19 October 2018

FDA committee backs aUS rituximab biosimilarThe first rituximab biosimilar has moved closer to entering the US market, after a US

Food and Drug Administration (FDA) committee voted unanimously to recommendapproval for Celltrion and Teva’s CT-P10 biosimilar candidate.

The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 16-0 to recommendapproval for the biosimilar ofBiogen andGenentech’sRituxan (rituximab) in three non-Hodgkin’slymphoma (NHL) indications. The agency will now take the Committee’s recommendation intoconsideration before acting on Celltrion’s biologics license application (BLA), Teva noted.

Ahead of the ODAC meeting, Celltrion revealed it was not seeking approval for a fourthNHL indication and three other indications, including rheumatoid arthritis and granulomatosis,“due to the current intellectual property and exclusive landscape” (Generics bulletin, 21September 2018, page 1). In January this year, Genentech and Biogen sued Celltrion and Tevain a New Jersey district court for alleged infringement of 40 Rituxan patents.

Teva – which signed an agreement with Celltrion in 2016 for CT-P10 commercialisationrights in the US and Canada – said the committee had based its recommendation on a review of acomprehensive data package “inclusive of foundational analytical biosimilarity data, non-clinicaldata, clinical pharmacology, immunogenicity and clinical efficacy and safety data”.

“The results of the clinical development program for CT-P10 demonstrated that therewere no clinically meaningful differences between CT-P10 and Rituxan in terms of thesafety, purity and potency of the product for the three proposed indications.” Small analyticaldifferences between the products were not clinically meaningful, the ODAC found.

In April this year, Celltrion received a complete response letter (CRL) from the FDA,rejecting CT-P10 on the basis of a warning letter previously issued against Celltrion’smanufacturing facility in Incheon, Korea (Generics bulletin, 13 April 2018, page 1). Thefollowing month, Sandoz also got a CRL for its rituximab biosimilar candidate.

The world’s first monoclonal antibody biosimilar approved by the European Commissionfor the treatment of cancer, CT-P10 was first launched in Europe last year, under namesincluding Truxima. It is currently approved in 47 countries across the globe. G

Accord named company of the yearAccord Healthcare and its Intas parent company have taken home a total of three prizes at

the Global Generics & Biosimilars Awards 2018 that were held on 9 October in Madrid,Spain, byGenerics bulletin and co-hosted by Iqvia. Accord Healthcare won the overall Awardfor Company of the Year as well as the Biosimilar Initiative of the Year Award – for its Pelgraz(pegfilgrastim) biosimilar – while Intas and Accord together won the Award for Company ofthe Year in the Asia-Pacific region.

Amneal took home the prize for Company of the Year in the Americas region, andStada for the equivalent Award in Europe, the Middle East and Africa (EMEA). Meanwhile,Aurobindo won the Award for Acquisition of the Year – for its deal to buy Apotex’ businessin five European countries – and Alvogen’s Robert Wessman was named Leader of the Year.

Chemo garnered theAward for Innovation of theYear,mAbxience for BusinessDevelopmentof the Year, Laurus Labs forActive Pharmaceutical Ingredient (API) Supplier of the Year, Mylanfor Regulatory Achievement of the Year and Piramal the prize for Industry Partner. Dr Reddy’swalked away with the Corporate Social Responsibility (CSR) Initiative of the Year Award. Nextyear, the Awards are due to take place on 5 November in Frankfurt, Germany. G

For details and photos of the winners, please see page 20 and the enclosed supplement.

COMPANY NEWS 3Ipca takes control of US player Bayshore 3

Mundipharma buys Infarco’s Cinfa unit 3

Johnson Matthey ramps up pipeline spending 4

Advanz aims to grow after Concordia switch 5

Lannett brings in help amid goodwill charge 5

Reddy’s antibiotic site bought by Neopharma 6

Cambrex invests in Italian APIs facility 6

Sun sets cost-control measure for generics 7

Nupharm rebrands itself to Neuraxpharm 8

Biocad targets 80% increase in exports 9

Ireland’s Chanelle is aiming at US liquids 9

MARKET NEWS 10UK powers on pricing may not go far enough 10

Firms fear Council could neuter waiver 10

Torrent tops awards as AOK cites savings 11

FDA aims to dissuade citizen petition abuse 11

Carve-outs should act to limit authorisation 14

Record ANDAs don’t solve all problems 14

France is aiming for a C500 mn savings total 15

FDA assists industry with topical guidance 15

EMA continuity plan enters its third phase 16

US president passes bio pay-for-delay bill 16

PRODUCT NEWS 17Merck shelves insulin but wins on Renflexis 17

US Copaxone patents confirmed as invalid 17

Pfizer ships its rival to Neupogen in US 18

Germany overturns Teva Inegy injunction 19

Sandoz eyes Europe entry for adalimumab 19

REGULARSEvents – Conferences and meetings 8

Price Watch UK – Our regular listing 19

People – Patel to lead Hikma’s 24Injectables in Europe

Issue No.372

See page 20 for coverageof the event and winners

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Gen 19-10-18 Pgs.1-24.indd 2 17/10/2018 16:17

3bulletin19 October 2018

COMPANY NEWS

MERGERS & ACQUISITIONS

Ipca takes control ofUS player BayshoreIpca Laboratories has paid just under US$10.3 million in cashfor 80% of the share capital in US generics player BayshorePharmaceuticals. The Indian company said that acquiring themajority stake in sales and marketing firm Bayshore through itswholly-owned US subsidiary Ipca Pharmaceuticals would “enablethe firm to commercialise its registered generic drug products in theUS market through this entity”.

A limited liability company, Bayshore last year more thandoubled its turnover to US$7.05 million from just over US$3.0 millionin 2016. The New Jersey-based firm moved into profitability in 2017with earnings before interest, tax, depreciation, tax and amortisation(EBITDA) of US$0.56 million compared to a similarly-sized lossrecorded by the company in 2016.

Founded in 2011 by its president, former Matrix and Mylanexecutive Mark Moshier, as a sales and marketing entity for genericsapproved by the US Food and DrugAdministration (FDA), Bayshorecurrently offers both abbreviated new drug applications (ANDAs)for which it has obtained approval itself as well as generics registeredby third-party partners.

In particular, Bayshore acts as the US sales and marketing partnerof Beximco Pharmaceuticals, having introduced the Bangladeshicompany’s first US product, carvedilol tablets, under the Bayshorelabel towards the end of 2016 (Generics bulletin, 18 November2016, page 15). Since then, Bayshore has also launched Beximco’smethocarbamol and sotalol tablets, as well as the Bangladeshi firm’smetformin extended-release tablets, winning accounts to supply majorUS retail chains.

Bayshore’s marketed product portfolio also includes benztropinemesylate, methscopolamine bromide and primaquine phosphate,all in tablet form. The US company positions itself as a “partnerof choice” that is able to manage sales and marketing, distributionand supply-chain projects “from concept to commercialisation”.Working closely with Florida’s Pinellas Pharmaceuticals, Bayshoreclaims to provide, on a fee-for-service basis, “the full range ofsales, marketing, promotion and distribution services” for its globalmanufacturing partners, as well as for internally developed andproduced products. Gn aidan.fry@generics-bulletin.com

MERGERS & ACQUISITIONS

Mundipharma buysInfarco’s Cinfa unitMundipharma has deepened its biosimilars platform “beyond

commercial excellence to development” by acquiring Europeandeveloper and manufacturer Cinfa Biotech, gaining immediate accessto the Spanish player’s Pelmeg (pegfilgrastim) biosimilar that wasbacked for a European marketing authorisation last month.

“Our biosimilars platform is a key component of our growthstrategy and the acquisition is the obvious next step in us ensuring weremain agile and innovative,” said Alberto Martinez, president andchief executive officer of Mundipharma International.

Headquartered in Pamplona, Spain, and with another office inMunich, Germany, Cinfa was founded five years ago as the biosimilarsarm of Spain’s Infarco group. Disclosing that the acquisition hadclosed immediately, a Mundipharma spokesperson told Genericsbulletin that the purchase price was being kept under wraps.

“By acquiring Cinfa Biotech we have now taken the first stepin our plans to, not only expand our biosimilars footprint,” Martinezsaid, “but to develop future biosimilars which will continue to affordhealthcare systems further savings and, in some cases, wider access.”

Cinfa’s B12019 or Pelmeg pegfilgrastim biosimilar, its leadproduct candidate, received a positive recommendation from theEuropeanMedicinesAgency’s (EMA’s)committee forhumanmedicinalproducts (CHMP) towards the end of September (Generics bulletin,28 September 2018, page 15). Cinfa also has another undisclosedbiosimilar candidate in development, according to Mundipharma.

Away fromEurope, Cinfa announced last year that it was preparingto start discussions with potential partners to help it market B12019 inthe US, as the company prepares a filing for the US Food and DrugAdministration (Generics bulletin, 22 December 2017, page 2).

Infarco successfully built Cinfa up, including through plansannounced in late 2014 to invest €70 million (US$81.2 million)into its Biotech business to help establish a portfolio of biosimilars,buying a majority stake in biotech developer 3P Pharmaceuticals andtaking full control of hormones specialist Cyndea Pharma (Genericsbulletin, 5 December 2014, page 25). However, Cinfa itself “has nomanufacturing capabilities”, Mundipharma noted.

Mundipharma currently does no biosimilar manufacturing itself,obtaining a biosimilars portfolio through distribution agreements withCelltrion for the firm’s Remsima (infliximab), Truxima (rituximab)and Herzuma (trastuzumab) biosimilars, including through its NappPharmaceuticals affiliate.

“Through our partnership with Celltrion on Remsima andTruxima,” he noted, “we estimate savings for healthcare systems ofapproximately €330 million from launch to the end of 2017.” Herzumaonly began rolling out in Europeanmarkets inMay this year, beginningwith Germany and the UK (Generics bulletin, 11 May 2018, page 14).

Days before the acquisition was announced, Mundipharmaappointed industry veteran Philippe Bastide – founder of Amgen’sbiosimilars organisation in Europe –as the new head of the company’sbiosimilars operation, reporting to Chris Surridge, European directorof strategy and commercial excellence.

“He will work in partnership with Cinfa’s senior managementteam to ensure a successful Pelmeg launch,” the Mundipharmaspokesperson toldGenerics bulletin. The role of biosimilars head waspreviously held by Richard Trollope.

“There are no planned changes to the management team andstructure,” the spokesperson revealed, in light of the acquisition. Gn dean.rudge@generics-bulletin.com

Figure 1: Bayshore Pharmaceuticals’ turnover and earnings before interest, tax,depreciation and amortisation (EBITDA) in the calendar years 2015, 2016 and2017 (Source – Ipca)

-1

0

1

2

3

4

5

8

EBITDATurnover

7

6

2015 2016 2017

2.523.01

7.05

-0.44 -0.57

+0.56

Value

(US$millions

)

Gen 19-10-18 Pgs.1-24.indd 3 17/10/2018 16:17

4 bulletin 19 October 2018

COMPANY NEWS

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ISSN 1742-0784

BUSINESS STRATEGY

Johnson Matthey ramps up pipeline spendingRampingup investment in its pipelineofgeneric activepharmaceutical

ingredients (APIs) will “drive incremental operating profit of £100million (US$130 million) per annum by 2025” for Johnson Matthey’sHealth bulk-drugs business sector. Insisting that the division has “alot of growth opportunities”, the segment’s chief executive, JasonApter – who joined the firm in March (Generics bulletin, 23 March2018, page 16) – has outlined three “key focus areas to deliverbreakout growth” as it competes in a US$440 billion global market foroutsourced small-molecule APIs (see Figure 1).

The company’s first focus area is to “enhance the performanceof our existing business”, through sales opportunities and operationalefficiency. “We are finding that certain molecules in our existingportfolio are being expanded into new applications such as additionaltherapies,” former MilliporeSigma executive Apter explained. “Sowe are developing and supporting new generics filings for existingmolecules, modified to meet these new requirements.”As an example,he cited the firm’s “high-purity, synthetic cannabidiol” for use in painmanagement and multiple sclerosis.

“We will also support sales growth through optimisation of ourmanufacturing footprint,” Apter divulged, noting that the firm hadexpanded its bulk-drugs site in Annan, UK, that the group acquiredin November 2014. “We have accelerated our industrialisation ofthis facility and over the past few months we have shipped ourfirst commercial batches,” he said, stating that this would give thecompany “more flexibility and efficient manufacturing and sufficientcapacity for growth”. Acknowledging that the firm had suffered from“limitations on capacity in certain specialist opiate products” such asbuprenorphine for addiction therapies, he said bringing Annan fullyonline would help create “a healthy balance” on facility utilisation.

“There are a lot of opportunities as we globalise further to increaseour operational effectiveness and achieve more throughput in ourexisting assets, gain higher productivity and reduce our cost base,”Apter said, noting that this included “strategic sourcing”, such asswitching raw materials for its core codeine product in Annan. “Wehave taken a close look at our processes to identify actions we can taketo improve our manufacturing efficiency,” he added.

Johnson Matthey’s second focus area centres on expanding itspipeline of both generic and innovative drugs. GenericAPIs currentlymake up around 70% of the firm’s Health sales, with just over four-fifths of bulk generics sales coming from controlled substancesthat have “extremely high barriers to entry”. “In the US,” Aptercommented, “we are not positioned in bulk opiates, which is wherethe primary concern has been.”

From over 3,000 off-patent compounds, Johnson Matthey hasselected “an initial 40-50 API products” in diverse therapeuticindications for which it is confident of adding value throughdevelopment and plans to work with partners to bring them to market.“We expect 20-25 of these to launch over the next three to four years,”he continued, adding that “we are not modelling any exclusivity dealsin that pipeline”. “We are very focused on where there is complexity,and where it is tough, which naturally means there will be fewerplayers in that space.”

Aptar said theHealth unit’s core competencies in complex chemistrysuch as particle technology also opened up significant opportunities inoriginator drugs, which currently accounted for 30% of the unit’s salesand offered long-term returns compared to faster generics profits.

Johnson Matthey’s third focus is to “build our capabilities tobetter support our customers for future growth”, including globalisingits development capabilities and building out its particle-technologyexpertise. “We are also working to improve our understanding offormulations, and the technical challenges with excipients,” Apterrevealed. “Most of this work will be through organic investments, butonce we have improved our base business and are well on the wayto delivering our pipeline of new products, we can consider selectivevalue-created mergers and acquisitions to enhance our capabilitiesand add new technologies.” Gn grace.montgomery@generics-bulletin.com

Issue 372l 19 October 2018

Outsourced small-moleculegeneric APIsUS$29 bn

+9% per annum

Outsourced small-moleculeinnovator APIs

US$11 bn+6% per annum

Outsourcedlarge-molecule APIs

US$20 bn

In-house APIsUS$110 bn

Figure 1: Breakdown by product type of the US$170 billion global API market in2017 (Source – Johnson Matthey)

Gen 19-10-18 Pgs.1-24.indd 4 17/10/2018 16:17

5bulletin19 October 2018

COMPANY NEWS

BUSINESS STRATEGY

Advanz aims to growafter Concordia switchConcordia International is looking to invest in licensing and

co-developmentdeals, aswell as inproduct andcompanyacquisitions,as it seeks to revive its fortunes under the new Advanz Pharma brandfollowing the completion of a recapitalisation transaction that tookplace in early September.

Chief executive officer Graeme Duncan acknowledged thatConcordia had “been through a tough time for the past two and a halfyears” due to a combination of industry-wide issues such as shifts inregulatory and pricing environments, as well as challenges specific tothe company, “not least of which was our debt burden”.

Speaking on 8 October at an event held in the Casino de Madrid,Spain, Duncan pointed out that a recapitalisation completed exactly amonth earlier hadwipedUS$2.4 billion off the firm’s balance sheet andreduced its annual interest costs by around US$200 million (Genericsbulletin, 4 September 2018, page 4). “The cash that is residing on ourbalance sheet, and that the business generates, has been safeguardedand earmarked for investment,” he told invited guests.

“As of 8 September,” Duncan continued, “the organisation istruly back in business and focused on growth. We are going to belooking to invest in licensing, in co-development, in acquisitions ofboth products and companies and in terms of commercial expansion.”

Going ‘beyond fulfilment’Duncan – who assumed the role of chief executive officer earlier

this year, stepping up from president of the group’s Internationalsegment to take over from Allan Oberman, initially on an interimbasis (Generics bulletin, 6 July 2018, page 20) – insisted that thecompany had an “unparalleled platform” that would serve as a basisfor its reconfigured leadership team to implement a revised strategyand vision under the Advanz Pharma banner. With the companyhaving worked with external branding experts to define its corevalues and promise via a ‘brand audit’, Duncan said the company’sethos revolved around “beyond fulfilment” and being “the preferredpartner” for its customers.

“Leveraging a new corporate identity, leadership team and capitalstructure, we are aiming to go beyond the fulfilment of orders of ourmedicines to become a trusted and respected partner to our customers,healthcare providers and patients,” Duncan explained, adding that thefirm offered “many niche, hard-to-make products” within its portfolioof more than 200 patented and off-patent drugs that were marketed inover 90 countries. “We aim to be the most idea-generative company inthe generics industry and look forward to working towards this goalwith all industry partners, and we thinkAdvanz Pharma represents this.”

Subject to approval from stock exchanges and shareholders,Concordia – which itself incorporated acquired companies includingGoldshield and Amdipharm – intends to officially rebrand to Advanzbefore the end of 2018. The shift requires approval from at least two-thirds of voting shareholders at a meeting to be held on 29 November.

Separately, the firm has announced that it has appointed FrancesCloud, expert industry consultant and founder of PharmacloudResearch, to join its board from 1 November.

“We are delighted to welcome Frances and believe that she willprovide crucial experience to our board and company,” said Duncan,citing her “more than 20 years of experience in the pharmaceuticalsector”. “Her expertise as a thought leader in the complex and dynamicEuropean pharmaceutical industry will be particularly useful.” Gn aidan.fry@generics-bulletin.com

BUSINESS STRATEGY

Lannett brings in helpamid goodwill chargeLannett is stepping up action to address the severe fallout of losing

its lucrative and key distribution contract with Jerome StevensPharmaceuticals (JSP), revealing that it has “engaged and/or expandedthe role of existing advisors to assist in evaluating a range ofalternatives” for the company’s debt and capital structure.

The announcement came days after Lannett disclosed that it wasto write off the entire carrying value of the company’s goodwill, worthapproximately US$339.6 million, in light of long-time partner and“primary finished-goods inventory supplier” JSP revealing earlier thisyear that it would not be renewing the firms’ exclusive distributionagreement when it expires in March 2019.

According to chief executive officer Timothy Crew, Lannett“continues to expect to remain in compliance with its debt covenants”through at least the end of its current financial year ended 30 June2019. “We welcome the specialised expertise our advisors bring tothe table, as we look to add revenues, reduce costs and more closelyanalyse financing options,” Crew said.

Pointing to an analysis the company had undertaken with respectto its goodwill and certain long-lived assets to determine “any potentialimpairment of such assets”, Lannett said that it had “concludedbased on market data that it expects to report an impairment chargeof approximately US$339.6 million relating to the goodwill of thecompany, resulting in a full impairment of goodwill”.

“This non-cash impairment will be reported in the company’sresults of operations for the three months ending 30 September2018,” Lannett noted, “and has no impact on the company’s financialcovenant leverage ratio.” Lannett was “still in the process of finalisingits assessment for impairment of certain long-lived assets”.

When the JSP news broke earlier this year (Generics bulletin,31 August 2018, page 14) Lannett determined that it representeda ‘triggering event’ under accounting principles – resulting in theanalysis – and opined that it would “likely result in a materialimpairment of goodwill and may result in an impairment of certainlong-lived assets”.

Levothyroxine sales, as part of the JSPagreement, wereUS$245.9million in Lannett’s financial year ended 30 June 2018, with grossmargins “of approximately 60%”. Total sales of the JSP portfolio,covering a further two products, were US$253.1 million.

Opting against renewing with Lannett, family-owned JSP hasinstead signed a 10-year licence and supply agreement with Amnealfor levothyroxine sodium tablets, which will come into effect from23 March next year, when the Lannett arrangement expires.

In response, Lannett announced it was “re-assessing its overallbusiness strategies”, with management “continuing to finalise plans tooffset the impact of the loss on a short- and long-term basis” (Genericsbulletin, 7 September 2018, page 8).

Referring to the failure to renew the JSP agreement, Crew saidLannett had “ramped up our efforts to address this eventuality andultimately grow our business”. “We are making solid progress andour plans continue to proceed, as evidenced by the launch of five newproducts in our recently completed fiscal 2019 first quarter.”

In the weeks following the initial announcement, Lannett hasbeen hit with numerous class-action lawsuits amid claims that theUS company “misled shareholders about its risk of losing its majorexclusivity agreement” with JSP (Generics bulletin, 28 September2018, page 4). Gn dean.rudge@generics-bulletin.com

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6 bulletin 19 October 2018

COMPANY NEWSMANUFACTURING

Cambrex invests inItalian APIs facilityCambrex is set to invest approximately US$3 million in its Paullo

plant in Milan, Italy, to “increase the capacity and efficiency” ofthe intermediates and active pharmaceutical ingredients (APIs) site.

The investment will include installing a 12,000-litre reactor atthe 1,350 sq m facility, as well as reconfiguring the layout to “allowfor the replacement of existing centrifuges with new, more efficientequipment”. The bulk-drugs producer said the investment was “part ofa campaign by Cambrex of continuous development across its globalnetwork of manufacturing sites”. In June, the company said it wasexpanding the research and development laboratories at Paullo, afterlate last year increasing the site’s capabilities to handle andmanufacturehighly-potent APIs (Generics bulletin, 20 October 2017, page 3).

“The generics portfolio is an important aspect of Cambrex’business strategy, and we have undertaken a number of improvementsand expansions at the site to ensure we have the ability to meet the futuredemands,” Cambrex Milan managing director Aldo Magnini stated.

Cambrex has revealed plans to establish a centre of excellencefor API clinical supply and process development at its US bulk-drugsand intermediates facility in High Point, North Carolina. The firm willacquire its currently leased facility, as well as an adjacent building thatwill be fitted out with kilo-scale and pilot-scale vessels, continuousreaction production, and chemistry, engineering and analytical-development laboratories. G

MANUFACTURING

Reddy’s antibiotic sitebought by NeopharmaDr Reddy’s has sold its US antibiotic manufacturing facility and

related assets in Bristol, Tennessee, to the United Arab Emirates’Neopharma. Under the terms of the agreement, the Indian firm “soldall the issued and outstanding membership interests” in the businessto Neopharma, “one of the largest pharmaceutical companies in theMiddle East and North Africa (MENA) region, with presence in over50 countries”. No financial details were disclosed.

The plant and associated facilities focus on manufacturing andpackaging amoxicillin-based products, including a semi-syntheticpenicillin. The 36,200 sq m site – which is dedicated to producing andpackaging secondary oral-solid dose penicillin – includes processing,packaging, development, printing andwarehouse spaces.Also includedin the transaction is a separate 2,200 sq m plastics-processing plant.

“This sale is in line with our stated priority to streamline andoptimise our global cost structures and help us focus on other businesspriorities to drive growth,” commented Reddy’s chief operatingofficer, Erez Israeli.

Meanwhile, Neopharma’s Therapia joint venture with Laxai LifeSciences has just agreed to buy from Dr Reddy’s an Indian activepharmaceutical ingredient (API) manufacturing unit in Jeedimetla,Hyderabad. Neopharma said the acquisition would “augmentNeopharma’s vertical integration advantage and provide us with ahigh quality manufacturing base in India”. G

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Gen 19-10-18 Pgs.1-24.indd 6 17/10/2018 16:17

7bulletin19 October 2018

COMPANY NEWS

BUSINESS STRATEGY

Sun sets cost-controlmeasures for genericsCost-control measures in its generics business and focusing on

innovative specialty products are “key priorities” for Sun Pharma,the Indian group’s chairman, Israel Makov, has revealed. Speaking atSun’s annual general meeting, Makov observed that the US genericsmarket “has undergone significant changes in the last two years, and theeconomics of this market has deteriorated in this period”. “Given thisbackdrop, we continue to make efforts towards optimising our costs,”he stated. “The focus will be on optimising our manufacturing footprintas well as generic research and development (R&D) investments.”

“Our R&D investments are targeted mainly at developingcomplex generics and specialty products,” Makov explained. “Wecontinue to be disciplined in identifying future R&D projects for thegenerics market while simultaneously investing in developing a globalspecialty portfolio. We are also investing in enhancing our productpipeline for emerging markets and other non-US developed markets.”

“We will continue our relentless focus on the generics business,and our attempt will be to find ways to grow the generics businessfaster than respective markets,” Makov continued. He pointed outthat the global demand for generics “will continue to grow”, with the“trend to favour generic use increasing the potential of our business”.“The generics market in the developed world is expected to reachUS$104 billion by 2022,” he noted. Including pharmerging markets,he observed, the “overall combined spending on generics and brandedgenerics is likely to cross US$400 billion by 2022”.

“The short-term outlook for the US generics market continues tobe challenging given the pricing pressures,” Makov acknowledged.The Indian business was expected to “normalise in the current year”following the goods and services tax (GST) transition last year.

Having “allocated significant resources in building the specialtybusiness”, Sun has “two main objectives” for the division. Firstly,it aims to “build an additional engine of future growth” (Genericsbulletin, 31 August 2018, page 7), and secondly, it plans to “moveup the pharmaceutical value chain through development andcommercialisation of branded patented products”.

Sun’s specialty portfolio targets dermatology, ophthalmic,oncology and central nervous system segments, and “currentlydoes not generate revenues commensurate to our investments”. Thefirm expects to introduce Ilumya (tildrakizumab-asmn) in the US,European Union (EU) andAustralia in the coming months, and Cequa(cyclosporine) in the US “towards the later part of this fiscal year”.

“We are targeting to increase the share of complex generics andspecialty products to our overall business in the coming years,” Makovconcluded. “This strategy will entail taking multiple initiatives, bothorganic and inorganic, as well as assuming measured risks. G

GLENMARK has “completed the formalities” for transferring itsorthopaedic and pain-management business in India and Nepal toprivate-equity investor True North, in an agreement that will seethe division incorporated into a new entity under the ‘Integrace’name. When the deal was first announced in August, Glenmarkpointed out that 6% of the Indian firm’s domestic sales came fromthe orthopaedic and pain-management division (Generics bulletin,31 August 2018, page 5).

VIVIMED LABS has received an establishment inspection report(EIR) from the US Food and Drug Administration (FDA) for itsactive pharmaceutical ingredient (API) facility in Cuernavaca,Mexico, following a successful “routine inspection” at the site.

RECIPHARM has completed its acquisition of Sanofi’s inhalationcontract-manufacturing business that includes a manufacturingfacility in Holmes Chapel, UK. The prime technologiesmanufactured at the site include metered-dose inhalers and nasalsprays, and it also houses several development suites specificallyfor dry-powder and other inhalation technologies. First announcedin June, the acquisition “forms part of Recipharm’s merger andacquisition growth strategy”. The Swedish contract-developmentand manufacturing firm has also released its first serialised productsto Europe from its facilities in Lisbon, Portugal, and Stockholm,Sweden. Other facilities across Europe “will also be ready to releasefully-serialised products to Europe by the end of the year”.

SANDOZ is inviting entries until 30 November to its secondHealthcare Access Challenge (HACk) competition. “This yearwe are broadening the competition to anyone, anywhere, with anidea that uses digital technology to help address a logical healthcareaccess challenge,” the firm revealed.

INTELLIPHARMACEUTICS has regained compliance withNasdaq’sminimumbidpricerequirement, after thefirm“evidenceda closing bid price of its common shares in excess of the US$1.00minimum requirement for at least 10 consecutive business days”.According to Intellipharmaceutics, the Nasdaq hearings panel “hasgranted its request for continued listing through 17 October 2018while the company works to regain compliance with Nasdaq’sUS$2.5 million stockholders’ equity continued listing requirement”.

TRACELINK – “the world’s largest pharmaceutical track and tracenetwork” – says that it “now serves over 1,000 customers in 43countries”. In the third quarter of 2018, the US-based group notedthat it reached 1,016 customers, representing a 46% increase intotal customers, of which over three-fifths were pharmaceutical andcontract manufacturers. Almost a third was made up of pharmacies,hospitals, clinics and health systems, while the remaining 5%represented wholesale distributors and parallel importers.

SAMSUNG BIOLOGICS says that its ‘Plant 3’ in Incheon, SouthKorea, is now “current goodmanufacturing practice (cGMP) readyand has started production after its successful validation”.As a result,the firm said it has “become the largest biologics manufacturingcontract manufacturing organisation (CMO) in the world”.

MIKART – a US-based contract development and manufacturingorganisation (CDMO) specialising in solid-dose and non-sterileliquid pharmaceuticals – has been acquired by Nautic Partners,a private-equity firm that focuses on healthcare, industrial productsand outsourced services. Michael Kallelis has been appointed asMikart’s chief executive officer. G

IN BRIEF

MANUFACTURING

Italy’s Cosma passes FDA auditItalian active pharmaceutical ingredient (API) manufacturer Cosmahas revealed that the US Food and Drug Administration (FDA)completed an inspection in September at the firm’s local facility inCiserano, Bergamo, with zero ‘Form 483’ observations.

Cosma belongs to the CFMGroup, along withAPI manufacturingunits Amsa and Clarochem Ireland. The Italian firm noted that Amsaalso recently passed an FDA audit with no Form 483 deficiencies. G

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8 bulletin 19 October 2018

BUSINESS STRATEGY

Nupharm rebrandsitself to NeuraxpharmNuPharm has rebranded to become Neuraxpharm, in an “exciting

new chapter” for the company that “positions Neuraxpharm as asingle and differentiated central nervous system (CNS) oriented firmwithin the European pharmaceutical industry”.

The group was created in 2016 by combining five companies– Spain’s Qualigen, Laboratorios Lesvi and Inke; Germany’sNeuraxpharm, which also operates in Poland; and Italy’s FB Health– with investment group Apax Partners. In July, the firm completeda deal to add France’s Biodim for an undisclosed sum (Genericsbulletin, 13 July 2018, page 3).

With “over 100 CNS molecules”, Neuraxpharm offers a “widerange of effective, differentiated and affordable” treatment options to

patients, healthcare professionals and industry partners, developingand selling both generic and branded pharmaceuticals.

“Neuraxpharm has a direct presence in Germany, Spain, Italy,France and Poland,” the company commented, “and plans furthergeographic expansion in the near term as part of its strategy tostrengthen its position as a European leader in CNS treatments.”

Jörg-Thomas Dierks, the company’s recently appointed chiefexecutive officer (Generics bulletin, 7 September 2018, page 16),pointed out that Neuraxpharm “is the existing name of our Germanaffiliate, which has been amajor player in the CNSmarket since 1985”.“Rebranding our European affiliates within the next months under thisname leverages this important history and excellent representation,while uniting all our companies together under a shared name andvision,” he stated. “As one company with one easily identifiable brand,our aim is to become the first partner of choice in CNS.” G

COMPANY NEWS

24-26 Octobern 21st APIC/CEFIC European Conference

Budapest, HungaryThis conference will discuss the latest development in the field ofGMP and regulatory compliance.Contact: Concept Heidelberg. Tel: +49 6221 84 44-0.E-mail: info@concept-heidelberg.de. Website www.api-conference.org.

29-30 Octobern World Biosimilar Congress

Basel, SwitzerlandThere will be networking receptions and lunches, an exhibitionand a conference included in this event.Contact: Terrapinn. Tel: +44 207 092 1257.E-mail: issa.mauthoor@terrapinn.com. Website www.terrapinn.com.

21 Novembern 2nd Value Added Medicines Conference

Brussels, BelgiumOrganised by Medicines for Europe, this one-day event will look atopportunities presented by value added medicines across the industry.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: events@medicinesforeurope.com. Register online atwww.medicinesforeurope.com/events.

26-27 Novembern EuroPLX 68

Athens, GreeceThis two-day meeting provides an opportunity to discuss andnegotiate agreements, development, in-licensing, marketing,promotion and distribution.Contact: RauCon. Tel: +49 6221 426296 0.E-mail: meetyou@europlx.com. Website: www.europlx.com.

30 January 2019n 12th Pharmacovigilance Conference

London, UKThis is a one-day Medicines for Europe conference which will lookat latest trends and the future direction of pharmacovigilance.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: events@medicinesforeurope.com. Register online atwww.medicinesforeurope.com/events.

30 January-1 February 2019n 18th Regulatory & Scientific

Affairs ConferenceLondon, UKThis conference will follow the Pharmcovigilance event at the samevenue and will provide updates on regulatory developments.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: events@medicinesforeurope.com. Register online atwww.medicinesforeurope.com/events.

EVENTS – October – January

SAVE THE DATE.....The Global Generics & Biosimilars Awards 2019

will be held on 5 November 2019 in Frankfurt, Germany

MANUFACTURING

Zydus’ Indian site gets US nodZydus Cadila has received an establishment inspection report (EIR)

from the US Food and DrugAdministration (FDA), closing out anaudit at the firm’s Biologics manufacturing facility in Ahmedabad,India. An agency inspection at Zydus Biologics from 14-24 Augustthis year identified zero ‘Form 483’ observations.

Separately, Zydus Cadila also now expects to conclude itsacquisition of a 51% stake in Windlas Healthcare “on or before 31October”, rather than by the end of September as previously announced(Generics bulletin, 31 August 2018, page 12). In a brief statement tothe Bombay Stock Exchange (BSE), the Indian firm revealed that“certain condition precedents are still under completion”. G

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9bulletin

BUSINESS STRATEGY

Biocad targets 80%increase in exportsBiotechnology and biosimilars specialist Biocad is seeking to increase

its exports by 80% over the next few years as supply agreementsfor its extensive pipeline begin to deliver and additional manufacturingcapacity comes onstream. To this end, the Russian company hasrecently struck licensing deals with companies in Greece, Mexico andthe Middle East and North Africa (MENA) region.

Through an alliancewith Greece’sWinMedica, Biocad anticipatessupplying more than 115,000 packs of adalimumab for the Greek andCypriotmarkets over five years. TheRussian firm anticipates receivingimminently approval for its biosimilar of Humira (adalimumab) inits domestic market, and with clinical trials scheduled to start nextyear, the company says its European adalimumab dossier is “beingprepared for submission for registration in 2021”.

A technology-transfer agreement that Biocad has struckwith Mexico’s Psicofarma covers three monoclonal antibodies –bevacizumab, rituximab and trastuzumab. In addition, the Russianfirm said it had, during the CPhI trade fair earlier this month, reacheda supply agreement with MENA-based company Julphar for anundisclosed product basket in the United Arab Emirates (UAE).

Biocad – which plans to build a biologics plant in Turku, Finland– is forecasting by 2023 turnover in European countries of US$198million, with a further US$516 million to be generated in Asia, LatinAmerica and the MENA region, including Turkey. G

BUSINESS STRATEGY/MANUFACTURING

Ireland’s Chanelle isaiming at US liquidsChanelle Pharma, “Ireland’s largest manufacturer of generic

pharmaceuticals”, is spending €11 million (US$13 million) on adedicated facility to produce liquid formulations for the US market.The plant, which is designed to comply with both US Food and DrugAdministration (FDA) and European quality standards, forms part of anoverall €86 million investment program that the firm has just unveiled.

Founder and managing director Michael Burke said Chanellewas picking up the pace of investment, having already since 2016spent more than €55 million on its global headquarters in Loughrea,Ireland. Over the next five years, he revealed, the company planned toput more than €45 million into research and development.

“Research and development is critical to our success,” Burkeinsisted. “We have doubled turnover in the last five years and expectto double turnover again within the next five years.”

Already holding more than 2,000 marketing authorisations forhuman health products around the world, Chanelle currently sellsproducts in around 100 countries around the world, including in keymarkets such as the European Union (EU), Australia, New Zealand,Japan, South Africa and the Middle East.

“We develop 15 to 20 new products every year, and currentlyhave over 96 products in our research and development pipeline,so we are well positioned to continue to expand into new markets,”Burke commented. G

COMPANY NEWS

19 October 2018

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10 bulletin 19 October 2018

MARKET NEWSPRICING & REIMBURSEMENT

UK powers on pricingmay not go far enoughNew powers allowing the UK Department of Health to ask

suppliers for more information on prices and expected shortagesmay not be enough to effectively tackle generic price rises similarto those seen in 2017, according to a report by the country’s publicaccounts committee (PAC).

“Clear signs” of price increases from June 2017 were not actedupon by the Department until November that year, the House ofCommons committee points out. This was because the Department“did not have the information it needed to take action”, relying on alertsfrom National Health Service (NHS) England which in turn relied oninformation from local clinical commissioning groups (CCGs). “TheDepartment will depend on this same process to take action shouldfuture pricing issues arise,” the PAC notes.

“The Department and NHS England should, by December 2018,establish clear and timely information flows between each other andlocal bodies to identify and inform about generic medicine supplyand/or pricing issues,” the PAC recommends, “and write to thecommittee to explain what they have done to ensure this.” Theseinformation flows “should include how clinicians can obtain greatertransparency on prices”.

While new powers acquired by the Department under 2017legislation and 2018 regulations would allow it to collect informationabout the generic medicines market, the PAC report acknowledges,“the Department has not yet set out how it will use its new powers,should similar price rises happen again”. “We are yet to be convincedthat the Department’s new powers, and accompanying regulations, aresufficient to enable it to act effectively.”

Weaknesses highlighted by the PAC include allowing firms togive “reasonable estimates” of sales data rather than actual figures,thus “limiting the accuracy of information available”. Also, whilecompanies are required to notify the Department if they intend tostop supplying a medicine or if they expect a supply shortage, “thisonly applies if the company itself judges that its actions will affectpatients, and does not give the Department any control over whichmedicines companies notify it about”.

Urging the Department by December 2018 to “write to thecommittee to set out the full range of actions it can take to addressrises in the prices of generic medicines”, the PAC says the Departmentshould by September 2019 ensure the first annual review of the powersassesses of how well the new information requirements are working.

Warwick Smith, director general of the British GenericManufacturers Association (BGMA), said the body welcomed“clarification of the government’s price-setting powers for wherecompetition isn’t working to protect the interests of the NHS”. Notingthat NHS prices were not those charged by manufacturers – includingalso distribution costs from wholesalers and £800 million (US$927million) retained margin for community pharmacy – Smith said thattypically actual selling prices were around half of reimbursementprices, and in many cases less. “Generic competition provides clearvalue for money for the NHS,” he insisted.

Meanwhile, on Brexit, the PAC says the Department of Health“should, by December 2018, share with the committee its plan formaintaining the supply of medicines pre- and post- the UK’s exitfrom the European Union (EU), and confirm how it will ensure thatpatients will be able to obtain the medicines they need”. “We echothe PAC’s call for clarity,” Smith agreed. Gn david.wallace@generics-bulletin.com

INTELLECTUAL PROPERTY/MANUFACTURING

Firms fear Councilcould neuter waiverVested interests based outside of the European Union (EU)

could persuade the European Council to “neuter” a proposedmanufacturing waiver that would allow EU-based generics andbiosimilars firms to manufacture products during the supplementaryprotection certificate (SPC) term, local industry fears. European off-patent industry association Medicines for Europe is calling on EUmember state governments, as well as health and industry ministers,“to rapidly improve the legislative proposal for a manufacturing waiverand withstand efforts to undermine it”.

According toMedicines for Europe, “disproportionate influence”being exerted on the EU Council is leading to a “concrete risk”of the draft SPC waiver legislation being rendered unusable. “Itis becoming increasingly clear that vested interests are exertingpressure on policymakers in the Council to remove clauses or addnew ones that will jeopardise the whole legislation in an attempt tolimit competition in unprotected markets at the expense of Europeancompetitiveness and growth,” the industry association asserted.

Commenting as the Council’s intellectual-property (IP) workinggroup reviewed amended proposals in private, Medicines forEurope’s director general, Adrian van den Hoven, warned that “highlyregressive revisions proposed by theAustrian Presidency will only actagainst the objectives of the legislative proposal and delay EU genericand biosimilar medicines entering the market”.

The American Chamber of Commerce to the EU had toldthe Austrian Presidency that an SPC waiver could “put Europeaninnovators at a disadvantage”.

But Medicines for Europe highlighted the potential jobopportunities in the EU and relief to healthcare budgets, citingresearch conducted for the European Commission that had found that,if implemented effectively, an SPCmanufacturing waiver could create25,000 skilled jobs and generate additional net sales of €9.5 billion(US$11.0 billion) for EU-based producers.

The Commission, Medicines for Europe maintained, had earlierthis year presented “a watered-down proposal” for an SPC waiver thatwould not allow EU-based manufacturers to stockpile products for a‘day-one’ launch immediately upon SPC expiry. A clear provision toallow such pre-SPC preparations within the EUmust be included in thefinal legislation so that the measure was not limited solely to exportsto third countries where no SPC was in place, the association insisted.

Furthermore, because the Commission’s current proposal wouldonly apply to SPCs prospectively, and thus not to SPCs alreadygranted, the waiver would not come into effect for another 15 to 20years, Medicines for Europe pointed out. It called for “an immediateapplication of the waiver to existing SPCs; otherwise it would negate theopportunities presented by the next significant ‘patent cliff’ as of 2020”.

Andbyrequiringmandatorydisclosureofcommerciallyconfidentialinformation to both generic and originator competitors – in contrast withthe existing EU rules on trade secrets and approved EuropeanMedicinesAgency (EMA) guidance on disclosure – the Commission’s proposal“would create a unique precedent in the entire EU legislation that couldgo beyond the pharmaceutical sector only”.

The association also wants legislators to “better clarify themeaning of ‘maker’ and ‘making’ to ensure a coverage of all activitiesthat would deliver fully on the expected jobs creation” and to remove“additional, burdensome and unnecessary requirements related to thedue diligence with each component of the supply chain”. Gn aidan.fry@generics-bulletin.com

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11bulletin19 October 2018

MARKET NEWS

REGULATORY AFFAIRS

FDA aims to dissuadecitizen petition abuseFactors the US Food and Drug Administration (FDA) will consider

in determining whether a citizen petition is submitted withthe “primary purpose of delaying the approval of a generic drugapplication” are described in revised draft guidance that has just beenpublished by the agency, as part of efforts by the FDA to also improveits own review process efficiency.

“If the agency determines that this is the case, the FDA willconsider whether the petition can be denied on that basis and mayin any case note this determination in the petition response,” FDACommissioner Scott Gottlieb commented, unveiling “new agencyactions to further deter ‘gaming’ of the generic drug approvalprocess”, a further part of his ‘drug competition action plan’ (DCAP)announced in June last year. “We will not shy away from callingout instances where we believe brand firms may be leveraging toolsintended to serve a useful purpose to instead thwart competition thatcan drive down prices for patients,” Gottlieb promised, drawingpraise from the US Association for Accessible Medicines (AAM).

The 17-page guidance, which updates a previous version fromlate 2014, describes the FDA’s current thinking on interpretingsection 505(q) of the Federal Food, Drug, and Cosmetic (FD&C)Act.This section governs certain citizen petitions and petitions for stayof agency action related to a pending agency application, includingabbreviated new drug applications (ANDAs), hybrid 505(b)(2)applications, and 351(k) biosimilar applications.

According to the guidance, the FDA may determine that apetition was submitted with the primary purpose of delaying anapplication’s approval based on a number of criteria, including thata petition raises the “same or substantially similar issues” as a priorpetition to which the FDA has already substantively responded; thesubmission of multiple petitions; an instance where a petitioner hastaken an “unreasonable length of time” to submit the petition; andrequests for a product to meet more rigorous standards of testing thanrequired for an originator product.

Giving an example of how the draft guidance would help “lessenthe impact that our review of petitions may have on pending approvalactions”, the FDA noted that once a drug application is submitted,the agency has a goal date of making an approval decision within10 months, or, for some priority applications, within eight months.

“If a citizen petition is received while a product applicationis already under review, and if the goal date for that review fallswithin the next 150 days, the draft guidance states that the FDAwould expect to respond to that petition within 150 days,” the agencyexplained. “This policy aligns the FDA’s 150-day timeline to reviewand respond to these petitions described in federal law with thetimeline for review of the applications themselves.”

To “further dissuade companies from improperly using thesepetitions”, the FDA also intends to highlight in its annual report toCongress “our determinations of petitions that are judged by theagency to have been submitted with the primary purpose of delayingan approval”, Gottlieb said. “The guidance also outlines our intentionto refer these matters to the US Federal Trade Commission (FTC)”.

“By addressing challenges associated with the 505(q) citizenpetition process,” Gottlieb summarised, “we aim to provide greaterregulatory certainty, improve the efficiency and predictability of thegeneric drug review process, and help to drive down costs of genericdrug development and create incentives for new market entrants.”n dean.rudge@generics-bulletin.com

PRICING & REIMBURSEMENT

Torrent tops awardsas AOK cites savingsTorrent Pharmaceuticals’ Heumann/Heunet bidding group has

secured the largest number of supply contracts in the 20th tenderround run by Germany’s AOK group of statutory health insurancefunds. With 62 regional supply deals, the Indian group’s Heumann/Heunet took 11.6% of all 536 contracts awarded by the funds, aheadof Teva with 56 and Stada’s Aliud Pharma with 51.

The AOK’s 20th tender round covers two-year deals, starting on1 October 2018, for 57 molecules or combinations, each divided intoeight bidding regions. For five of those 57 active ingredients – thehigh-volume molecules candesartan, dexamethasone, metformin,metoprolol and olanzapine – the AOK awarded contracts using a“three-partner model”. Deals for the remaining 52 active ingredientswere awarded on an exclusive basis in each of the eight regions,representing 416 individual contracts.

Heumann/Heunet joined Mylan/Meda and Krka’s Tad Pharmain winning contracts to supply candesartan to all eight of theAOK funds’ regions, while the Torrent affiliates will also providebrinzolamide, etoricoxib, exemestane, galantamine, telmisartan andvalganciclovir nationwide, along with irbesartan/hydrochlorothiazideand olanzapine in specific regions.

Teva secured contracts to supply the funds on an exclusive basiswith drugs including ciclopirox, clonidine, ipratropium bromide,lovastatin and ribavirin. Aliud’s exclusive deals cover bezafibrate,naproxen, raloxifene, ticlopidine, tilidine/naloxone and zoledronic acid.

The top seven suppliers captured around three-fifths of all AOKcontracts (see Figure 1). Other notable recipients of AOK supplycontacts included Sun Pharma’s Basics with 27 and Aurobindo/Purenwith 25, while Cipla, Neuraxpharm and Pfizer each won 16 regionaldeals. Sandoz’Hexal/1APharma bidding group was just behind with 15contracts as part of three-supplier deals for metformin and metoprolol.

Commenting on the tender round, theAOK funds’chief negotiator,Christopher Hermann, said rebates secured through such tenderprocesses had saved the 11 regional AOK funds more than €678million (US$779 million) in the first half of this year, an increase ofalmost 5% versus the prior-year period. Gn aidan.fry@generics-bulletin.com

Figure 1: Breakdown by recipient company of the 536 regional supply contractsawarded by Germany’s AOK statutory health insurance funds in their 20th tenderround that began on 1 October (Source – AOK)

Heumann/Heunet62

Teva56

Stada/Aliud51

Mylan/Meda46 1

Accord39 2Krka/Tad

34

Zentiva32

Others216

1 includes six contracts for budesonide awarded to a biddingconsortium comprising Meda, Infectopharm and Chiesi

2 includes eight contracts for quetiapine awarded to a biddingconsortium comprising Accord and Glenmark

Gen 19-10-18 Pgs.1-24.indd 11 17/10/2018 16:17

BULLSEYE!ANOTHER

Alvogen and Alvotech would like to thank you all for stopping by ourbooth at CPhl in Madrid this year.

Whether it was to meet our staff regarding a current project, inquireabout our businesses or just have some fun by competing in this year’sdarts competition, it was great to see you.

Our special congratulations go to John Larsen, the General Manager fromTiefenbacher Nordic, who won the contest, thanks to his outstandingdarting skills and ability to strike his targets.

This year‘s CPhl was a great success and a bullseye for us all. Alvogen willcontinue to dart forward in this rapidly evolving sector, determined morethan ever to remain at the forefront of change with our approach to com-plex generics, brand medicines, injectables, OTC’s and biosimilar products.

See you in Frankfurt next year!

The winner, John Larsen (second fromleft), took home the 1st prize,a beautiful professional darts board.

Here he is with Alvogen CEO RobertWessman (left) and Michael vanGerwen, the international Dutchprofessional darts champion known tothe world as Mighty Mike (right) alongwith 2nd and 3rd runners up.

Gen 19-10-18 Pgs.1-24.indd 12 17/10/2018 16:17

MANUFACTURINGAND R&D CENTERS

5

75PIPELINE ANDA‘S

59%CAGR SINCE 2009

35COMMERCIALNETWORK

Connect with Alvogen on www.alvogen.com

Gen 19-10-18 Pgs.1-24.indd 13 17/10/2018 16:17

14 bulletin 19 October 2018

MARKET NEWSREGULATORY AFFAIRS/INTELLECTUAL PROPERTY

Carve-outs should actto limit authorisationNotifications from generics firms that they intend to ‘carve out’

indications or dosage forms from leaflets and summaries ofproduct characteristics should be interpreted by European authoritiesas requests to limit the relevant marketing authorisations, according toan opinion delivered by Juliane Kokott, advocate general of the Courtof Justice of the European Union (CJEU).

Kokott was responding to a request for a preliminary rulingsubmitted by a Court ofAppeal in The Hague, the Netherlands, in a caseinvolving Pfizer’sWarner-Lambert andAurobindo that revolved aroundcarving out the neuropathic pain indication for Lyrica (pregabalin)protected by European patent EP0,934,061. Earlier protection forepilepsy and generalised anxiety disorder had already expired.

After the Dutch CBG authority published on its website afull-label version of the summary of product characteristics for thegeneric pregabalin – without taking into consideration a subsequentlyintroduced carve-out, notified by Aurobindo to the CBG before itsgeneric was placed on the market – Warner-Lambert complained thatthe CBG was encouraging generics to be prescribed for the patentedindication, thus depriving the carve-out of its effectiveness underEuropean Directive 2001/83/EC.

The Dutch government’s position was that a subsequent carve-out has no effect on the scope of a previously-granted marketingauthorisation. ButWarner-Lambert demanded that the government ofthe Netherlands should be ordered to instruct the CBG to replace thepublished full-label summary with the carved-out version.

“It is not expressly regulated what effects the introduction of acarve-out in the summary of characteristics of a generic medicinalproduct has on the scope of themarketing authorisation for that genericmedicinal product,” Kokott observed. “In particular, it is unclearwhether, if a carve-out is introduced after a marketing authorisationhas already been granted for the generic medicinal product concerned,this marketing authorisation still applies to the indications or dosageforms which were deleted from the summary of characteristics bythe carve-out, or whether, in contrast, the subsequent notification ofa carve-out means that the marketing authorisation must be limited tothe remaining indications and dosage forms not affected.”

“The Netherlands’ government’s view that a subsequent carve-out does not affect the scope of the previously-granted marketingauthorisation for a medicinal product is not persuasive,” Kokottstated, “as this would lead to a discrepancy between the authorisedversion of a medicinal product and the version placed on the market.”It was a “fundamental principle of the law on medicinal products”,she observed, that the authorised version of a drug and the versionplaced on the market must be identical.

Thus, Kokott said, Directive 2001/83/EC must be interpreted asmeaning that a communication from a genericmarketing authorisationholder or applicant requesting a carve-out for the summary of productcharacteristics and package leaflet “should be considered as a requestto limit the marketing authorisation for that generic medicinalproduct to the remaining indications or dosage forms”.

Addressing whether a full version of the summary should stillbe published even if it went beyond the scope of the marketingauthorisation, Kokott said there was a “risk of confusion” due to thediscrepancy. However, if the marketing authorisation was varied inaccordance with the carve-out and there was no discrepancy, “theproblem of inadequate patient information does not arise at all”. Gn david.wallace@generics-bulletin.com

REGULATORY AFFAIRS

Record ANDAs don’tsolve all problemsArecord number of final and tentative abbreviated new drug

application (ANDA) approvals by the US Food and DrugAdministration (FDA) in the agency’s fiscal year ended 30 September2018 is welcome, but only goes part way to alleviating the pressuresbeing exerted on theUS generics industry, according to theAssociationfor Accessible Medicines (AAM).

A total of 971 final and tentative approvals granted by the FDA’sOffice of Generic Drugs (OGD) during the 2017-2018 financial yearwas 3.6% higher than the 937 issued in the previous fiscal year (seeFigure 1). Within that total, 781 final approvals included 137 ANDAsauthorised after their first review cycle, a proportion of 17.5%. The first-cycle proportion for tentative approvals was lower, with 24 out of 190ANDAs giving 12.6%. The agency said the 971 total also included 95first-time generics and three that had competitive generic therapy (CGT)designations, while 12% of approvals were for complex generics.

During the period, the FDA received 1,044 original ANDAs,7.0% more than the number of final or tentative approvals.

The agency refused to receive 123 ANDAs, 92 of which wereunder priority review through either the first or second iteration of theGeneric Drug User FeeAmendments (GDUFA).Applicants withdrew548 ANDAs, 394 of which had already been approved, a potentialindication of the pricing and commercial pressures that have ledmany leading generics players to prune their US portfolios.

“We appreciate the efforts of the FDA, under the leadership ofCommissioner Scott Gottlieb, to lower overall drug prices by seekingto increase the number of generic drug applications on an annualbasis,” the AAM commented. However, the US industry associationcontended, “it is important to recognise that in the current UShealthcare system, more generic approvals does not automaticallytranslate into more competition”.

“Not all new generic approvals make their way to market – bysome estimates less than half do – which means the full benefit ofgeneric competition to help counter increasing brand drug prices isnot being realised,” the AAM continued. Citing recent commentsmade by US Health and Human Services (HHS) Secretary AlexAzar, the association observed that “there are a combination of forcesthat keep generics off the market and out of the hands of patients”.n aidan.fry@generics-bulletin.com

Figure 1: Final and tentative abbreviated new drug application (ANDA) approvalsgranted by the US Food and Drug Administration (FDA) in its financial years ended30 September 2013 to 2018 (Source – FDA)

0

200

400

600

800

1,000

TentativeFinal

2013 2014 2015 2016 2017 2018

440

95

409

91

492

120

651

184

763

174

781

190

Num

berof

approv

als

Total

535 500

612

835

937 971

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15bulletin19 October 2018

MARKET NEWS

REGULATORY AFFAIRS

FDA assists industrywith topical guidanceGuidance documents that will “advance the development of generic

transdermal and topical delivery systems (TDS)” have beenreleased by the US Food and Drug Administration (FDA), alongside25 product-specific guidance documents, the latest of the agency’sfervent efforts to promote drug competition and patient access.

Providing updated advice for the “design and conduct of studiesevaluating the adhesive performance of a proposed generic TDS”,the FDA has revised a prior draft guide on ‘Assessing adhesion withtransdermal and topical delivery systems for abbreviated new drugapplications (ANDAs)’, which was released in 2016 (Generics bulletin,10 June 2016, page 11).

The revised nine-page document provides recommendations onhow to evaluate adhesion, comprising both study design and conductand considerations for statistical analysis, as well as the combinedevaluation of adhesion and bioequivalence.

“FDA recommends that applicants consult this guidance inconjunction with any relevant product-specific guidances and inconjunctionwith any relevant guidances for industry,when consideringthe design and conduct of studies that may be appropriate to supportthe bioequivalence of a proposed generic TDS product to its referencelisted drug and/or reference standard product,” the agency said.

A second draft guidance entitled ‘Assessing the irritation andsensitization potential of transdermal and topical delivery systemsfor ANDAs’ provides “recommendations for the design and conductof studies to evaluate the in vivo skin irritation and sensitizationpotential of a proposed generic TDS”, according to the FDA.

The 12-page document offers general considerations, as well as afour-point ‘combined evaluations of skin irritation and sensitisation’,covering study design and conduct, considerations for statisticalanalyses – for both irritation and sensitisation – vehicle TDS andpositive control TDS, and partial cut TDS. The document also offersrecommendations on the overall assessment of adverse event data.

Meanwhile, the 25 product-specific guidance documents, includetwo new and 23 revised guidances, supporting industry in “identifyingappropriate science-based methodologies and evidence for developinggeneric TDS products”.

Acorda Therapeutics’ Qutenza (capsaicin) topical patch andNoven Pharmaceuticals’ Combipatch (estradiol/norethindrone acetate)extended-release transdermal film are the new guidance documents,while the almost two-dozen revised documents comprise 20 transdermalfims and three topical patches.

“These draft guidances are aimed at ensuring that we provideas much scientific and regulatory clarity as possible with respect tocomplex generic drugs, FDACommissioner Scott Gottlieb commented.

Gottlieb added that, “in the coming months”, the agency wasgoing to “advance other new policies to promote more genericcompetition for these complex drugs”, including the development ofnew analytical tools and in vitro tests that may be more accurate andsensitive, and reproducible tools for demonstrating sameness betweengeneric and branded versions of complex drugs.

“We’ll also be issuing an umbrella guidance to help genericdrug developers address some of the most challenging regulatory andscientific issues encountered when they try to make generic copiesof complex drugs,” Gottlieb pledged. “A series of more targetedguidances to help address legal questions that are blocking genericcompetition” are to follow. Gn dean.rudge@generics-bulletin.com

REGULATORY AFFAIRS

France is aiming for a€500mn savings totalFrench healthcare savings of around €500 million (US$579 million)

are expected by the country’s government in 2019 from changes tothe structure of prescribing that include driving up the use of genericsand biosimilars, the country has announced.

The savings target forms part of a €3.83 billion overall savingsgoal that will see France limit growth in health insurance spending to2.5% in 2019, resulting in overall spending of just over €200 billion.As well as the €500 million figure from modifications to prescribingstructure, action on prices and rebates for healthcare products isexpected to result in savings of €895 million.

These figures were revealed shortly after France’s governmentpublished an initial budget document containing proposals to modifythe country’s substitution framework in two ways (Generics bulletin,5 October 2018, page 1).

First, France’s government plans to establish – in conjunctionwith local medicines agency ANSM – a list of “objective medicalcriteria” that must be used by doctors who want to mark prescriptionsas non-substitutable, to provide justification for barring genericsubstitution at the pharmacy level.And second, the country plans from1 January 2020 to reimburse patients that refuse generic substitutiononly for the value of the equivalent generic, not for the value of thecounterpart brand. The proposals were welcomed by local off-patentindustry association Gemme. G

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16 bulletin 19 October 2018

MARKET NEWS

INTELLECTUAL PROPERTY

Germany bars Praluent licenceGermany’s federal patent court, the Bundespatentgericht, has refused

to grant a compulsory licence to a European patent protecting thePraluent (alirocumab) cholesterol-lowering biologic that is marketedin Europe by Sanofi. Written reasoning has not yet been released, andthe ruling is not yet in force. Responding to an application made byan undisclosed “French medicines manufacturer” for a licence toAmgen’s European patent EP2,215,124, the patent court said it hadturned down the petition for two reasons.

Firstly, it explained, the applicant had not made sufficient attemptsto agree rights to the ‘124 patent withAmgen on reasonable commercialterms and within a reasonable timeframe. Secondly, the applicant hadnot made a strong enough case that greater access to Praluent wassufficiently in the public interest to justify a compulsory licence. G

REGULATORY AFFAIRS

EMA continuity planenters its third phaseAdditional activities have been “temporarily suspended or reduced”

by the European Medicines Agency (EMA) as it enters into thethird phase of its business continuity plan (BCP) in the wake of theUK’s ‘Brexit’ decision to leave the European Union (EU).

As well as ensuring “resources can be redeployed so that its coreactivities can continue without interruption and to the same quality”,scaling back further activities will also “help the agency cope withanticipated staff loss”, the EMA insisted. The “main reason” forlaunching phase three, it added, was because the agency “will losemore staff than initially anticipated”.

Set out late last year, the BCP aims to “safeguard continuity ofEMA’s operations to protect public health while the agency preparesfor its relocation to a new host city” (Generics bulletin, 3 November2017, page 12). Having started the first phase of the plan on 1 May2017, phase two was launched on 1 January 2018, and phase three wasentered on 1 October.

Each phase is characterised by a temporary suspension and/or scaling back of a set of EMA activities, starting with the lowestpriority activities in ‘category 3’, moving to medium priority activitiesin ‘category 2’ – split into lower-medium priorities under ‘category2B’ and higher-medium priorities under ‘category 2A’ – and then thehighest priority activities in ‘category 1’.

As part of the third phase, a number of ‘category 2B’ activitieshave been identified for a temporary suspension and/or scalingback from 1 November 2018. These include international activities;guideline development; secretariat activities; programs and projects;stakeholder interaction; and clinical data publication.

Despite temporarily reducing guideline development andrevision, the EMA said that seven guidelines that “address either anurgent public/animal health need, or are necessary to support andfacilitate preparations for Brexit or the implementation of new orrevised legislation” will “exceptionally continue”. Among these areguides on: evaluating anticancer medicines; manufacturing sterilemedicines; importers of medicinal products; and good manufacturingpractice and marketing-authorisation holders.

“Meetings of product-related working parties will continue asscheduled,” theEMAadded,while “allmeetings of non-product relatedworking parties have been temporarily put on hold”. “Temporarysuspension and scaling back of activities is currently scheduled tolast until 30 June 2019, but will be reviewed in April 2019, oncethe agency has completed its move to its temporary building inAmsterdam, the Netherlands.”

The EMA has also published more information on cut-off datesfor switching rapporteurships currently held by the UK’s Medicinesand Healthcare products RegulatoryAgency (MHRA) to EU memberstates. Separately, the MHRA has opened until 1 November aconsultation on how its legislation and regulatory processes wouldhave to be modified in the event of the UK not securing a deal withthe EU after Brexit, with no implementation period.

“As part of this contingency planning, it is necessary to makesure the UK’s regulatory processes for medicines, clinical trialsand medical devices are legally coherent on exit day,” the agencyexplained. “The overall approach in the unlikely event of a no-dealscenario is for the MHRA to be a standalone medicines and medicaldevices regulator, taking any decisions and carrying out any functionswhich are currently taken or carried out at EU-level.” Gn grace.montgomery@generics-bulletin.com

REGULATORY AFFAIRS

US president passesbio pay-for-delay billAbill requiring reverse-payment settlement deals between

manufacturersofbiosimilars and their brandedbiologiccounterpartsto be disclosed to the US Federal Trade Commission (FTC) has beenpassed by US President Donald Trump.

Labelled the ‘Patient Right to Know Drug Prices Act’, US Senatebill S.2554 has a section on ‘modernising the reporting of biological andbiosimilar products’that states that so-called pay-for-delay deals relatingto biosimilars should be referred to the FTC for scrutiny, alongsidethose relating to generics as occurs under the current framework.

The bill was recently passed by the country’s Senate with a 98-2majority (Generics bulletin, 28 September 2018, page 9). After beingintroduced to the Senate in March, the bill was examined by the SenateCommittee on Health, Education, Labour and Pensions (HELP) inlate July, before being passed with a single amendment in September.A counterpart bill, H.R.6143, was introduced in the US House ofRepresentatives in June, but is yet to progress through the House.

At the same time, Trump has also signed into law US Senatebill S.2553, entitled ‘Know the Lowest Price Act of 2018’. This Act“prohibits Medicare Part D plans from restricting pharmacies frominforming individuals regarding the prices for certain drugs andbiologicals”. The Senate bill was passed in early September, with theUS House of Representatives also passing the Act shortly after.

The Pharmaceutical Care ManagementAssociation (PCMA) saidthe ‘pharmacy gag clause’ legislation “aligns with standard practiceused by pharmacy benefit managers (PBMs) in the marketplace”and “will help ensure America’s patients always pay the lowest costfor their medications at the pharmacy counter, whether it’s the cashprice or the patient’s cost-sharing”. “In addition,” the PCMA added,“S.2554 takes an important step toward increasing competition byrequiring drug manufacturers to report to the FTC pay-for-delayagreements that could slow biosimilars from entering the market.”

The American Pharmacists Association (APhA) said it “applaudsCongress and the Administration’s actions against PBM practices thatnegatively affect patients”. “For years pharmacists have been providinggreat care but have been prohibited by contractual restrictions fromsharing information on how patients might better navigate theirprescription drug costs,” the association said. “This new law allowspharmacists to have those needed conversations with patients.” G

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PRODUCT NEWS

MULTIPLE SCLEROSIS DRUGS

US Copaxone patentsconfirmed as invalidFour patents protecting Teva’s Copaxone (glatiramer acetate) 40mg/

ml thrice-weekly formulation are invalid as obvious, the US Courtof Appeals has confirmed in two parallel decisions. The decisionsremove the threat of damages against Mylan and Sandoz, whichlaunched glatiramer acetate (GA) 40mg pre-filled syringes ‘at risk’pending Teva’s appeal (Generics bulletin, 16 February 2018, page 15).

In both cases, the Court of Appeals noted that “for analysing theobviousness of theCopaxone patents, a key limitation of the claims is theadministration of a 40mgGAdose in three subcutaneous injections overseven days”. Certain claims of three patents – US patents 8,232,250;8,399,413 and 9,155,776 – further require improved tolerability and/orreduced injection reactions compared to the 20mg formulation.

Teva’s partner Yeda Research & Development had appealedagainst Delaware District JudgeGregory Sleet’s decision to invalidateas obvious all asserted claims of the ‘250, ‘413 and ‘776 patents, aswell as of US patent 8,969,302, all of which expire on 19 August2030. That district court finding had favoured not only Mylan andSandoz plus its partner Momenta, but also Amneal, Dr Reddy’s,Pfizer and Synthon (Generics bulletin, 3 February 2017, page 1).

Having found no error in Sleet’s claim construction, the Courtof Appeals panel denied Teva’s argument that the district courthad engaged in an impermissible ‘obvious to try’ analysis with thebenefit of hindsight. “We hold that the 40mg GA three-times-a-weekregimen is obvious in light of the prior art, and find no clear error inthe conclusion that a person of skill in the art (POSITA) would bemotivated to combine the 40mg GAdose, which had proven efficacy,with a three-times-a-week frequency, which was desirable becausethe prior art indicated that less frequent administration increasedpatient adherence while maintaining efficacy.”

In parallel, the three appeals judges found in favour of Mylanand Amneal in rejecting Yeda’s appeal against final written decisionsof the US Patent and Trial and Appeal Board (PTAB) finding theclaims of the ‘250, ‘413 and ‘302 patents unpatentable as obvious inthree inter partes review proceedings.

The PTAB had ruled that Teva’s own Pinchasi patent application– covering a 40mg GA dosing regimen every other day for treatingrelapsing-remitting multiple sclerosis (RRMS) – disclosed everylimitation of the independent claims in the three Copaxone patents,except for the dosing regimen of three doses per seven-day period.A skilled person, the board said, would have been motivated to usea 40mg dose with a reasonable expectation of success, and furtherwould have had reason to modify Pinchasi’s dosing regimen of 40mgevery other day to 40mg three times per week, rendering the three-times-a-week limitation obvious. Tolerability and reaction claimswere similarly obvious.

“We conclude that substantial evidence supports the board’sreliance on the clinical data and its conclusion that a POSITA wouldbe motivated to combine Pinchasi’s 40mg every-other-day dosewith a less frequent dosing regimen, such as three times a week, andwould have had a reasonable expectation of success in therapeuticeffectiveness and patient compliance,” the appeals panel stated.

“Having already found the 40mg glatiramer acetate three-times-a-week limitation obvious, merely identifying the specific days forthe thrice-weekly regimen is the natural application of the method,with a finite number of identified and predictable solutions, andrequires not innovation but ordinary skill and common sense.” Gn aidan.fry@generics-bulletin.com

NEUTROPENIA TREATMENTS

Kabi progresses pegfilgrastimFresenius Kabi’s biosimilar candidate of Amgen’s Neulasta

(pegfilgrastim), MSB11455, has met its primary endpoint in twopivotal clinical trials, enabling the German firm to move a step closerin obtaining a marketing authorisation for the drug in the EuropeanUnion (EU) and US.

The first study was a randomised, double-blind, crossover studycomparing the pharmacokinetic andpharmacodynamic bioequivalenceof a single injection of MSB11455 and Neulasta in healthy adults. Thesecond trial, also randomised and double-blind, was a parallel-group,controlled study comparing the immunogenicity and safety of Kabi’sbiosimilar candidate with the reference product in healthy adults.“Similar adverse events” were observed in both treatment groups. G

DIABETES DRUGS

Merck shelves insulinbut wins on RenflexisMerck Sharp & Dohme has decided that it will not commercialise its

tentatively-approved follow-on version of Sanofi’s Lantus (insulinglargine) in the US, citing issues around the pricing environment for thediabetes treatment, aswell as the highmanufacturing costs. Developmentpartner Samsung Bioepis revealed in a stock exchange filing that it hadreceived a US$155 million termination fee or ‘disposal price’.

Nevertheless, Merck insists that it is committed to the pipeline ofoncology and immunology biosimilars being developed through itspartnershipwith SamsungBioepis. The partners’Renflexis (infliximab-abda) has just become the infliximab product available on the USDepartment of Veterans Affairs (VA) national formulary, after beingawarded a federal contract as “the lowest priced offer”.

“After a comprehensive assessment of the current and futuremarketenvironment for insulin glargine,” a Merck spokesperson told our sisterpublication, Scrip, “which included an assessment of anticipatedpricing and cost of production, we made the business decision toterminate our agreement on the commercialisation of Lusduna penand vial.” The decision, however, “does not affect the other biosimilarassets currently in development with Samsung Bioepis”.

The US firm won tentative US Food and Drug Administration(FDA) approval in July last year for Lusduna through the 505(b)(2)hybrid new drug application (NDA) pathway (Generics bulletin,28 July 2017, page 1). Merck is currently embroiled in two Lantuspatent-litigation actions with Sanofi in Delaware and New Jersey.

Developed with Samsung, Lusduna would be the third Lantusproduct on the market in the US, behind Sanofi’s original and theBasaglar follow-on product developed by Eli Lilly and BoehringerIngelheim, which they launched at the end of 2016 under a settlement(Generics bulletin, 6 January 2017, page 18).

Mylan and Biocon are attempting to get a follow-on versionof Lantus to market in the US, but saw their progress stymied withan FDA complete response letter (CRL) earlier this year (Genericsbulletin, 8 June 2018, page 1).

Forged in 2013, Merck’s biosimilars partnership with Samsunghas seen the firms rack up a number of approvals in various developedmarkets. This includes Renflexis in Australia, Canada and the US,where it competes with Janssen’s Remicade and Pfizer’s Inflectra(infliximab-dyyb) biosimilar; Brenzys (etanercept) in Australia andCanada; and Ontruzant (trastuzumab) in the European Union (EU).G

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PRODUCT NEWSNEUTROPENIA TREATMENTS

Pfizer ships its rivalto Neupogen in USPfizer has introduced the firm’sNivestym (filgrastim-aafi) biosimilar

in the US, at the previously-promised “significant discount” to thecurrent wholesale acquisition cost (WAC) of Amgen’s Neupogenoriginal, and a double-digit reduction on the price of competingbiosimilar and follow-on products.

Revealing that shipments to wholesalers had begun on 24September, Pfizer announced that the biosimilar had been availablesince 1 October, at a WAC of US$350.40 for the 480µg pre-filledsyringe formulation, a price that is 30.3% lower than the WAC ofNeupogen. This offered “the potential for immediate savings toCenters for Medicare and Medicaid Services (CMS) and commercialpayers”, Pfizer said.

Meanwhile, that price is a fifth – 20.3% – lower than the WACof Sandoz’ Zarxio (filgrastim-sndz) biosimilar, and 14.1% lower thanthat of Teva’s Granix (tbo-filgrastim) follow-on product, accordingto Pfizer. “WAC is not inclusive of discounts to payers, providers,distributors and other purchasing organisations,” the US player noted.

Pfizer’s fourth biosimilar approved in the US, Nivestym wasgreenlit by the US Food and Drug Administration (FDA) in July thisyear. Around the same time, Pfizer was sued by Amgen for infringingUS patent 9,643,997 protecting Neupogen, with the originator seeking“injunctive relief to prohibit Pfizer from practicing the patentedinvention prior to the expiry of this patent” (Generics bulletin, 27July 2018, page 16).

“Pfizer does not comment on pending litigation,” a companyspokesperson told Generics bulletin in response to an enquiry onthe matter. “Meanwhile, we are committed to bringing biosimilars topatients as soon as possible and we evaluate business opportunitiesaccording to the benefits and risks present in each individual case.”

Sales of Neupogen in the first six months of this year wereUS$128 million, down a third on the prior-year figure. G

CONTRACEPTIVES

Dutch council backs Qlaira SPCBayer is entitled to a supplementary protection certificate (SPC) for its

Qlaira (estradiol valerate/dienogest) contraceptive, the Netherlands’Council of State has confirmed in rejecting an appeal brought by thecountry’s patent office, the OCNL.

In 2011, the OCNL had refused Bayer’s SPC application onthe grounds that Qlaira contained the same active ingredients, albeitin a different dosage regimen, to an existing hormone replacementtherapy, Climodien. Thus, the patent office said, Qlaira did not qualifyas a new product that was entitled to protection under the EuropeanUnion’s (EU’s) SPC Regulation.

But in 2017 Bayer successfully challenged that position in aHague court. The originator relied on the landmark Neurim decisionby the Court of Justice for the EU (CJEU) to show that a newtherapeutic use of a known compound or combination was entitled toSPC protection.

On appeal, the Council of State rejected the OCNL’s argumentthat the Hague court had interpreted Neurim too broadly. Taking ateleological view of the purpose of the SPC Regulation, it foundthat research to discover new therapeutic uses of active substancesalready used in medicines merited SPC exclusivity. G

PFIZER AND DAIICHI SANKYO face lawsuits and petitionsfor provisional disposition orders filed by Chugai in a district courtin Tokyo, Japan, in a bid to stop the two firms manufacturing anddistributing biosimilar versions of Herceptin (trastuzumab). TheJapanese originator alleges that the 60mg and 150mg injectableformulations infringe apatent that it licenses fromRoche’sGenentech.

ALKEM has become the first company to secure US Foodand Drug Administration (FDA) approval for a generic rival toLupin’s Suprax (cefixime) 400mg capsules. Other recent first-time generics approvals by the FDA include Cipla’s alternative toGlaxoSmithKline’sAlbenza (albendazole) anthelmintic tablets andNavinta’s version of Bristol-Myers Squibb’s Bicnu (carmustine).

JHL BIOTECH says China’s National Medical ProductsAdministration (NMPA) has approved its application to conductPhase I and III clinical trials for its JHL1149 bevacizumabbiosimilar candidate.

AMNEAL will be given “a non-exclusive right to sell a limitedvolume” of an authorised generic of Xyrem (sodium oxybate) oralsolution from 1 July 2023, or earlier under circumstances, underthe terms of a US patent-litigation settlement struck with originatorJazz. The deal, which includes a “meaningful royalty”, ends on 31December 2025, at which point Amneal will get a non-exclusivelicence to make and market its own generic of the narcolepsy drug.Jazz said it had now settled with all nine filers for generic Xyrem.

TANVEX BIOPHARMA has submitted its first biologics licenseapplication (BLA) to the US Food and DrugAdministration (FDA).The Taiwan-listed company that is headed byWatson founderAllenChao has filed for US approval of its TX-01 filgrastim candidate.

HEALTH CANADA found, based on a recent US Food and DrugAdministration (FDA) inspection, that Zhejiang Huahai’s Chuannanmanufacturing site does not comply with good manufacturingpractices (GMP) requirements for active pharmaceutical ingredients(APIs). The Canadian agency noted that all valsartan made by theChinese firm had already been recalled in Canada, but said the siteproduced other bulk sartans as well as levetiracetam, nevirapineand repaglinide. The FDA has just posted a laboratory analysis ofnitrosodimethylamine (NDMA) impurity levels in recalled valsartanproducts fromHetero Labs, Prinston, Teva andTorrent, while the USregulator has also posted a gas chromatography-mass spectrometrymethod for detecting both NDMA and N-nitrosodiethylamine(NDEA) in valsartan.

AUROBINDO has seen its US patent dispute versus Gilead over USpatents 6,642,245 and 6,703,396 protectingTruvada (emtricitabine/tenofovir) up to 2021 dismissed by a Delaware district court.

PRAC – the pharmacovigilance risk assessment committee withinthe European Medicines Agency (EMA) – has recommendedrestrictions on using fluoroquinolone and quinolone antibioticsdue to the potential for “disabling and potentially long-lasting butvery rare side effects”.

PERRIGO has been sued by Bausch Health and Dow in a NewJersey district court for allegedly infringing US patents protectingthe Jublia (efinaconazole) 10% topical solution for treating fungaltoenail infections. Perrigo has also introduced in the US a genericof AbbVie’s AndroGel (testosterone) 1.62% topical gel that willcompete with an authorised generic. G

IN BRIEF

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19bulletin19 October 2018

PRODUCT NEWS

AUTOIMMUNE DISEASE TREATMENTS

Sandoz eyes Europeentry for adalimumabAfourth biosimilars player, Sandoz, has brokered a global patent

litigation settlement agreement with AbbVie over Humira(adalimumab), providing guaranteed market entry dates for Sandoz’biosimilar, as the market forms in Europe.

Under the terms of the agreement, AbbVie will grant Sandoz anon-exclusive license to the originator’s intellectual property relatingto the world’s best-selling drug, beginning on “certain dates incertain countries in which AbbVie has intellectual property”.

Like two of the three other biosimilar players that have settled,Amgen and Samsung Bioepis, Sandoz’ license period in most countriesin the European Union began on 16 October, as Generics bulletinwent to press. Mylan, the final settler, agreed terms that excludedEurope, but said it had begun “commercial activity” immediately aftera key Humira supplementary protection certificate (SPC) expired.Amgen, Samsung and Sandoz have also announced launches.

Amgen was the first firm to receive a pan-European marketingauthorisation from the European Commission for the firm’s Amgevitaand Solymbic biosimilars on 22March 2017. Samsung Bioepis’ Imraldifollowed, then Boehringer Ingelheim’s Cyltezo in November, beforeSandoz’ Hyrimoz, Halimatoz and Hefiya biosimilars in July.

Mylan is the latest firm to receive an approval for its Huliobiosimilar with Fujifilm Kyowa Kirin Biologics (FKB) in September(Generics bulletin, 28 September 2018, page 12). Boehringer is theonly one of these players that has not publicly announced a settlement.

European health services, including England’s National HealthService (NHS), have been busy preparing for the market entry ofadalimumab biosimilars, in a bid to deliver savings and improveaccess. Recently, the NHS’ Specialist Pharmacy Service release aquestion-and-answer document for clinicians to use with patients indiscussions around switching (Generics bulletin, 5 October 2018,page 20). Notably, the document forecasts that biosimilars are likelyto be available to patients from December 2018 onwards.

Sandoz’ settlement provides for the latest launch date in the USannounced thus far. In the US, Sandoz’ license period will begin on 30September 2023, a full eight months after the earliest entrant Amgen,which became the first biosimilars player to announce a settlement inSeptember last year, with an entry date of 31 January 2023 (Genericsbulletin, 6 October 2017, page 1).

Market entry for biosimilars in the US under the separatesettlements is to be staggered, with the entry dates matching thechronology of the settlements. Thus, following Amgen on 31 January,Samsung may launch on 30 June 2023 under terms announced inAprilthis year. Mylan, which settled in July this year, can enter on 31 July2023, followed by Sandoz on 30 September 2023.

Sandoz has agreed to pay royalties to AbbVie for licensing itsHumira patents, while all litigation pending between the parties willbe dismissed. AbbVie, meanwhile, will make no payments to Sandoz.

Humira racked up global sales of US$9.89 billion in the firstsix months of this year, of which US$3.37 billion was from non-USmarkets, and the remaining US$6.52 billion stemming from the US.Outside of the US, AbbVie does not provide more granularity fornon-US ‘International’ markets, although Mylan recently put theEuropean figure at around US$4.4 billion for the 12 months endedJune 2018. The originator’s chief executive officer, Rick Gonzalez, haspreviously predicted that non-US sales of Humira will fall by no morethan a fifth by the end of next year. Gn dean.rudge@generics-bulletin.com

Up to the minute live retail market pricing is available for the UK and Eireon Wavedata Live at wavedata.net.Alternatively, contact Charles Joynson at WaveData Limited, UK.Tel: +44 (0)1702 425125. E-mail: cjoynson@wavedata.co.uk.

Price WatchIndex

PharmacyProfit Index58.9 59.3

Monthly change +3.3 Monthly change -4.2

September 2018 September 2018

Rising ex-factory prices and a slight drop in reimbursement ledprofits enjoyed by UK independent pharmacists to slip in

September, following a sharp rise inAugust, according toWaveData.As the reimbursement price for the basket declined very

slightly to £2,251.94 (US$2,978.63) – compared to £2,252.48 inAugust (Generics bulletin, 14 September 2018, page 13) – thebasket price rose to £1,253.90 from the previous month’s figureof £1,183.34. This meant the pharmacy profit value was morethan £70 lower, once again dropping below the £1,000 mark at£998.04, although this still represented a significant improvementon values seen earlier in the year.

As a result, the Pharmacy Profit Index dropped by 4.2 indexpoints to 59.3, while the Price Watch Index reversed exactly the3.3 decline seen in August, rising by the same value to 58.9. G

The Price Watch Index is based on the actual average trade price according to WaveData of a representativebasket of 20 popular generic products in March 2016, when the Index was 100. The basket reflects recentofficial prescribing data for England and Wales and represents what an average pharmacy would pay forthe products, which were selected as being the top cash generators within pharmacy. The Pharmacy ProfitIndex is calculated on the same basis by applying Drug Tariff reimbursement prices to the basket.

September 2018

PRICE WATCH ....... UK

Basket Price Reimbursement Price Pharmacy Profit£1,253.90 £2,251.94 £998.04

CHOLESTEROL-LOWERING DRUGS

Germany overturnsTeva Inegy injunctionTeva’s German Ratiopharm affiliate has persuaded a regional court

in Düsseldorf to drop an interim injunction issued earlier this yearto block generic competition to Merck Sharp & Dohme’s (MSD’s)Inegy (ezetimibe/simvastatin) cholesterol-lowering combination.

Based on European basic patent EP0,720,599, which until 14September 2014 protected combinations of ezetimibewith a cholesterolsynthesis inhibitor, MSD had obtained a German supplementaryprotection certificate (SPC) for Inegy that runs until 2 April 2019.However, several actions to invalidate the SPC are pending beforeGermany’s federal patent court.

According to the Düsseldorf court, MSD had during the course ofproceedings “failed to give any credible grounds for an injunction”.Noting that MSD had already benefitted from an SPC for ezetimibealone, the court believed the ezetimibe/simvastatin SPC wouldultimately be invalidated.

“The combination of ezetimibe and simvastatin does not representthe inventive core of the basic patent,” the court objected, adding thatthe combination was already protected by the basic patent at the timeat which MSD filed its SPC application, with simvastatin specificallyidentified in claim 17 of the ‘599 patent. Thus, the Düsseldorf courtconcluded, the requirement in Article 3c of the European Union (EU)SPC Regulation 469/2009/EC – that “the product has not already beenthe subject of a certificate” – was not satisfied. G

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Recognisinggg the best innn the globbbalgenerics annnd biosimilarrrs industrrriiieeesss

5thAnnualAwardsTuesday 9 October 2018Palacio Municipal de CongresosMadrid, Spain

WINNERSGALLERY

Presented by

In association with

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21bulletin19 October 2018

AWARDS WINNERS

SAVE THE DATE ...The Global Generics & Biosimilars Awards 2019 will take place onTuesday 5 November 2019 and be held in Frankfurt, Germany.

Award: Company of the YearSponsor: IqviaWinner: Accord Healthcare

Award: Company of the Year, AmericasSponsor: Masters Speciality PharmaWinner: Amneal Pharmaceuticals

Award: Company of the Year, Asia-PacificSponsor: Generics bulletinWinner: Intas/Accord

Award: Company of the Year, EMEASponsor: PanaceaWinner: Stada

Award: Acquisition of the YearSponsor: PharmawiseWinner: Aurobindo

Award: Leader of the YearSponsor: PharmacloudWinner: Alvogen – Robert Wessman

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22 bulletin 19 October 2018

AWARDS WINNERS

Award: API Supplier of the YearSponsor: IqviaWinner: Laurus Labs

Award: Biosimilar Initiative of the YearSponsor: SanaClisWinner: Accord Healthcare

Award: Regulatory Achievement of the YearSponsor: mAbxienceWinner: Mylan

Award: Industry Partner of the YearSponsor: Teva/TapiWinner: Piramal Pharma Solutions

Award: Corporate Social Responsibility (CSR) Initiative of the YearSponsor: International Health Partners (IHP)Winner: Dr Reddy’s

Award: Innovation of the YearSponsor: Piramal Pharma SolutionsWinner: Chemo Group

Award: Business Development of the YearSponsor: West Pharmaceutical ServicesWinner: mAbxience

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23bulletin19 October 2018

AWARDS

With thanks to our sponsors:

To find out more about sponsoring an Award atthe Global Generics & Biosimilars Awards 2019,please contact awards@generics-bulletin.com

or visit www.generics-bulletin.com

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24 bulletin 19 October 2018

PEOPLE

RESHUFFLES

Mass departures from MomentaMomenta Pharmaceuticals is changing its executive management

team as part of the firm’s recently-revealed restructuring efforts.Alejandra Carvajalwill assume the role of chief legal officer, generalcounsel and secretary, succeeding current general counsel and secretaryBruce Leicher, whileMichelle Robertsonwill become chief financialofficer and treasurer, taking over both roles from Scott Storer. BothLeicher and Storer are departing from Momenta this month.

Three other senior executives are also leaving the company, theUS firm divulged: chief operating officer and chief scientific officerGanesh Kaundinya, senior vice-president of pharmaceutical scienceJames Anderson, and head of commercial Robert Ciappenelli. Allfive departing members have agreed to help the company transitionto its new leadership team under consultancy agreements.

Continuing executives will have “expanded roles andresponsibilities”, Momenta stated. Young Kwon will assume therole of chief business officer, Anthony Manning will become chiefscientific officer, and Jo-Ann Beltramello will become chief humanresources and infrastructure officer. Ian Fier will assume the role ofchief manufacturing and program officer, while Santiago Arroyowill continue as chief medical officer.

In early October, Momenta announced plans to restructure itsmanagement and cut its workforce by “approximately 50%”, with theloss of 110 jobs (Generics bulletin, 5 October 2018, page 3). G

APPOINTMENTS

Patel to lead Hikma’sInjectables in EuropeHikma has appointed Sagar Patel as European commercial head

for its Injectables business, effective immediately. In his “newlycreated” role based in London, UK, Patel will “focus on developingbusiness growth strategies and partnerships with key stakeholdersacross the region”. Joining from Fresenius Kabi where he mostrecently served as senior vice-president of global alliance managementand third-party manufacturing, Patel will report to Riad Mechlaoui,chief executive officer (CEO) of Hikma’s Injectables division.

“Sagar’s leadership skills, strategic business planning and excellentcommercial experience will be a major asset for our Injectables divisionand our European business as we look to grow internationally,”commented Mechlaoui. Hikma noted that Patel was joining “at atime of organisational change to boost the group’s senior leadershipcapabilities and expand its reach across Europe”.

Meanwhile, Hikma has selected Samuel Park as global head ofintellectual property and general counsel for the US, also effectiveimmediately. He joins from global law firm Winston & Strawn.

Hussein Arkhagha, Hikma’s global general counsel, said thatPark “brings a wealth of legal experience and has an impressive recordof challenging patents”. “Sam will play a pivotal role in enhancingour research and development program, enabling us to bring moredifferentiated products to the market,” he stated.

InAugust, the Jordanian firm appointedKristy Ronco to becomeexecutive vice-president with responsibility for sales and marketing inits US non-injectable Generics division (Generics bulletin, 31August2018, page 24). This came after Hikma recruited Teva’s HenrietteNielsen as chief transformation officer (Generics bulletin, 15 June2018, page 16). G

APPOINTMENTS

Perrigo strategy shiftleads to CEO changeFresh from announcing plans to “separate” the company’s ‘Rx’

Prescription US generics business, Perrigo has brought in consumergoods veteran Murray Kessler as its new president and chiefexecutive officer, in line with Perrigo’s own shift to a consumer-focused strategy.

Also appointed as a member of Perrigo’s board of directors,Kessler replaces with immediate effect Uwe Röhrhoff, who hadonly taken on the role in January (Generics bulletin, 12 January2018, page 1). Röhrhoff – who has stepped down as president, chiefexecutive officer and board member – would “make himself availableto ensure a smooth and successful transition”, Perrigo said, withoutproviding further details.

“The board and Uwe mutually agreed the transition was in thebest interest of the company and, given the previously announcedseparation of the Rx business, now is the appropriate time to makethis change,” commented Rolf Classon, chairman of the boardof directors. “The board determined that Murray is the right chiefexecutive officer for Perrigo’s consumer-focused strategy goingforward. We are thankful for Uwe’s leadership, including the decisionto separate the Rx business.”

Announced in August, Perrigo’s planned separation of its Rxbusiness could take one of several forms, including a spin-off toshareholders, a sale or a merger (Generics bulletin, 31 August 2018,page 4). It is expected to be completed during the second half of 2019,the firm said at the time.

With a “proven track record for over 30 years in leadershippositions among multiple consumer products goods companies”,Kessler most recently served as the chairman of the board of directorsand chief executive officer of Lorillard Tobacco Company, from 2010to 2015. He also previously held senior roles with consumer goodsfirms including UST, Vlasic Foods International, Campbell SoupCompany and The Clorox Company.

“He has advanced corporate strategy through innovation,inorganic opportunities, and continuous portfolio improvement,”Classon said. “We are confident that his track record in drivingshareholder value and running highly successful businesses willadvance Perrigo’s consumer strategy and help the company deliver onour commitments to consumers and customers.” G

APPOINTMENTS

Bird heads up MEA for AcinoAcino has appointedAndrewBird to become the Swiss firm’s general

manager for the Middle East and Africa (MEA) region. As part ofthe appointment, Bird will also join the firm’s executive committee.

Citing Bird’s “25-year career in the pharma industry” – duringwhich he has held sales, brand-management and management rolesin the MEA region –Acino noted that since 2009, he had held “seniorpositions in the region, including South Africa, and most recently asgeneral manager of the Gulf, at Bristol Myers-Squibb”.

Acino said that Bird had an “excellent track record in developingeffective strategies and consistently delivering growth”. Bird observedthat “the healthcare landscape in the MEA is rapidly changing, andnow more than ever it is important to deliver high-quality affordablemedicines to all patients in these markets”. G

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