COMPANY NEWS US ruling opens door to October infliximabe ntry … · 2016. 8. 6. · COMPANY NEWS 2...

Pfizer’s Hospira could introduce its biosimilar rival to Janssen’s Remicade (infliximab)in the US in early October after Massachusetts District Judge Mark Wolf ruled that

a key patent expiring in September 2018 was invalid for obviousness-type double-patenting.Hospira’s partner, Celltrion, obtained US approval for its Inflectra (infliximab-dybb)biosimilar on 5 April, starting a 180-day countdown to launch from 3 October by renderingeffective Hospira’s statutory notice of commercial marketing.

Wolf granted Celltrion’s motion for summary judgement that Janssen’s US patent 6,284,471 –which expires on 4 September 2018 and claims a genus of antibodies encompassing infliximab –was invalid. Noting that the parties agreed that the ‘471 patent was “not patentably distinct”from US patent 6,790,444 that expired on 11 July 2011, Wolf said the US Court of Appeals’decision on Tamiflu (oseltamivir) in favour of Natco (Generics bulletin, 2 May 2014, page 17)showed that “a later-issuing, earlier-expiring patent can act as a double-patenting reference foran earlier-issuing, later-expiring patent”. Thus, five key claims of the ‘471 patent were obvious“in light of the patentably indistinct, earlier-expiring ‘444 patent”.

Furthermore, Wolf stated, the asserted claims of the ‘471 patent were invalid for double-patenting over expired US patents 5,698,195 and 5,656,272, which cover antibodies for treatingrheumatoid arthritis and Crohn’s disease respectively. “The ‘471 patent specification describesthe infliximab antibody and discloses the same uses for infliximab that are claimed in the‘195 and ‘272 patents,” Wolf pointed out.

Turning to US patent 7,598,083, Wolf construed the disputed term ‘cell culture media’ tomean “nutritive media for culturing cells”. He granted the originator’s request to bifurcatedamages until liability had been settled and to consolidate proceedings with the parties’ litigationover whether cell-culture media supplied to Celltrion by HyClone infringed the ‘083 patent(Generics bulletin, 24 June 2016, page 9). A trial is scheduled to start on 13 February 2017.

Janssen – which reported US Remicade sales up by 14.2% to US$2.45 billion in thefirst half of this year – intends to appeal. The originator, which is also appealing against arejection of the ‘471 patent in re-examination proceedings, stressed that any introduction byHospira before the outcome of its appeals would be “considered an at-risk launch”. G

26 August 2016

Valeant responds to 2investigation reportWockhardt is hit by a third import alert 3Mylan closes deal for Sweden’s Meda 3Teva adds to Actavis by acquiring Anda 4Pfizer suspends work 5at ex-Hospira facilityBeximco becomes first to launch in US 6Mallinckrodt decline is less than expected 7Lupin grows by 40% across 8a broad baseJapan’s Sawai sets more ambitious goals 9Piramal plots move to buy Ash Stevens 10Endo makes progress on 11restructuring planEU sales rise enables Alkaloid to advance 12Generics have been 13a challenge for Perrigo

MARKET NEWS 14

Draft FDA labelling guide splits opinions14US biosimilars found 15comparable to brandsItaly misses chance to end 15patent linkage

PRODUCT NEWS 17

Merck’s Lantus rival accepted by FDA 17Lacosamide patent is found valid in US 18AbbVie sues Amgen over 20US adalimumabAmphastar adds 33 21injectables from UCBPfizer pulls plug on Pfenex’ ranibizumab 21

REGULARS

Price Watch UK – UK pricing trends16Events – Our regular listing 18Pipeline Watch – Agalsidase 22People – Retzlaff resigns from 24Stada chairman role

COMPANY NEWS 2 US ruling opens door toOctober infliximab entry

Cipla has lined up its global chief operating officer Umang Vohra to succeed Subhanu Saxenaas the Indian firm’s new managing director and global chief executive officer from 1 September.Former Novartis executive Saxena, who joined Cipla as chief executive officer in February

2013 (Generics bulletin, 14 December 2012, page 26), will officially step down from hisposition the day beforehand “to attend to emergent family priorities”.

Vohra joined Cipla as global chief financial and strategy officer in October last year, havingpreviously served as head of North American generics with fellow Indian firm Dr Reddy’s(Generics bulletin, 11 September 2015, page 27). He transitioned to the role of chief operatingofficer “early this year as part of a planned progression” (Generics bulletin, 17 June 2016, page 16).

Meanwhile, Cipla’s Samina Vaziralli will become the firm’s executive vice-chairman, alsofrom 1 September. The daughter of non-executive vice-chair MK Hamied, Vaziralli is currentlyglobal head of strategy and mergers and acquisitions, as well as head of Cipla’s New Venturesunit. She will “focus on board and governance issues, in addition to growing Cipla’s strategicpriorities through key global partnerships, corporate brand building and public advocacy”.G

Cipla appoints Vohra as chief

Next issue – 9 September 2016

Gen 26-8-16 Pg. 1_Gen 18/11/05 Pg. 1 23/08/2016 16:34

COMPANY NEWS

2 GENERICS bulletin 26 August 2016

Bethesda NorthMarriott Hotel and Conference Center - North Bethesda, MD - October, 24-26, 2016

Technical ConferenceFall

Register Today!Join us at the 2016 GPhA Fall Technical Conference to hear

presentations from experts from the FDA, industry and academia as theyaddress key regulatory and technical issues impacting the generic industry.

Each year, more than 700 generic industry professionals attend this unique educational conference.Register online at www.gphaonline.org.

Sponsorship OpportunitiesRaise your company profile by sponsoring at this prestigious event.

Opportunities include logo placement, company recognition and much more!

Formore information, contact Jennifer Soup at [email protected] or +1(202) 249-7127

hnicaFalllTechnicalFall

nf rel Cal Confereenenceth Marriott HorBethesda No enrefonCel andtthMarriott Ho

Technical Conferenceer - North Bethesda, MD - October, 24-26, 2016tenCec

Technical Conferenceer - North Bethesda, MD - October, 24-26, 2016

Technical Conferenceer - North Bethesda, MD - October, 24-26, 2016

ormoreFFor mor

emenplacofile bpronsorship OpS

ennifer St Jontace information, c

tmeny sponsofile b

tuorpprship OOpp

g.orrg or +1(202) 249-7127oup at jsoup@gphaonlineennifer S g or +1(202) 249-7127

Hikma expects full-year sales for its enlarged US Generics businessto be US$640-US$670 million in 2016, “including 10 months

contribution” from Roxane. Having made “considerable progress”on integrating its acquisition of Boehringer Ingelheim’s Roxane USgenerics business at the end of February (Generics bulletin, 4 March2016, page 6) – now known as West-Ward Columbus – Hikma saidthe unit contributed sales of US$193 million in the first half of 2016,a total that was “lower than our previous expectations due to slowerapprovals for certain new products”.

“We remain confident in the quality of the West-Ward Columbuspipeline,” Hikma said, outlining plans for the business’ sales to rise toUS$700-US$750 million in 2017 as “product launches accelerate”.

Estimating full-year group sales of US$2.0-US$2.1 billion in2016, the Jordanian firm said this would “reflect strong revenuegrowth across all three business segments”.

Sales from the US solid-dose Generics business were US$257million in the first half of 2016. Hikma’s legacy US Generics salesof US$64 million compared with US$79 million in the same periodlast year, reflecting “lower revenue from specific market opportunities”.

Hikma’s Injectables business “continued to perform well”, withsales growth of 3% to US$356 million on several product approvals.Branded sales in the Middle East and North Africa declined by 7%to US$264 million amid a focus on higher-margin products. G

RESULTS FORECAST

Slower approvals hitHikma’s US business

Valeant is refusing to comment on “rumours about investigations”amid media reports that the Canadian firm is facing possible

criminal charges for defrauding insurers by covering up ties to nowdefunct specialty pharmacy Philidor.

An article in The Wall Street Journal states that US prosecutors“are investigating whether Philidor…made false statements to insurersabout its ties to Valeant”. “At issue is whether insurers thought Philidorwas neutral rather than in the service of Valeant,” the article summarises.

In response, Valeant said it could not “comment on or speculateabout the possible course of any ongoing investigation”. “Valeantpreviously disclosed in October 2015 that the US Attorney’s Office forthe Southern District of NewYork commenced an investigation involvingValeant,” the firm stated, around the same time that Valeant severedties with Philidor (Generics bulletin, 6 November 2015, page 4).

The Canadian firm added that it had moreover been “fullycooperating with the authorities” and had also been in “frequent contact”with the New York office concerning the “ongoing” investigation.

Reports of the latest setback for Valeant came as the firm reportedflat sales in Emerging Markets – largely from branded generics – ofUS$497 million in the second quarter of this year. Acquisitionsoffset a “small decline” by the existing business and adverse exchange-rate fluctuations. In the US, Valeant’s Neuro & Other/Genericssales fell by 11% to US$467 million. G

PRICING & REIMBURSEMENT/SECOND-QUARTER RESULTS

Valeant responds toinvestigation report

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

Mylan has completed its acquisition of Meda after shareholdersholding approximately 94% of the Swedish firm’s shares and

voting rights accepted Mylan’s cash-and-shares offer. The US FederalTrade Commission (FTC) had approved the deal at the end of July,subject to certain divestments (Generics bulletin, 5 August 2016,page 2). Mylan paid around US$6.6 billion for Meda, comprisingUS$5.3 billion in cash and 26.4 million newly-issued Mylan shares.

“We are very excited about the completion of our Meda transaction,as well as the Renaissance topicals transaction that we completed inJune,” said Heather Bresch, Mylan’s chief executive officer. Notingthat these acquisitions would create “even greater scale, breadth anddiversity across products, geographies and sales channels”, Breschadded that Meda “positions us to be a leader in the global respiratoryand allergy market”.

Mylan’s president, Rajiv Malik, said that with the addition ofMeda, the US firm now had six US$1 billion therapeutic franchises,and the acquisition would “open up a number of opportunities for us,such as significantly expanding our over-the-counter (OTC) presenceinto a US$1 billion business”. Meda, he stated, would moreover“accelerate our expansion in attractive emerging markets, such asChina, South-East Asia, Russia and the Middle East”. Mylan now hasa portfolio of over 2,700 products, including oral solids, injectables,transdermals and respiratory therapies.

In the second quarter of this year, Mylan increased its groupturnover by 8% to US$2.56 billion. Global Generics turnover grew by4% to US$2.14 billion, driven by 6% rises in both North Americaand Europe to US$1.01 billion and US$604 million respectively.

North American growth came largely from recent launches suchas armodafinil and doxycycline, while the European rise was due toa combination of launches and higher volumes on existing products,as pricing was “essentially flat”. Stronger sales in France outweigheda slight decrease in Italy.

Despite higher sales in Japan on recent launches and highervolumes for existing drugs, Generics sales in Mylan’s Rest of Worldregion fell by 2% to US$523 million (see Figure 1). The companyblamed lower prices in Australia as well as weaker prices and volumesthroughout the region, including for its antiretrovirals franchise.

Sales by Mylan’s Specialty segment climbed by a third to US$403million, aided by the “realisation of the benefits of customer-contractnegotiations” over the EpiPen (epinephrine) auto-injector.

Higher EpiPen sales and recent launches helped to improveMylan’s group operating profit by 49% to US$411 million. G

COMPANY NEWS

3GENERICS bulletin26 August 2016

MERGERS & ACQUISITIONS/SECOND-QUARTER RESULTS

Mylan closes dealfor Sweden’s Meda

Second-quarter sales Change Proportion(US$ millions) (%) of total (%)

North America* 1,010 +6 39Europe 604 +6 24Rest of World* 523 -2 20Generics 2,137 +4 83

Specialty 403 +33 16

Other 21 +41 1

Mylan 2,561 +8 100

* Brazilian sales of US$11.1 million were reclassified from Rest of World to North America

Figure 1: Breakdown of Mylan’s sales in the second quarter of 2016 (Source – Mylan)

Wockhardt has seen its active pharmaceutical ingredient (API)unit in Ankleshwar, India, become its third production plant to

be subjected to an import alert by the US Food and Drug Administration(FDA). The US agency had in 2013 placed similar bans on importsinto the US from Wockhardt’s Indian facilities in Chikalthana andWaluj that produce solid-dose formulations and cephalosporinantibiotics respectively (Generics bulletin, 6 December 2013, page 3).

Announcing that the agency had posted the Ankleshwar alert onlinein early August, Wockhardt said it was awaiting formal communication.“The company has already initiated required steps to address theconcerns raised by the FDA and is putting all efforts to resolve thematter,” the firm stated.

The FDA’s Ankleshwar alert covers all drugs and drug productsmade at the bulk-drugs site, including antibiotics. The agency has notyet indicated its reasons for issuing the alert.

Wockhardt has already received from the FDA establishmentinspection reports (EIRs) for three units – one at Chikalthana and twoat Waluj – that include certain observations. And in January this year,

the Indian company revealed that an FDA inspection of its new Shendrasterile parenterals site near Auranagabad, India – which does not yetsupply any products to the US – had resulted in nine observations(Generics bulletin, 22 January 2016, page 3).

US sales accounted for 18% of Wockhardt’s group turnover thatdeclined by 4% to Rs10.9 billion (US$163 million) in the Indian group’sfinancial first quarter ended 30 June 2016.

Sales in the US fell by 16% as reported, and by 19% on a local-currency basis, to Rs1.91 billion as Wockhardt had 84 abbreviated newdrug applications (ANDAs) awaiting approval by the end of the quarter.

Turnover in India and Emerging Markets increased by 4% toRs4.91 billion (see Figure 1), driven by a 10% rise in India following11 product launches during the quarter.

But the Indian gain was wiped out by European sales sliding by7% to Rs4.09 billion as turnover in the UK tumbled by 19% to Rs2.98billion. However, Wockhardt said its sales in the UK – where it receivedone approval and made three filings during the quarter – grew by 26%excluding a “one-time opportunity” in the prior-year period.

A 2.4 percentage-point decline in gross margin to 61.9%, combinedwith higher staff costs and interest expenses, slashed Wockhardt’spre-tax profit by 94% to Rs72.8 million. G

MANUFACTURING/FIRST-QUARTER RESULTS

Wockhardt is hit bya third import alert

First-quarter sales* Change Proportion(Rs millions) (%) of total (%)

India/Emerging 4,910 +4 45

UK 2,980 -19 27Ireland 320 -18 3France 190 +27 2Other 600 – 5Europe 4,090 -7 37

US 1,910 -16 18

Wockhardt 10,910 -4 100

* rounded to nearest Rs10 million

Figure 1: Breakdown by region of Wockhardt’s sales in its financial first quarterended 30 June 2016 (Source – Wockhardt)

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

Teva has followed up its acquisition of Allergan’s Actavis genericsbusiness by agreeing to purchase the company’s Anda

distribution unit for US$500 million.The deal – which is expected to close by the end of 2016 – came

shortly after Teva completed its acquisition of Actavis for US$38.8billion (Generics bulletin, 5 August 2016, page 1).

Billing Anda as “the fourth largest distributor of genericpharmaceuticals in the US”, Teva said the unit was “a natural fit intoour business in general and our extensive supply-chain network inparticular”. Noting that it would enable Teva and its customers to“improve capabilities and flexibility given the changes the pharmaceuticalindustry is currently undergoing, in order to provide access to morepatients throughout the country”, the Israeli firm said it would “leverageour size and scale” to Anda’s advantage.

As part of the deal for Anda – which Teva expects to generate“more than US$1 billion in third-party net revenue” in 2016 – theIsraeli company will acquire three distribution centres, in Olive Branch,Mississippi; Weston, Florida; and Groveport, Ohio, with a total ofmore than 650 employees. With a ‘Chinese wall’ separating the unitfrom the rest of Teva’s operations, Anda will continue to operate asa standalone business reporting directly to Teva’s president and chiefexecutive officer of Global Generic Medicines, Siggi Olafsson.

Teva ‘most logical buyer’ for Anda businessAllergan said it had not included Anda as part of the original deal

with Teva for its generics business because it had focused on Actavis“as a result of the short timing from negotiation to announcement ofthe original Teva generics agreement”. Following the announcementof the Actavis deal, Allergan said it had evaluated options for Andaand concluded that Teva was “the natural and most logical buyer”.

Under the deal with Allergan, Teva will continue to distribute theformer’s products “for a period of time” after the transaction closes.Until then, Allergan said it would “continue to operate Anda in abusiness-as-usual mode”.

Meanwhile, following the close of the deal for Actavis, Teva is

preparing to divest “in the near future” a “viable standalone business”in the UK and Ireland based on Actavis’ assets, under the terms ofthe European Commission’s approval of the deal (Generics bulletin,18 March 2016, page 1). These assets include “a portfolio of genericmolecules, Actavis’ Barnstaple manufacturing plant, and the managementand people to run this business unit in the UK and Ireland”. Theremainder of Actavis in the UK and Ireland will be integrated with Teva.

In the first half of 2016, a drop of almost a third in US sales throughTeva’s Global Generics unit to US$1.87 billion – on lower sales ofaripiprazole, esomeprazole and budesonide – contributed to groupturnover slipping by 1% to US$9.85 billion (see Figure 1).

In Europe, currency fluctuations meant static growth translated toa 1% drop to US$1.33 billion for Global Generics. Meanwhile, a riseof more than two-fifths in local currencies for the Rest of the Worldsegment represented growth of 29% as reported to US$1.27 billion.

Allergan reported first-half sales by its Actavis generics andAnda distribution units down by 14.4% to US$3.75 billion. G

COMPANY NEWS


26 August 2016 Issue 274

Editor: Aidan FryDeputy Editor: DavidWallaceAssistant Editor: Dean RudgeBusiness Reporter: Grace MontgomeryProduction Controller: Debi MinalProduction Editor: Jenna MeredithDirector of Subscriptions: Val DavisGroup Sales Manager: Rob CoulsonAwards Manager: Natalie CornwellManaging Director: Mike Rice

Editorial enquiries: GENERICS bulletin,4 Poplar Road, Dorridge, Solihull,West Midlands B93 8DB, UK.Website: www.Generics-bulletin.comTel: +44 (0)1564 777550 Fax: +44 (0)1564 777524E-mail: [email protected] enquiries:As above, or [email protected]

SUBSCRIPTIONSSubscription rates are published atwww.Generics-bulletin.com/subscribe.

Individual subscriptionsAn annual subscription comprises:■ 46 Generics bulletin online editions■ a searchable archive of more than 100 back

editions dating back over five years■ 46 optional hard-copy print editions, delivered

by airmail.

Choice of formatsGenerics bulletin can be accessed from:■ desktop and laptop computers AND■ Apple and Android tablets and smartphones.

Multiple subscriptionsDiscounts are available for multi-usersubscriptions for colleagues at the samelocation. Please ask for a quotation.

Corporate subscriptionsCorporate subscriptions provide location-, country-or company-wide access to Generics bulletin.Please ask for a quotation.

Subscription enquiries:Contact [email protected]

Terms & Conditions:These can be viewed in full atwww.Generics-bulletin.com/subscribe.No part of this publication may be copied, reproduced,stored in a retrieval system, distributed or transmittedby any means, including electronic, mechanical,photocopying or recording, without the prior writtenpermission of the publisher, or under the terms andconditions of a Global Site Licence or of a licenceissued by the Copyright Licensing Agency (CLA) inLondon, UK, or rights bodies in other countries thathave reciprocal agreements with the CLA.Neither may this publication be exported, distributedor circulated by any means without the prior writtenpermission of the publisher.While due care has been taken to ensure the accuracyof information contained in this publication, thepublisher makes no claim that it is free of error anddisclaims any liability whatsoever for any decisions oractions taken as a result of its contents.

© OTC Publications Ltd. All rights reserved.Generics bulletin® is registered as a trademark inthe European Community.

ISSN 1742-0784.

Company registered in England No 2765878.Printed byWarwick Printing Company Limited,Leamington Spa CV31 1QD, UK.

MERGERS & ACQUISITIONS/FIRST-HALF RESULTS

Teva adds to Actavis by acquiring Anda

First-half sales Change Operating(US$ millions) (%) margin (%)

US 1,868 -32 –Europe* 1,331 -1 –Rest of World 1,265 +29 –Generics 4,464 -12 26.8

Copaxone 2,147 +9 80.7

Other Specialty 2,276 +10 31.1

OTC/Other 961 +18 6.7

Teva 9,848 -1 15.5**

* European Union, Norway, Switzerland, Albania and former Yugoslavia

** includes US$2.18 billion of corporate general and administrative costs

Figure 1: Breakdown by business segment of Teva’s sales and operating marginin the first half of 2016 (Source – Teva)

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

Stada Arzneimittel’s newly appointed chief executive officer,Matthias Wiedenfels, is promising “evolution, not revolution” of

the company’s strategy. “The fundamental business model is absolutelyworthwhile pursuing – we are not reinventing Stada,” he told investorsas he presented the group’s financial results for the first time since takingover from Hartmut Retzlaff (Generics bulletin, 10 June 2016, page 1).

Outlining plans for a clearer delineation at local level betweenthe group’s core Generics and Branded Products business segments,Wiedenfels described the Generics unit as Stada’s “bread-and-butterbusiness” that was “a solid fundament” generating attractive margins.In the medium term to 2019, Stada expects to generate 5% organicturnover growth on average at constant exchange rates, comprisingaround 3% per year from Generics and 9% from Branded Products.

In the first half of this year, Stada raised its group turnover by1% to C1.03 billion (US$1.17 billion), despite Generics slipping by2% to C604 million on adverse exchange rate movements. Adjustedfor currency and acquisitions, Generics sales were 1% stronger.

As Figure 1 shows, Generics sales in Stada’s Central Europe regionfell by 6% to C296 million. This was due in large part to a 37% slumpto C40.8 million in Belgium where the firm’s local distributionpartner, Perrigo’s Omega Pharma, changed its “purchasing strategy”.“If they are not contributing, we have to think about the contract withOmega Pharma,” commented chief financial officer Helmut Kraft.

Stada blamed “a temporary delivery bottleneck of a supplier” forGenerics turnover sliding by a fifth to C10.3 million in the UK, whilesales slipped by 2% to C52.8 million in Spain against a strong prior-year period. But Italian Generics sales edged up by 1% to C79.8 millionon higher volumes, while turnover in France climbed by 13% to C40.4million despite “strong pricing and discount competition”.

In the German group’s domestic market, Generics turnover fellby 2% as reported to C154 million, but rose by 4% on an adjustedbasis, allowing for the reclassification of export sales. Stada said itsAliud marketing unit had fared well in tenders.

A 7% Generics rise to C113 million in Eastern Europe and theCommonwealth of Independent States (CIS) was due in part toreclassified exports by Germany’s Hemofarm, as well as to 19% growthto C49.3 million in Russia. This balanced a 31% slide to C25.5 millionin Serbia, where wholesalers were reluctant to purchase amiduncertainty on planned reimbursement cuts. G

COMPANY NEWS


BUSINESS STRATEGY/FIRST-HALF RESULTS

Stada chief promisessteady evolution path

Central EuropeC296.3m, -6%

GermanyC153.5m, -2%

Eastern Europe/CISC112.6m, +7%

Asia-Pacific & MENAC41.4m, +11%

Figure 1: Breakdown by region of Stada’s Generics sales that decreased by 2%to C604 million in the first half of 2016 (Source – Stada)

Pfizer has “temporarily paused production” at its manufacturingfacility in Irungattukottai, near Chennai, India, following a recent

inspection of the former Hospira site “to allow an assessment ofobservations by appropriate experts”. “Pfizer has formally respondedto the inspection findings issued following the recent inspection,” aPfizer spokesperson told Generics bulletin, adding that the US originatorwas at the facility “implementing actions to address the findings”.

A statement of non-compliance with good manufacturingpractice issued by the UK’s healthcare regulatory agency revealedthat a “critical finding that was in regards to sterility assurance” wasidentified following an inspection last month.

More than three years ago, the Irungattukottai site received awarning letter from the US Food and Drug Administration (FDA).

Meanwhile, Pfizer’s chairman and chief executive officer, Ian Read,says that the firm’s upcoming decision on whether to split into standaloneoperations its established and innovative business segments is not“make-or-break” for the company.

“[The decision] continues to be based on four questions: Are thebusinesses doing well within Pfizer? Could the businesses perform wellas standalone entities? Is there trapped value in a combined entity?

And can the trapped value be unlocked efficiently?” Read explainedto investors. “We will be thoughtful in evaluating the virtues of a splitover the coming months. I don't view there being a wrong answer here.”

Moreover, Pfizer was “now the worldwide leader in biosimilars,according to IMS revenues”, Read noted. Reporting biosimilars salesof US$78 million in the second quarter of this year, Read reiteratedthat Pfizer “expected to compete in the first wave of biosimilar launchesin the US”. The US originator, which has numerous biosimilarcandidates in registration or Phase III clinical trials, has howeverjust terminated its collaboration agreement with Pfenex to developbiosimilar ranibizumab (see page 21).

In the second quarter of this year, a contribution of US$1.14 billionfrom legacy Hospira to Pfizer’s newly-rebranded Essential Healthglobal established products operation helped the firm overcome depletedsales of its peri-loss-of-exclusivity (peri-LOE) brands, and raiseEssential Health turnover by 16% as reported and by 19% on anoperational basis to US$6.04 billion (see Figure 1). Minus the effectof Hospira, Essential Health sales slid by 6%, and on an operationalbasis by 3%, to US$4.90 billion. Group turnover rose by 11% toUS$13.1 billion, but higher sales costs caused Pfizer’s pre-tax profitto tumble by a third to US$2.41 billion. G

MANUFACTURING/SECOND-QUARTER RESULTS

Pfizer suspends workat ex-Hospira facility

Second-quarter sales Reported Operational(US$ millions) change(%) change (%)

Innovative Health 7,105 +7 +9

Legacy brands 2,864 -2 +2Sterile injectables 1,497 +99 –Peri-LOE products 1,111 -21 -19Infusion systems 295 – –Pfizer CenterOne 196 +47 +48Biosimilars 78 – –Essential Health 6,042 +16 +19

Pfizer 13,147 +11 +13

Figure 1: Breakdown by division of Pfizer’s sales in the second quarter of 2016(Source – Pfizer)

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

Fresenius Kabi has unveiled plans to transform its US generic sterileinjectables manufacturing site in Melrose Park, Illinois, into a

“manufacturing campus” through a 10-year, US$250 million investment.The German firm plans to break ground on the “multi-stage, multi-

year project” next year, with final project completion at the formerAPP Pharmaceuticals site scheduled for 2026.

Noting that the expansion would create “multiple new buildingsconnected to the existing manufacturing site”, the German firmdisclosed that the finished project would include fully-automated asepticfilling lines, expanded lyophilisation capabilities, formulation areas,a “dedicated” warehouse for raw materials and office space.

“Kabi operates more than 70 manufacturing sites across the globeand the Melrose Park location will be one of the largest,” said the firm,which has its US headquarters in nearby Lake Zurich, and additional USmanufacturing sites in New York, North Carolina and Pennsylvania.

Kabi obtained the facility in North Carolina at the beginningof this year through the firm’s acquisition of Becton, Dickinson andCompany’s ‘BD Rx” business (Generics bulletin, 15 January 2016,page 11), which also gave Kabi a portfolio of seven marketed drugsin ready-to-administer pre-filled glass syringes.

In the first half of this year, sales rising by 6% to C1.09 billion(US$1.2 billion) in North America enabled Kabi to avoid an overallgroup turnover fall, following slides in the German firm’s Asia-Pacificand Latin America and Africa businesses, alongside stagnant salesin Europe (see Figure 1).

Marginally Kabi’s largest market by value, ahead of Europe, NorthAmerican sales advanced as the firm again capitalised on intravenousdrug shortages. This enabled Kabi to report group turnover that wasstagnant year-on-year at C2.95 billion. The firm’s earnings beforeinterest and tax (EBIT) rose by 8% to C616 million.

“In general, drug shortages keep on influencing our business morepositively than thought,” noted chief executive officer of the Freseniusgroup, Stephan Sturm, who stepped up to the position from 1 Julyfollowing Mark Schneider’s resignation to become Nestlé’s chiefexecutive (Generics bulletin, 1 July 2016, page 16)

Furthermore, Sturm reiterated that, “as indicated earlier”, Kabiexpected “drug launches to be rather backend loaded” in North Americafor the remainder of this year. “So far we have launched three newproducts, in line with our expectation to end the year near the topend of our six-to-ten target range,” he commented.

Breaking down Fresenius Kabi’s organic sales by product type,Intravenous Drugs remained the firm’s strongest seller, with salesrising by 7% to C1.25 billion. Clinical Nutrition sales grew by 6% toC770 million, while Infusion Therapy sales increased by the sameamount to C419 million. Kabi’s Medical Devices and TransfusionTechnology sales also advanced, rising by 4% to C506 million. G

COMPANY NEWS


MANUFACTURING/FIRST-HALF RESULTS

Kabi to transform itsMelrose Park facility

Region First-half sales Reported Organic(C millions) change (%) change (%)

North America 1,086 +6 +6Europe 1,048 ±0 +2Asia-Pacific 531 -6 +7Latin America/Africa 281 -3 +21

Fresenius Kabi 2,946 ±0 +6

Figure 1: Breakdown by region of Fresenius Kabi’s sales in the first half of 2016(Source – Fresenius)

Beximco says it has become “the first Bangladeshi company tolaunch pharmaceutical products in the US”, after commencing the

export of carvedilol, which the firm expects to produce annual salesof approximately US$3-4 million. The prescription hypertension drug –available in 3.12mg, 6.25mg, 12.5mg and 25mg tablets – was approvedby the US Food and Drug Administration (FDA) in November lastyear (Generics bulletin, 9 December 2015, page 20).

The carvedilol tablets are produced at Beximco’s FDA-approvedfacility in Tongi, Bangladesh, which passed an inspection in Januarylast year without any Form 483 observations of good manufacturingpractice deficiencies (Generics bulletin, 13 March 2015, page 10).A few months later, the FDA officially approved Beximco’s Tongiplant (Generics bulletin, 10 July 2015, page 6)

Describing the export as a “significant milestone” for Beximco, thefirm’s vice-chairman, Salam Rahman, said delivering the first shipmentof carvedilol to the US would begin a “new era for the pharmaceuticalindustry in Bangladesh”. “We believe our continued focus on buildingand strengthening the group’s presence in Western markets will cementBangladesh’s position as a major exporting company,” Rahman added.

“These initiatives are in line with our aspirations to expand ourreach by taking products to the world. The US is the largest and mostlucrative market in the world,” stated Beximco’s managing director,Nazmul Hassan, highlighting the firm’s differentiated generics. G

BUSINESS STRATEGY

Beximco becomesfirst to launch in US

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

Mallinckrodt says its projected sales decline for its SpecialtyGenerics operation “was somewhat less steep than we had

anticipated” during the firm’s financial third quarter ended 24 June2016. But Mallinckrodt was also “nowhere near out of the woods yetin the Specialty Generics business”, chief financial officer MatthewHarbaugh informed investors.

Having last year forecasted weaker Specialty Generics sales inits 2016 financial year (Generics bulletin, 23 October 2015, page4), Mallinckrodt reported generics turnover that slid by 14.5% toUS$263 million for the three-month period.

The double-digit Specialty Generics decline was largely attributableto a fall of almost a fifth in sales of extended-release methylphenidateto US$24.3 million, and a similar decline in turnover from ‘othercontrolled substances’ to US$125 million. A 2.1% rise to US$38.2million in sales of finished-dose and bulk hydrocodone offset a 3.2%decline to US$30.6 million in turnover from finished-dose and bulkoxycodone. Other generics contributed US$45.6 million.

“While this quarter’s performance was more positive, ourexpectations remain consistent with those we described a year ago, andwe foresee pressure on this segment for at least the next several quarters,”president and chief executive officer Mark Trudeau summarised. “Thissegment continues to generate solid cash flow,” he reasoned, havingearlier this year played down suggestions that Mallinckrodt might divestits Specialty Generics unit (Generics bulletin, 13 May 2016, page 4).

Commenting on Mallinckrodt’s business strategy for SpecialtyGenerics, Trudeau said it would “make very good sense” to furtherenhance the firm’s pipeline of abbreviated new drug applications(ANDAs)”. However, he acknowledged, Mallinckrodt’s “primaryfocus” remained on Specialty Brands.

“We do have a few ANDAs that we have been working on overtime and that we are looking to accelerate, with internal organisationaldevelopment, as well as licensing-in products,” Harbaugh added.“There are a number of organisations out there that have reached out tous and want to work collaboratively on bringing products to market.”

Specialty Brand sales that increased by just under a third toUS$589 million ultimately drove Mallinckrodt to a turnover rise, asgroup sales increased by 10.6% to US$971 million. Mallinckrodt’soperating profit jumped by three-fifths to US$203 million. G

COMPANY NEWS


THIRD-QUARTER RESULTS

Mallinckrodt declineis less than expected

Sun Pharma’s managing director, Dilip Shanghvi, is confident thatremediation efforts at the Indian firm’s manufacturing facility in

Halol, India, will be sufficient to restore the plant to complianceahead of a US Food and Drug Administration (FDA) re-inspection.

“I do not think that we have a Plan B on not passing the re-inspection, because I think we have worked hard to address all thecompliance-related anxieties or issues which were raised,” Shanghvitold investors as Sun presented financial results for its financial firstquarter ended 30 June 2016.

“We have indicated to investors in the past that we will informFDA before June [this year] for a re-inspection, which is what wehave done,” he revealed, adding that Sun would not forecast apotential date when the re-inspection would take place.

Launching the first US generic version of Novartis’ Gleevec(imatinib mesylate) with 180 days of generic market exclusivity inFebruary helped compensate for US supply disruptions arising from

Halol, as Sun increased its US sales by almost a third to Rs40.7 billion(US$609 million) in its financial first quarter.

“[US] sales for the quarter were stable despite competitive pressureon some products and supply constraints arising from remediationefforts at the Halol facility,” Shanghvi noted, adding that Sun had,however, also benefitted from non-recurring sales of approximatelyUS$35 million, “which is unlikely to repeat in the remaining quartersof this financial year”. Meanwhile, Sun has just lost its monopoly ongeneric Gleevec following Apotex’ and Teva’s launches (see page 20).

Sun currently has 150 abbreviated new drug applications(ANDAs) pending US Food and Drug Administration (FDA) approval,including 15 tentative approvals, after filing one ANDA and receivingseven final approvals during the quarter. Sun has just received FDAapproval for its US rival to Santarus’ Glumetza (metformin) 500mgand 1,000mg extended-release tablets and expects to be in the market“in few weeks.”

Sales rises in Sun’s domestic market – where Sun launched 15products – and Emerging Markets region more than outweighed aslight slip in the firm’s Rest of the World operation as Sun’s totalFormulations sales climbed by a fifth to Rs75.2 billion (see Figure 1).Including Bulk Drugs turnover that soared by almost three-quartersto Rs4.70 billion, and other income that added Rs2.55 billion, Sun’sgroup sales rose by 21.9% to Rs82.4 billion.

Meanwhile, Sun’s pre-tax profit trebled to Rs26.3 billion, althoughthe firm had last year been hit with a one-off Rs6.85 billion charge. G

MANUFACTURING/FIRST-QUARTER RESULTS

Sun’s chief confidenton fixing Halol plant

First-quarter sales Change Proportion(Rs millions) (%) of total (%)

US 40,706 +31.7 49India 18,543 +7.6 22Emerging Markets 10,311 +22.1 13Rest of World 5,625 -2.2 7Formulations 75,185 +20.6 91

Bulk Drugs 4,698 +73.1 6

Other/eliminations 2,546 -0.6 3

Sun Pharma 82,430 +21.9 100

Figure 1: Breakdown by region and business of Sun Pharma’s net sales in itsfinancial first quarter ended 30 June 2016 (Source – Sun Pharma)

Decreases in National Health Insurance (NHI) reimbursement pricesimposed in April this year combined with double-digit rises in

operating costs to more than halve Towa Pharmaceutical’s operatingprofit in its financial first quarter ended 30 June 2016.

The Japanese firm said the NHI price cuts had caused it to missboth value and volume targets for sales, which increased by 3.8% to¥20.2 billion (US$200 million).

The lower prices and volumes led to a 5.6 percentage-point dropin gross margin to 45.0%, while selling, general and administrativecosts increased by 13.7% to ¥7.74 billion, the main components ofwhich were staff expenses 11.4% higher at ¥3.32 billion and researchand development spending that rose by a quarter to ¥1.97 billion. Asa result, Towa’s operating margin fell by nearly nine points to 6.6%. G

FIRST-QUARTER RESULTS

Price reductions trouble Towa

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

Impax has reduced its full-year sales forecast for 2016 due to avariety of factors impinging its US Generics business, “primarily”

an “unexpected and rapid decline” in sales of diclofenac and metaxalone,caused group turnover to fall in the second quarter of this year.

The US firm now anticipates full year sales of US$900-US$940million for 2016, having earlier this year projected group sales ofaround US$1 billion by improving “by at least 15%” 2015 sales ofUS$860 million (Generics bulletin, 26 February 2016, page 6).

Addressing investors as Impax reported generics sales that tumbledby 30.3% to US$122 million in the second quarter of this year, presidentand chief executive officer Fred Wilkinson commented that a “changein the diclofenac market quickly moved us from an exclusive supplierposition to a five-competitor market”. Impax had “recorded shelf-stock adjustments totalling approximately US$15.0 million ondiclofenac and metaxalone as a result of decline in price”, he revealed.

“The swiftness of the change in both [diclofenac and metaxalone]combined with lower sales of mixed amphetamine salts [genericAdderall XR that Impax launched in April] more than offset solid

growth from our epinephrine auto-injector and oxymorphone products,as well as growth in sales across our Specialty Pharma portfolio.”

Meanwhile, Impax has also been affected by a “five-week delay”in completing its acquisition of a US basket of approved generics andpipeline assets from Teva, stemming from the Israeli firm’s protractedtakeover of Actavis (Generics bulletin, 24 June 2016, page 1).

But, Wilkinson stated, “following the close of the acquisition, wecontinue to have the financial resources and flexibility to invest in organicgrowth, as well as judiciously pursue external growth opportunities.”

Moreover, Impax’ sales would be hurt by a “delay in supply ofa third-party generic product and deferred timing of certain targeted2016 generic product launches”, Wilkinson explained. Having launchedthree products so far this year, Impax was continuing to target 12 to14 potential generic product launches, “now more heavily weighted tothe second half, with the greatest impact being recognised in fourthquarter”, Wilkinson noted.

Speaking less than two weeks after joining from Perrigo aspresident of Impax’ generics division (Generics bulletin, 29 July 2016,page 16), Doug Boothe commented that “despite a challenging secondquarter”, it was “absolutely exciting times for Impax”. The firm was“looking at commercial opportunities” for its backlog of “pent-upabbreviated new drug applications (ANDAs)” stemming from thelong-standing warning letter at Impax’ Hayward facility, which wasresolved in September last year, Boothe revealed.

Specialty Pharma sales rising by 28.8% to US$50.9 millionallayed somewhat Impax’ overall decline in the second quarter, as groupsales fell by just under a fifth to US$173 million (see Figure 1). Butoperating expenses staying largely the same year-on-year saw Impax’operating profit tumble by three-quarters to US$4.40 million. G

COMPANY NEWS


RESULTS FORECAST/SECOND-QUARTER RESULTS

Impax cuts guidancefollowing sales drop

Division Second-quarter sales Change Gross(US$ millions) (%) margin (%)

Generics 121.7 -30.3 30.7Specialty Brands 50.9 +28.8 70.0

Impax 172.6 -19.4 42.3

Figure 1: Breakdown by division of Impax Laboratories’ sales and gross margin inthe second quarter of 2016 (Source – Impax)

Lupin raised its group net sales by two-fifths to Rs43.1 billion(US$645 million) in its financial first quarter ended 30 June 2016.

Managing director Nilesh Gupta said the rise had been “driven byrobust growth across all our key markets – the US, India and Japan”.

North American Formulations sales surged by 82.3% to Rs21.9billion, albeit against a relatively weak prior-year quarter due to aslowdown in abbreviated new drug application (ANDA) approvals(Generics bulletin, 7 August 2015, page 5). Subsequently, Lupinbolstered its US portfolio and pipeline by paying US$880 million forGavis Pharmaceuticals and its Novel affiliate (Generics bulletin,18 March 2016, page 3).

Three US launches during the quarter took Lupin’s total numberof generics marketed in the US to 123. Having filed two ANDAs andreceived seven approvals, the firm had 149 pending approval as of30 June, including 45 that it believes are first-to-file opportunities. Chiefexecutive officer Vinita Gupta highlighted US pipeline opportunitiesincluding generic Epzicom (abacavir/lamivudine) and Minastrin(norethindrone/ethinylestradiol/ferrous fumarate), as well as prospectsin the controlled-substance and dermatology niches.

In the Indian company’s domestic market, Formulations salesincreased by 5.2% to Rs9.31 billion (see Figure 1) as Lupinrestructured the local business.

Local-currency sales in Japan rose by 11.1% to ¥6.86 billion(US$68.4 million). Lupin said it was set to become the fifth-largestgenerics player in Japan by acquiring 21 ‘long-listed’ off-patent brandsfrom Japan’s Shionogi through the Indian company’s local Kyowasubsidiary (Generics bulletin, 5 August 2016, page 14). This dealwould allow Lupin to capitalise on its local central nervous systemfranchise to establish a specialty portfolio.

Including sales in the Philippines ahead by nearly two-thirds,Lupin’s total turnover in its Asia-Pacific region grew by nearly a thirdto Rs5.42 billion. Sales in Latin America shot up by 76.8% to Rs1.09billion, with increases in Brazil and Mexico.

Growth of just over a fifth to Rs2.19 billion in Lupin’s Europe,Middle East and Africa (EMEA) region included an 88.2% leap toC6.4 million (US$7.2 million) in Germany and a rise of almost a thirdto ZAR205 million (US$15.3 million) in South Africa.

A global 46.2% surge in Formulations sales was tempered slightlyby a 12.4% dip to Rs2.87 billion in worldwide turnover from activepharmaceutical ingredients (APIs). G


Lupin grows by 40%across a broad base


North America 21,886 +82.3 51India 9,313 +5.2 22Asia-Pacific 5,416 +32.9 13Europe/Middle East/Africa 2,194 +20.6 5Latin America 1,089 +76.8 3Rest of World 369 +117.1 –Formulations 40,267 +46.2 93

APIs 2,869 -12.4 7

Lupin 43,136 +40.0 100

Figure 1: Breakdown by region and business segment of Lupin’s turnover in itsfinancial first quarter ended 30 June 2016 (Source – Lupin)

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

Sawai Pharmaceutical intends to ramp up its investment in bothproduct development and manufacturing infrastructure as part of a

revised business plan that foresees the Japanese firm reaching net salesof ¥157 billion (US$1.55 billion) in its financial year ending 31 March2018, a ¥10 billion increase to what it had previously been targeting.

To achieve the ambitions set out in its revised ‘M1 Trust 2018’medium-term business plan that runs until March 2018, Sawai intendsto explore new areas of business, including overseas markets andbiosimilars. The Japanese company also plans to considerably bolsterits manufacturing capacity, thereby helping it to establish the leadingposition in its fast-expanding domestic generics market.

Sawai is pledging to “accelerate efforts” to build a foundationoverseas, not least by developing products for the US that will buildon the abbreviated new drug application (ANDA) for pitavastatin thatit submitted two years ago. The US pipeline investments form partof a plan to spend ¥28.0 billion on research and development overthe next three years, ¥4.5 billion more than originally envisaged inthe original M1 Trust outline.

Capital expenditure on production capacity is also to be increasedahead of the original plan, rising from ¥44.0 billion to ¥55.0 billionover the three-year period to March 2018. This ¥11.0 billion increaseis intended to support moves to raise the firm’s capacity from 10.0 to15.5 billion tablets as a step towards “building a production system for20.0 billion tablets by March 2021”.

As the Japanese government strives towards generics accountingfor 70% to 80% by volume of Japan’s off-patent pharma market, Sawai

also intends to respond rapidly to spikes in demand by using contractmanufacturers for certain products. “Attaining the target goal of 70%by mid-2017 is expected to be difficult,” Sawai commented, addingthat the 80% goal to be reached as soon as possible before 2021 undergovernment plans unveiled last year implied Japan’s generics marketexpanding to more than 100 billion tablets.

To maintain its leading domestic position, Sawai has increasedits target for volume share in Japan’s generics market by 0.7 percentagepoints to 16.0% in its financial year ending March 2018. This, itbelieves, will fuel average annual turnover growth of 14.1% to ¥157billion as the group’s operating profit grows to ¥26.0 billion.

In the first quarter of Sawai’s financial year ending 31 March 2017,the company advanced its net sales by 12.1% to ¥32.9 billion as volumegrowth of around a fifth was tempered by National Health Insurance(NHI) price cuts. Turnover from products listed for NHI reimbursementduring the previous financial year contributed ¥1.15 billion.

“Market movements associated with measures to promote genericdrugs have been slower than anticipated, causing sales to progressat a lower rate than previous years,” Sawai acknowledged. “Profitshave progressed as anticipated, and performance projections are firm.”

The Japanese group achieved during the quarter 23.0% of its annualturnover target of ¥143 billion. Sawai made slightly more progresstowards its annual goal of an operating profit of ¥25.0 billion, eventhough its first-quarter operating profit fell by 7.3% to ¥5.89 billion,“mainly due to increased research and development costs for productsaimed at the US market”. G

COMPANY NEWS


BUSINESS STRATEGY/FIRST-QUARTER RESULTS

Japan’s Sawai sets more ambitious goals

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

US approval for ANI Pharmaceuticals’ nilutamide 150mg tabletsin mid-July came as a shock to reference-brand owner, Concordia

International. Due to the unexpected competition to its Nilandron(nilutamide) brand and further competition to its authorised genericof Plaquenil (hydroxychloroquine sulfate), Concordia took a US$567million impairment charge in the second quarter of this year, leadingthe Canada-based group to report a US$494 million operating loss ona turnover of US$232 million as it also suffered from exchange-rateshifts in the wake of the UK’s ‘Brexit’ vote to leave the European Union.

ANI’s US market entry with its nilutamide oncology drugfollowing approval represented the first generic competition toNilandron (Generics bulletin, 29 July 2016, page 9).

“This was obviously a tough quarter for us,” admitted Concordia’schairman and chief executive officer, Mark Thompson. “Two eventsthat happened, Brexit and generic Nilandron, were really unexpected.”

Executive vice-president Ed Borkowski said the firm was nowcurtailing its recent sales and marketing investment behind theNilandron prostate-cancer brand that it acquired in April last yearthrough its US$1.2 billion takeover of Covis. Concordia, he revealed,was working with a partner on launching an authorised generic.

However, Borkowski continued, Concordia’s own US authorisedgeneric of Plaquenil had “seen steep and rapid price erosion” towardsthe end of the second quarter as a rival generic announced its entry.

A full-quarter contribution from the Covis business enabledConcordia to raise its North American turnover by 7% to US$77.5million. The International business that the group gained by acquiringAMCo in October last year contributed US$151 million, with itsOrphan Drug unit adding US$2.74 million.

Noting that a strategic review was underway (Generics bulletin,29 April 2016, page 1), Thompson said the firm’s board was “evaluatingone specific opportunity which we think would be very beneficial tothe company”. “But until we get more clarity,” he added, “I cannotprovide any further details.” G

COMPANY NEWS


BUSINESS STRATEGY/SECOND-QUARTER RESULTS

Concordia shockedby nilutamide launch

Increased prices and volumes enabled Akorn to raise its group salesby 27.1% to US$281 million in the second quarter of this year. The

former was most significant for Akorn, adding US$41.6 million tooperations, while increased volumes added US$20.4 million.

Nevertheless, the US company said it had, “as forecasted”,experienced a “mid-single-digit pricing decline” across “the balance”of its portfolio. “As expected, we experienced a higher loss in marketshare and margins, which were isolated to some of our key productssuch as clobetasol, lidocaine and hydralazine due to increasedcompetition in 2016,” chief executive officer Raj Rai told investors.

Meanwhile, Rai revealed that Akorn was “continuing to work withthe US Food and Drug Administration” over its “key filings” for ageneric version of Allergan’s Restasis (cyclosporine) and the firm’sOTC fluticasone and ephedrine sulphate products.

Despite higher selling, general and administrative expenses,Akorn’s operating profit jumped by two-fifths to US$92.4 million, asthe injectables and ophthalmics specialist’s operating margin climbedby three percentage points to 32.9%. G

SECOND-QUARTER RESULTS

Price and volume help Akorn

Piramal has agreed to pay up to US$53 million for US-based high-potency active pharmaceutical ingredient (HPAPI) specialist

Ash Stevens. As no antitrust approval was needed, India’s Piramal saidit expected imminently to complete the deal for US$42.95 million plusan earn-out consideration capped at US$10 million.

“The acquisition of Ash Stevens fits well with our strategy to buildan asset platform that offers value to our partners and collaborators,”insisted Vivek Sharma, chief executive officer of Piramal PharmaSolutions. “Currently, around 25% of the molecules in clinicaldevelopment are potent,” he noted, adding that Ash Stevens wouldoffer synergies with the group’s existing injectables and antibody drugconjugate (ADC) capabilities.

“North America is a key market that we can now service with ourthree local facilities – the Coldstream Labs facility in Kentucky forfill-finish needs, the Torcan facility in Toronto for complex high-valueAPIs, and now Ash Stevens in Michigan for HPAPIs,” Sharma stated.

Piramal Pharma Solutions has just committed to a US$25 millionexpansion of the Coldstream sterile-manufacturing site in Lexington,Kentucky, that it acquired early last year (Generics bulletin, 6 February2015, page 8). The planned upgrades include increasing vial-fillingand lyophilisation capacity.

With its plant in Mahad, India, having cleared its first US Foodand Drug Administration (FDA) audit without any observations, PiramalPharma Solutions reported static turnover of Rs5.75 billion (US$85.8million) in the company’s first quarter ended 30 June 2016. G

MERGERS & ACQUISITIONS

Piramal plots moveto buy Ash Stevens

SAMSUNG BIOLOGICS has made an application for an initialpublic offering (IPO) on the Korean Composite Stock Price Index(KOSPI) stock exchange. With an 85% holding in the SamsungBioepis joint venture with Biogen that was set up in 2012, SamsungBiologics is a major player in the biosimilars arena (Generics bulletin,6 May 2016, page 3). According to the filing, Samsung Biologicsstated it has sales of KRW91.3 billion (US$83.2 million) and employs1,213 staff. Furthermore, the company noted Benepali (etanercept),its rival to Amgen’s Enbrel, was the firm’s “main product”.

AEMPS – Spain’ medicines and medical device agency – has foundsites operated by Jinan Jinda and Alcor to be non-compliant withgood manufacturing practice (GMP) requirements followinginspections. Jinan Jinda’s site in Zhangqiu, China, was pulled up for30 deficiencies, including critical faults on raw data safety, control andout-of-specification review. A total of 29 deficiencies at Alcor’s sitein Guadalajara, Spain, had not satisfactorily been addressed by thefirm’s corrective action plan, Aemps found. In another entry on theEudraGMP database, German inspectors found problems with bulksimvastatin made at Artemis Biotech’s industrial development area inHyderabad, India. “Repackaging operations were conducted withoutany documentation,” the entry states, adding that labels for activepharmaceutical ingredients (APIs) were “inadequately controlled”.

ZHEJIANG MEDICINE “conducted unofficial testing” and failedto ensure the integrity of data generated at its facility in Xinchang,China, according to a warning letter issued by the US Food andDrug Administration (FDA). G

IN BRIEF

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

Cipla promised a “ramp-up in US portfolio and filing intensity”as it raised its research and development investment by around

40%, equivalent to 6.6% of group turnover that declined by 6% toRs35.9 billion (US$538 million) in the Indian company’s financialfirst quarter ended 30 June 2016.

The group – which will from 1 September see Umang Vohrareplace Subhanu Saxena as global managing director and chiefexecutive officer (see front page) – said it had made four US filingsduring the quarter, “including some oncology filings”, “as compared tofive filings during the whole of our 2015-2016 financial year”. Thisinvestment formed part of a “significant ramp-up in product filingsacross key markets” as Cipla aims to spend around 7% of its annualturnover on product development, including on bevacizumab trials.

In the US, Cipla has just acquired three products that were divestedas part of antitrust clearance for Teva’s takeover of Actavis. Thisincludes “the rights to a limited-competition product with a likelyfiling date in the [financial] second quarter”, Teva’s pending genericversion of Celgene’s Abraxane (protein-bound paclitaxel) injectablecancer therapy (Generics bulletin, 5 August 2016, page 5).

Having introduced six products in the US from its own pipelineover the past six months, Cipla also launched one product from thepipeline of the InvaGen business that it acquired in mid-February thisyear. The Indian company said integration of InvaGen and its Exelanaffiliate was “progressing smoothly”, with processes “streamlined acrosskey functions” including commercial, manufacturing and quality control.

While Cipla’s first-quarter North American turnover fell by justover a fifth to Rs6.57 billion as reported – and by a quarter in local-currency terms to US$98 million – the Indian firm said it had enjoyedgrowth of more than 30% in its “base business” excluding InvaGenand supplies of esomeprazole. Cipla claimed to be the third fastest-growing generics player in the US by absolute prescriptions filled, witheight of 38 marketed products being market leaders.

Strong anti-infectives and respiratory sales pushed up Indianturnover by 5% to Rs14.5 billion, while Cipla blamed price declinesin partnership-led Middle Eastern markets in part for a 6% slide toRs7.58 billion in Emerging Markets (see Figure 1).

In its ‘key’ South African market, Cipla raised its share of the privatemarket to 5.3% as it focused on higher-margin tenders. Sales climbedby 4% to Rs4.03 billion, equivalent to a 22% local-currency rise. InEurope, the Indian firm said it was making progress on transitioningfrom direct-to-market to partnership models in certain countries. G

COMPANY NEWS


BUSINESS STRATEGY/FIRST-QUARTER RESULTS

Cipla ramps researchas it raises US filings

First-quarter sales* Change Proportion(Rs millions) (%) of total (%)

India 14,490 +5 40Emerging Markets 7,580 -6 21North America 6,570 -21 18South Africa 4,030 +4 11Europe 1,400 +5 4Global API 1,310 -37 4Others 550 -33 2

Cipla 35,940 -6 100

* rounded to nearest Rs10 million

Figure 1: Breakdown by region of Cipla’s sales in its financial first quarter ended30 June 2016 (Source – Cipla)

Endo’s US Generics business “substantially completed” theintegration of Par Pharmaceutical during the second quarter of this

year, the US firm has announced, as Endo also continued to makeprogress on returning to “long-term, organic growth” under restructuringplans laid out earlier in 2016.

In May, Endo unveiled a broad restructuring initiative – whichincludes slashing around 740 jobs across two of its US manufacturingsites and discontinuing more than 60 products from within its legacyQualitest portfolio – after factors impinging US Generics caused thefirm to revise its full-year sales forecast for 2016 (Generics bulletin,13 May 2016, page 3). Subsequently, Endo revealed a five-point ‘actionplan’ to combat these issues (Generics bulletin, 27 May 2016, page 14).

“We continue to make progress on key growth drivers like our[hybrid] 505(b)(2) and sterile injectable programmes, as well aslaunching a steady stream of new differentiated products this year,”Paul Campanelli, president of Endo’s Par Pharmaceutical US Genericsunit, told investors.

Campanelli disclosed that two 505(b)(2) projects Endo wastargeting were “two forms of potassium”. “One is a liquid and one is a

powder form. We have started to receive positive feedback from theFDA in terms of removing unapproved sources,” he noted. Moreover,Endo recently secured a new patent for its hybrid 505(b)(2)Vasostrict (vasopressin) injectable that expires in January 2035.

Endo had launched 11 new generic products in the US andsubmitted seven filings to the US Food and Drug Administration(FDA) as of 1 August, Campanelli noted, with the firm stating it was“on track” to reach its prior target of launching around 30 productsin the US in total this year, and submitting 25-30 filings.

Campanelli added that Endo had also “largely completed thetransition of the legacy Qualitest business onto the Par platform”,including “commercial insight, forecasting, wholesaler datamanagement and other capabilities”.

Meanwhile, president and chief executive officer Rajiv De Silvaplayed down suggestions of selling off non-core assets to pay downdebt. “From a company perspective, we do not feel compelled to divestany assets,” he said. “We are confident in our business and the naturaldelevering nature of the business given our substantial cash flows.”

In the second quarter of this year, the addition of Par to Endo’sUS Generics operation, including US$126 million worth of sterileinjectables turnover, helped sales to leap by two-thirds to US$565million. US Generics sales amounted to more than three-fifths of groupturnover that rose by a quarter to US$921 million, brought down bylower US Brands and International sales (see Figure 1).

In the wake of much higher operating costs, Endo reported anoperating loss of US$48.4 million, down from a US$1.49 millionprofit in the second quarter of last year. G

BUSINESS STRATEGY/SECOND-QUARTER RESULTS

Endo makes progresson restructuring plan

Business Second-quarter sales Change Proportionunit (US$ millions) (%) of total (%)

Par Pharmaceutical 565 +67 61US Brands 288 -9 31International 67 -17 7

Endo 921 +25 100

Figure 1: Breakdown by business unit of Endo’s sales in the second quarter of2016 (Source – Endo)

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

COMPANY NEWS


Get GenericsGet Generics bulletinbulletin on youron yourtablet and smartphonetablet and smartphone

Please contact [email protected] if you have forgottenyour personal login details. Please also contact us if you do not havea subscriber personal account, possibly because your company hasa Corporate subscription.

Download the FREE Generics bulletin-i App foroptimised viewingon your Apple and/orAndroid tablet andsmartphone.

Use the links belowto login with yoursubscriber personalaccount* details.

* Please contact [email protected] if you have forgotten

Each Friday you will receive the latest issue –wherever you are worldwide

http://tinyurl.com/krxxrflhttp://tinyurl.com/ov7uleq

Make the most of your subscription –

get FREE access to

Launching products including linezolid and rabeprazole in the UK,as well as achieving success in several German tenders, helped

Glenmark Pharmaceuticals to increase its group turnover by 17.9%to Rs19.4 billion (US$291 million) in the Indian firm’s financialfirst quarter ended 30 June 2016.

European Formulations sales climbed by 36.5% to Rs1.50 billion.“The UK business rebounded strongly, growing in excess of 100%during the quarter,” Glenmark commented. “The German subsidiaryrecorded a good performance and won several tenders.”

Noting that its German operation ranked among the country’s top15 generics players, the Indian company said it had introducedanastrozole, duloxetine, linezolid and modafinil in Germany, as well as

injectable bendamustine in both Poland and Slovakia, and the OTCAlfasilver wound spray in the Czech Republic.

In the US, Glenmark increased its turnover by almost a quarterto Rs6.98 billion (see Figure 1) as the company secured final approvalsfor rufinamide tablets and nystatin/triamcinolone ointment, along withtentative approvals for olmesartan tablets, norethindrone/ethinylestradiol/ferrous fumarate tablets, and adapalene/benzoyl peroxide gel.

During the quarter, the Indian company filed 4 abbreviated newdrug applications (ANDAs), and moreover plans to follow up withfive US submissions during its current financial quarter. At present,Glenmark has 62 applications pending US approval, of which 23contain paragraph IV patent challenges.

The Indian firm’s domestic sales rose by just over a tenth toRs5.14 billion as it introduced Digihaler, “India’s first digital doseinhaler” that includes a digital dose counter to aid adherence in asthmaand chronic obstructive pulmonary disease (COPD) patients.

“Good traction” from the launch of Oflomil (ofloxacin) naillacquer and “good momentum” from the recently launched MomatRino Advance (mometasone/azelastine) nasal spray lifted sales inRussia as Glenmark improved its turnover in its Africa, Asia and theCommonwealth of Independent States (CIS) region by nearly a quarterto Rs1.95 billion. In Asia, the Indian firm said it had achieved double-digit growth in Malaysia, the Philippines and Vietnam.

However, a significant sales drop in Venezuela contributed toLatin American sales sliding by 28.8% to Rs1.56 billion. “The Brazilianand Mexican subsidiaries did not perform as per expectations,”Glenmark admitted. Global active pharmaceutical ingredient (API)turnover climbed by 41.7% to Rs1.91 billion, aided by “good growth”from olmesartan in the US and tenegliptin in India.

Glenmark improved its pre-tax profit by 35.1% to Rs3.48 billion. G


Launches in UK liftGlenmark’s turnover


US 6,982 +24.4 36India 5,138 +10.4 26Africa/Asia/CIS 1,949 +23.4 10Latin America 1,556 -28.8 8Europe 1,500 +36.5 8API 1,912 +41.7 10Licensing/other 394 – 2

Glenmark 19,431 +17.9 100

Figure 1: Breakdown of Glenmark Pharmaceuticals’ sales in its financial firstquarter ended 30 June 2016 (Source – Glenmark)

Pharma sales in the European Union (EU) increasing by just undera tenth to C10.7 million (US$11.9 million) helped Macedonia’s

Alkaloid to improve on more minor growth in other regions in thefirst half of this year and report group turnover that was 3.5% higherat C68.0 million. Over four-fifths of this total stemmed from Pharmasales that rose by 1.9% to C56.2 million, while other operations thatgrew by 11.7% contributed the remaining C11.8 million.

In Alkaloid’s domestic market, Pharma sales inched ahead by0.3% to C21.5 million, while turnover was only 0.8% higher atC20.0 million in the firm’s South-East Europe region. The remainingC3.95 million of the firm’s Pharma total came from Russia and theCommonwealth of Independent (CIS), representing growth of 1.3%.

Taken by therapeutic category, double-digit growth for Alkaloid’scardiovascular lines helped overcome sales slips for Alkaloid’s OTCand central nervous system drugs. Cardiovascular drug sales advancedby 11.9% to C12.2 million, accounting for a little over a fifth of totalPharma turnover. Just over another fifth of the Pharma total came fromOTC products, sales of which dipped by 1.2% to C12.0 million.Antibiotics and central nervous system therapies each contributed alittle under a sixth of Pharma turnover with sales of C9.2 million andC8.4 million respectively.

Alkaloid’s gross margin increased slightly from 46.6% to 46.9%while the firm’s operating profit rose by 4.6% to C6.22 million. G

FIRST-HALF RESULTS

EU sales rise enablesAlkaloid to advance

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

A13.9% sales decline in the US caused Zydus Cadila to report groupgross turnover down by 2.1% to Rs22.6 billion (US$338 million)

in the firm’s financial first quarter ended 30 June 2016.Formulation sales slipped to Rs8.48 billion in the US, where the

Indian company on 1 August started to distribute an authorisedgeneric of Asacol HD (mesalamine) 800mg delayed-release tablets.The firm has also just boosted its US diabetes portfolio with approvalfor nateglinide 60mg and 120mg tablets made at its Pharma SpecialEconomic Zone (SEZ) site in Ahmedabad, India.

A deal to acquire two abbreviated new drug applications (ANDAs)from Teva – approved minocycline capsules and pipeline rotigotinepatches (Generics bulletin, 5 August 2016, page 5) – closed this month.

In India – where Zydus has just strengthened its dermatologyportfolio by acquiring the Melgain (deca-peptide) vitiligo treatmentfrom Hyderabad-based Issar Pharma – the firm raised its Formulationsales by 6.2% to Rs7.86 billion.

A 7.3% rise to Rs1.34 billion in its Emerging Markets regioncancelled out single-digit turnover declines by Zydus’ European andLatin American Formulations businesses to Rs792 million and Rs527million respectively.

Total Formulations turnover slipped by 4.7% to Rs19.0 billion,while global active pharmaceutical ingredient (API) turnover stalledat Rs976 million. Alliances and other revenues added Rs2.65 billion. G

COMPANY NEWS


OTC DISTRIBUTION IN EUROPE:

THE NEW GLOBAL AGENDA

Download Executive Summary and order online at

www.james-dudley.co.uk®

JAMES DUDLEYM A N A G E M E N T

®

A study of the factors driving change and presenting challenges and opportunities to manufacturers

An exploration of changes in retail customer and shopper needs and the unfolding strategies required to achieve competitive success

An in-depth source of current statistics, discussion and opinions about the European consumer healthcare market –plus consumer insights, market sizes, salestrends and distributors’ market shares

A window into leading retail pharmacy chains and their strategies for market share through digital innovation and newconcepts in multi-channel shopping

NOW IN ITS 10TH EDITION,OTC DISTRIBUTIONIN EUROPE IS A COMPREHENSIVE STRATEGICANALYSIS OF THE SUPPLY NETWORK SERVINGEUROPE’S OTC SELF-MEDICATION SECTORS

COVERS 20 COUNTRIESIN OVER 590 PAGES AND

300 GRAPHS, TABLES & FIGURES


Zydus Cadila slideson a sales slip in US

Perrigo chief John Hendrickson has admitted that the firm’sPrescription US generics business “has been our most challenging

[business] to predict given price erosion and the competitive dynamicsin the sector” as he reflected on an “intense and challenging” first100 days in the job.

In Perrigo’s financial second quarter ended 2 July 2016,Prescription sales rose by 5% to US$293 million, driven by turnoverstemming from the firm’s recent additions of Entocort (budesonide)and tretinoin products, which added US$43.7 million, and ‘new productsales’ – “primarily” Perrigo’s generic version of Valeant’s BenzaClinPump (clindamycin/benzoyl peroxide) gel that the firm launched in May(Generics bulletin, 13 May 2016, page 11) – adding US$25.6 million.

Hendrickson, who replaced Joe Papa as group chief executiveofficer in May, announced that Perrigo had also “very recentlypurchased the remaining portion of the generic BenzaClin royaltystream that we did not own previously”.

But sales of Perrigo’s ‘existing’ products tumbled by US$50.3million, owing to lower volumes, pricing pressure and a loss of marketleadership position for two “key” products. Discontinued productsand an “unfavourable” foreign exchange movement together wiped anadditional US$4 million from the firm’s total Prescription sales.

Meanwhile, the Prescription segment currently lacks a permanentleader following Doug Boothe’s resignation last month. JohnWesolowski, senior vice-president of the Prescription segment’scommercial operations, has stepped up to manage the operation onan acting basis (Generics bulletin, 29 July 2016, page 16).

Addressing investors, Hendrickson said he nevertheless believedthe Prescription unit to be a “fundamentally sound business with solid,strong long-term prospects”.

Prescription sales made up a fifth of group sales that slipped by 3%to US$1.48 billion in the wake of lower Consumer Healthcare andBranded Consumer Healthcare sales (see Figure 1), as Perrigo’soperating profit rose by 5% to US$238 million. “Our financial results”,Hendrickson emphasised, “were below our expectations primarilydue to competition and price erosion in the Prescription business.”

Perrigo is meanwhile set to strengthen its US distribution andretail network after agreeing to acquire US-based OTC and consumergoods distributor Geiss, Destin & Dunn (GDD) for an undisclosed sum.The transaction is set to close before the end of this month.

And the firm has also just completed the sale of its US vitamins,minerals and supplements (VMS) business to US-based InternationalVitamin Corporation following an initial agreement in June (Genericsbulletin, 24 June 2016, page 4). G

SECOND-QUARTER RESULTS

Generics have been achallenge for Perrigo

Business Second-quarter sales Change Operatingsegment (US$ millions) (%) margin (%)

Consumer Healthcare 686.3 -8 16.2Branded Consumer Healthcare 393.7 -2 9.8Prescription 293.3 +5 33.0Specialty Sciences 89.9 +7 14.8Other 17.8 -19 -7.1

Perrigo 1,481.0* -3 16.1

* includes second quarter net sales of US$44 million from ‘held-for-sale’ businesses

Figure 1: Breakdown by business segment of Perrigo’s sales and operatingmargin in its financial second quarter ended 2 July 2016 (Source – Perrigo)

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

MARKET NEWS


Standard formularies issued for 2017 by US pharmacy benefitmanagers (PBMs) CVS Health and Express Scripts favour

biosimilar and follow-on versions over their reference brands.CVS insists it is “embracing the future with biosimilars and follow-

on biologics” by favouring Sandoz’ Zarxio (filgrastim-sndz) biosimilarover Janssen’s Neupogen reference brand, and by replacing Sanofi’sLantus (insulin glargine) on its formulary with Eli Lilly’s Basaglarrival that was approved through the hybrid 505(b)(2) pathway.

Several ‘multi-source brands’ such as Crestor (rosuvastatin),Gleevec (imatinib) and Nexium (esomeprazole) are also excludedfrom CVS’ 2017 formulary. The PBM said it was also addressing“limited-source generics” from a limited number of suppliers thatwere “resulting in significant cost”. “These products will be evaluatedand, if appropriate, be excluded during the year,” it stated.

“We anticipate significant savings for many clients and members,as the removal of higher-cost products will enable near-term value,with additional future opportunities for savings resulting from marketcompetition as more products are launched,” stated CVS, which managesprescription-drug programmes for employers and health insurers.

Between 2012 and 2017, CVS expects its “rigorous approachto formulary management” to save its clients more than US$9 billion.Express Scripts says participating plan sponsors will save aroundUS$1.8 billion in 2017 through its exclusion of 85 drugs from itsnational preferred formulary.

For example, in the diabetes category, Express Scripts prefersgeneric extended-release metformin to Salix’ Glumetza (metformin)500mg extended-release tablets. “The basal insulins category maybe reassessed later this year to reflect anticipated product launches,”noted the PBM that currently favours Lilly’s Humulin (human insulin)and Humalog (insulin lispro) pens. G

PRICING & REIMBURSEMENT

Formularies favourfollow-on drugs in US

Supply contracts for 133 molecules or combinations, spread across143 bidding lots, have been awarded by major German health

insurance fund Barmer-GEK in its ninth tender round. Contracts willbegin on 1 January next year and run through to 30 September 2018.

For 104 of the 143 lots awarded, Barmer-GEK chose two or threecompanies, while 39 lots went to an exclusive supplier. For 17 lots, thefund received no satisfactory offers. In total, the drugs covered by thetender – which includes osteoporosis and respiratory drugs – haveannual sales through the fund of C360 million (US$408 million).

“When choosing our tender partners, we place the focus onsecuring reliable supplies of high-quality medicines and not just onprice,” insisted Barmer-GEK chairman Mani Rafii.

According to market researcher IMS Health, 74% of the total 251million generics packs dispensed through Germany’s statutory healthinsurance system in the first half of 2016 were covered by tenderrebates. The proportion for patented drugs market was 28%.

A survey commissioned by the association of the Germanpharmaceutical industry, the BPI, found that 41% of Germans said theywould consider changing their insurance fund if their current fundagreed a contract for a chronic medicine with a single supplier. Almostthree-fifths said they would feel “unsettled” by such a situation. G

PRICING & REIMBURSEMENT

German fund awards contracts

Acollection of over 60 biosimilar and biologic developers, payorsand consumer groups shared contrasting opinions on draft US

Food and Drug Administration (FDA) guidance for biosimilar labellingthat the agency released for comment earlier this year.

Having set a 60-day deadline for comments of 3 June when theguidance was released earlier this year (Generics bulletin, 8 April2016, page 5), the FDA later extended the deadline by a further 60days (Generics bulletin, 17 June 2016, page 5).

Interested parties’ divisions focused on the FDA’s proposals onthe extent to which biosimilar labelling should differ from thebiosimilar’s reference product, including over whether to include astatement of biosimilarity and details of clinical studies.

Sandoz – which last year launched the first US biosimilar, its Zarxio(filgrastim-sndz) rival to Amgen’s Neupogen – said the inclusion of astatement of biosimilarity “would certainly be perceived as a ‘Scarlet B’,an effective caveat or caution, highlighting to healthcare professionalsand the public that there may be a clinically meaningful issue with theproduct being a biosimilar”. The Novartis affiliate added that“highlighting” on the biosimilar’s label indications that had beenextrapolated from clinical data – as certain parties have proposed,including AbbVie in a citizen petition last year – was an attempt “to raisedoubts as to the safety and efficacy of the biosimilar for those indications,and perhaps to also imply inferiority of biosimilars across the board”.

Meanwhile, US pharmacy benefit managers industry body, thePharmaceutical Care Management Association (PCMA), also expressed“concern” at the FDA’s plans to include a statement of biosimilarity,but sided with the agency’s proposal to omit clinical studies on thelabel as these would “not likely be relevant to a healthcare practitioner’sconsiderations regarding safe and effective use”.

Amgen, which primarily develops novel biologics but is alsodeveloping biosimilars such as adalimumab (see page 20), supportedthe FDA’s recommendation to include a statement of biosimilarity. TheUS firm also called for the FDA to include clinical studies on the label.

Many parties also urged the FDA to swiftly address the issue oflabelling for interchangeable biosimilars. The agency has just promisedthat it will release a draft guideline on ‘Considerations in demonstratinginterchangeability with a reference product’ this calendar year, alongwith guidance on biosimilar labelling and on statistical approaches toevaluating analytical data to support demonstrations of biosimilarity.

Also scheduled for publication by the FDA’s Center for DrugEvaluation and Research (CDER) during 2016 is industry guidance on180-day generic exclusivity and on three-year exclusivity determinationsfor drug products. The FDA will also focus on issues aroundabbreviated new drug application (ANDA) filings, including a reviseddraft of content and format, identifying reference products and updatingANDA labelling after the marketing application for the reference-listeddrug has been withdrawn.

Assessing adhesion for ANDAs with transdermal delivery systemsand topical patches is also on the agenda, following draft guidancereleased recently on the “design and conduct” of adhesion studies(Generics bulletin, 10 June 2016, page 11). Further guidance duethis year will discuss bioequivalence studies with pharmacokineticendpoints and determining whether to submit an application underthe 505(b)(2) hybrid or 505(j) generic pathway.

Further topics will cover the agency’s thinking on drug master files(DMFs), risk evaluation and mitigation strategies (REMS), data integrityand compliance with current good manufacturing practice (cGMP). G

REGULATORY AFFAIRS

Draft FDA labellingguide splits opinions

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

MARKET NEWS


We are looking for potentialsuppliers for the finished dosage

forms listed below, for aEuropean market:

❍ Trastuzumab Vial❍ Bevacizumab Vial❍ Rituximab Vial❍ Bortezomib Vial❍ Cabazitaxel Vial❍ Panitumumab Vial❍ OnabotulinumtoxinA Vial❍ Ertapenem Vial❍ Daptomycin Vial❍ Esmolol Solution for Infusion❍ Pemetrexed Vial❍ Azacitidine Vial❍ Aripiprazole Long Acting Injectable❍ Paliperidone Long Acting Injectable

For further information, please email:[email protected]

quoting Box No.534

Biosimilars “are just as safe and effective as many of the expensivebrand biologics prescribed”, according to an analysis of biosimilar

safety and efficacy published in US journal the Annals of InternalMedicine. Welcomed by the US Generic Pharmaceutical Association(GPhA) and its Biosimilars Council, the report focused on rheumatoidarthritis, psoriasis and inflammatory bowel disease medicines.

The report – carried out by the Johns Hopkins Bloomberg Schoolof Public Health – analysed data from 19 studies conducted throughApril this year. It concluded that “while there weren’t a large numberof studies, the available data suggests that biosimilar drugs have verysimilar safety and effectiveness as their branded counterparts”.

By 2017, the article noted, sales for biologics are “expected torepresent approximately 20% of the total pharmaceutical market”. Withthe findings coming “at a time when many of these biologics arecoming off-patent”, the report contended that “the wide adoption ofbiosimilars could eventually save the health system billions of dollars”.

“The Biosimilars Council is pleased to see more science-basedevidence that patients can trust biosimilars and that providers canconfidently prescribe these medicines,” said the GPhA’s ChristineSimmon, who is also the Biosimilars Council’s executive director.“This data reinforces the importance of core scientific principlessuch as bioequivalence and can help inform policymaker efforts toencourage patient access and promote biosimilar competition.” G

MARKET RESEARCH

US biosimilars foundcomparable to brands

Italy is among the last countries in Europe to maintain patent linkageafter the industry committee of the country’s senate rejected three

legislative amendments that would have eliminated the practice, accordingto local generics and biosimilars industry association Assogenerici.

“Allowing these practices delays the market entry of generic drugs,leading to lost savings for the public purse,” argued Assogenerici’spresident, Enrique Häusermann. Italians, he argued, should be madeaware that the “unjustified burden” of linking patent status to marketingand reimbursement approval was forcing the Italian health service,the SSN, to pay more for drugs than other European countries.

Pointing out that the European Commission had expressly declaredpatent linkage to be contrary to Community law in its 2009 reporton the pharmaceutical sector, Assogenerici said Italian legislation wasallowing private intellectual-property rights to be distorted. Contraryto suggestions, the association clarified, granting marketing andreimbursement clearance for a generic drug during the reference brand’spatent term did not constitute an illegal act.

A report presented to the Italian senate in May last year arguedthat removing patent linkage should be one of the “key policy priorities”and claimed that Italy could save as much as C1.4 billion (US$1.6billion) annually by maximising on generics penetration (Genericsbulletin, 22 May 2015, page 12).

Thereafter, Assogenerici renewed its call on Italy’s governmentto remove patent linkage from its reimbursement framework, claimingthat the presence of this mechanism – “denounced several times bythe European Commission” – led to Italy’s national health servicehaving to spend an extra C18 million on drugs in 2014 (Genericsbulletin, 20 November 2015, page 12).

In May this year, Assogenerici urged the government to “takeadvantage of the potential offered by generics to generate savings thatcould be reinvested in the healthcare system” (Generics bulletin, 27May 2016, page 8), amidst claims that Italy would see patent expiriesfor drugs worth C3.7 billion annually between 2017 and 2023. G

REGULATORY AFFAIRS/INTELLECTUAL PROPERTY

Italy misses chanceto end patent linkage

Groups of “accordion” panels that can be opened to reveal new andenhanced features and contact information are among the features

added to an “improved” online version of the Orange Book patentregister maintained by the US Food and Drug Administration (FDA).

Following the “first major revision of the web-page”, the OrangeBook site now features an updated design that helps users “customisetheir research experience and collect search and browse options ontothe homepage. Users can now also search approved drug products byactive ingredient, proprietary name, applicant, application number,dosage form, route of administration or patent number.

First made available as an online database in 1997, the OrangeBook – officially known as the Approved Drug Products withTherapeutic Equivalence – details patents and exclusivity periods forapproved drug products.

Separately, the FDA has released draft guidance for industry onregulatory classification of co-crystal solid-state forms. The agencylays out the data it expects from applicants for different formscontaining co-crystal forms. G

REGULATORY AFFAIRS

FDA improves Orange Book

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

PRICE WATCH .............UK


Independent pharmacists who in June latched onto £0.99 (US$1.32)offers for 28-capsule packs of duloxetine 30mg were disappointed

in July to find that wholesaler Forte Direct had discontinued thepromotion. The 40% July increase when the lowest June offer waswithdrawn, however, had little effect on the product’s average price,which fell slightly to £2.90 in July (see Figure 1).

In the event, pharmacists were doubly-disadvantaged as the newDrug Tariff of pharmacy reimbursement prices for the July-Septemberquarter slashed the value of dispensing duloxetine 30mg from £8.47 inJune to just £4.81 in July. A potential dispensing margin of 88% inJune thus became just 71% in July. Pharmacists who paid the averageprice saw their margins retreat from 65% to 40%.

Even double-digit falls in the prices of 100-tablet packs ofnortriptyline were wiped out by the July changes to the Drug Tariff,which saw the reimbursement price fall by more than 16% to £47.56.

The best deal on the product was £37.95 in June (Generics bulletin,22 July 2016, page 10), giving a margin of 33%. But the margin wasonly lifted to 35% in July, despite an 18% fall in the lowest price ofnortriptyline 10mg to £30.99. The effect of the Tariff changes was moremarked on average nortriptyline prices, with a 14% margin in Junebecoming a 9% margin in July, despite a 12% monthly fall in theproduct’s average price.

Three strengths of ropinirole were among the fastest-rising pricesin Figure 2, as were two strengths of aspirin. Prices for pioglitazonefalling from highs earlier this year were responsible for three strengthsof the diabetes treatment among the fastest price-fallers in Figure 3,along with trimethoprim 100mg.

Atorvastatin 20mg had more price offers than usual in July, pushingit up the ratings to second place and breaking the leadership hold of theproton-pump inhibitors omeprazole and lansoprazole (see Figure 4). G

Figure 1 (above): Comparison between the periods 1-30 June 2016 and 1-31 July2016 of UK trade prices of the most recently-launched generics listed in category Mof the Drug Tariff of pharmacy-reimbursement prices. Averages calculated from atleast 25 data points. Figure 2 (top right) and Figure 3 (centre right): Biggestaverage trade-price changes between 1-30 June 2016 and 1-31 July 2016. Averagescalculated from at least 10 data points. Figure 4 (bottom right): Ranking of fastest-moving products subject to the most price offers made to independent UK pharmacists(one strength per ingredient; offers recorded by 31 July). Data for Figures 2, 3and 4 from a basket of about 750 commonly-dispensed generics. Recently-launchedproducts in Figure 1 excluded from Figures 2 and 3 (Source – WaveData).

WANT MORE LIKE THIS?

RECENT LAUNCHES

Product/Strength/Pack size Lowest Change Average Changeprice (%) price (%)

Aripiprazole tabs 10mg 28 £0.89 -1 £1.74 -6Benzydamine 0.15% 300ml £4.85 +2 £5.59 +1Carbimazole tabs 5mg 100 £59.80 -8 £69.95 -6Celecoxib caps 200mg 30 £0.77 -3 £1.42 -5Cilostazol tabs 100mg 56 £1.89 ±0 £3.28 -10Cyclizine tabs 50mg 100 £5.75 -1 £7.98 +2Desogestrel tabs 75µg 84 £1.18 ±0 £2.10 +19Duloxetine caps 30mg 28 £1.39 +40 £2.90 -1Entacapone tabs 200mg 30 £3.75 -4 £5.49 -2Eplerenone tabs 25mg 28 £3.45 -3 £5.55 -10Escitalopram tabs 10mg 28 £0.24 +20 £0.74 -4Fusidic acid cream 2% 15g £1.22 ±0 £1.63 +3Memantine tabs 10mg 28 £0.56 ±0 £0.95 +6Mometasone furoate 0.1% 30g £1.21 -3 £1.93 -4Montelukast tabs 10mg 28 £1.02 -27 £1.65 -8Nortriptyline tabs 10mg 100 £30.99 -18 £43.13 -12Oxcarbazepine tabs 300mg 50 £4.90 ±0 £6.18 ±0Rabeprazole tabs 10mg 28 £0.85 +8 £1.25 +2Raloxifene tabs 60mg 28 £2.65 ±0 £3.64 ±0Riluzole tabs 50mg 56 £11.25 ±0 £16.91 -2Rizatriptan tabs 10mg 3 £0.76 -5 £1.59 +10Sevelamer tabs 800mg 180 £48.40 -12 £71.25 -11Sildenafil tabs 100mg 4 £0.23 -4 £0.57 +16Telmisartan tabs 80mg 28 £0.74 ±0 £1.42 +4Tolterodine tabs 2mg 56 £1.32 +2 £1.75 -4

FAST MOVERS

Price offers as at 31 July 2016Product/Strength/Pack size May June July

Omeprazole caps 20mg 28 129 133 122

Atorvastatin tabs 20mg 28 106 102 112

Lansoprazole caps 30mg 28 109 104 103

Sertraline tabs 50mg 28 93 102 94

Fluoxetine caps 20mg 30 86 87 93

Co-codamol tabs 8mg/500mg 100 83 81 91

Ramipril caps 2.5mg 28 74 71 90

Gabapentin caps 300mg 100 94 84 90

Tramadol caps 50mg 100 85 101 89

Clopidogrel tabs 75mg 28 91 91 89

BIGGEST FALLERSProduct/Strength/Pack size Lowest Change Average Change

price (%) price (%)

Pioglitazone tabs 45mg 28 £2.49 -28 £9.12 -38


Chlordiazepoxide caps 5mg 100 £1.93 -8 £3.39 -32


Trimethoprim tabs 100mg 28 £0.29 -15 £0.51 -32

Pramipexole tabs 350µg 100 £0.50 ±0 £4.01 -29

BIGGEST RISERSProduct/Strength/Pack size Lowest Change Average Change

price (%) price (%)

Aspirin tabs 300mg 32 £0.17 -6 £1.66 +493

Ropinirole tabs 2mg 28 £1.05 -5 £10.74 +434

Ropinirole tabs 0.25mg 12 £0.65 +16 £7.25 +200

Naratriptan tabs 2.5mg 12 £2.49 +3 £9.40 +188

Ropinirole tabs 0.5mg 28 £1.09 +4 £14.63 +172Aspirin tabs 75mg 1,000 £1.79 -1 £10.01 +157

Duloxetine disappoints dispensers in July

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].

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

The US Food and Drug Administration (FDA) has accepted for filingMerck & Co’s 505(b)(2) hybrid new drug application (NDA) for

a biosimilar version of Sanofi’s Lantus (insulin glargine).The US originator noted that the “development programme” it

had submitted in support of its MK-1293 insulin glargine filing –which is being developed in collaboration with Samsung Bioepis –was “designed to meet rigorous regulatory standards for follow-onbiologics of clinical and nonclinical safety, efficacy and quality”.

“In addition to Phase I studies assessing its pharmacokinetic andpharmacodynamic properties, the NDA submission for MK-1293includes results of two Phase III studies, one conducted in people withtype 1 diabetes, and one in people with type 2 diabetes [againstLantus],” the originator noted, referring to data announced earlier thisyear (Generics bulletin, 17 June 2016, page 8).

Merck has already, in December last year, submitted a Europeanmarketing authorisation application for MK-1293, with the EuropeanMedicines Agency. The application is “currently under review.”

The US-based firm’s proposed rival to Lantus is, moreover, oneof five biosimilars that the firm last year disclosed plans to makeregulatory filings for by the end of this year (Generics bulletin, 13March 2015, page 19). Merck said it was also preparing to submitfilings for biosimilar versions of Enbrel (etanercept), Herceptin(trastuzumab), Humira (adalimumab) and Remicade (infliximab)through its alliance with Samsung. All five candidates were in Phase IIIclinical trials at the time of Merck’s announcement.

Under the terms of a patent-litigation settlement brokered last year,Eli Lilly and its partner Boehringer Ingelheim will be able to launchthe first US alternative to Lantus – their Basaglar (insulin glargine)hybrid biosimilar – from 15 December 2016 (Generics bulletin, 23October 2015, page 25). The settlement came several months beforethe FDA granted final approvals to the firms’ biosimilar, which hasalready been rolled out in markets across the world (Generics bulletin,8 January 2016, page 14). G

PRODUCT NEWS


BIOLOGICAL DRUGS

Merck’s Lantus rivalaccepted by the FDA

Accord Healthcare has convinced a Netherlands district court thatthe local part of Medac’s European patent EP2,046,332 covering

certain methotrexate concentrations is invalid.The Hague district court ruled that formulating the patented

50mg/ml concentration of methotrexate would have been obvious to askilled person looking to solve the problem of how to minimise painupon injection and improve patient compliance for the arthritis treatment.

In finding that key claims of the ‘332 patent were not inventive,the Dutch court referred to a similar ruling by the UK Patents Courtearlier this year (Generics bulletin, 22 January 2016, page 11).

Separately, the Hague court has granted AstraZeneca a preliminaryinjunction to stop Sandoz from marketing a generic version of theoriginator’s Faslodex (fulvestrant) breast-cancer treatment.

Noting that Sandoz had in June this year obtained a listing for itsfulvestrant 50mg/ml solution on the Netherlands’ G-Standaardreimbursement index, the court said there was “too much doubt”whether AstraZeneca’s European formulation patent EP1,250,138lacked an inventive step in light of prior-art documents. G

ARTHRITIS DRUGS

Accord defeats Dutch patent

Generics companies seeking to ‘clear the way’ through patent-revocation actions in the UK cannot avoid counterclaims for

threatened infringement by indicating that they will only launch if theyrevoke the patents, Justice Colin Birss has ruled in a lengthy decision.Birss upheld one patent protecting Eli Lilly’s tadalafil-based Cialisand Adcirca erectile-dysfunction and cardiovascular drugs, but foundat least one claim of another patent to be valid and infringed.

Actavis and Mylan argued that applying to revoke a patent with theintention to launch if they could clear the patent out of the way did notamount to a threat to infringe. Counterclaims for infringement inrevocation actions, the generics firms submitted, resulted in “significantand unjustified added costs”, including from supplying samples.

Observing that Actavis and Mylan had applied for marketingauthorisations with a view to marketing tadalafil once a UKsupplementary protection certificate (SPC) linked to European patentEP0,740,668 expired in November 2017, Birss identified the UK partsof European patents EP1,173,181 and EP1,200,092 as “potentialobstacles” to generic entry. “Bringing proceedings to revoke them isnot proof of an intention to sell,” he acknowledged, “but it also supportsthe inference, based primarily on the marketing authorisation.”

Pointing out that “the UK market for tadalafil is large and valuable”– worth around US$100 million annually – Birss surmised that Actavisand Mylan would have “substantial supplies of tadalafil once the SPCexpires” and might be tempted to launch at-risk. “A surreptitious launchof a generic product can be very attractive and profitable, even if itis subsequently stopped by an emergency injunction,” he observed.

“The logic of clearing the way covers both infringement andvalidity,” Birss insisted. Pointing out that the fear of infringementstemmed not so much from the revocation action as from the marketing-authorisation application, he said there was “a sufficiently strongprobability that an injunction would be required to prevent Actavisand Mylan from infringing after expiry of the SPC to justify bringingthe infringement counterclaim”.

Addressing the ‘181 dosing patent, Birss ruled that at least Claim 7– covering daily doses up to 5mg for treating sexual dysfunction –would be valid and infringed by generic tablets at 2.5mg and 5mgstrengths. And while a prior-art Daugan article would have renderedit obvious for a skilled team to test tadalafil as a treatment for erectiledysfunction, the team would not have had “a reasonable expectation”that a 5mg dose would be an effective treatment.

Turning to the ‘092 formulation patent, Birss found all of thepatent’s claims to be invalid. Claims 8 and 9, along with thosedependent upon them, lacked novelty in light of particle sizes disclosedin the Oren prior-art document. Furthermore, he stated, “micronisedtadalafil in a formulation for the treatment of erectile dysfunction isobvious over Daugan”. Thus, Claim 1 of the ‘092 patent was obvious,as were the patent’s use claims. Several of the patent’s claims werealso held by Birss to be insufficient for being too broad. G

ERECTILE-DYSFUNCTION DRUGS

Clearing way in theUK cannot cut costs

COHERUS has submitted a US biologics license application (BLA)for its CHS-1701 pegfilgrastim candidate. A recent pharmacokinetic(PK) and pharmacodynamic (PD) biosimilarity study for the US firm’sbiosimilar version of Neulasta (pegfilgrastim) met all of its primaryendpoints (Generics bulletin, 22 July 2016, page 12). G

IN BRIEF

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:33

PRODUCT NEWS


19-21 September

■ Strategic Project & PortfolioManagement for GenericsPrague, Czech RepublicKey topics covered at this three-day event will include alignmentbetween country and global portfolio levels, key market drivers andintegrating innovation, added-value and diversification in products.

Contact: Marcus Evans. Tel: +357 22 849 308.E-mail: [email protected]. Website: www.marcusevans.com.

29-30 September

■ Biosimilars EuropeLondon, UKThis two-day conference will look at developments in the biosimilarguideline framework and legislation in both Europe and the US.

Contact: SMi. Tel: +44 207 827 6000.E-mail: [email protected]. Website: smi-online.co.uk.

3 & 4-6 October

■ CPhI WorldwideBarcelona, SpainCPhI Worldwide is an exhibition and networking opportunity whichwill include the co-located events iCSE, P-MEC and Innopack.The event will be preceded by the Pre-Connect Congress.

Contact: UBM Information. Tel: +31 207 081 637.E-mail: [email protected]. Website: cphi.com

24-26 October

■ GPhA Fall Technical ConferenceMaryland, USAThis GPhA conference will cover regulatory issues with speakersfrom the industry and the US Food and Drug Administration (FDA).

Contact: GPhA. Tel: +1 202 249 7100.E-mail: [email protected]. Website: gphaonline.org.

21-22 November

■ EuroPLX 62Nice, FranceThis meeting provides an opportunity to discuss and negotiateagreements, in-licensing and marketing and distribution.

Contact: Raucon. Tel: +49 6221 426296 0.E-mail: [email protected]. Website: europlx.com.

Hotel Porta Fira, The Gran Via complex, Barcelona, SpainHotel Porta Fira, The Gran Via complex, Barcelona, SpainContact: [email protected]: [email protected]

Cocktail Reception andAwards Presentation

4 October 2016

21-22 November

15-16 November

■ World Biosimilar CongressBasel, SwitzerlandThis conference is co-located with the European Antibody Congress,World HPAPI Congress and the World Immunotherapy Congress.The event will look at topics including biosimilars uptake, pricing,development and interchangeability. There will be speakers fromfirms including Biogen, Merck and Sandoz. The meeting will alsoinclude networking and business development opportunities.

Contact: Terrapinn. Tel: +44 207 092 1000.E-mail: [email protected]. Website: terrapinn.com.

EVENTS – September, October & November

Alvogen and its development partner Natco can begin preparationsto introduce the first generic version of Roche’s Tamiflu

(oseltamivir) 30mg, 45mg and 75mg capsules after the US Food andDrug Administration (FDA) approved Natco’s abbreviated new drugapplication (ANDA).

Under a patent-litigation settlement brokered at the end of lastyear, Alvogen is entitled to roll out an alternative to the antiviralbrand – which Roche licenses from Gilead – “before the expirationof the paediatric exclusivity period listed in the FDA’s Orange Bookfor US patent 5,763,483, which is 23 February 2017” (Genericsbulletin, 8 January 2016, page 14).

Citing IMS Health data, Natco said Tamiflu had US sales ofaround US$403 million last year.

Tamiflu was one of numerous “niche and complex” paragraph IVpatent challenge opportunities within Natco’s pipeline, which alsoincludes lucrative brands such as Copaxone (glatiramer acetate), Gilenya(fingolimod), Revlimid (lenalidomide) and Treanda (bendamustine),the Indian firm disclosed earlier this year (Generics bulletin, 8 July2016, page 14). G

ANTIVIRALS

FDA approves rival to Tamiflu

Asserted claims within UCB’s sole US patent shielding its Vimpat(lacosamide) anticonvulsant tablets until March 2022 are valid, a

US district court has ordered in patent-litigation proceedings.Ruling in favour of the Belgian originator, Delaware district court

judge Leonard Stark rejected multiple allegations of invalidity broughtagainst reissued patent RE38,551 by a collection of 11 abbreviatednew drug application (ANDA) filers.

After weighing up arguments presented by Accord, Actavis,Alembic, Amneal, Apotex and Aurobindo, as well as Breckenridgeand its partner Vennoot, Mylan, Sun and Zydus, Stark ruled that thefirms had “failed to prove by clear and convincing evidence” that the‘551 patent was invalid due to obviousness-type double patenting.Contentions of statutory obviousness, anticipation, indefiniteness, andthat the ‘551 patent was improperly reissued, also failed.

Of the defendants, Actavis, Alembic, Aurobindo, Mylan, MSNLabs – which was substituted for Vennoot in litigation – and Suncurrently hold final US Food and Drug Administration (FDA)approvals for lacosamide 50mg, 100mg, 150mg and 200mg tablets.UCB’s brand had US sales of C513 million (US$578 million) in2015, amounting to three-quarters of global Vimpat sales thatreached C679 million.

Generics firms Hetero, Glenmark, Sun affiliate Ranbaxy andSandoz had earlier dropped out of litigation, having previously beenamongst the group of at least 16 paragraph IV patent challenge filerswhen the FDA began accepting generic filings three years ago (Genericsbulletin, 6 September 2013, page 24).

However the ‘551 patent remains under threat from invalidationafter the US Patent and Trademark Office’s (USPTO’s) Patent Trial& Appeal Board earlier this year granted Argentum’s petition to institutean inter partes review against all of the patent’s claims (Genericsbulletin, 3 June 2016, page 12). The USPTO has also instituted anex parte re-examination of the same claims within the patent. G

EPILEPSY DRUGS

Lacosamide patentis found valid in US

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:34

All that’s happening inconsumer healthcareWritten by OTC specialists from an OTC industry perspectiveThe best decision-makers in the OTC industry don’t have the time to go looking forgood information. They let it come to them. They subscribe to OTC bulletin.

Join thousands of subscribers from competitor companies in over 35 countries who arealready benefitting from commercial intelligence about business opportunities in theglobal non-prescription medicines and dietary supplements markets.

GOOD VALUEIndividual

subscription ratesstart from just

£975

INDIVIDUAL SUBSCRIPTIONSAn annual subscription comprises:

n 20 OTC bulletin newsletters;

n AND at least 45 weekly news@OTCbulletinelectronic newsflashes containing the week’s topnews stories (currently delivered by email).

CHOICE OF FORMATSThe 20 OTC bulletin newsletters are available:

n EITHER as the digital OTC bulletin-i for online accessby desktop AND tablet and smartphone. These mobiledevices can have Apple or Android operating systems.

n OR in traditional hard-copy print format, delivered by airmail;

CORPORATE SUBSCRIPTIONSA Corporate Subscription provides location-, country- orcompany-wide access to OTC bulletin-i.

Contact [email protected].

AVAILABLE INSTANTLY WORLDWIDEOTC bulletin-i is the digital i-edition of OTC bulletin. Now available online fordesktop access, it delivers the latest OTC bulletin on the day of publication withno postal delay. It also comes – at NO EXTRA CHARGE – as an app for mobileaccess by tablet and smartphone.

OTC bulletin-i subscribers also get access to a fully-searchable archive. Thiscontains over five years of OTC news and analysis in more than 100 back issues.These offer an invaluable resource for researching marketing opportunities,benchmarking competitive strengths, evaluating regulatory changes and assessingproduct developments.

Generics bulletin subscribers get 20% OFF if they take out a subscriptionto OTC bulletin-i. Contact [email protected].

Take out a subscription TODAYContact: [email protected]

Bulletin Publishing Group, OTC Publications Ltd, 4 Poplar Road, Dorridge, Solihull B93 8DB, UK. (Tel: +44 (0)1564 777550; Fax: +44 (0)1564 777524).Registered in England No: 2765878. VAT No: GB 608 0432 69

OTC Sister Ad BLUE JAN 2016_Generics Sister Advert 27/01/2016 13:47 Page 1

PRODUCT NEWS


Amgen has for the first time been sued for patent infringementby fellow US originator AbbVie in a US district court over its

bid to introduce in the US its recently-backed biosimilar version ofAbbVie’s Humira (adalimumab) blockbuster.

As part of the multi-step process for identifying and litigatingbiologic patents within the Biologics Price Competition and InnovationAct (BPCIA), AbbVie has identified 61 US Humira patents it claimsare infringed by Amgen’s proposed biosimilar.

However, as Amgen was entitled to do so under the rules of theBPCIA, it capped at six the number of patents each side would litigatein the ‘first wave’ of patent-litigation proceedings. As there was anoverlap of two patents that both sides had identified, the lawsuitinvolves “for now” 10 patents.

“At this time, AbbVie seeks an injunction to prevent infringementof at least 227 claims of the 10 asserted AbbVie patents. If and whenAmgen files a notice of commercial marketing, or as circumstancesotherwise warrant, AbbVie will assert additional patents from itsestate,” AbbVie states in its complaint.

AbbVie claims Amgen “refused to engage in good-faithnegotiations over which patents should be the subject of this litigation”,and instead “waited until the last day possible to provide AbbVie withthe number of patents that it would agree to be sued on”.

The action in a Delaware district court comes less than a monthafter the Arthritis Advisory Committee to the US Food and DrugAdministration (FDA) unanimously voted – by 26-0 – to recommendfor approval Amgen’s ABP-501 adalimumab candidate (Genericsbulletin, 22 July 2016, page 11). AbbVie’s reference brand had USsales of US$8.41 billion last year.

The FDA previously set a Biosimilar User Fee Act (BsUFA) targetaction date for Amgen’s abbreviated biologics license application (aBLA)of 25 September 2016 (Generics bulletin, 29 January 2016, page 16).

Within its complaint, AbbVie alleges that Amgen is attempting tosidestep legal procedures it wants other biosimilar developers tofollow. “In speaking to defend its copycat actions here, Amgen isspeaking out of both sides of its mouth. When biosimilars attemptto knock off its biologic products, Amgen tells a different story.”

“Indeed,” AbbVie continued, “Amgen has made arguments to theUS Patent and Trademark Office (USPTO) that are directly at oddswith those it is advancing in this case in order to secure numerouspatents covering methods of using, formulating, and manufacturingdrugs – especially biologic drugs.”.

AbbVie also points out that the USPTO earlier this year deniedAmgen’s petition requesting an inter partes review of two Humirapatents (Generics bulletin, 22 January 2016, page 13). However,other firms have been successful in persuading the USPTO to reviewHumira patents, including US-based biosimilars developer Coherus,which recently saw the USPTO agree to conduct an inter partesreview of Humira dosing regimen patent 18,889,135 (Genericsbulletin, 20 May 2016, page 12).

Meanwhile, Amgen has successfully opposed Hospira’s motionto dismiss Amgen’s appeal against a Delaware district court’s refusalto compel Hospira to provide certain cell-culture manufacturinginformation for its biosimilar rival to Epogen (epoetin alfa).

Pfizer’s Hospira had moved to dismiss the appeal on the groundsthat the district court had not yet issued a final judgement. But theUS Court of Appeals said the parties should file briefs addressingboth the merits of the case and jurisdiction issues. G

BIOLOGICAL DRUGS

AbbVie sues Amgenover US adalimumab

WOCKHARDT has expanded its range of oral liquids in the UKby launching morphine sulfate 10mg/5ml solution. Trade listprices for 100ml, 300ml and 500ml bottles are £1.82 (US$2.37),£5.45 and £9.08 respectively.

TEVA AND APOTEX have introduced imantinib mesylate 100mgand 400mg tablets in the US after Sun Pharma’s 180-day exclusivityperiod ended in early August. Sun – which had entered the marketwith its generic of Novartis’ Gleevec (imatinib) oncology brandat the start of February – responded by extending its savings cardprogramme for patients. Apotex is offering a similar savings card.

BIOGEN has got clearance to introduce its Flixabi (infliximab)biosimilar in Germany at a list price of C856.80 (US$966.07) fora 100mg vial of powder for concentrate. The European Commissionapproved Flixabi in May this year.

APOTEX has failed in its appeal against a ruling by the US Patentand Trademark Office (USPTO) in an inter partes review that 23claims of Pfizer’s US tigecycline formulation patent 7,879,828 werenot unpatentable as obvious. The US Court of Appeals deniedApotex’ argument that the USPTO had “imported an epimeric stabilitylimitation into the claims” and said the office had also correctlyconsidered several motivations to combine prior art.

MOMENTA expects this year to receive tentative approval fromthe US Food and Drug Administration (FDA) for its generic versionof Teva’s Copaxone (glatiramer acetate) 40mg injectable multiplesclerosis therapy. A Delaware district court trial on four of the fiveCopaxone 40mg patents listed in the FDA’s Orange Book isscheduled to take place between 26 September and 7 October, whileTeva expects a ruling at around the same time as the first 30-monthstay on FDA approval for generic glatiramer 40mg expires inFebruary 2017. Meanwhile, a decision in an inter partes review ofthree patents brought by Amneal and Mylan is anticipated imminently.Teva stressed that any generic launch before a non-appealable courtruling on all five listed parents – which was unlikely to occur beforethe second half of 2018 – would be at-risk.

VALEANT has relaunched ofloxacin 0.3% otic solution in the US.The Canadian firm temporarily discontinued the antibiotic in April2015 due to an issue with the active pharmaceutical ingredient(API) supplier, which it has now resolved.

NHS ENGLAND increased its spending on primary-care diabetesprescriptions by 10.1% to £957 million (US$1.25 billion) in the12 months ended 31 March 2016. That total – equivalent to 10.6%of all prescription spending – comprised £423 million on anti-diabetes drugs, £344 million on insulins, £187 million on diagnosticand monitoring devices, and £3.7 million on other drugs, accordingto an NHS Digital analysis.

HIKMA has added to its US injectables portfolio with levoleucovorin50mg/ml vials, a generic of Spectrum’s Fusilev folate analogue forwhich the Jordanian firm has secured 180-day generic marketexclusivity. Hikma has also added the antifungal agent Cresemba(isavuconazole) to its licensing and distribution agreement withBasilea for Middle East and North Africa (MENA) markets.

AMNEAL AND PAR have won an inter partes review ruling fromthe US Patent and Trademark Office (USPTO) that the claims ofsix patents related to the distribution system for Jazz’ Xyrem(sodium oxybate) are unpatentable and cannot be enforced. G

IN BRIEF

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:34

Amphastar Pharmaceuticals has acquired 33 marketing authorisationsfor generic injectables, spread across 11 molecules, in the UK,

Ireland, Australia and New Zealand. The US firm gained the producttrademarks and other related product assets by paying UCB US$7.7million in cash for the Belgian group’s International MedicationSystems (IMS) UK operation.

Injectables and inhalation specialist Amphastar said the acquireddrugs contained 11 off-patent chemical entities: adrenaline; amiodarone;atropine; calcium chloride; furosemide; glucose; lidocaine; magnesiumsulphate; morphine; naloxone; and sodium bicarbonate.

Subject to approval by the UK’s Medicines and Healthcareproducts Regulatory Agency (MHRA) following a plant inspection, theUS firm intends to transfer production to its US facility in South ElMonte, California, where it already produces the IMS portfolio forthe US market. “We anticipate that such regulatory approval and launchwill take approximately 12 to 18 months, and expect peak sales ofUS$4-5 million from these products in two to three years,” statedAmphastar’s president, Jason Shandell.

Acquisition allows international expansion“This acquisition allows us to further expand into the international

market and provides for great synergies, given that we already makethese products for the US market,” Shandell added.

Amphastar overcame an 11% fall to US$17.3 million in enoxaparinsales on lower prices to report a 26% turnover rise to US$68.0 millionin the second quarter of this year. The firm credited higher sales ofepinephrine, lidocaine, naloxone and phytonadione.

The US firm warned that its sales could be hit during the secondhalf of this year – during which it plans to file three abbreviated newdrug applications (ANDAs) – by having terminated a retail-marketdistribution deal for enoxaparin with Actavis. “This presents us withseveral possible opportunities, including entering into a new partnershipagreement or directly distributing our enoxaparin to the retail market,”Shandell maintained. G

PRODUCT NEWS


Pfizer has terminated its collaboration agreement with Pfenex forthe development of the latter firm’s PF582 biosimilar version of

Roche’s Lucentis (ranibizumab) following a “strategic review of thecurrent therapeutic focus of its biosimilar pipeline”.

Bertrand Liang, the US-based biosimilars developer’s chiefexecutive officer, said Pfenex would “consider strategic options forPF582 following the expeditious transition of the full developmentprogramme” back to the firm.

Pfizer had obtained the development agreement through itstakeover of Hospira in September last year. Seven months earlier,Hospira had struck a deal worth up to US$342 million to jointly developthe ophthalmic biosimilar, and market it worldwide (Generics bulletin,27 February 2015, page 23).

Pfenex had disclosed several months ago that it expected Pfizerduring 2016 to begin a “pivotal” clinical comparator trial for PF582(Generics bulletin, 20 May 2016, page 13).

Following termination of the agreement, the US originator addedthat it intended to “focus on other assets”.

The US brand company recently committed to further investmentin biosimilars after announcing plans to build a global biotechnologycentre in China’s Hangzhou economic development area, Pfizer’s firstin Asia, at a cost of approximately US$350 million (Generics bulletin,1 July 2016, page 3).

Pfizer’s pipeline of biosimilars currently undergoing Phase IIIclinical trials or in registration includes versions of adalimumab,bevacizumab, epoetin alfa, infliximab, rituximab and trastuzumab.

Addressing investors as Pfizer presented its financial second quarterresults (see page 5) John Young, president of Global EstablishedPharma, said Pfizer’s PF-06438179 internal biosimilar infliximabcandidate – for which Sandoz earlier this year acquired marketing rightsin the European Economic Area (EEA) – was “progressing on track”.“We expect to have the readout from our pivotal Phase III trials fromthat programme towards the end of this year,” he said.

Moreover, through Hospira, Pfizer holds exclusive US marketingrights for Celltrion’s Inflectra (infliximab-dyyb) biosimilar that wasapproved by the US Food and Drug Administration (FDA) in April.

Concurrently, Pfenex announced positive results of a three-monthPhase I/II clinical trial for PF582, comparing the safety and tolerabilityof the biosimilar against Lucentis in patients with neovascular age-related macular degeneration. Results of the study included “nomeaningful differences” with respect to intra-ocular pressure andbest corrected visual acuity.

Alongside Pfenex, Formycon and its partner are also developingbiosimilar ranibizumab. Earlier this year, Bioeq began patient enrollmentin the firms’ Phase III clinical trial concerning their FYB201 biosimilarLucentis candidate (Generics bulletin, 4 March 2016, page 13). G

BIOLOGICAL DRUGS

Pfizer pulls plug onPfenex’ ranibizumab

INJECTABLE DRUGS

Amphastar adds 33injectables from UCB

Sandoz says it can make its Reletrans (buprenorphine) analgesicpatches available for use through the UK’s National Health Service

(NHS) after a Court of Appeal ruling upheld an earlier finding that itdid not infringe patents protecting Napp’s BuTrans reference brand.

Along with Dr Reddy’s, Sandoz had recently won a Patents Courtruling that its formulations did not infringe the UK parts of Napp’sEuropean patents EP2,305,194 and EP1,731,152 (Generics bulletin,8 July 2016, page 11). A further court ruling dismissed Napp’sargument that Sandoz should not have been granted a marketingauthorisation for its Reletrans 5µg, 10µg, 15µg and 20µg per hourpatches (Generics bulletin, 5 August 2016, page 11).

“Pending the [appeal] hearing, Sandoz had undertaken not to sellits generic seven-day buprenorphine patch, but the court’s decisionclears the way for the launch,” Novartis’ generics division stated, addingthat the court’s ruling would be published by the end of this month. “Theavailability of alternative products to the NHS from 3 August will seethe price of this medicine decrease through increased competition.” G

ANALGESICS

Sandoz clears path for patch

APOTEX is seeking an inter partes review of all 24 claims of Amgen’sUS patent 8,952,138 that covers methods of refolding proteins. TheCanadian firm argues that all the patent claims are anticipated orobvious in light of prior art. The two firms are currently contestinginfringement of the ‘138 patent in a Florida district court. Celltrion haspetitioned for a similar review of Biogen’s US patent 7,820,161covering intravenous rituximab administered with methotrexate.G

IN BRIEF

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:34

PIPELINE WATCH


Two agalsidase-based recombinant enzyme brands indicated fortreating Fabry’s disease – Shire’s Replagal (agalsidase alfa) and

Sanofi’s Fabrazyme (agalsidase beta) – face the expiry of theirsupplementary protection certificates (SPCs) in major Europeanmarkets during August.

According to IMS Health’s Ark Patent Intelligence service,SPCs for both brands run out during August in Denmark, France,Greece, Italy, Luxembourg, Spain and the UK. Replagal also losesprotection in Austria, the Netherlands, Portugal and Sweden, whileFabrazyme faces SPC expiries in Belgium, Germany and Ireland.

While Sanofi’s Genzyme eventually secured its GB13/069 SPCin the UK with an expiry date of 6 August 2016, the process provedsomewhat contentious. On 25 November 2013 – just four days beforethe 29 November expiry of the basic patent on which the applicationrelied, European patent EP2,210,947 – the patent holder, the IcahnSchool of Medicine at Mount Sinai, applied for an SPC to the UK’sIntellectual Property Office (IPO).

Extensive correspondence between the IPO and the applicant’sagent ensued throughout 2014, with the main bone of contentionbeing whether the application met the requirements of Article 3(a)of the European SPC Regulation 469/2009. Article 3(a) requiresthat for a product to qualify for an SPC, it must be “protected by abasic patent in force”.

IPO hearing officer Lawrence Cullen decided that the applicationmet the strictures of Article 3(a) because agalsidase beta wasidentified in the sole claim of the ‘947 patent “as the product derivingfrom the process described”. Furthermore, he found, agalsidase betawas a different product for the purposes of the SPC Regulation toagalsidase alfa, for which Shire had already secured an SPC. Thus,the application did not fall foul of the Regulation’s Article 3(c), whichstates that for a product to obtain an SPC, it must not already havebeen the subject of a certificate.

Six-month paediatric extensions to SPC expire during August forPfizer’s Vfend (voriconazole) in the Czech Republic, Finland andSlovenia (see Figure 1). Similar extensions for the antifungal agentended in much of Europe last month (Generics bulletin, 22 July

2016, page 6). As a result, for example, more than a dozen genericsplayers in Germany recently secured clearance to offer voriconazolein both coated tablet and powder for infusion formats.

Turning to data exclusivity, Ark Patent Intelligence observesthat August brings the end of 10 years of exclusivity in Switzerlandfor Bristol-Myers Squibb’s Baraclude (entecavir) antiviral agent.

But while the entecavir molecule patent is set to expire inSwitzerland this October, the originator has secured six-monthpaediatric extensions to SPCs based on European patent EP0,481,754,extending its entecavir monopoly in many markets until April 2017.

August also brings the expiry of eight years of data exclusivityin the European Union (EU) for Daiichi-Sankyo’s Sevikar (amlodipine/olmesartan) fixed-dose combination (see Figure 2). This will befollowed by a two-year period during which generics companiescan use the proprietary data to apply for marketing authorisations,but not market their products.

Noting that, in several major EU member states, SPCs forolmesartan medoxomil are set to expire in February next year, Arkobserves that several generics producers have already secured marketingauthorisations for the antihypertensive drug, including in combinationwith hydrochlorothiazide. G

This monthly update of key patent, SPC and data exclusivity data is extracted from Ark Patent Intelligence Expiry Database. Coveringover 50 countries and 2,200 INNs, Ark Expiry Database contains watertight data teamed with the ultimatein generic launch analysis.

For further information, visit www.arkpatentintelligence.comor e-mail: [email protected].

INN Country

Agalsidase alfa Austria, Denmark, France, Greece, Italy, Luxembourg,Netherlands, Portugal, Spain, Sweden, UK

Agalsidase beta Belgium, Denmark, France, Germany, Greece,Ireland, Italy, Luxembourg, Spain, UK

Ciclesonide France, Greece, Italy, Netherlands

Nitric oxide Austria, Belgium, Denmark, France, Germany,Greece, Luxembourg, Spain

Voriconazole Czech Republic*, Finland*, Slovenia*

* expiry of paediatric extension to SPC

Figure 1: Molecules for which supplementary protection certificates (SPCs)expire in certain markets in August 2016 (Source – Ark Patent Intelligence)

SPC expiries in August

INN Country/Region

Amlodipine/Olmesartan European Union**Amlodipine/Telmisartan KoreaAzacitidine KoreaCrizotinib USDasatinib KoreaDeferasirox European UnionDenosumab Canada*Entecavir SwitzerlandIcatibant USIndacaterol KoreaLacosamide KoreaPalonosetron SwitzerlandPazopanib KoreaPeramivir KoreaRanibizumab SwitzerlandSitaxentan European UnionTelbivudine SwitzerlandToltrazuril Canada*Velaglucerase alfa TurkeyVemurafenib US

* This will be followed by a no-marketing period of two years during which a notice ofcompliance will not be granted to a generic manufacturer.

** This will be followed by two years of market exclusivity, where a generic will not beplaced on the market.

Data exclusivity expiries in August

Figure 2: Molecules for which data exclusivity expires in certain markets inAugust 2016 (Source – Ark Patent Intelligence)

SPC expiries hit two agalsidase brands

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:34

Recognising the best in the global generics and biosimilars industries

Presented by Generics bulletin in association with IMS Health

Sponsored by:

Cocktail Reception &Cocktail Reception &Cocktail Reception &Cocktail Reception &Awards PresentationAwards PresentationAwards Presentation

Tuesday 4 October 2016Tuesday 4 October 2016Tuesday 4 October 2016Hotel Porta Fira,The Gran Via complex, Barcelona, Spain

Presented by:

In association with:

Sponsor and join us at the eventFind out more about sponsoring and joining us on the night:

Visit: www.generics-bulletin.com Email: [email protected] Call: +44 1564 777550

®

JAMES DUDLEYMANAGEMENT

®

GGB 2016 Full Pg 28-7-16 V3_Layout 1 28/07/2016 10:49 Page 1

Valeant’s general manager for its US neurology, generics andObagi dermatology businesses, Barbara Purcell, has been

added to the Canadian firm’s executive committee as part of abroader series of leadership and organisational changes engineeredtowards creating “the new Valeant”.

Purcell, who will now report directly to chief executive officerJoe Papa, has been with Valeant since August 2013, when the Canadiangroup acquired her employer Bausch & Lomb. Her appointment to hercurrent position came after Brian Stolz earlier this year stepped downfrom the Canadian company “to pursue other opportunities” (Genericsbulletin, 3 June 2016, page 20). Valeant executives Dennis Asharin,Joe Gordon, Tage Ramakrishna and Kelly Webber have also beenadded to Valeant’s realigned executive committee.

Leadership changes announced by Valeant include the appointmentsof investor and analyst Scott Hirsh as senior vice-president for businessstrategy and communications, and Christina Ackermann as generalcounsel. Ackermann replaces general counsel and chief legal officerRobert Chai-Onn, who will be leaving Valeant after a transition period.

Also departing the Canadian firm is president and general managerof the firm’s Europe operation, Pavel Mirovsky, who will “retirelater this year”, as well as investor relations head Laurie Little,who will be “leaving the company in the coming months”.

Moreover, Valeant has expanded the roles of joint group chairmenAri Kellen and Anne Whitaker, and also elevated to the role ofcompany group chairman, its former president of the firm’s Asia-Pacificregion, Tom Appio, who will now have responsibility for “all ofValeant’s markets outside of the US and Canada”. G

PEOPLE


RESHUFFLES

Valeant reshuffles asit looks to the future

Stada’s Hartmut Retzlaff has resigned from his position as chairmanof the management board at the German company “due to personal

circumstances”. Retzlaff had recently taken leave from his role aschief executive officer (CEO) at the firm “due to a serious, long-termillness” (Generics bulletin, 10 June 2016, page 1). Executive boardmember, Matthias Wiedenfels, took over the CEO role “until furthernotice”, also taking responsibility for corporate strategy and production.

Joining Stada in 1986 as sales and marketing director for itsStadapharm division, Retzlaff became head of Stadapharm in 1991. Hestepped up to lead the German group two years later, and in Septemberlast year, Stada extended Retzlaff’s employment contract by five yearsuntil August 2021 (Generics bulletin, 2 October 2015, page 35).

Retzlaff will be released from his board duties and will receiveboth a severance payment and his salary until the end of this year. G

RESIGNATIONS

Retzlaff resigns fromStada chairman role

Recordati’s chairman and chief executive officer, GiovanniRecordati, has died “following a long illness”.He served as the Italian company’s chief executive since 1990

and held the chairman position since 1999.Under his management, the family-owned firm “grew vigorously”

into a “well-known, international pharmaceutical player withsubsidiaries in Europe, North America, South America and NorthAfrica, as well as developing a presence in the rare disease segment”.

Alberto Recordati has been appointed chairman of the boardof directors, and the firm’s chief operating officer, AndreaRecordati, has been named vice-chairman and chief executive. Theformer joined the company in 1984 as a researcher in the biochemistrylaboratories, and the latter started with Recordati in 1998 as projectleader for a sales and marketing investments project.

The change in leadership comes after the company made tworecent acquisitions – closing a deal with Swiss company Pro Farmafor SFr16 million (US$16.6 million) and Italy’s Italchimici, whichwas valued at around C130 million (US$146 million). G

OBITUARY

Obituary: Giovanni Recordati

Akorn has named Walgreens Boots Alliance (WBA) executive RobertMonahan as its senior vice-president of corporate development.Monahan was most recently the US-based retailer and wholesaler’s

vice-president of mergers & acquisitions, and was “involved in morethan 40 transactions totalling more than US$50 billion” during hisseven-year spell with Walgreens. G

APPOINTMENTS

WBA’s Monahan joins Akorn

Gen 26-8-16 Pgs. 2-24_Layout 1 23/08/2016 16:34

COMPANY NEWS US ruling opens door to October infliximabe ntry … · 2016. 8. 6. · COMPANY NEWS 2...

Documents

Transcript of COMPANY NEWS US ruling opens door to October infliximabe ntry … · 2016. 8. 6. · COMPANY NEWS 2...