229million),helped of over US$550 millionduringthe year,”notedZydus, which bought by sales in theSpecialty Chemicalssegmentwhich advanced by over commercial-stage specialty pharma pain-management specialist Sentynl afifth to Rs4.52 billion (see Figure 1). Meanwhile, Pharmaceuticals Therapeutics –based in San Diego –atthe beginning of the year sales moved up by 3.7% to Rs10.1 billion. G (Generics bulletin,27January 2017, page 4). Moreover,Zydus recentlytook astep towards launching its generic versionofShire’sLialda (mesalamine) 1.2gdelayed-releasetablets in IN BRIEF theUSafter aUSCourt of Appealsaffirmed alower court’sdecision that the Indian firm’s abbreviatednew drug application (ANDA) does VALEANT is continuing to simplify its operatingmodel and strengthen not infringe akey patent shielding the brand (see page 13). its balance sheet, according to chairmanand chief executive officer In the firm’s domestic market –where Zydusatthe turn of the year, Joe Papa,after agreeing the saleofthe firm’s iNovaPharmaceuticals acquiredadiverse lot of six branded products from Merck, Sharp & to fundsmanagedbytwo private-equitygroups for US$930 million Dohme, and certain of the US firm’s subsidiaries, for an undisclosed in cash. The sale of the business is anticipated to complete in the fee (Generics bulletin,13January2017, page 11) –formulationsales second halfofthisyear,subject to customaryclosing conditions. G grew by 9% to an undisclosed amount “on the back of more than 75 new products, including line extensions”. G

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2 GENERICS bulletin 16 June 2017 COMPANY News

MERGERS &ACqUISITIoNS MERGERS &ACqUISITIoNS Xantis Pharma buys Takeover deal values Russia’s Alsi Pharma AMRI near US$1bn

wiss-based pharmacompany Xantis Pharma has acquiredRussian lbany Molecular Research Inc (AMRI) has signed adefinitive Smanufacturer Alsi Pharma for an undisclosed fee. Alsi primarily Aagreement to be acquiredbyaffiliates ofprivate-equity firmsThe focuses on supplying cardiovascular, central nervous system (CNS) and Carlyle Group and GTCR in adeal that values the global contract gastrointestinal medicinesthroughRussian wholesalers, “but by becoming research and manufacturing organisation at around US$934 million. part of Xantis they gain access to acommercial platform reaching The valuation is basedonapurchasepriceofUS$21.75per shareand pharmacy chains,doctorsand, in the future, the hospital tenders market”. 42.96 million shares outstanding as of 5June. Furthermore, Xantis also intends to distribute Alsi’s portfolio “in Noting that the US$21.75 price represented “a 42% premium to selected Commonwealth of Independent States (CIS) markets”. the 60-dayweighted average closingstockprice leading up to 5April As wellasasales and administration office in Moscow, Russia’s 2017, the last trading day prior to public rumours in the press regarding Alsi operates amanufacturing facility in Kirov that Xantis intends to bring apotentialsaleprocess”,AMRIsaidthe deal had been“unanimously to “full capacity utilisation”and will consider expanding in the future. approved”byits board of directors. Subject to closing conditions, On acombined basis, the company employs around 500 people the deal is expected to closeshortly after aspecial meetingofAMRI’s and offers aportfolio that extends beyond cardiovascular, CNS and stockholders to voteonthe transaction in thethird quarterofthisyear. gastrointestinal drugs to cover men’s health, pain relief, allergy, Bill Marth, AMRI’s president and chief executive officer, said arthritis and OTC products. the agreement was “a strong endorsement of our strategy”. Citing “Our team has an impressive track record in building profitable Carlyle and GTCR’s “deephealthcare industry expertise and financial market share in the region where we operate and we have strong resources”, Marth saidthe “attractivepartners” offered“acompelling aspirations for this combination,” commented Xantis’chief executive opportunity to accelerate our growth”. officer, Lars Ramneborn. “By joining forces with Alsi, we see an For 2016, AMRI reported sales aheadbymorethan two-fifths to opportunity to enhance our position in Russia and neighbouring US$570 million (Generics bulletin,3March 2017, page 6) following countries and lay astronger foundation for future growth in the region.” acquisitions of European operator Euticals in July 2016 (Generics Foundedin2015 by Thor Bjorgolfsson’sinvestmentfirmNovator– bulletin,29July 2016, page 6) and Spanish group Gadea Grupo whichremains the primary owner –and experiencedpharma executives, Farmacéutico in late 2015 (Generics bulletin,7August 2015, page 7). many of whom had worked together at Actavis, Xantis has a“vision Dean Mihas, managing director and head of GTCR’s healthcare of building afully integrated pharmaceutical company in the markets group, said the investors “strongly believe in AMRI’s strategic where it operates, which are currently Russia, Ukraine, the CIS and direction and havebeenvery impressedwith management’sability to Central and Eastern Europe (CEE)”. transform the business intoatrusted partner for the biopharma industry”. The firm has headquarters in Zug, Switzerland, and operates a He suggested that AMRIwas “uniquely positionedtocapitaliseonan regional hub in Moscow, as well as representative offices across increased trendfor outsourcingofpharmaceuticalproductsand services”. the CIS and CEE region. G Meanwhile, Carlyle’s managing director and global head of healthcare, Stephen Wise, pointed to AMRI’s “strong track record” and “great potential and talent withinthe organisation”, adding that the MANUFACTURING investorswould help “createlong-term value through targeted growth andsuperior customer service” by building uponits existingoffering. As well as a“no shop” provision that restricts AMRI from Chemo opens two new plants soliciting alternativeoffers, the deal includesatermination fee of US$35 pain’s Chemo Group says it now has six local manufacturing facilities million for AMRI and of US$70 million for the acquiring firms. Safter opening two new plants, which will produce injectables. In amessage to AMRI employees, Marth said the firm would Opening the firm’s Farmalan facility in Léon brings to three the “continue to operate substantially as it does today” under its new firm’s number of plants in the province, where Chemo’s mAbxience owners. But “working in aprivate setting, we will have greater biosimilars subsidiary hasafacility thatwas earlier this yearcertified operational flexibility to invest and grow our business”, he stated, by localagency AEMPS(Generics bulletin, 24 February2017, page 7). putting the firm “well on our way to becoming atop player in the Meanwhile, Chemo has also begun operations at its 8,000 sq m contract-development and manufacturing industry”. Universal Farma facility in Azuqueca de Henares, Guadalajara, adding “Weanticipate minimal disruption to our businessinconnection to another plantinthe city.Chemo has afurtherfacility in Alcala de withthe closing of the proposedtransaction,”Marth said, adding that Henares, northeast of Madrid. “AMRI’s current management team is expected to continue to lead The twonew plants have aworkforce of nearly 80 professionals, the company and implement the strategy that we have been following”, who “are experts in sterile injectables”,according to Chemo, “mainly for the foreseeable future. “We anticipate ‘business as usual’ and working in the areas of maintenance and safety, quality, production there are currently no plans to change any of the initiatives we have and research and development”. underway,” Marth affirmed. “The addition of these plants is part of the company’s growth AMRI said GTCR and Carlylehad “no current plans for asset sales strategy,” commented director of Chemo Group’sindustrial division, or spin-offs”, adding that the acquirers were expected to “encourage Lucas Sigman, “which aims to cover all of the industry’s technology the company to continue pursuing strategic acquisitions and expand needs for the development of affordable, high-quality medicines.” our resources and capabilitiestoaddress our customers’ needs”. Marth Additionally, he added, Chemo was “fully committed to Spain, had indicated earlier this year that AMRI would be “back on the so we maintain astrong and sustained investment effort and aclear acquisition trail in 2018”. G commitment to the creation of jobs”. G n [email protected]

16 June 2017 GENERICS bulletin 3 COMPANY News

BUSINESS STRATEGy IN BRIEF ORCHID PHARMA joined amultitudeofgenerics players holding Reddy’s eyes profits final abbreviated new drug application (ANDA) approval in the US for ageneric version of Otsuka’s Abilify (aripiprazole) shortly before reporting annual sales that fell by 13.9% to Rs7.66 billion (US$119 million) during the Indian firm’s financial year from its bio portfolio ended 31 March 2017. However, incurring Rs8.09 billion worth of operating costs, on top of asignificant finance cost –Rs3.31 rReddy’s Laboratories expects to derive profits of between US$150 billion –led the firm to aRs4.45billion pre-tax loss. Dmillion and US$200 million from the firm’s biologic drugs in developed markets by the Indian firm’s financial year ending in March SANOFI has signed apartnership agreement with the CFAO Group’s 2025, according to apresentation delivered to delegates to the recent Eurapharma subsidiary “designed to accelerate” the French firm’s Jefferies2017Global Healthcare ConferenceheldinNew York, US. Maphar businessdevelopment in Morocco and “other Africanmarkets”. The Indian player has aroster of four follow-onbiologics –Cresp “The agreement will come into effect in June2017,” Sanofi explained, (darbepoetin alfa), Grafeel (filgrastim), Peg-Grafeel (pegfilgrastim) “with Eurapharma taking a majority 51% stake in Maphar. There and Reditux (rituximab) –but only currently markets them in India will also be closer co-operating between Eurapharma, Sanofi and other developing markets. Since 2014, however, Reddy’s has been Morocco and Maphar, backed by amajor business development running clinical programmes in the European Union and US for plan for Morocco and other African markets.” pegfilgrastim and rituximab, while the company is also in these markets engaged in clinical trials for aproposed alternative to Genentech’s MALLINCKRODT has moved to “correct inaccuracies” in reports and Avastin (bevacizumab). Moreover, in emerging markets, Reddy’s is stories about the company, including that the US-focused firm is US$8 also developing bevacizumab, as well as trastuzumab. billionindebtand that Mallinckrodt would be in default on alldebt Reddy’s told the Jefferies conference that by the firm’s 2020 covenants and go bankruptshouldsalesofits HP Acthar (corticotropin) financial year it anticipated having six registered biologic products, gel “drop by 50%”. The company –which only weeks ago refuted comprising 50 filings across 14 major countries, as well as five new media reports that cited allegations made by certain “short-seller” products in clinical-stage development and afurther fivenew products investors that theUSfirm’sprofitsrely solely on HP Acthar (Generics in early-stage development. Ahead of the firm’s ambitions for 2025, bulletin,2June 2017, page 6) –saidthese latest allegations by “self- Reddy’s projectsby2020 to bringinsalesofUS$150-US$200 million in acknowledged short sellers” were “not based on fact”. emerging markets, leadingtosales of US$300-US$400 million by 2025. During Reddy’s recent 2017 full-year earnings conference call, UPS saysithas made afurther strategic investment in healthcare Abhijit Mukherjee, the company’s chief operating officer,told investors logistics in Latin America “to serve the growing pharmaceutical, that Reddy’s this year anticipated bagging an emerging market biosimilars biopharma and medical devices industry” after opening anew 7,060 approval in one “reasonablylarge country”, as well as “two moresmaller sq mhealthcare-dedicated facility in Funza, Colombia. ones”, depending on “how the regulatory pathway proceeds”. G STRIDES SHASUN’S formulations facility in Bangalore, India, received three ‘Form 483’ observations following arecent US Food ANNUAL RESULTS and Drug Administration (FDA) inspection. “None of these observations relate to data integrity and quality control,” the firm stated. “The Natco nearly doubles its sales company will address these observations comprehensively.” ncreased US sales of generic oseltamivir and “continued growth” OLON – an Italian active pharmaceutical ingredient (API) contract Iin its domestic formulations business has enabled India’s Natco development and manufacturing organisation–saysithas strengthened Pharma to report group turnover that has almost doubled to Rs20.8 its offering to the pharmaceutical and biotech industry by acquiring billion (US$323million) in the yearended 31 March 2017. Domestic the chemical division of US-based contract research organisation formulations rose by nearly two-fifths to Rs8.81 billion as international Ricerca Biosciences for an undisclosed sum. By acquiring the research formulations more than trebled to Rs8.37 billion. and manufacturing base in Concord, Ohio, the Italian firm insisted Through an alliance with Alvogen, Natco developed the first it would “have the opportunity to accelerate growthby adding new generic equivalentto Roche’s Tamiflu (oseltamivir phosphate)30mg, contract development and manufacturing organisation projects 45mg and 75mg capsules (Generics bulletin,16December 2016, and to develop new generic products”. page 11). This year, Natco plans to “extend its Tamiflu franchise” by launching the drug in asuspension formulation. LUBRIZOL –aspecialty chemicalsproviderthat is part of the Berkshire With a“focus on complex generics” in the US, Natco noted that Hathawayconglomerate –ismaking a US$60 millioninvestment into as of 31 March 2017, the firm held 22 final abbreviated new drug the firm’s LifeSciences businessfocusedonnew product solutions, application (ANDA) approvals, with “one yet to be launched”.Of43 capacity expansion and additionalcurrentgood manufacturingpractice ‘niche’ ANDA filings, 20 included paragraph IV challenges. manufacturing. “These investments will strengthen the excipients, Meanwhile, Natco’s global active pharmaceutical ingredient (API) polymers, drug formulation and manufacturing, and medicaldevice sales lifted by 13% to Rs1.84 billion,making up almostatenthofthe contract-manufacturing capabilities at LubrizolLifeSciences’ global grouptotal. The remaining Rs1.77 billion –or9%–came fromother facilities,” commented the Ohio-based company. operations, including contract-manufacturing businesses. Setting out goals for 2017, Natcosaid it saw“near-term approval CLARIS LIFESCIENCES saysthe firm, including itsClaris Injectables forsome key molecules”, including aUStarget action date in June for operation, underwent arecent US Food and Drug Administration (FDA) its generic rival to Teva’s blockbusterCopaxone (glatiramer acetate), pharmacovigilance audit with no ‘Form483’observations. TheIndian for which the Indian firm partnered with Mylan (Generics bulletin, firmisinthe process of divesting its Injectables business to Baxter 8July 2016, page 15). Natco also anticipates further approvals for under aUS$625 million deal agreed at the end of last year. G lanthanum, azacitidine and bosentan. G

4 GENERICS bulletin 16 June 2017 MARKeT News

MARkET RESEARCh INTELLECTUAL PRoPERTy Savings of US$253bn UPC operation date are registered in US is pushed into 2018

sing generics saved US$253 billion in 2016 forthe US healthcare target date for the European unified patent court (UPC) to enter Usystem, contributing to genericssavings of US$1.67 trillion over Aintooperationbythe end of this year “cannot be maintained”,the the past 10 years,according to areportcompiled by the QuintilesIMS preparatory committee charged with overseeing the project has admitted. Institute that has just been published by the country’s Association Atimetable for starting the UPC’s provisional application and for Affordable Medicines (AAM). The 2016 figure represents a9% the entry into force of the UPC agreement depended “on the timely increase over savings of US$232 billion achieved in 2015. finalisation of national procedures” to ratify the UPC agreement and Nearly 3.9 billion generic prescriptions were dispensed in 2016, to participate in the protocol on provisional application, the committee the report states, representing 89% of totalprescriptions byvolumeat pointed out. “In particular,” it noted, “a few member states must just 26% of the cost. According to thereport’s findings, savings within still agree to be bound by the protocol beforethe period of provisional the Medicare health insurance programme were US$77billion –equating application can start.” to savings of US$1,883 per enrollee –while Medicaid savings of US$37.9 According to the European Council, as of 8June, Belgium, Finland billion translated to US$512 per enrollee. and the Netherlands had not yet signed the protocol on provisional Viewed by therapeutic area,the mostsavings from generics in 2016 application. Germany and the UK –two of the three mandatory were in mental health medicines, with savings of US$44 billion. participants, along with France –are among 13 of 25 participating Antihypertensive generics saved US$29 billionand cholesterol-lowering member states that have yet to notify the Council that they have generics US$28 billion. Brokendown by molecule,the most savings ratified the UPC agreement. were generated by atorvastatin (see Figure 1). SpeakingataCompetitiveness Council press conference held at “For the first time,”the AAM noted, “the third-party researchers the endofMay,Internal Market andIndustry CommissionerElżbieta whoconducted the study analysed the differences betweenbrand and Bieńkowska expressed surprise that the three member states had not generic ‘abandonment’ behaviours.” This referred to how often patients yet signed the provisional protocol. “We should agree to start the that request aprescription at the pharmacy fail to pick it up. “The report provisional application by the summer break,” she insisted. “Otherwise, concludes that new patient abandonment rates for brand-name drugs it will be too late to launch the unitary patent this year.” are 266% higher than for generic drugs,” the AAM said,with the branded Bieńkowska acknowledged that progress towards the UK ratifying rate at 20.5%, compared to 7.7% for generics for new patients. the UPC agreementhad been held up by ageneral election that took The association suggested that “copays playasignificant role in place on 8June. Therefore, she noted, UK ministers had been unable to abandonment”, with 90% of generic copays under US$20, compared offer assurances on how the new government would act on the UPC. to just 39% for branded copays. “Stickershock is believed to beaprimary The British Chambers of Commerce recently teamed up with reason for abandonment,” the report indicates. European counterpart Eurochambres to urge the UK government “to do “We must nevertakehealthcare access and savings for granted,” everything within its powers” to complete the unitary patent ratification said Chip Davis, the AAM’s president and chief executive officer. process, “regardless of the general election and Article 50 negotiations” “AAM looks forwardtoworking with all stakeholders to ensure and over the UK’s exit from the European Union (EU). expandaccess to genericsand biosimilars: the proven, reliable way to The preparatory committee said it was monitoring the progress drive down the cost of medicine, which helps patients, strengthens of national procedures on both ratification of the UPC agreement and our economy and benefits our society.” the provisional protocol “with aview to publish anew timetable” as The report urged US policy-makers to recognise“the very different soon as possible. Furthermore, anew timeline for recruiting UPC dynamics that exist between branded and generic drug business models judges would be communicated “as soon as possible” to candidates and marketplaces, and adopt policies to enhance the competitive who had submitted applications. prescription drug market”. G “An operational team is currently overseeing the final preparations n [email protected] for the recruitment of judges, testing the information-technology and case-managementsystems,and ensuring that resources are trainedand in Generic 2016 savings Discount place before the UPC’s entry into operation,” the committee stated. G entry year (US$ billions) to brand (%) Liptor (atorvastatin) 2011 14.4 97

Prilosec (omeprazole) 2002 11.1 98 PRICING &REIMBURSEMENT Zofran (ondansetron) 2006 10.0 99 Cymbalta (duloxetine) 2013 8.2 90 Commission strives for balance Zocor (simvastatin) 2005 6.9 99 he challenge of balancing rewards for pharmaceutical innovation Neurontin(gabapentin) 2004 5.8 92 Twith acompetitive environment “is further complicated by the high degree of regulation at Europeanmember statelevel, which leads Norvasc(amlodipine) 2007 5.6 99 to significant national variations of medicine pricing and wholesale Singulair (montelukast) 2012 4.7 95 and pharmacy margins”, the European Commission insists in astaff working document on areport on competition policy. 2015 4.6 83 Abilify (aripiprazole) In the document, the Commission reviews lastyear’s citalopram Seroquel (quetiapine) 2012 4.5 95 pay-for-delay patent-settlement ruling by the European Union’s General Figure 1: Top 10 generic drugs ranked by savings achieved in the US in 2016, Court, as well as competition clearance for Teva’s acquisition of the with discount to the pre-expiry brand price (Source –AAM) Actavis generics operation. G

16 June 2017 GENERICS bulletin 5 MARKeT News

REGULAToRy AFFAIRS REGULAToRy AFFAIRS BGMA responds to Brand body calls for EMA’sBrexit guide biosimilar label shift

single European regulatory system should be maintained in the hree changes are needed to biosimilar labelling requirements in AUK as part of the country’s ‘Brexit’ negotiations to leave the TEurope in the interest of “an enhanced level of transparency”, European Union (EU), the British GenericManufacturers Association according to originator organisation EuropaBio.The three “smallbut (BGMA) has reiterated in response to guidance published by the meaningful” changes are: adding astatement with the definition of European Medicines Agency (EMA) and the European Commission on biosimilarity; adding adirect link to the European public assessment preparing for the withdrawal (Generics bulletin,9June 2017, page 9). report (EPAR); and moving the biosimilarity statement to the top of Covering implications for marketing-authorisation holders, the the summary of product characteristics (SmPC). guidance is the first of aseriesofquestion-and-answer documents for “EuropaBiomembers believe thatthe current EuropeanUnion (EU) industry, following the publication by the two organisations of anotice approach to labelling does not reflect the specificities of biosimilars, and to marketing-authorisationholdersofcentrally-authorisedhumanand that the SmPC of abiosimilar product should contain additional veterinary medicines (Generics bulletin,12May 2017, page 9). information to facilitate greater transparencyfor physicians and patients,” The document points out that the marketing-authorisation holder the brand body stated. must be established in the EU –extended to include Iceland,Liechtenstein “The European Medicines Agency (EMA) and the European and Norwaythrough the European Economic Area (EEA) agreement – Commission are going to great lengths to increase physicians’ and and clarifies that for centrally-authorised products, the marketing- patients’ understanding of biosimilars,” said EuropaBio healthcare authorisation holder will therefore normally need to transfer its biotech director, Ronald Jager. “We areconvincedthat amore transparent authorisation to aholder established in the EU or EEA. labelling approach wouldcontribute to furtherfacilitate theunderstanding “Wehaveconsistentlystated that theexistence of asingle European and acceptance of biosimilars.” G regulatory system for medicines has generated considerable benefits for patients, the UK National Health Service(NHS) and the industry,” commented Warwick Smith, director general of the BGMA. Stating REGULAToRy AFFAIRS that theBGMAhad “urged both sides in the Brexitnegotiations to find a way of maintainingthesebenefitsinthe interests of their citizens”, Smith China releases inspection data said it was “concerning that the Commission appears to be unwilling even to try to find apositive way forward in everyone’s interests, rather etails of inspections carried out by the China Food and Drug than assuming the worst outcome before thenegotiations evenbegin”. DAdministration (CFDA)in2016 have been publishedbythe agency. When the UK voted to leave the EU last June, Smith insisted that The CFDA said 16 initial good manufacturing practice (GMP) inspections thegovernment should “do everything possible to maintain thisEuropean of pharmaceutical manufacturers had been arranged, 16 inspection marketing-authorisation system in the forthcoming negotiations with reportswere received and 14 were reviewed during 2016. Furthermore, the EU” (Generics bulletin,1July 2016, page 5). He said that a 12 manufacturerspassed aGMP inspection, while two failed and five unified marketing-authorisation system “reducescost andcomplexity were issued with awarning letter. for manufacturers, facilitating the production and regulation ofhigh- On follow-up inspections, the CFDA said that 170 of 228 planned quality medicines and their availability to patients”. G inspections across215 companies were conducted. G

INTELLECTUAL PRoPERTy REGULAToRy AFFAIRS Five seek compulsory sharing FDA creates industry toolkit iveWorld Trade Organization(WTO)member countries –Brazil, “supply chain security toolkit” for medical products has been FChina, Fiji, India and South Africa –have called for delegations Acreatedbythe US Foodand Drug Administration (FDA) to to “share their national experiences and examples of using compulsory “maximise available global resources and to deliverquality trainings licences” during ameeting of the WTO’s council for trade-related and best practices”. Working in collaboration withAsia-Pacific economic aspects of intellectual-property rights (TRIPS). co-operation (APEC) countries, the FDA noted that the toolkit –which In particular, the five countries want delegations to share: the grounds contains materials to educate regulators, industry and healthcare available in national laws to issue compulsory licences; difficultiesand professionals –coversthe entiresupply chainand lifecycle of medical constraints faced, such as insufficient capacities; whether such licences products, from raw materials to use by patients. have been used by governments to obtain price cuts; and what the “Protecting the integrity of the medical-product supply chain is results of issuing compulsory licenceshave been on priceand access. complex and requires aglobal approach,”the FDA commented. Calling Under the 2001 Doha Declaration on the TRIPS agreement, the the toolkit a“comprehensive resource”, theagency saidthatit“addresses countries pointed out, each WTO member has the freedom not to areas of vulnerability in the medical-product supply chain, and contains onlytograntcompulsory licences, but also “the freedom to determine recommendedbest practices and tools to prevent and detect substandard thegrounds upon which such licences are granted”. Such grounds were and falsified medical products before they reach consumers”. not limited to emergencies. “In spite of the clarity of this language,” The toolkit covers 10 categories, including good manufacturing they said, “WTO members around the world seeking to make use practice, good distribution practice, good import/export practice, of compulsory licences as atool to increase access to affordable and clinical/retail pharmacy practice. Product security, detection medicines have faced various challenges and/or barriers.” G technologies and track-and-trace systems are also covered. G

6 GENERICS bulletin 16 June 2017 MARKeT News

REGULAToRy AFFAIRS PRICING &REIMBURSEMENT AAM report warns of Teva and Aliud top REMS abuse scale latest AOK tender buseofUSgovernmentsafety programmes such as Risk Evaluation he Teva/Ratiopharm bidding consortium and Stada’s Aliud Pharma AMitigation Strategies (REMS) could block from competition as Tledthe way in securing two-yearsupply contractsunder the18th much as US$22.7billion in brand sales,accordingtoaMatrixGlobal tender round run by Germany’s AOKgroup of statutoryhealth insurance Advisors report sponsored by the US Association for Accessible funds. The 108 active ingredients and combinations covered by the Medicines (AAM). The restricted-access segment identified by the tenderthat beganon1June have acombined annual turnover through report comprises 41 REMS-restricted drugs with sales of US$11.5 the funds of C1.8billion(US$2.0 billion). In total, the AOK now has billion in 2016, along with33drugs restricted by non-REMS programmes 275 ingredients and combinations under contract. with 2016 sales totalling US$11.2 billion. Seven of the 74 drugs are For 15 molecules or combinations –such as the antidepressant blockbusters with sales above US$1 billion. mirtazapine; the antihypertensives amlodipine and losartan; theantibiotics “Given the size and scope of the pharmaceutical market subject to cefaclor,ceftriaxone,ciprofoxacin, clarithromycin and roxithromycin; aREMS or asimilar distribution restriction, this issue warrantsattention the proton-pump inhibitor omeprazole; and the cholesterol-lowering on the scale of other high-priced drugs that have generated headlines agent simvastatin–the AOK awarded supply deals in each of its eight and Congressional inquiries,” the report advocates. “There are valid bidding regions to three companies, amounting to 360 individual contracts. public-health reasonsfor restricted-access programmes for certain drugs, Afurther 16 regional deals to supply cefuroxime were split between but misuse of these programmes to block generic competition has a Aliud, Sun Pharma’s Basics unit and Torrent’s Heumann Pharma. direct negative impact on consumers and taxpayers.” With the tender divided into 110 bidding lots, 94 of those lots were Chip Davis, the AAM’s president and chief executive officer, said awarded on an exclusive basis in each of the eight regions, representing “we need to tear down the barriers that are keeping more affordable 752 individual supply contracts to give an overall total of 1,128. generic drugs from reaching patients, and stopping this anti-competitive Teva andits Ratiopharm affiliate ledthe waywith 245 contracts, behaviour is agood place to start”. or 21.7% of the total1,128awarded. Aliudfollowed with 174, almost Proposed legislation to address abusesincludes the Creating and double the 88 won by third-placed Heumann and its Heunet sister Restoring Access to Equivalent Samples (CREATES) Act and the Fair company. Another Indian company, Aurobindo and its Puren label, Access for Safe and Timely (FAST) Generics Act. AREMS-related ranked fourth with 84 contracts, ahead of localplayer Aristo Pharma provision was recently removed from user-fee legislation (see page 8). G on 77 and Sanofi’s Zentiva with 73 (see Figure 1). Other major recipients of awards includedBasicswith 48, Dexcel with 40, Glenmark with 38 –including eight for paricalacitol in collaboration with Sun Pharma –and Neuraxpharm 37. But several leadingglobal genericsplayerseither chose not to take part in amajor way or failed to securecontracts.Sandoz’ Hexal picked up just eight deals, for metoprolol/hydrochlorothiazide across all regions, while Mylan Dura faired alittle better with 24 contracts. Insisting that successful bidders had been given ample time to prepare, the AOK’s chief negotiator,Christopher Hermann, saiddrug tenders had saved the AOK funds around C1.6 billion last year, and saved all German statutory funds C3.85 billion. “As we launched the first medicines tenders 10 years ago, large pharma producers tried to thwart them–theydid not succeed,”Hermann remarked. “Thanks to our initiatives, the statutory health insurance system has sinceachievedsavings of C20 billion,”heclaimed. G

Aliud Pharma** Teva/Ratiopharm* 174 245 15.4% 21.7% Heumann/Heunet 88 7.8% Aurobindo/Puren 84 7.4%

Aristo Pharma 77 Others 6.8% 387 Sanofi/Zentiva 34.4% 73 6.5% *Includes seven lots through ajoint bidwithAlmirall Hermal ** Includes one lot through ajoint bidwithMicro Labs Figure 1: Breakdown by company of contracts awarded for 1,128 bidding lots in the 18th tender round run by Germany’s AOK health insurance funds (Source –AOK)

16 June 2017 GENERICS bulletin 7 MARKeT News

events – June –november REGULAToRy AFFAIRS 20-22June House drops REMS n CPhI China Shanghai, China Offering conferences, networking opportunities and exhibitions, from user-fees bill this event will also provide market updates and regulatory news. Contact:UBM Asia. Tel: +852 2827 6211. namendmenttothe draft US Food and Drug Administration (FDA) E-mail: [email protected]. Website: www.cphi.com/china. AReauthorization Act (FDARA) intended to tackle abuse of risk 12-13September evaluation and mitigation strategies (REMS) that restricts generic competition has been dropped during deliberations by the US House of n AAM Biosimilars Council Conference Representatives’ energy and commerce committee on the user-fee bill. Washington, USA However, the version of FDARA –also known as HR 2430 – The key topics to be discussed at this two-day conference will passed unanimously by thecommittee includes sixotheramendments include regulatory affairs, pricing and reimbursement and the and also adjusts amendments made by aHouse sub-committee on policy environments surrounding access to biosimilars. health last month, including asection that seeks to enhance generic Contact: AAM. Tel: +1 202 249 7100. competition by offering incentives such as six-month exclusivity and E-mail: [email protected]. Website: www.accessiblemeds.org. pre-submission meetings with the FDA. An amendment offered by Vermont Democrat Peter Welch would 27-28September have barredoriginators from using REMS andsimilarprogrammes to n Biosimilars &Biobetters block access for generics and biosimilars developers to the brandsamples London, UK they need for comparability tests. Samples would have had to be This event will look at the commercialisation of biosimilars as well as made available at “commercially reasonable, market-based prices”. regulatory guidelines, interchangeability, clinical trials and pricing. Welch withdrew the bipartisan amendment that he had devised Contact:SMi. Tel: +44 207 827 6000. with Republican David McKinley, with committee chairman Greg E-mail: [email protected]. Website: www.smi-online.co.uk. Walden suggesting that “there are some issues in it that we felt needed additional work”. Democrat Anna Eshoo objected that the amendment 24-26october “conflates samples issues with shared-system REMS”. However, n CPhI Worldwide Welch urged the House to pass identical text in the standalone Fair Frankfurt, Germany Access for Safe and Timely (FAST) Generics Act. The Congressional CPhI Worldwide is an exhibition and networking opportunity that Budget Office (CBO), he stressed, had estimated that the measure will be preceded by the Pre-Connect Congress, which will look at would save US$2.8billion. According to figures justreleased by the the latest developments in the pharma industry. US Association for Affordable Medicines (AAM), abuse of safety Contact programmes such as REMS could improperly protect from competition :UBM Information. Tel: +31 207 08 1637. E-mail: [email protected]. Website: www.cphi.com. US$22.7 billion in brand sales (see page 7). For example, Welch outlined, Celgene had used aREMS programme 6-8 November to delay access to samples of Thalomid (thalidomide) for four years, n AAM Fall Technical Conference during which time it switchedmultiple myeloma patients to its follow-on Maryland, USA drug Revlimid (lenalidomide). “Now we are seeing arepeat of that This conference will cover regulatory issues with speakers from delaying tactic applied to Revlimid,” he added. the industry and the US Food and Drug Administration. McKinley noted that the FDA had not levied any fines against originators abusing REMSprogrammes. And in any case, he said, the Contact: AAM. Tel: +1 202 249 7100. prospective fines were so low that it would still be worth originators E-mail: [email protected]. Website: www.accessiblemeds.org. abusing such systems to extend their market monopoly. 27-28November An adopted ‘manager’s amendment’ includes Section 703 on n euroPLX 65 ‘Incentivizing competitive generic therapy’ that offers 180-day exclusivity for “any first approved applicant” that has started marketing the first London, UK generic rival to an off-patent brand. Such exclusivity would be forfeited This meeting provides an opportunity to discuss and negotiate if the first-generic applicantdid not launch within 75 days of approval. agreements, development, in-licensing and marketing, promotion Section 705 of thesameamendment requires the US comptroller- and distribution. general to conductastudy of the rate of first-cycle finaland tentative Contact:RauCon. Tel: +49 6221426296 0. approvals for generics between October 2012 and September 2017. In E-mail: [email protected]. Website:www.europlx.com. any 12-month period in which the first-cycle rate is below 20%, the study should detail the reasons. Chairman Waldeninsistedthe agreements on the Generic Drug User Fee Amendment (GDUFA) and Biosimilar User Fee Act (BsUFA) reauthorisations would help to clear the FDA backlog of generic applications and streamline how generic and biosimilar applications were reviewed. This, he said, would drive down drug prices. During the meeting, severalspeakers called for the committee to hold additional sessions to discuss potential solutions to rising drug prices in the US. Welch’s proposed amendment to allow importation of lower-price drugs from Canada was voted down. G n [email protected]

8 GENERICS bulletin 16 June 2017 PRODUCT News

BIoLoGICAL DRUGS ANTIBIoTICS Coherus pegfilgrastim WHO splits antibiotics knocked back by FDA into three categories

oherus BioSciences has received acomplete response letter(CRL) rouping antibiotics into three categories and adding medicines for Cfrom the US Food and Drug Administration (FDA) identifying GHIV, hepatitis C, tuberculosisand leukaemia are amongthe updates deficiencies in the firm’s biologics license application (BLA) for its in the latest edition of the World Health Organization’s (WHO’s) model CHS-1701 proposed biosimilar version of Amgen’s Neulasta essential medicineslist (EML). Additions to the listinclude 30 medicines (pegfilgrastim). The company revealed the letter after the biosimilar for adults and 25 for children. userfee act (BSUFA) action date for the application passedon9June. In revising theantibiotics section,the WHO has categorisedsuch “The CRL primarily focused on the FDA request for areanalysis drugs into three sections: ‘access’, ‘watch’ and ‘reserve’, along with of asubset of subject samples with arevised immunogenicity assay,” recommendations on when each category should be used. “The change Coherus revealed, as well as “requests for certain additional aims to ensure that antibiotics areavailablewhen needed, and that the manufacturing-related process information”. The FDA “did not request right antibiotics are prescribed for the right infections,” the WHO aclinical study to be performed in oncology patients”, Coherus explained, noting that 10 antibiotics had been added to the list for emphasised, following the firm’s rebuttal of an Apotex petition that adults, and 12 for children. had urged the FDA to requireall biosimilarpefilgrastim applicants to Antibiotics in the access group are to be available at all times as conduct comparative clinical efficacy studies in at least one intended treatments for awide range of common infections, the WHO proposes, patient population, rather than in only healthy volunteers (Generics citing amoxicillin as an example. Meanwhile, the watch group includes bulletin,2June 2017, page 10). antibiotics like ciprofloxacin that are recommended as first- or second- Notingthatitwould“work with the FDA to address the information choicetreatments for asmall number of infections. Colistin andsome requests”, Coherus observed that “the CRL does not indicate additional cephalosporins are included in the reserve group, as antibiotics that process-qualification lotswould be requiredorraise concerns over the “should be considered last-resort options”. good manufacturing practice (GMP) status of CHS-1701 bulk “Initially, the new categories apply only to antibiotics used to treat manufacturing and fill-finish vendors”. 21 of the most common general infections,” the WHO stated. “Ifshown Denny Lanfear, Coherus’president and chiefexecutive,saidthat to be useful, it could be broadened in future versions of the EML to the firm was “disappointed in the delay that this additional request has apply to drugs to treat other infections.” caused”but would “remain confident in our abilitytoaddressthe FDA’s Medicines added to the EML include two oral cancer drugs, dasatinib requests”. “We expect thatwewill be able to respond to the FDA andnilotinib –which are used to treat chronic myeloid leukaemia –and andmeet with them to define apathforward in the coming months.” fentanyl skin patches and methadonefor pain reliefincancer patients. Meanwhile, as part of ongoing US patent litigation with Amgen Noting that the WHO was currently updating its treatment over Neulasta, Coherus has filed aheavily-redactedmotion in aDelaware recommendations for hepatitis C, the group observed that its district court to dismiss the originator’s action because there is “no sofosbuvir/velpatasvir addition to the list was the “first combination plausible interpretation under which Coherus would infringe” US therapy to treat allsix typesofhepatitis C”. Further additions include chromatography process patent 8,273,707. “Non-infringement is so dolutegravir to treat HIV infections and new paediatric formulations clear that Coherus surmises Amgen is pursuing this case not for its of medicines for tuberculosis. merits,but ratherto throw acostly and artificial wrench intoCoherus’ Expressing “concerns about the high price of some medicines”, plans to launchabiosimilar of Neulasta,”the firm stated. G the committee said it supported the objectives of the WHO’s recent fair pricing forum (Generics bulletin,2June 2017, page 9) “as one initiative to increase awareness and participation of all relevant IN BRIEF stakeholders”. Access to affordable essential medicines was also discussed DR REDDY’S haslaunched ageneric version of The Medicines –notably for cancerand diabetes drugs –aswell as supporting aproposal Company’s Angiomax (bivalirudin) in the US after receiving approval for aWHO list of essential in vitro diagnostics. Furthermore, the fromthe US Food and Drug Administration (FDA). The Indian firm’s committee recommended the “formation of expert groups to support bivalirudin for injection is available in packs of 10 single-dose future work for EML reviews and applications”, particularly for cancer 250mg/vials. Citing QuintilesIMS data, Reddy’s said Angiomax medicines and antibiotics. G and its generics had annual US sales of around US$198 million.

LG LIFE SCIENCES has made progress on biosimilar etanercept oPhThALMoLoGy DRUGS after astudy foundthat the firm’s LBEC0101 candidate shown similar pharmacokinetics, immunogenicity and tolerability to Pfizer’s Enbrel Teva ships Pataday rival in US brand. Arandomised, double-blind crossover study was conducted in 48 healthy males, using asingle subcutaneous injection. eva has launched the first generic version in the US of Alcon’s TPataday (olopatadine hydrochloride) 0.2% ophthalmic solution INTELLIPHARMACEUTICS has announced that marketing and with 180 days of genericmarketexclusivity.Alcon’s sistercompany, distribution partner Mallinckrodt has launched ageneric rival to Sandoz respondedbyoffering an authorised generic. In its accompanying AstraZeneca’s Seroquel XR (quetiapinefumarate)extended-release abbreviatednew drug application (ANDA) approval letter, the agency tablets following approvalfromthe US Food andDrug Administration pointed out that Teva had previously been engaged in litigation with Alcon (FDA). Used to treat schizophrenia and bipolar disorder, thedrugis in an Indiana district court over US patents 7,402,609 and6,995,186, available in 50mg, 150mg, 200mg, 300mg and 400mg strengths. G whichexpire in December 2022 and May 2024 respectively. “You have notified theagency that thiscasewas dismissed,” the FDA said. G

16 June 2017 GENERICS bulletin 9 PRODUCT News

BIoLoGICAL DRUGS BIoLoGICAL DRUGS EMA adds infliximab US bevacizumab and to CHMP review list trastuzumab date set

new application for biosimilar infliximab is under review by the n13 July 2017, Mylan’s proposed biosimilar rival to Herceptin AEuropean Medicines Agency (EMA),according to an update on O(trastuzumab) and Amgen’s planned biosimilar version of Avastin applications for new human medicinesunder evaluation by the regulator’s (bevacizumab)willbeconsidered by the Oncologic Drugs Advisory committee for human medicinal products (CHMP). Committee (ODAC) within the US Food and Drug Administration As of 1June 2017, the EMA said its CHMP was reviewing one (FDA) at apublic meeting held at the agency’s White Oak campus. application for biosimilar infliximab. Other biosimilars that are still Adocket for public comment –with reference number under review by the European agency include four applications for FDA-2017-N-2732 –has been opened, with electronic or written adalimumab, two forbevacizumab, onefor insulin glargine,three for comments able to be submitted up to 10 July. All submissions to the pegfilgrastim and four for trastuzumab. docket on or before 26 June will be provided to the committee. Although the EMA does not reveal the identity of marketing- During the morning session on 13 July, the ODAC will discuss authorisation applicants for filingsunderconsideration by the CHMP, Amgen’s ABP 215 bevacizumab candidate.The proposed indications Sandoz recently revealed that the agency had accepted for review its are for treating: metastatic carcinoma of the colon or rectum in dossiers for both biosimilar adalimumab and infliximab (Generics combination with intravenous 5-fluorouracil-based chemotherapy; bulletin,9June 2017, page 1), soon after the agency backed the firm’s metastatic colorectal cancer, in combination with fluoropyrimidine- etanercept and rituximab candidates earlier this year (Generics bulletin, irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy; 28 April 2017, page 1). unresectable, locally advanced,recurrent or metastatic non-squamous, Also added to theCHMP’sreview list since the EMAreleased its non-small cell lung cancer in combination with carboplatin and previous update on 3May is acentralised marketing-authorisation paclitaxel; glioblastoma with progressive disease in adults following applicationfor generic doxorubicin, as well as afiling for prasugrel. prior therapy as asingle agent; metastatic renal cell carcinoma in Thenext CHMP meeting is scheduled for 19-22 June. G combination with interferon alfa; and persistent, recurrent, or metastatic carcinoma of the cervix in combination with paclitaxel and cisplatin or paclitaxel and topotecan. ANTIBIoTICS Mylan’s MYL-1401O trastuzumab candidate will be discussed during the afternoon session.Proposedindicationscoverbreast cancer in several regimens: as part of atreatment regimen consisting of Baxter launches clindamycin doxorubicin, cyclophosphamide, and either paclitaxelordocetaxel; with axter International has launched in the US the “only available” docetaxel and carboplatin; or as asingle agent following multimodality Bpre-mixed clindamycin 0.9% injection in asalinepresentation anthracycline-based therapy. Indications alsocover HER2-overexpressing after obtaining approval from the US Food and Drug Administration metastatic breast cancer in combination with paclitaxel,orasasingle (FDA) for the antibiotic in three dosage formulations. Available in agentinpatientswho have received one or morechemotherapyregimens 300mg/50ml, 600mg/50ml and 900mg/50ml doses, the antibiotic is for metastatic disease; and HER2-overexpressing metastatic gastric “widely prescribed for serious infections”. or gastroesophageal junction adenocarcinoma who have not received Robert Felicelli, Baxter’s president of Pharmaceuticals,saidthat prior treatment for metastatic disease, in combination with cisplatin adding clindamycin to Baxter’s portfolio of ready-to-use pre-mixed and capecitabine or 5-fluorouracil. G medicines “reinforces the company’scommitment to hospital pharmacies and to be aleader in the generic injectable pharmaceuticals space”. “Only Baxter currently offers clindamycin in saline, making this ANAESThETIC DRUGS importantantibioticsuitable foruse with alargerpatientpopulation,” Felicelli added. The firm said its pre-mix portfolio was “madepossible by aunique US Diprivan patent is voided combination of proprietary technicalcapabilities in drug formulation, laims within aUSpatent shielding Fresenius Kabi’s Diprivan packaging and sterilisation”. Baxter’s clindamycin injection in saline C(propofol)have beeninvalidated by the US Patent and Trademark willuse the firm’sproprietary ‘Galaxy’container technology,a“non- Office’s (USPTO’s) Patent Trial and Appeal Board (PTAB), following PVC and non-DEHP system that enables pre-mixed medicinestohave an inter partes review launched by hedge fund manager Kyle Bass and his alonger shelf-life when stored at room temperature”. colleague, intelligence solutions chief executive Erich Spangenberg. “Using pre-mixed versions of standard doses of commonly prescribed In afinal decision, the PTAB saidthe petitioner had “established drugs can help enhancepatient safetybyeliminating potential dosing by apreponderanceofthe evidence” that claims 1, 13-15,17, 18, 20, errors,” Baxter commented, adding that pre-mixed medications also and 24-28 of US patent 8,476,010 –which is directed to apropofol “offer efficiencies for hospitals by simplifying the preparation process”. formulation in acontainerwith aclosure –were unpatentable as obvious Baxter developed the drug through apartnership with Water in light of amultitude of prior-art documents. Asix-month paediactric Street HealthcarePartners.The strategic investor’s company, Celerity extension to the ‘010 patent –the only one listed by the US Food Pharmaceuticals, was “funding and leading the development and and Drug Administration (FDA) –expireson1June 2025. approval of nine product families using [Baxter’s] proprietary container Claim 1includes the instruction that the container’s closure is selected technology, enhanced packaging platform, and aseptic-filling from the group consisting of siliconisedbromobutyl rubber, metal, and manufacturingprocess”. “The approval of clindamycin in saline is siliconised chlorobutyl rubber. “A person of ordinaryskill in the art would the third molecule developedand approved as part of this joint effort,” have had areason to use asiliconised bromobutylrubber stopper with Water Street noted. G Diprivan given the knownbenefits of doing so,” the board found. G

10 GENERICS bulletin 16 June 2017

PRICe wATCH .....UK Olanzapine dominates price rises in May verage UK pricerises of up to 15 timeswere seenfor olanzapine Of our basket of recent launches, rizatriptan 10mg tablets experienced Ain May, pushing five presentations of the antipsychotic into the the steepest average price rise, with an increase of 25% to £1.44 top six ‘biggest risers’ for the month as their averages shot up. This (seeFigure1). Thiswas linked to Numark introducing the product to was despite relatively minor shifts in their lowest available price to their ‘Numerics Teva’ list –aspart of apartnership with the Israeli independent UK pharmacists (see Figure 2). firm announced in late May –atover £2.00 per pack. While aprice concession was grantedbythe Department of Health Numark boasted that the partnership would give customers “access (DoH) for the other item that appears alongside olanzapine in the to extremelycompetitive pricing and pack consistency, combined with ‘biggest risers’ table –packs of six sumatriptan 50mg tablets, which an enhanced and simplified discount structure based on spend and received aconcession price of £28.65 (US$36.55), more than matching payable monthly via arebate”.Over700 of the1,600Numerics portfolio the average price thatshot up by 1,123%to£14.68–no concessions would come from Teva, Numark indicated. were granted in May forolanzapine. Atorvastatin 20mg tablets generated the most interest in terms of Meanwhile, among the ‘biggest fallers’, venlafaxine XL extended- offers during May, with 28-count packs leading our ‘fast movers’ with release capsulesin75mgand 150mg strengths both saw average price 177 price offers to independentUKpharmacists recorded by the end drops of 68% to £2.03 and £3.45 respectively for 28-capsule packs, of the month (see Figure 4). Omeprazoleand hydrocortisone were close despite their lowest offers remaining unchanged (see Figure 3). behind, followed by sertraline and lansoprazole. G

RECENT LAUNCHES BIGGEST RISERS Product/Strength/Pack size Lowest Change Average Change Product/Strength/Pack size Lowest Change Average Change price (%) price (%) price(%) price (%) Aripiprazole tabs 10mg 28 £0.64 +2 £1.07 +6 Olanzapine tabs 20mg 28 £1.12 ±0 £22.67 +1508 Benzydamine 0.15% 300ml £4.87 ±0 £5.65 ±0 Olanzapine tabs 15mg 28 £0.99 +13 £18.16 +1426 Carbimazole tabs 5mg 100 £42.50 -3 £53.37 ±0 Olanzapine tabs 10mg 28 £0.89 +9 £15.09 +1337 Celecoxib caps 200mg 30 £0.89 +5 £1.37 +4 Sumatriptan tabs 50mg 6£0.85 ±0 £14.68 +1123 Cilostazol tabs 100mg 56 £2.09 -30 £3.69 -3 Olanzapine tabs 7.5mg 56 £0.99 +1 £11.33 +681 Cyclizine tabs 50mg 100 £5.19 ±0 £7.07 +10 Olanzapine tabs 5mg 28 £0.65 +10 £6.41 +682 Desogestrel tabs 75µg 84 £1.15 +1 £1.84 +17 Duloxetine caps 30mg 28 £0.89 ±0 £1.51 -1 BIGGEST FALLERS Entacapone tabs 200mg 30 £3.19 -3 £4.36 +1 Product/Strength/Pack size Lowest Change Average Change Eplerenone tabs 25mg 28 £2.99 +3 £3.80 +3 price(%) price (%) Escitalopram tabs 10mg 28 £0.34 ±0 £0.73 +3 Frovatriptan tabs 2.5mg 6£7.50 -4 £9.96 +1 Venlafaxine XL caps 150mg28£1.65±0£3.45 -68 Memantine tabs 10mg 28 £0.57 +8 £0.98 -3 Venlafaxine XL caps 75mg 28 £0.85 ±0 £2.03 -68 Mometasone furoate 0.1% 30g £1.15 ±0 £1.68 -7 Galantamine solution 4mg/ml 100ml £85.50 +8 £118.70 -45 Montelukast tabs 10mg 28 £0.38 -52 £1.19 ±0 Ramipril tabs 5mg 28 £0.34 +6 £0.87 -24 Nefopam tabs 30mg 90 £19.43 -7 £33.92 -7 Simvastatintabs 10mg 28 £0.10 -9 £0.28 -20 Nortriptyline tabs 10mg 100 £14.50 -12 £22.97 -6 Paracetamolsolubletabs 500mg 100 £3.95 -7 £6.63 -20 Oxcarbazepine tabs 300mg 50 £4.79 +1 £5.89 +1 Rabeprazole tabs 10mg 28 £0.60 ±0 £0.96 +3 FAST MOVERS Raloxifene tabs 60mg 28 £2.20 ±0 £3.15 ±0 Rasagiline tabs 1mg 28 £0.83 +5 £1.78 +1 Price offers as at 31 May 2017 Product/Strength/Pack size March April May Rizatriptan tabs 10mg 3£0.76 +3 £1.44 +25 Sevelamer tabs 800mg 180 £25.00 ±0 £37.49 -2 Atorvastatin tabs 20mg 28 150 139 177 Sildenafil tabs 100mg 4£0.23 +5 £0.46 +2 Omeprazole caps 20mg 28 181 151 167 Telmisartan tabs 80mg 28 £0.99 -1 £1.45 -8 Hydrocortisone tabs 10mg 30 146 140 165

Figure 1(above): Comparison between the periods 1-30 April 2017 and 1-31 May Sertraline tabs 50mg 28 140 120 142 2017 of UK trade prices of the most recently-launched generics listed in category M Lansoprazole caps 30mg 28 152 119 140 of the Drug Tariffofpharmacy-reimbursement prices.Averages calculated from at least Chloramphenicol eye ointment 1% 4g 83 104 139 47 data points. Figure 2(top right)and Figure 3(centre right): Biggest average trade- price changes between1-30 April 2017 and 1-31 May 2017. Averagescalculated Simvastatin tabs 40mg 28 151 120 139 from at least 24 data points. Figure 4(bottom right): Ranking of fastest-moving Fluoxetine caps 20mg 30 143 102 136 products subject to the most price offers made to independent UK pharmacists (one strength per ingredient; offers recorded by 31 May). Data for Figures 2, 3and 4 Ramipril caps 2.5mg 28 142 93 134 from abasket of about 750 commonly-dispensed generics. Recently-launched Phenytoin tabs 100mg 28 94 103 131 products in Figure 1excluded from Figures 2and 3(Source –WaveData).

Want more like this? Up to the minute live retail market pricing is available for the UK and Eire on Wavedata Live at wavedata.net. Alternatively, contact Charles Joynson at WaveData Limited, UK. Tel: +44 (0)1702 425125. E-mail: [email protected].

12 GENERICS bulletin 16 June 2017 PRODUCT News

PRoSTATE CANCER DRUGS GASTRoINTESTINAL DRUGS UACT urges denial of Zydus’ rival to Lialda Xtandi patent in India receives US approval

fforts made by the University of California to obtain apatent on ydus Cadila has received US Food and Drug Administration (FDA) EAstellas Pharma’s Xtandi (enzalutamide) in India should be withdrawn, Zapproval for its generic version of Shire’s Lialda (mesalamine) the Union for Affordable Cancer Treatment (UACT) has urged –along 1.2g delayed-release tablets in the US, which the Indian firm said would with 56 other organisations –inaletter to the university. be produced at its Indian key finished-dose formulations facility in Astellas sells enzalutamide at “a high price in India that is Moraiya, Ahmedabad. The approval follows shortly after aUSCourt of unaffordable to most cancer patients”, the UACT commented. “The Appealsaffirmed without comment aUSdistrict court’s decision that grant of apatent on enzalutamide in India would prevent generic the Indian firm’s abbreviated new drug application (ANDA) did not competitors from supplying the drug at an affordable price, both in infringe US patent 6,773,720 (Generics bulletin,19 May2017,page 13). Indiaand in other countrieswherethere is no patent, or where Astellas In September last year, Delaware District Judge Kent Jordan found has abused its patent rightsby charging prices that are excessive and that Zydus’ ANDA did not directly infringe claims 1and 3ofthe ‘720 create access barriers forthisimportantdrug,”the Union maintained. patent, the only patent listedagainst Lialda in the FDA’s Orange Book Recently, the UACT noted, Fresenius Kabi and India’s BDR (Generics bulletin,23September 2016, page 12). Nor was Zydus Pharmaalong withthe Indian Pharmaceutical Alliance challengedthe responsible for any induced or contributory infringement of the patent, university’s attempt to obtain apatent on enzalutamide in pre-grant which expires on 8June 2020, the district court had ruled. opposition proceedings. The Indian Patent Office denied the patent, Noting that Zydus was the first ANDA applicant for ageneric leading the university to file apetition before the Delhi High Court. version of the ulcerative colitis treatment,the FDA said thatthe firm “We request that the University of California withdraw its case might be eligible for 180 days of exclusivity. However, the agencysaidit and ceaseits efforts to obtain apatent on enzalutamide in India,” the would not “make aformal determination at this time”, after pointing UACT urged. “The high price of Astellas branded Xtandi in India is out that Zydus had failed to obtain tentative approval within 30 months shocking to anyonewho thinks cancerdrugs shouldbeaccessible and of the ANDA being filed. affordable,regardless ofwhereyou live.” Globalsales of Xtandireached Earlier this year,aUSCourt of Appeals alsoclearedthe way for US$1.87billionin2015,the UACTobserved, with projected annual Actavis to launch aversion of mesalamine 1.2g delayed-release tablets, global sales of US$4.78 billion by 2020. G after reversing afinding that the firm’s product infringed the ‘720 patent (Generics bulletin,17February 2017, page 12). Zydus observed that estimated brand sales for mesalamine 1.2g hoRMoNE REPLACEMENT ThERAPIES delayed-release tablets were around US$1.15 billioninthe 12 months ended April 2017. The FDA’s database currently does not list any Mithra strikes aCanadian deal other tentative or final genericapprovals. G ithra Pharmaceuticalsisaiming to introduce the first tibolone-based Mhormone replacementtherapy in Canada,after signing an exclusive oPIoID ANALGESICS license and supply agreement for the women’s health specialist’s Tibelia (tibolone) with an undisclosed local partner in the market. FDA pulls Endo’s Opana ER The product –for which Mithra hassubmitted adossier seeking marketing approval –isageneric version of the Livial hormone he US Food andDrugAdministration(FDA) has forthe first time replacement therapy that the Belgian women’s health specialistdeveloped T“taken steps to remove acurrently marketed opioid pain medication for Merck, Sharp &Dohme (MSD).“There arecurrently no tibolone-based from sale due to public health consequences of abuse”, after requesting products on the market in Canada for the relief of post-menopausal that Endo pull from the market the firm’s reformulated Opana ER symptoms and prevention of osteoporosis in post-menopausal women,” (oxymorphone hydrochloride) extended-release tablets. the Belgian firmexplained. “Subject to obtaining marketingapproval The US firm said it was “evaluating the full range of potential from Health Canada, Tibelia would therefore be launched as anew options as we determine the appropriate path forward”. Endo’s US treatment option for these indications in Canada.” Opana ER sales fell by 10% to US$159 million last year. “The Canadian menopausal health market is currently valued at The FDA’s decision –which comes after an agency advisory approximately C80 million (US$89.9 million), with further growth committee in March voted by 18 to eight, with one abstention, that the potential” Mithra commented. The firm intends to produce Tibelia at benefits of Endo’s reformulated Opana ER did not outweigh risks of its own research and production facilitytoreapthe benefits of milestone abuse (Generics bulletin,24March 2017, page 12) –isbased on “a payments,aswell as additional revenuesthrough supply agreements. review ofall available post-marketing data”. This data demonstrated According to François Fornieri, Mithra’schiefexecutive officer, a“significant shift in the route of abuse of Opana ER from nasal to the agreement follows the completion of the decentralised approval injection following the product’s reformulation”, accordingtothe FDA. procedure for Tibelia in Europe and demonstrates the increasing While multiple generics players currently hold abbreviated new momentum and interest in Tibelia in agrowing number of markets. drug application (ANDA)approvals for Endo’s discontinuedoriginal Tibelia is already on the market in the Netherlands, Spain and formulation Opana ER, there are currently no generics referencing the UK through existing supply and licence agreements signed in 2016. Endo’s reformulated version. LaunchesinFinland, Italy and Sweden were “expectedinthe coming “The FDA has requested that the company voluntarily remove months”, Mithra said recently, with “further agreements” anticipated reformulatedOpana ER from themarket. Should the company choose this year, including in France, where the firm has just received amarketing not to removethe product, the agency intends to take steps to formally authorisation for the product (Generics bulletin,9June 2017, page 15).G requireits removal by withdrawingapproval,” the FDAinsisted. G

16 June 2017 GENERICS bulletin 13 BUsINess sTRATeGY Inhalers and biosimilars star in Orion’s future firmament

Rivals both to leading sFinns this year celebrate the centenary of securing to biosimilar rituximab in Scandinavia and Estonia. independence from Russia, the country’s leading Generics, biosimilars and OTC self-care products respiratory inhaler A pharmaceutical company, Orion, is marking comprise Orion’s Specialty Products division that has brands and to major the same milestone of its foundation acouple of months morethandoubledin size overthe pastdecadetoreach before Finland became anation in its own right. saleslastyear of C508 million, representing 47% of biological therapies Reflecting on Orion’s past and outlining its future group turnover (see Figure 1). during arecent capital marketsday, the firm’spresident As Figure 2shows, generics last year accounted for are central to Orion’s andchief executive officer, Timo Lappalainen, noted 71%, or about C360 million, of the Specialty Products total, plans as the Finnish that the firmhad lastyear achieved agroup turnover of with OTC products adding just over C100 millionand the C1.07 billion(US$1.20 billion)and an operating profit Remsima biosimilar another C42.3 million. firm prepares for of C315million. Orion had invested C118 million in Reflecting Orion’s market-leading position in the research and developmentin 2016, whileits workforce Finnish generics market “with a42% market share”, the its next century. of almost 3,500 people included its own sales operation group’s domestic market makes up nearly three-fifths Aidan Fry reports. in 26 European countries. of all Specialty Products sales (see Figure 3). Other TheFinnish firm achieves around athird of its Scandinavian and Nordic countries contributed C82 groupturnover in its domesticmarket, 16% in the rest million, or 16%, last year, and Eastern Europe and of Scandinavia and the Nordic region, and almost another Russia another C59 million, or 12%. third in other European markets, such as Germany, Italy, While Orion’s entacapone-based Parkinson’sdisease Spain and the UK. Outside ofEurope, the firm operates therapiessuchasComtessand Stalevoremain the group’s through local sales and marketing partnerships. best-selling pharmaceutical franchise despite growing Having achieved success with Parkinson’s disease generic erosion, the Easyhaler range of respiratory inhalers treatments such as Comtess (entacapone) and Stalevo is increasingly important. Sales of the Easyhaler family (levodopa/carbidopa/entacapone) –aswell as with of treatmentsfor asthma and chronic obstructive pulmonary OTC brands including Burana (ibuprofen) –Lappalainen disease (COPD) climbed by nearly aquarter to C63.7 said the group had consciously decided in 2005 to focus million last year. on both branded and generic drugs. And more recently, Given their branded nature and general lack of Orion had, he pointed out, pushed into the biosimilars interchangeability, the Easyhaler products form part arena through an alliancewith SouthKorea’s Celltrion of Orion’s C350 million Proprietary Products division that initially covered Remsima (infliximab) and hadrecently that is headed by Markku Huhta-Koivisto. been extended to include sales and marketing rights Around half of Easyhalerturnover, Huhta-Koivisto

Contract manufacturing Biosimilars C38.5m C42m Fermion Specialty Products 8% C47.6m C507.8m Diagnostic C54.8m Generics OTC ~C360m ~C106m Animal Health 71% C77.3m 21%

Propriety products C350.4m

Figure 1: Breakdown by business division of Orion’s group Figure 2: Breakdown by product type of sales by Orion’s turnover that increased by 5.7% to C1.07 billion in 2016 Specialty Products division that rose by 7.8% to C508 million (QuintilesIMS/Orion) in 2016 (Source –QuintilesIMS/Orion)

Other Europe Elperhaler Forspiro ~C20m (Sandoz) Finland (Elpen) Seretide Diskus 1% Other countries C300m 1% (GlaxoSmithKline) ~C46m +9% Polish Diskus 60% generics Eastern Europe/ 2% Russia Sirdupla C59m (Mylan) +11% 4%

Scandinavia C82m Seretide Evohaler +10% (GlaxoSmithKline) 32% Figure 3: Breakdown by region of sales by Orion’s Specialty Products division that rose by 7.8% to C508 million in 2016 Figure4:BreakdownofEurope’s C1.31 billion salmeterol/fluticasone (Source –QuintilesIMS/Orion) market in 2016 by inhaler type (Source –QuintilesIMS/Orion)

14 GENERICS bulletin 16 June 2017 BUsINess sTRATeGY

160 2014 2015 2016 80 140 70 120 60 100 millions) 50 80 40 60 30 Volume (SU) 40 20

20 Market value ( C 10

0 0 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Finland Sweden Denmark Norway 2013 2014 2015 2016 Figure 6: Infliximab market value in the Nordics Figure 5: Infliximab volume sales by standard unit (SU) in the Nordics (Source –QuintilesIMS/Orion) (Source –QuintilesIMS/Orion) outlinedduring the capital markets day, currently came into using the Easyhaler device for other respiratory from sales of its Bufomix (budesonide/formoterol) drugs, Huhta-Koivisto revealed. combination, predominantly in Sweden, Hungary, To prepare for the anticipated demand from Denmark, Belgium and Finland. Relatively low levels expandingBufomix’geographic footprintand securing of sales in Italy and Spain would, he predicted, pick approval for the salmeterol/fluticasone combination, up significantly now that Orion had struck aregional Orion is currently expanding its Easyhaler facility in co-marketing deal with Menarini to capitalise on the Espoo, Finland. That capacity extension is one of the Italian firm’s local salesforces. Asimilar deal withHikma group’stwo major capital expenditure projects at present, promisedtoboost Bufomix sales in the Middle East and the other being the construction of an active pharmaceutical North Africa(MENA) region, he added, stressing Orion’s ingredients (APIs) plant in Hanko, Finland, for its competitive advantage from offering three strengths. Fermion bulk-drugs division (Generics bulletin,20 “Orion is just launching Bufomix in Germany, May 2016, page 4). and will be launching in the UK and France during SpecialtyProducts head Liisa Hurme pointed out 2017,”Huhta-Koivistorevealed. France,Germany and that the division had last year passedthe C500 million the UK had been among several countries withdrawn turnover milestone, having expanded its portfolio to from afirst-wave decentralised procedure for the over 2,300 marketing authorisations and almost 3,500 budesonide/formoterol inhaler, he acknowledged, but stock-keeping units. now that the firm had supplied additional data, launches While they currently accounted for less than atenth were now underway or planned across Europe. of Specialty Products sales, biosimilars were the division’s Given the considerable investments needed to fastest-growing product category, Hurme highlighted. develop respiratory formulations delivered through “Biosimilars are driving the market growth,”Hurme inhaler devices,Huhta-Koivisto saiddirect competition asserted,citing datashowing low single-digit generics to AstraZeneca’s Turbuhalerwas limited, enabling the growthinNordic markets, comparedtobiosimilar values Symbicort Turbohaler reference brand to hold onto that were doubling or even trebling. 88% of the combinationdrug’s C1.03 billion European “Infliximab use has expanded in the Nordic markets market last year. Bufomix Easyhaler had gained a3% with biosimilar entries,” she pointed out, noting that share, behind the 8% secured by Teva’s DuoResp an average 20% uplift in infliximab volumes across the Spiromax, but ahead of the 1% held by Elpen’s region last year ranged from a9%rise in Sweden to a Pulmoton Elpenhaler,according to QuintilesIMS data. 32% increase in Denmark. “That means 20% more TotalEuropean sales ofgeneric rivals to Symbicort patients are getting treated, and we are only at the totalled C119 millionlast year. beginning of this curve,” she stated, outliningagradual Europe’s salmeterol/fluticasonemarket waslarger volume increase quarter by quarter (see Figure 5). “Orion is just launching at C1.31 billion, he noted (see Figure 4). However, it Biosimilarinfliximab volumesinNordic countries was split between C838 million fordry-powder inhalers had more than doubled last year, driven in particular Bufomix in Germany, and (DPIs) and C471 million for metered-dose inhalers (MDIs). by triple-digit gains in Finland and Sweden. “However, “In DPIs, as our product will be, there is much less the total market value has not increased,” Hurme will be launching in the UK generic competition,” he stated, observing that the lack observed, citing data that showed the infliximab value and France during 2017” of substitutability had resulted in Sandoz and Elpen market was smallerin2016 thanin2014 in Denmark, eachhaving taken around a2%market share, with local Finland, Norway and Sweden (see Figure 6). generics in Poland capturing another 3% against the While Remsima’s initial penetration had been faster 93% share still held by GlaxoSmithKline’s Seretide in countries in Denmark and Norway due to winning Diskus original.TotalEuropean sales ofthe DPI generics national tenders, these markets had provedvolatile due to totalled C57 million in 2016. the winner-takes-all nature of contracts. In the fourth By contrast, in the MDI segmentofthe salmeterol/ quarter of last year, the Remsima biosimilar completely fluticasone market, agreater willingness to substitute dominated the Danish market,but had just a1%share had made price more of adetermining factor, enabling in Norway due to Pfizer having won the annualtender Mylan’s Sirdupla brand to take atenth of the market, with its Inflectra rival.Meanwhile, Remsima’s market well ahead of Cipla’s combination MDI with 1%. share in Finlandand Sweden –whichhave more regional Seretide Evohaler held an 89% share last year. purchasing schemes –had built up to 34% and 24% Orion wascurrently conducting feasibilitystudies by the end of 2016. G

16 June 2017 GENERICS bulletin 15 PeOPLe

RETIREMENTS APPoINTMENTS Perrigo board forms a Mylan hits back over team to identify chief controversy on Coury

errigo’sboard of directors has formed adedicatedsearchcommittee ylan chairman Robert Coury brings “immense value” to the Pto identify anew chief executive officer, in the wake of John Mcompany and will “continue to have akey leadership role in all Hendrickson’s announcement thatthe 28-yearcompany veteran will important decisions of company strategy”, the firm has insisted,following retire once Perrigo names his replacement as group head. complaints by shareholders over Coury’s compensation package and Hendrickson will remain with Perrigo for up to 60 days following handling of an ultimately fruitless takeover bid by Teva. the appointment of hissuccessor,and willmoreovercontinue to stand Responding to concernsraised by InstitutionalShareholder Services for election to thefirm’s board at Perrigo’s annual general meeting (ISS), Mylan in aletter to the group sought to “address and clarify any next month. However, he also intends to stand down from the board confusion that ISS may have regarding Mr Coury’s continuing role” upon the appointment of anew chief executive officer. by emphasising that his role as chairman and leader of the board of Having joined Perrigo in 1989, Hendrickson held positions of directors “is not merely an honorary title, but rather avitally important increasingresponsibility before replacing Joe Papa as chief executive role for the company”. “Inadditiontoproviding Mylan’s overall strategic officer upon Papa’s decision to take up the equivalentrole with Valeant leadership, Mr Coury also remains actively involved in any material in April lastyear(Generics bulletin,29April2016,page 1). Laurie transaction or other matter involving the company,” Mylan outlined, Brias absorbed Papa’s otherrole as chairmanofthe board, aposition calling him “the key architect” in the firm’sgrowth over the past15years. she continues to hold. “In light of the board’s desire to retain Mr Coury’s leadership Since being appointed company head, Hendrickson has seen over the critical coming years, the board focused on structuring his Perrigo’s shares lose almost aquarter of their value, faced mounting compensation in this new role to ensure long-term retention for at pressure from activist investor Starboard Value, and confronted delayed least afive-year period,” Mylan said. “As you know, others in our quarterlyand annual report filings with the US Securities and Exchange industry have not properly planned for leadershipsuccession,” Mylan Commission (SEC), whichare now fully up to date, accordingto the insisted, in contrast to thefirm’s “prudent planning”. These companies, firm. “I am privileged to have led Perrigo, particularly as we have Mylan said, have “faced terrible consequences –most notably Teva and met the challenges we faced and stabilised the business in atime of now again Perrigo, which experienced another episode of management transition,” Hendrickson commented. G turmoil” with the planned retirement of John Hendrickson. Moreover,inresponse to complaints that “entrenched management” hadled its boardtorejectanoffer by Teva out of adesire to be “enriched by lucrative compensation packages into the future”, Mylan insisted OTC DISTRIBUTION IN EUROPE that “nothing could be farther fromthe truth”, claiming that the Israeli THE NEW GLOBALAGENDA firm had “never made an offer to acquire Mylan”. “We believe that the preoccupation with Teva’s alleged ‘offer’ that has lingered with your team and certain shareholders is asettled Now in its 10th edition, this issue thatserves, at this point, only as adistraction,”Mylan toldISS. Mylan also expressed disappointment that it would not be given an in-depth study identifies the opportunity to review adraft of the ISS reportconcerning the generics factors driving change in firm before it was issued. the supply network serving The letter to ISS was signed by non-executive directors Wendy Europe’s non-prescription and Cameron, Neil Dimick and Mark Parrish,all of whom had been among those directors recommended for removal in previous OTC self-medication sectors. shareholdercomplaints(Generics bulletin,9June 2017, page 24). G

It provides a comprehensive, data-driven analysis of the APPoINTMENTS unfoldingstrategies required to achievecompetitive success. Matal follows Lee at USPTO

SPatent and Trademark Office(USPTO) associate solicitor Joseph COVERS20COUNTRIES UMatal has been appointed on an interim basisasUSPTO director IN OVER 590PAGES AND and under-secretary of commerce for intellectual property. Themove 300 GRAPHS, TABLES &FIGURES follows the resignation of Michelle Lee.“Matalwillserve in this role during the nomination and confirmation process for anew director,” the US department of commerce stated. In his role as associate solicitor, Matal has “briefed and argued appeals of patent and trademark decisions before the US Court of Download Executive Summary and order online at ® JAMES DUDLEY ® Appeals for the Federal Circuitand theUSDistrict Court,and assisted www.james-dudley.co.uk MANAGEMENT in thedevelopment of legal positions taken by the US solicitor general in patent and copyright cases before the US Supreme Court”. He also recentlyserved as acting chief of staff for the USPTO. G

16 GeneriCs bulletin 16 June 2017