Mylan and Biocon obtain firstUSr ival to Herceptin · 2018. 11. 20. · 2 GENERICSbulletin 8D...

8 December 2017

Mylan and Biocon obtainfirst US rival to Herceptin

COMPANY NEWS 2Reddy’s can resume producing for Europe 2

AMRI is doubling up on aseptic capacity 2

Polpharma invests in local biosimilar plant 3

Pharmathen divests operations in Greece 3

Biocad strikes a deal to produce in Africa 4

Sweden’s Recipharm to close 4two local sites

Adamed targets Asia with deal in Vietnam 5

Mayne awaits “soft”results but has a plan 5

Johnson Matthey is investing for growth 6

MARKET NEWS 7EU broadens scope of 7biosimilars document

FDA aims to improve complex 7

drug process

EU Commission sees results of promotion 8

Dutch body proposes compulsory licensing 9

EMA offers guide on preparing for Brexit 9

Belgian brand deals are growing problem 10

Volumes and margins key 10to French savings

PRODUCT NEWS 11Mylan and Biocon get EU 11refilings accepted

Pharmathen sues for Tecfidera 11

filing delay

Pfizer takes Viagra on OTC path in UK 12

Samsung Bioepis must 12disclose over Brenzys

Pfizer faces dismissal of US infliximab suit 13

Formycon sets 2020 US 14ranibizumab date

Mutual and Reckitt settle over Mucinex 15

Glenmark’s Seretide rival nears in Nordic 15

REGULARSEvents – Our regular listing 8

Price Watch UK –Our regular listing 12

People – Wavelength appoints 16

Seri as company head

Issue No.333

Mylan and Biocon can press on with plans to introduce the first biosimilar of Genentech’sHerceptin (trastuzumab) monoclonal antibody in the US after the US Food and

Drug Administration (FDA) gave the firms’ Ogivri (trastuzumab-dkst) 420mg multi-dosevials the green light, meeting the 3 December target action date the agency had set earlierthis year (Generics bulletin, 8 September 2017, page 17). Sales of Herceptin in the USwere SFr2.00 billion (US$2.03 billion) in the first nine months of this year.

Holding exclusive commercialisation rights for Ogivri in the US, Mylan anticipates potentiallybeing the first company to introduce biosimilar trastuzumab under the global settlement agreementsigned with Genentech and parent company Roche in March this year. With confidential datesfor market entry, the agreement gives Mylan global patent licences for its biosimilar, providing thefirms a clear pathway to commercialise Ogivri (Generics bulletin, 17 March 2017, page 15).

Mylan also holds exclusive commercialisation rights for Ogivri in Canada, Japan, Australia,New Zealand, European Union (EU) and European Free Trade Association countries. Meanwhile,Mylan noted that the approval was the first from the FDA resulting from its global co-developmentpartnership agreement with Biocon, which currently covers six biologics.

Ogivri has been approved for all indications included in the label of Herceptin, Mylan noted,including for the treatment of HER2-overexpressing breast cancer and forms of metastatic stomachcancer. In July, the FDA’s Oncologic Drugs Advisory Committee (ODAC), in a unanimous decision,recommended granting a marketing approval for the biosimilar, finding “no clinically meaningfuldifferences” to Herceptin (Generics bulletin, 28 July 2017, page 18). Ogivri is the eighth biosimilarapproved by the FDA, and the second to treat cancer, following Amgen and Allergan’s Mvasi(bevacizumab-awwb) in September (Generics bulletin, 22 September 2017, page 11).

Mylan and Biocon have just resubmitted Ogivri to the European Medicines Agency (EMA),as well as the firms’ biosimilar Neulasta (pegfilgrastim) candidate (see page 15). Mylan notedthat the trastuzumab biosimilar was also under review by regulatory authorities in Australia andCanada, as well as in “several additional markets”. “It is already approved in 19 countries aroundthe world, including India,” Mylan noted. G

Australia is promoting BrenzysMerck, Sharp & Dohme’s Brenzys (etanercept) has become the first biosimilar to benefit from

specific uptake drivers through Australia’s Pharmaceutical Benefits Scheme (PBS). Underthe terms of a 2017-2018 budget agreement with industry and pharmacists, doctors are nowencouraged to prescribe the Brenzys biosimilar rather than Pfizer’s Enbrel reference brand fortreatment-naïve patients, while Australia’s Department of Health has streamlined the prior-authorisation process for Brenzys but not for Enbrel.

A note placed in the PBS schedule encourages prescribers to favour biosimilars in a bid toreduce costs, in line with recent advisory committee recommendations (Generics bulletin, 10November 2017, page 12), but does not make biosimilar prescribing mandatory. “Changes toprescribing software may in future also provide reminders or hints during the prescribing process,” theDepartment of Health added. A specific code included on the PBS schedule now gives doctors‘streamlined authority’ to write repeat prescriptions for Brenzys. But for Enbrel, prescribers mustobtain written authorisation from Australia’s Department of Human Services.

While Brenzys has been listed on the PBS since 1 April this year with an ‘a-flag’ substitutablestatus (Generics bulletin, 7 April 2017, page 11), the Department acknowledged that use ofthe biosimilar to date had been “low”. G

2 GENERICS bulletin 8 December 2017

COMPANY NEWSMANUFACTURING

Reddy’s can resumeproducing for EuropeDr Reddy’s has been permitted by German regulators to resume

production for European Union (EU) markets at its sterile injectablesfacility in Duvvada, India. The Indian company said in a filing withthe Bombay Stock Exchange (BSE) that the regulators had accepteda corrective and preventive action (CAPA) plan that it had submitted,and were set to re-inspect the plant by the end of 2018.

In September this year (Generics bulletin, 15 September 2017, page 3),Reddy’s revealed that regulators from Bavaria, Germany, had identifiedsix “major observations” at the Duvvada finished-dose site, but nocritical observations. Products made at the plant were not currentlyexported to the EU, the company stressed.

At that time, Reddy’s said that regulatory approval of its CAPA planwould be essential for the Duvvada plant to maintain its EU goodmanufacturing practice (GMP) status through to November 2018, atwhich point authorities would review the firm’s compliance with theCAPA plan and other applicable regulations.

The same German regulator had previously revoked the GMPcertificate for the Indian group’s Unit II solid-dose formulations facilityin Bachupally, India (Generics bulletin, 1 September 2017, page 7).

More recently, Reddy’s received an establishment inspection report(EIR) for the Duvvada plant from the US Food and Drug Administration(FDA). However, this was in the interests of transparency, and did notclose out an FDA audit conducted in March this year. G

BUSINESS STRATEGY/MANUFACTURING

AMRI is doubling upon aseptic capacityContract research, development and manufacturing organisation

AMRI has more than doubled its aseptic active pharmaceuticalingredient (API) production capacity. The US-based group has added amulti-purpose aseptic API line at its facility in Valladolid, Spain, whichthe firm believes will complement its former Euticals aseptic APIproduction plants in Bon Encontre and Tonneins, France.

“This investment supports our intent to serve our customers’ increasingdemand for aseptic APIs, linked to the need for physical control ofthese APIs and customised packaging configuration to improve assemblingwith customers’ drug-product production sites,” commented AMRI’schief commercial officer, George Svokos. The installed lines, he added,could handle “pilot-scale to multi-ton scale manufacturing”.

AMRI – which recently added an aseptic line for pre-filled syringesat its US manufacturing facility in Alberquerque, New Mexico – pointedout that “our sterilisation capability can be integrated with API productionor operate as a separate outsourced step for customers that do not havebulk sterile facilities or who may need additional capacity”.

“Bolstered by a range of supporting technologies, includingcustomised packing, seeding, milling and micronisation,” AMRIcontinued, “this new line ensures aseptic processing of APIs with tailor-made specifications and control of the physical properties of the finalproduct, including particle-size distribution.” The company stressed that itcould offer further integration with its finished drug-product capabilities.G

3GENERICS bulletin8 December 2017

COMPANY NEWSBUSINESS STRATEGY

Pharmathen divestsoperations in GreecePharmathen has agreed to sell for an undisclosed fee its Greek

commercial operations to a management buy-out team “as part ofits long-term strategy to become a leader focused on the developmentof innovative and complex pharmaceuticals”.

“This transaction completes the next step in our strategy forPharmathen,” explained Nikos Stathopoulos, managing partner of theBC Partners private-equity firm that acquired a majority stake two yearsago (Generics bulletin, 26 June 2015, page 3).

“Pharmathen, now based in Amsterdam, [the Netherlands], is 100%dedicated to its international markets. It will continue to invest significantlyin the research, development, production and marketing of innovativeand complex pharmaceuticals and technologies for the US market andthe 85 countries its products are already sold into globally,” he stated.

Excluding the Greek operations slated for sale, Pharmathen saidits roster of more than 265 customers worldwide enabled it to generateannual turnover of over C160 million (US$190 million) and earningsbefore interest, tax, depreciation and amortisation (EBITDA) in excessof C50 million. The company “continues to grow at double-digit rates”.

“Once the transaction closes, Pharmathen will be fully focused onthe development and out-licensing of differentiated and innovativepharmaceuticals,” the Netherlands-based group said.

Pointing out that its Sapes oral solids and injectables productionplant in eastern Greece had recently passed an audit by the US Foodand Drug Administration (FDA), the company said this would allowit to “produce and market its products in the US for the first time,which is the largest pharmaceuticals market globally.” “Pharmathenis a front-runner and has developed a portfolio of innovative products,including a number of long-acting injectables, which will accelerateits growth in the US and globally,” the firm stressed (Genericsbulletin, 20 October 2017, page 22).

The Greek operations will be “carved out and acquired by aconsortium of investors”, led by Pericles and Petros Vassilopoulos,and the firm’s existing local management team in Greece. “Pharmathenwill retain its name and the sold operations will be subsequentlyre-branded,” the company added.

“We are a group of dynamic entrepreneurs, with many years ofexperience in the pharmaceuticals market and we strongly believe inthe long-term potential of the new company,” commented PericlesVassilopoulos, who will lead the new enterprise in Greece. G

MANUFACTURING

Glenmark has faults at BaddiGlenmark is “providing a comprehensive response” to seven ‘Form

483’ observations made by US Food and Drug Administration (FDA)inspectors following an audit of the firm’s oral solids, semi-solids andliquids facility in Baddi, India, on 6-11 November.

The Indian company said it “would be replying to the FDA shortlyon the observations”, but did not disclose details of the faults listed bythe FDA auditors. Glenmark revealed that the Baddi facility – whichalso produces respiratory drugs – currently contributed around 10%of the firm’s US sales.

In the six months ended 30 September 2017, Glenmark – whichhad 126 generics authorised for distribution in the US as of that date– increased its US sales by a fifth to Rs17.7 billion (US$274 million),equivalent to nearly two-fifths of group turnover. G

MANUFACTURING

Polpharma invests inlocal biosimilar plantPoland’s Polpharma has announced that it is building a local biosimilars

production centre in Duchnice, Warsaw, and has invested aboutPLN1 billion (US$846 million) in the “infrastructure necessary forthe development of biosimilars”.

Speaking at the Innovative Europe Conference in Wroclaw in lateNovember, Polpharma’s corporate and external affairs director, MalgorzataMaurer, said that with a biologics patent cliff approaching it was thefirm’s “dream to produce biosimilars, responding to not only the needsof the Polish market, but also developing our global output”.

Claiming that “what constitutes the greatest challenge to thebiotechnology sector in Poland is now manpower shortage”, Maurerrevealed that Polpharma wants to employ 300 scientists in biotechdevelopment in “the near future”. She added that the company had engagedin biotechnology as “biologic medical products and follow-on biologicalsare the future of medicine”. “Polpharma’s investments in biotechnologyconstitute an opportunity not only for the company itself, but also forthe whole Polish economy,” she insisted.

Poland’s Industrial Development Agency announced that thecountry’s Development Fund would launch a biotechnology fund wortharound PLN3 billion in 2018. And according to Hubert Niewiadomski,director of the innovations department at the Ministry of Development,the Polish government is working on a biotechnology programme, whichwill involve constructing a biotechnology hub in Poland, financialsupport for clinical trials, and giving access to laboratory infrastructureto small and medium-sized enterprises.

Furthermore, Niewiadomski noted, the Polish government wasfocusing on the “mechanisms that will implement the drug financingsystem as well as on drug-coverage development”. “We also want tobring about a situation in which 17% of the budget for healthcare isallocated to pharmaceuticals,” he said. G

MERGERS & ACQUISITIONS

CVS eyes Aetna for US$69bnCVS Health, the largest US drugstore chain, has agreed to acquire

Aetna, the country’s third-largest health insurer by sales, in a cash-and-shares deal that values Aetna at US$69 billion. According to CVS,the transaction “fills an unmet need in the current healthcare system andpresents a unique opportunity to redefine access to high-quality carein lower-cost, local settings”.

Subject to regulatory approvals, customary closing conditions andapproval from both firms’ shareholders, the transaction is scheduledto close in the second half of 2018. It has been approved by both firms’boards of directors and values Aetna at around US$207 per share,comprising US$145 in cash and the remainder in CVS shares. Includingassumed debt, the total value of the deal is US$77 billion.

Describing benefits for consumers resulting from the transaction,CVS says Aetna’s “extensive network” of providers will offer greaterconsumer access through CVS. “This includes more than 9,700 CVSPharmacy locations and 1,100 MinuteClinic walk-in clinics.”

Aetna will operate as a stand-alone business unit within CVSand will be led by members of its current management team. Aetnachairman and chief executive officer Mark Bertolini will join CVSHealth’s board of directors. Recent strategic moves made by Aetnainclude launching Aetna Medicare Rx Select, a new prescription planoffering generics at a “low and predictable cost”. G


COMPANY NEWS

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Issue 333 l 8 December 2017

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Terms & Conditions: See www.generics-bulletin.com/subscribe.While due care has been taken to ensure the accuracy of information contained in this publication,the publisher makes no claim that it is free of error and disclaims any liability whatsoever for anydecisions or actions taken as a result of its contents.

Published by OTC Publications Ltd, 4 Poplar Road, Dorridge, Solihull B93 8DB, UK.Tel: +44 (0) 1564 777550 Fax: +44 (0) 1564 777524Company registered in England No 02765878.© OTC Publications Ltd. All rights reserved.Generics bulletin® is registered as a trademark in the European Community.Printed by Warwick Printing Company Ltd. ISSN 1742-0784

MANUFACTURING

Biocad strikes a dealto produce in AfricaRussia’s Biocad has struck a deal with Moroccan firm Sothema Labs

that will allow the companies to manufacture in Morocco biosimilarsbased on Biocad’s technology, the Russian firm has revealed. Theseoncology biosimilars – versions of MabThera (rituximab) and Avastin(bevacizumab) – will imminently be launched into several marketsin North Africa, Biocad announced, including in Morocco as well asthe Ivory Coast, Gabon and Senegal.

Citing the high demand for oncology biosimilars both in developedand developing countries, Biocad said the Moroccan market formonoclonal antibodies (mAbs) was worth around US$40 million. “Theoriginal drug is 30% more expensive than Biocad’s biosimilar,” theRussian firm stated, adding that “being the first supplier of the cancerdrug biosimilars, Biocad may become a leader in the field”.

Once the manufacturing site reaches its full production capacity,Biocad and Sothema expect to capture “more than 50% of the relevantcancer drugs market”.

“The efforts of our company, combined with the eager enthusiasmof our Moroccan colleagues, in transferring the production of biosimilarsto North Africa has brought remarkable results,” said Biocad chiefexecutive officer Dmitry Morozov. “In my opinion, this is eloquentevidence that Russian companies can compete with leaders of theinternational market.” Moreover, Morozov stated, the deal represented“the first successful case of transferring technologies for mAb drugproducts manufacturing to North Africa, amid the refusal of westerncompanies to implement such projects”.

Noting that the collaboration with Sothema was first instigatedfour years ago, Biocad said this was “time needed for technology transferand validation, the study of stability and quality of the produced drugs,and their authorisation”. The two biosimilars had been approved inthe first half of October 2017, Biocad noted.

Meanwhile, Biocad said it had also struck a separate deal to “localisethe manufacturing of finished-dosage forms for Biocad’s products inAlgeria, using the production capacities of their strategic partner”.

While no further details of the Algerian agreement were offered bythe Russian company, the announcement follows the signing of aco-operation deal between Biocad and local firm Biomad, as part of avisit to Algeria by Russian Prime Minister Dmitry Medvedev. Morozovsigned the agreement on Russia’s behalf, while Biomad chief executiveMohammed Amin Courabi signed on Algeria’s behalf. G

BUSINESS STRATEGY/MANUFACTURING

Sweden’s Recipharm toclose two local sitesSwedish contract developer and manufacturer Recipharm has

announced plans to discontinue manufacturing operations at two ofits local facilities in Stockholm and Höganäs as part of the company’s“ongoing initiative to improve profitability and competitiveness”.

Since 2015, Recipharm said it had “been implementing efficiencyactivities in the Swedish part of the business segment known as Solidsand Others”. These initiatives, it noted, included reducing headcountand rationalising low profitability contracts.

“While this is a strategic choice made to optimise our manufacturing,”commented chief executive officer Thomas Eldered, “it is a difficultdecision as the closure affects approximately 225 of our Swedishemployees.” Insisting that the firm would “see immediate efficiencyimprovements”, he added that in the long term, Recipharm would“offer a more competitive manufacturing structure for oral solids”.

Recipharm operates two sites in Stockholm, covering solid-dosageforms in a tablet presentation, and employing approximately 180 people.The firm plans to close these facilities during the second half of 2019.Recipharm’s Höganäs operation – which employs around 45 people –specialises in “sachet and stick-pack filling, primarily for powdersand granules”. Pointing out that the company would “evaluate differentoptions for the facility”, Recipharm said this included divesting thesite, with plans to “discontinue its involvement in operations by theend of 2018 at the latest”. Final decisions regarding both lossmakingfacilities will be made by the end of this year.

Separately, Recipharm has equipped its site in Brescia, Italy, andits Swedish facilities in Karlskoga and Uppsala, to supply serialisedproducts to the US in preparation for the US deadline in late November,as well as for European implementation.

In February 2016, Recipharm unveiled a three-year plan to investC40 million (US$47.3 million) in serialisation technology and processesto comply with the European Union’s Falsified Medicines Directive.And “while the FDA has announced a grace period ahead of the USDrug Supply Chain Security Act (DSCSA) deadline, companies canstill be penalised for failing to meet the mandate by 27 November 2017”,stated Staffan Widengren, Recipharm’s director for corporate projects.The contract-development and manufacturing firm said it could now“refocus our attention on ensuring we realise the additional benefits of

serialisation implementation, including improving line efficienciesand streamlining logistics operations”. G


COMPANY NEWSBUSINESS STRATEGY

Adamed targets Asiawith deal in VietnamPoland’s Adamed has struck a US$50 million deal to take a controlling

stake in Vietnam’s Dat Vi Phu, in what the Polish firm’s director-general Malgorzata Adamkiewicz called “a launchpad for the furtherdynamic expansion of the Adamed group into the Asia-Pacific region”.

“Dat Vi Phu manufactures a wide range of medicinal productsfor both the Vietnamese and neighbouring markets,” Adamkiewiczobserved, including territories such as the Philippines, Cambodia andMyanmar. Established in 2004, it claims to be “the fastest-growingcompany in the Vietnamese pharmaceutical market”. Based in the BinhDuong province near Ho Chi Minh city, it makes “nearly 300 medicinalproducts in most therapeutic classes” and employs around 200 staff.

“The deal provides for an extensive investment plan, includingthe transfer of Adamed’s knowledge and expertise,” the Polish firmoutlined. Describing the investment as forming “part of theinternationalisation of the Adamed group”, the company pointed out thatits export sales had increased by 15% in 2016.

Pham Tai Truong, founder of Dat Vi Phu, said Adamed’s investmentwas “an opportunity for our continued dynamic development”. Notingthat the Vietnamese firm had captured “a sizeable share of the Vietnamesepharmaceutical market” in more than the decade since it was founded,Truong said “co-operation with such an experienced partner will enableus to reinforce our position in the local market and to expand in theAsia and Pacific region”.

The deal took place against the backdrop of an official visit by PolishPresident Andrzej Duda to Vietnam as part of a trade mission. Theagreement was signed by Adamkiewicz and Truong in the presence ofDuda and Vietnamese President Tran Dai Quang.

“I am convinced that, in view of the scale of this transaction andfurther investments into the development of the company, our undertakingwill constitute a milestone in strengthening economic relations betweenPoland and Vietnam,” Adamkiewicz stated. The transaction constitutes“the largest direct Polish investment in Vietnam to date”. G

RESULTS FORECAST/BUSINESS STRATEGY

Mayne awaits “soft”results but has a planMayne Pharma is bracing for a “soft” set of financial results for its

financial first half ended 31 December 2017, chief executive officerScott Richards has warned.

However, he insists the Australian firm is “working on a rangeof initiatives which we expect will vastly improve future performance”,including generic launch opportunities.

Richards was speaking during Mayne’s recent annual generalmeeting that was held in Melbourne, as the firm presented four-monthfinancial results for the period ended 31 October, as well as a strategyand pipeline update. Six-month results are expected in February 2018.

With “price deflation pressures” in the US generic market drivingthe decline, the firm’s Generic Products Division (GPD) sales fell by atenth to US$88 million. Richards pointed to lower sales of certain oralcontraceptives acquired as part of the Teva portfolio acquisition (Genericsbulletin, 5 August 2016, page 5), as well as a decline in sales of thefirm’s butalbital/acetaminophen/caffeine (BAC) franchise.

To mitigate the current pricing pressures impinging the GPD, Richardssaid Mayne was focused on executing a number of initiatives. Theseinclude expanding and diversifying channels to market, extracting costsavings from optimising Mayne’s supply network, growing share of thefirm’s marketed products through aggressively pursuing new opportunities,and maximising the launch of new products.

Richards revealed that the firm currently had around 35 genericpipeline assets, including 17 filings pending US Food and DrugAdministration (FDA) approval. This was after filing three drugs andadding two products into development in the four months to 31 October.

Including the already-approved rivals to Clozaril (clozapine) tabletsand Monodox (doxycycline) capsules, Mayne is anticipating six productapprovals during its current financial year ending June 2018. “Clozapinetablets launched [in early November] and doxycycline capsules willlaunch in the new year,” Richards noted. “Other approvals expectedinclude a potential first-to-market opportunity.”

However, with approximately eight potential launches, Richardssaid Mayne was expecting a “much stronger generic pipeline to drivegrowth” in the firm’s 2019 financial year. “The most significant ofthese is Myring (ethinylestradiol/etonogestrel),” he noted, referringto the generic NuvaRing candidate being developed with Mithra.

Mayne also faced a number of abnormal one-off items during thefour months until 31 October, including losing US$7 million throughobsolete stock as well as the sell-through of short-dated stock belowcost following “the significant investment in inventory to support theTeva portfolio acquisition”. Richards said Mayne had also sufferedfrom lower Doryx (doxycycline hyclate) sales after the product wasgenericised in May 2016. Together, these effects caused Mayne’s groupsales to decline by 12% to A$151 million (US$114 million).

To cover the abnormal stock obsolescence and Doryx returns, aswell as the renegotiation of certain supply-chain contracts and other“expense-management initiatives”, Mayne has taken a A$13mrestructuring charge, Richards said. The group anticipates this will drivesavings of A$5m in the second half of the firm’s current financial year,and A$7m annually.

With a “solid balance sheet, a diverse operating model that includesspecialty brands and contract services, and an experienced team of peopleto lead and execute on our strategies, including stabilising our genericbusiness and bringing it back to growth”, Mayne was in a “strong positionto weather these challenging conditions”, Richards insisted. Gn [email protected]

COMPLIANCE

Concordia faces Nasdaq exitConcordia International could be forced to delist from the Nasdaq

Global Select market stock exchange if its share price does notimprove. The Canada-based off-patent drugs specialist has receivedan initial notification letter from Nasdaq’s listings qualification department,notifying the company that it has 180 days to regain compliance withthe exchange’s minimum bid-price requirement.

Nasdaq’s continued listing rules require that companies maintaina minimum bid price of US$1.00 per share. A failure to meet theminimum bid-price requirement ensues if a deficiency continues fora period of 30 consecutive business days.

Acknowledging that its shares had traded below US$1.00 for 30consecutive business days between 17 October and 28 November thisyear, Concordia said it had until 29 May 2018 to regain compliance,and maintain its Nasdaq listing, by achieving a closing bid price forits shares of at least US$1.00 for a minimum of 10 consecutive businessdays. As Generics bulletin went to press, Concordia’s shares were tradingat around US$0.52 on Nasdaq. The Canadian firm – which is alsolisted on the Toronto Stock Exchange (TSX) – noted that it could alsoapply to Nasdaq for additional time to regain compliance. G


COMPANY NEWS

BusinessSector

Six-monthsales

(£ millions)

Reportedchage (%)

Constant-currencychange (%)

Clean Air 1,194 +13 +7

Natural Resources 458 +9 +5

New Markets 143 -1 -7

Generics 82 +2 -1

Innovators 37 +27 +21

Health 119 +9 +5

Eliminations -61 - -

Johnson Matthey 1,853 +11 +5Figure 1: Breakdown by business sector of Johnson Matthey’s sales, excluding preciousmetals, in the six months ended 30 September 2017 (Source - Johnson Matthey)

BUSINESS STRATEGY/FIRST-HALF RESULTS

Johnson Matthey isinvesting for growthJohnson Matthey is investing heavily in broadening the product

pipeline of its Health bulk drugs business sector with a view to theunit delivering double-digit sales growth and an operating marginapproaching 30% by the chemicals group’s 2019-2020 financial year.

During the first six months of its financial year running until 31March 2018, the firm spent £8 million (US$11 million) on developingits pipeline of generic active pharmaceutical ingredients (APIs).

Chief executive officer Robert Macleod said a search for a sectorhead was “making good progress” and should be concluded by earlyin 2018. Former sector head John Fowler joined Piramal Pharma Solutionsas the Indian firm’s chief operating officer earlier this year (Genericsbulletin, 15 September 2017, page 20).

To increase capacity and improve operating efficiency, JohnsonMatthey is upgrading a bulk-drugs facility in Annan, UK, that the groupacquired in November 2014. “This is taking longer than we hadoriginally hoped, but we are making progress and should be in a positionto begin commercial-scale manufacturing in 2018,” Macleod said.He insisted “the foundations are set for break-out growth in themedium term”, but admitted that the Health sector did not yet have“a deep, broad portfolio”. “We expect our current generics pipelineto add £100 million of operating profit per annum by 2025,” he stated.

“We have commenced the reorganisation of our [Health] businessto better address the generic and innovator markets, and to optimisethe utilisation of our global manufacturing and development footprint”.

In the six months ended 30 September 2017, Generics sales withinthe Health sector edged up by 2% as reported, but fell by 1% at constantexchange rates, to £82 million as a contribution from the launch ofdofetilide in June 2016 helped to offset an anticipated decline in APIsfor attention deficit hyperactivity disorder (ADHD) drugs amid“increased competition”. “We saw increased demand for specialityopiates, led by customer orders ahead of an anticipated product launch,while sales of bulk opiates were slightly lower,” Johnson Matthey said.

Innovator API sales climbed by 27% to £37 million on “improvedpricing as well as increased volumes”. As a result, total turnover bythe Health sector in the six-month period advanced by 9% to £119million, equivalent to a 5% constant-currency rise (see Figure 1).

Johnson Matthey also credited “improved pricing” with the Healthsector’s operating profit – excluding the effect of a prior-year £2.4million credit linked to a US post-retirement medical benefit (PRMB)plan – growing by 12% to £21.7 million. G

HIKMA VENTURES – the venture-capital arm of the Jordanian group –has participated in a US$10 million financing round for “next-generation, minimally-invasive biosensor technology company”Biolinq. US-based digital health specialist Biolinq’s first commercialproduct is a biosensor patch that allows diabetes patients to monitortheir blood glucose levels continuously. Hikma Ventures has alsotaken part in a US$20.5 million financing round for clinical diagnosticdata and artificial intelligence company Prognos.

BEXIMCO PHARMA increased its turnover by 13.6% to BDT4.28billion (US$51.9 million) in its financial first quarter ended 30September 2017. The Bangladeshi company slightly improved itsgross margin to 46.1%, while its operating profit advanced by 11.0%to BDT958 million.

GRINDEKS raised its group turnover by almost a third to C95.9million (US$114 million) in the first nine months of 2017. Thegrowth was driven by a 37% increase in export sales to C88.8 million,as sales in Russia, the Commonwealth of Independent States (CIS)and Georgia climbed by 54% to C58.9 million. The Latvian companysaw a slight drop in domestic sales to C5.4 million, but turnover inother countries, including other Baltic States, rose by 11% to C30.7million. Finished-dosage form sales shot up by 36% to C89.7 million,while turnover from active pharmaceutical ingredients (APIs) suchas zopiclone and oxytocin rose by 12% to C5.3 million.

NAVITAS LIFE SCIENCES claims it is bringing “end-to-endresearch and development solutions to the generic drugs industry”.Having brought the Ecron Acunova and Intelent legacy brands underthe Navitas umbrella, the US-based group says its services coverbioequivalence and bioavailability studies, clinical-data management,and pharmacovigilance software and services. Navitas boasts“multiple study sites with a ready volunteer pool of over 20,000”and 210 beds.

WALGREENS BOOTS ALLIANCE (WBA) has advised its shareholdersto reject an unsolicited ‘mini-tender’ offer by TRC Capital to purchaseup to 2 million shares in the wholesaling and retailing giant. Theoffer, WBA commented, was more than 4% below its share priceon the last trading day before TRC made its approach for around0.2% of the firm’s shares.

SUN PHARMA says its holding in subcutaneous developmentspecialist ScPharmaceuticals has been reduced from 14.58% to12.31% following an initial public offering and series of sharetransactions. Having converted 13.0 million preferred shares into1.81 million of common stock equivalent to a 10.3% holding in theUS firm, Sun then spent around US$5 million on another 357,143shares. The lead off-patent molecules that the US company intendsto deliver subcutaneously through its Sc2Wear infusor are the diureticfurosemide and the antibiotic ceftriaxone.

JULPHAR said 16% sales growth in the United Arab Emirates (UAE)helped it to achieve a group turnover of AED992 million(US$270 million) in the first nine months of this year.

GUANGDONG ZHANJIANG JIMIN has received a warning letterfrom the US Food and Drug Administration (FDA) due to faults atits site in Zhangjiang, China, that included labelling an OTC drugas containing hydrocortisone when records showed the activepharmaceutical ingredient (API) was dexamethasone acetate. TheFDA placed the Chinese firm on import alert in August this year. G

IN BRIEF


MARKET NEWSREGULATORY AFFAIRS

EU broadens scope ofbiosimilars documentApatient question-and-answer document on biosimilar medicines has

been published by the European Commission in 23 languages, ina move that has been welcomed by industry stakeholders includingEuropean off-patent industry association Medicines for Europe. Thedevelopment broadens the scope of an existing document, publishedat the start of this year, that was previously available in seven Europeanlanguages (Generics bulletin, 4 November 2016, page 11).

“Access to such information on biosimilar medicines is fundamental,in order to improve European patients’ knowledge and empowerment,”Medicines for Europe stated, alongside European brand industry bodyEFPIA, the European Patients Forum (EPF), EuropaBio and doctorsassociation CPME. The bodies congratulated the European Commissionon “delivering clear, scientific and impartial information on biological– including biosimilar – medicines to European Union (EU) patients”.

Covering questions relating to the nature of biosimilars, how theyare manufactured and approved, their safety and their efficacy, as wellas addressing concerns over switching, side-effects and extrapolation,the publication updates a question-and-answer document publishedas part of the ‘Tajani’ consensus paper released in 2013 (Genericsbulletin, 3 May 2013, page 1).

“Empowering patients to engage, discuss and participate in decisionson their treatment options is key to improving patient outcomes andcontributing to the effective treatment of their individual conditions,”the associations concluded. G

INTELLECTUAL PROPERTY

Germany faces delay over UPCAConstitutional Court challenge in Germany appears to be the major

obstacle to a unified patent court (UPC) coming into effect inEurope. Germany is one of three of the 25 signatory states that haveto ratify the UPC agreement, along with France, which has alreadyratified, and the UK, which is in the final stages of doing so.

During a meeting held at the end of November, the European Councilnoted that while the UPC agreement had been ratified by 14 of theparticipating states – one more than the quorum of 13 states – Germanywas not among those 14 countries. “Germany’s President put ratificationon hold following an informal request by the federal ConstitutionalCourt on 12 June 2017,” a Council note remarked, adding that “Germanyand the UK must deposit their instrument of ratification of the UPCagreement before it can enter into force”.

In the UK, the Council observed, the “last steps” of the ratificationprocess were set to be finalised shortly. In a recent UK parliamentaryhearing on passing a draft UPC order on immunities and privileges,Jo Johnson – minister for universities, science, research and innovation –voiced the UK government’s commitment to “completing the legislativesteps” to ratify the UPC. However, he acknowledged, the UK wouldhave to “negotiate a new relationship with the UPC” following itswithdrawal from the European Union (EU) after March 2019.

The British Generic Manufacturers Association (BGMA), alongwith European off-patent association Medicines for Europe, recentlyurged the UK and the remaining 27 European Union (EU) memberstates to safeguard access to medicines with a “clear transition periodand future co-operation agreement after Brexit”, including in the area ofintellectual property (Generics bulletin, 1 December 2017, page 10). G

REGULATORY AFFAIRS

FDA aims to improvecomplex drug processVigorous competition expected from generic drugs in the US “is not

materialising”, US Food and Drug Administration (FDA)Commissioner Scott Gottlieb has claimed, as he outlined agency plansto improve processes for both generic drug approvals and developmentpaths for complex generics.

At the agency’s ‘Generic Drug Science Day’, Gottlieb stated thata key area of focus was “the general throughput of our own approvalprocess”. He acknowledged that speculators would acquire older off-patentdrugs with little or no competition and “jack up the price”, knowingthat it could take years before another generic competitor would enterthe market. Gottlieb said the agency had taken steps to “curb thisregulatory arbitrage”, as well as to “make its approval process moreefficient, at the same time that we vow to expedite the approval ofapplications for drugs that fall into these categories”.

In late June, the FDA implemented a new policy to accelerate thereview of abbreviated new drug applications (ANDAs) for drugs withfewer than three approved generics (Generics bulletin, 7 July 2017,page 7). At the same time, the agency published a list of off-patentUS brands with no approved generics, which it said should “help toreduce the financial incentive to play games with these drugs”.

Gottlieb pointed out that “the hurdle to approval can be higherwhen the drug is developed through a complex device like a metered-doseinhaler or an auto-injector”. In these cases, he noted, the branded drugmaker may still hold intellectual property preventing certain featuresof the device from being copied by generics firms.

“We have taken steps to provide industry with greater guidanceon the types of information and analyses that sponsors that want to copya branded product – like an auto-injector or a metered-dose inhaler –should submit to the FDA to support approval of such products,” Gottliebnoted. This includes generics that have “design differences relative tothe branded drug they are copying”, and how these differences “couldimpact the clinical effect or safety profile of the generic, and thus thesubstitutability of the medicine”.

The final guidance would clarify new policies related to thesesituations, Gottlieb said, including a principle allowing a generic tohave “certain labelling differences from the branded product, if suchlabelling changes stem from permitted design differences”.

Drug-device combinations were “just one type of complex generic”which endure obstacles to generic competition, Gottlieb pointed out,acknowledging that “other products raise complicated policy issues”.The FDA is also creating guidance for industry with “the aim ofclarifying ‘sameness’ requirements” for ANDAs, which would “beparticularly useful for complex generics”.

Meanwhile, the FDA on 9 January next year will host a publicworkshop on complex generics, focusing especially on orally inhaledand nasal drug products (OINDPs), to be held at its campus in SilverSpring, Maryland (Generics bulletin, 1 December 2017, page 1). Theworkshop aims to present the outcomes of the research projects initiatedunder the Generic Drug User Fee Amendments (GDUFA) regulatoryscience research programme, as well as provide “insights on factorsthat influence the performance of generic OINDPs”.

Furthermore, the agency will share its experience on the utility ofnovel analytical tools and methods for generic OINDP developmentand bioequivalence assessments, and consider how analytical methodsand procedures should be applied in the development and review ofANDAs for complex OINDPs. Gn [email protected]


MARKET NEWS

24 Januaryn 11th Pharmacovigilance Conference

London, UKThis one-day Medicines for Europe conference will lookat implementing pharmacovigilance legislation and currentdevelopments within the industry.

Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: [email protected]. Register online atwww.medicinesforeurope.com/events.

25-26 Januaryn 17th Regulatory and Scientific

Affairs ConferenceLondon, UKThis conference will follow the Pharmacovigilance event at thesame venue. There will be updates on regulatory developmentsand representatives from competent authorities in attendance.


12-14 Februaryn Access! 2018 – AAM Annual Meeting

Florida, USAThis event, organised by the Association for AccessibleMedicines, will look at regulatory topics and the challengesfacing the US generics industry.

Contact: Association for Accessible Medicines. Tel: +1 202 249 7100.E-mail: [email protected]. Register online atwww.accessiblemeds.org/events.

1-2 Marchn 2nd OTC Innovation & Business

Development ConferenceLondon, UKOrganised jointly by the Pharmaceutical Licensing Group andOTCToolbox, this event will focus exclusively on businessdevelopment and innovation in the consumer healthcare/OTCmarket. The theme for this event is capitalising on change.

Contact: OTCToolbox. Tel: +44 121 314 8757.E-mail: [email protected]: plg-group.com/events/3rd-otc-event.

25 Apriln 14th Legal Affairs Conference

London, UKThis one-day conference organised by Medicines for Europe willcover legal and intellectual-property developments regardinggenerics and biosimilars.


EVENTS – January – April 2018

SAVE THE DATE...Tuesday 9 October 2018, Madrid, Spain

MARKET RESEARCH

EU Commission seesresults of promotionPromoting the use of generics is helping to cut healthcare costs in

Belgium, Denmark and Finland, according to individual ‘CountryHealth Profiles’ published by the European Commission. Prepared inco-operation with the Organisation for Economic Co-Operation andDevelopment (OECD) and the European Observatory on Health Systemsand Policies, the 28 reports provide an “in-depth analysis of EuropeanUnion (EU) member states’ health systems”.

The report on Belgium notes that over the past decade, the countryhas “expanded its effort to encourage the use of generics”, by introducingfinancial incentives for patients, prescription quotas for doctors, mandatorypharmacy substitution for certain drug categories, and education andinformation campaigns for patients. “Reinvestment in the coverage ofnew innovative medicines is funded at least partly by promoting theuse of generics and biosimilars, and greater competition in the post-patentmarket,” the report states.

Meanwhile, a “number of policies” have been implemented in bothDenmark and Finland to “control the growth of pharmaceutical spending,including price controls and the promotion of generics”. In Denmark,generic volume share had “increased rapidly” from less than 40% in2007 to over 60% in 2015. Meanwhile, in Finland, “pharmacists areobliged to dispense the cheaper product and replace the prescriptionby a generic if available”.

In France, the volume share nearly doubled from 14.5% to 26.5%between 2006 and 2015, and the country’s ‘2017 National Action Plan’for the promotion of generics aims to increase this by a further fivepercentage points by 2018. Measures taken to incentivise genericprescribing and purchasing include linking remuneration for doctorsto generic prescribing and making mandatory international non-proprietaryname (INN) prescribing.

Generics shares in Germany and the UK are “among the highest inEurope”. The former has been “successful at shifting pharmaceuticalconsumption to generics – almost 80% of prescribed pharmaceuticals –although pharmaceutical prices remain comparatively high”. In the UK,generics now make up 78% of volumes and 39% of the value of reimbursedpharmaceuticals, “a much higher proportion than in most other EUcountries”. Meanwhile the report notes that pharmaceutical spending inSpain has “been curbed by a greater use of generics and price reductions”.

Countries with “low generic penetration” include Bulgaria, Hungary,Ireland and Italy, while the country with the lowest market share inthe EU “by far” is Luxembourg. And while the Czech Republic’sgeneric penetration was “below average”, the report insists this “does notrepresent any real burden for public health insurance”.

Although “comparable data on the share of generics in Croatia arenot readily available”, the report suggests the country’s share was“decreasing”. And despite measures to encourage generic prescribingin Romania, there is underuse due to the country’s clawback tax.

According to the Cyprus report, generic substitution is requiredin the public sector, although there are “no incentives for doctors andpharmacists to prescribe generics” in the private sector.

Generics in Greece are promoted through compulsory prescribingby active substance, mandatory generic substitution in pharmacies anduse of generics in hospitals. Latvia encourages the use of generics byobliging pharmacists to offer the cheapest version of prescribedpharmaceutical products and allowing substitutions.

The Netherlands report notes that cost-control measures includethe tendering of generics. Gn [email protected]



EMA offers guide onpreparing for BrexitGuidance has been published by the European Medicines Agency

(EMA) outlining “the practical and simplified requirements thatcompanies should follow when they apply for changes to their marketingauthorisation to allow for the continued marketing of their medicinein the European Economic Area (EEA) after the UK withdraws fromthe European Union (EU)”.

Noting that the guidance had been prepared “on the basis thatthe UK will become a ‘third country’ as of 30 March 2019”, the EMAobserved that the document built on previous guidance offered by theagency in May (Generics bulletin, 12 May 2017, page 9). EU lawrequires that marketing authorisation holders are established in the EUor EEA and that some activities relating to pharmacovigilance or batchrelease must be performed in the EU or EEA.

“Marketing authorisation holders of centrally-authorised medicinalproducts for human and veterinary use are reminded of certain legalconsequences that need to be considered in a timely manner,” the EMAstates in its guidance document. “Preparing for the consequences ofthe UK’s withdrawal from the Union is a significant matter for Europeanand national administrations, and also equally important for privateparties,” the guidance emphasises.

Subjects covered by the guidance include the possibility of marketingauthorisation holders grouping Brexit-related variations. These “canbe grouped, where the grouping does not delay implementation ofchanges which need to be in place by the time of the UK’s withdrawalfrom the EU”, the guidance states.

Other issues include how to classify Brexit-related changes impactingon manufacturing activities; whether several changes relating tomanufacturing can be grouped under a single Type II variation; howto submit an application for the transfer of a marketing authorisation;how to handle planned or ongoing regulatory procedures during thetransfer; and whether it is possible to submit a transfer of an orphandesignation in parallel with a transfer of a marketing authorisation.

In answer to a question on how to simplify Brexit-related transferapplications, the guidance states that “requirements for marketingauthorisation transfers are embedded in European Regulation 2141/96and cannot be waived”.

However, “in order to facilitate handling of a large volume oftransfer applications from one UK-based marketing authorisation holderto the same legal entity in the EEA, a combined version of each requiredsupportive document – except product information, and, when applicable,mock-ups – can be created covering all products affected”. In suchcases, these should be submitted with each related transfer application. G

INTELLECTUAL PROPERTY/PRICING & REIMBURSEMENT

Dutch body proposescompulsory licensingCompulsory licensing offers one feasible means to address “often

very high” prices for new medicines in the Netherlands, anindependent advisory body to the country’s government has proposed.

In a report commissioned by the Dutch minister for medical care,Bruno Bruins, the Dutch Council for Public Health and Society, theRVS, urges ministers to “use every available legal possibility” totackle drug prices that are “unacceptable for society”.

Issuing compulsory licences to override originators’ patents is putforward as one of four solutions, along with tackling abuses of dominantpositions, encouraging pharmacists to prepare compounded magisterialproducts for individual patients, and allowing patients to order medicinesabroad for delivery to the Netherlands.

Noting that several experts have called for medicines to be excludedfrom patenting on public-health grounds, the RVS observes thatcompulsory licensing is permitted under the World Trade Organization’s(WTO’s) agreement on trade-related aspects of intellectual-property rights(TRIPS). The advisory body observes that “countries are, however,extremely reluctant to use such measures because of the fear of traderepercussions”, such as a threat by the US Trade Representative to cancela trade agreement if Thailand issued a compulsory licence for clopidogrel.It points out that WTO rules allow for sanctions to be imposed oncountries that seek to intimidate others from using such freedoms.

Recognising that trade ministers seeking to strike internationaldeals may come into conflict with health ministers looking to limit drugcosts nationally, the RVS suggests that ministers responsible for publichealth should issue compulsory licences, rather than ministers with amore economic remit. The Netherlands’ National Health Care Institutehas, it points out, already “drawn up clear criteria” for when suchlicences are appropriate. G

INTELLECTUAL PROPERTY

AAM defends the IPR processConducting inter partes reviews (IPRs) through the US Patent and

Trademark Office (USPTO) is an “important tool established byCongress for efficiently weeding out invalid patents”, the US Associationfor Accessible Medicines (AAM) has argued in an amicus curiae brieffiled with the US Supreme Court in a dispute between energy firms.

The AAM argued that “because manufacturers of brand-nameprescription drugs can, and frequently do, use patents of dubious validityto prevent the introduction of competing generics, IPR is an importantcontinuation of Congress’ longstanding effort ‘to get generic drugsinto the hands of patients at reasonable prices – fast’”. G

REGULATORY AFFAIRS

WHO points to falsified drugsOne in 10 medicines in developing countries is substandard or falsified,

the World Health Organization (WHO) has claimed, as it callson governments to “take urgent actions to tackle this global problem”.Warning that substandard and falsified products were “becoming more andmore prevalent”, the group has published two documents on the subject.

The ‘Global surveillance and monitoring system’ report suggestsactions needed to prevent, detect and respond to substandard andfalsified medical products. Preventive actions include a “comprehensivelegal framework, multi-stakeholder engagement, education and awareness,and supply-chain integrity”. Meanwhile, “field detection and reportingsystems need to be improved and their use expanded”, the WHO insisted.

Issuing recalls, strengthening regulations, creating an evidence-based policy and a transparent legal process were among the suggestedresponses. The WHO also called for the “removal of barriers to the sharingof information, allowing more rigorous data analysis and research”.

The WHO’s study on the ‘Public health and socioeconomic impact’of substandard and falsified products, also launched by the WHO inGeneva, Switzerland, focuses on surveys conducted between 2007 and2016. According to the report, anti-malarial treatments and antibiotics“are the most common substandard or falsified products”, while othersrange from oncology drugs to contraceptives. Moreover, although mostcases received are from Africa, the WHO insisted that the data was “thetip of the iceberg, as many more are unreported”. G



Belgian brand dealsare growing problemConfidential ‘managed entry agreement’ (MEA) supply deals signed

between Belgian payers and originators for new brandedpharmaceuticals are a “major problem” that is putting growing pressureon Belgium’s medicines budget, according to local generics industryassociation FeBelGen. The country is seeking to save C188 million(US$223 million) from its medicines budget in 2018 – through acombination of 16 different savings measures, mainly on off-patentmedicines – to close a funding gap that represents around 4.5% ofBelgium’s total pharmaceutical budget.

Describing MEAs as a ‘Trojan horse’, FeBelGen said they were the“root cause for the budget overrun”. Although such deals had “hardly beenmentioned” in a 2015 stability pact with industry – including FeBelGenand originator body Pharma.be (Generics bulletin, 7 August 2015, page17) – they “took very quickly an important share of expenditure”.

FeBelGen managing director Joris van Assche told Generics bulletinthat the lack of transparency around the terms of MEAs was a particularconcern. “We know that they exist, but that’s all,” he observed, withretrospective gross spending figures revealing that 71 MEAs existedin 2016, representing around 16% of pharmaceutical spending. FeBelGenindicated that several stakeholders have expressed the concern thatthis proportion could rise to around a quarter by 2019.

Emphasisng this “growing concern” amid healthcare industrystakeholders over MEAs – articulated in a number of parliamentaryquestions on the subject – van Assche suggested the matter wouldbe a key issue for Belgium’s next government to address from 2019.

“So far, we have managed to cope with the budget for 2018, butit is clear the MEAs are becoming an increasing threat for thesustainability of the generics business segment,” van Assche stated.“We will not be able to eternally seek savings from the off-patent segmentto fund exponentially rising costs of innovation.” “The stability pact endsin 2018,” van Assche noted, “and we will definitely have to envisageother concepts afterwards.”

Under the Belgian budget plans, around C35 million will be savedby lowering reimbursement rates for medicines purchased by hospitals,with around C22 million to come from off-patent medicines and anotherC13 million saved on infliximab alone, FeBelGen stated. While thiswould have “no direct impact on generic and biosimilar companies”,pressure to grant deeper rebates would increase.

An additional C9 million is expected to be saved through increasingmedical specialists’ targets for prescribing the cheapest available medicine.Meanwhile, a further C56 million in spending will be cut through a‘ceiling price model’ being introduced in the retail market, which willsee only the lowest-priced versions reimbursed for medicines with anidentical active ingredient, a comparable pack size, and the same dosageform and strength.

While FeBelGen welcomed this model, van Assche said its quarterlyschedule for reviewing prices to determine which medicines wouldbe reimbursed was too short, and could have a chilling effect oncompetition. “We would have preferred six months,” he stated, suggestingthat some firms might not be prepared to accept the risk of having tobe prepared to supply the market with such a short lead time.

Moreover, FeBelGen had protested against a delay on implementingthe ceiling price model until two years after generic market entry. Callingthis two-year moratorium “a lost opportunity for savings”, the associationsaid it constituted an “artificial prolongation of the privileged positionof the brand company, after patent expiry”. Gn [email protected]

REGULATORY AFFAIRS

Volumes and marginskey to French savingsAdditional healthcare savings of C1.13 billion (US$1.33 billion)

could be unlocked in France by raising the volume penetration rateof generics in the country to around 85%, according to a report bylocal financial auditory body the Cour des Comptes. At the same time,the organisation suggested, further savings of around C800 million couldbe achieved by reducing margins for manufacturers and wholesalerssupplying generics to pharmacies.

Pointing out that the volume share of the market enjoyed by genericsin Germany and the UK was higher than 75%, the Cour des Comptessaid that data from local health insurance group CNAMTS indicatedthat the French share was “still only 45%”. This, the financial bodystated, was due to doctors’ prescribing habits that favoured originalbrands, representing “an obstacle to the spread of generics”.

“In particular,” the Cour des Comptes added, “the developmentin coming years of biosimilar medicines in a market estimated at C1billion is of major importance in terms of the potential savings thatthey can generate.” However, the average biosimilar penetration ratewas only 6.2% in France, the report noted, compared to 13.5% inGermany and 42.5% in Italy.

Meanwhile, the report also pointed out “considerable margins ongenerics agreed by manufacturers and wholesalers with pharmacies”.By reducing these margins through price cuts, the Cour des Comptessuggested, around C800 million could be saved. G

PRESCRIBING GUIDELINES

BGMA hails clearer NHS guide

Clarifications to English National Health Service (NHS) prescribingguidance that is aimed at saving £190 million (US$256 million)

per year by cutting prescriptions for ineffective treatments or drugsfor minor conditions have been welcomed by the British GenericManufacturers Association (BGMA).

While the guidance continues to advise against prescribing OTCproducts such as herbal and homoeopathic remedies, NHS England hasmodified its stance on certain “low-value prescription items”, includingliothyronine, lidocaine plasters and immediate-release fentanyl (Genericsbulletin, 14 April 2017, page 7).

On liothyronine – which is currently the subject of a pricing probeby the UK’s Competition and Markets Authority (Generics bulletin,1 December 2017, page 12) – the guidance has been softened to advise‘de-prescribing’ the thyroid therapy “in all appropriate patients”, notevery patient. A specialist exemption for post-herpetic neuralgia hasbeen added to advice not to prescribe lidocaine plasters, while usingimmediate-release fentanyl “in palliative care by a recognisedmulti-disciplinary team professional” is now deemed “acceptable”.

BGMA director-general Warwick Smith observed that NHSEngland’s consultation on its guidance had “caused concern amongstsome patients that they would no longer receive the medicines thatthey truly needed”. “That was never the intention,” he noted, “and wewelcome the fact that NHS England has clearly listened to concernsexpressed and has clarified its proposals as a result.” Smith pledgedto work with the NHS and the UK’s Department of Health to ensurethe policies were “properly understood and implemented”. G


PRODUCT NEWSMULTIPLE SCLEROSIS TREATMENTS

Pharmathen sues forTecfidera filing delayPharmathen is suing partner Lachman Consultant Services for the

consultancy firm’s alleged failure to timely file the Netherlands-based company’s abbreviated new drug application (ANDA) for ageneric version of Biogen’s Tecfidera (dimethyl fumarate) in the US.

Claiming a breach of contract, gross negligence and negligentperformance of services, Pharmathen asserted in a New York districtcourt that “Lachman’s failure in this regard caused Pharmathen to forfeitits right to achieve critical first-filer status for its ANDA under theHatch-Waxman Act, and precluded Pharmathen from obtaining potentialmarketing exclusivity rights for a generic version of Tecfidera and therevenue streams those first-to-file rights bring”.

The first possible filing date for ANDAs referencing Tecfidera– one year before the expiration of the New Chemical Entity (NCE)exclusivity date, the so-called ‘NCE-1’ date – was 27 March this year,Pharmathen notes. The firms signed a partnership agreement two monthsearlier, on 23 January, court documents show.

“Despite assuring Pharmathen that Pharmathen had provided allof the information required for Lachman to timely file the ANDA, anddespite representing to Pharmathen time and again that the ANDAwould be filed on 27 March, Lachman inexplicably failed to do so,”the Greek firm alleges. “Lachman filed Pharmathen’s ANDA for dimethylfumarate on 28 March…with full knowledge that 27 March was thesteadfast and critical filing deadline.”

As Generics bulletin reported earlier this year, Tecfidera attractedat least 26 ANDA filers on the ‘NCE-1’ date (Generics bulletin, 11August 2017, page 20). These included the biggest firms in the industry –Teva, Sandoz and Mylan – as well as significant US players such asAmneal, Aurobindo, Lupin and Par. US sales of Tecfidera were US$2.46billion in the first nine months of this year. G

CHOLESTEROL-LOWERING DRUGS

Dutch Crestor appeal defeatedActive pharmaceutical ingredients (APIs) supplier Resolution

Chemicals has failed to persuade the Netherlands’ Supreme Courtto overturn an appeals court’s ruling that the Dutch part of Europeanpatent EP0,521,471 – and its associated supplementary protectioncertificate (SPC) running until 29 December 2017 – is valid. The‘471 patent and the SPC cover rosuvastatin acid “or a non-toxicpharmaceutically acceptable salt thereof”, and thereby protectAstraZeneca’s Crestor (rosuvastatin calcium).

On appeal to the Supreme Court, Resolution – which holds a Dutchmarketing authorisation for rosuvastatin zinc – had argued that the ‘471patent’s reference to a “non-toxic pharmaceutically acceptable salt”limited the scope of the patent and the SPC to a number of specificsalts. But the Supreme Court said that a skilled person would haveunderstood the patent’s inventive concept to be a new group of statins,including rosuvastatin, without being limited to specific salts cited asexamples in the patent specification.

Addressing Resolution’s argument that the ‘471 patent was invaliddue to added subject matter beyond sodium or calcium salts ofrosuvastatin, the Supreme Court said the Court of Appeal had been correctto find that the disclosed sodium and calcium salts were “non-exhaustiveexamples” and did not preclude the disclosure of other salts (Genericsbulletin, 18 March 2016, page 12). G

BIOLOGICAL DRUGS

Mylan and Biocon getEU refilings acceptedMylan and Biocon have had their European applications for

biosimilar pegfilgrastim and trastuzumab accepted for review bythe European Medicines Agency (EMA), following withdrawal of bothapplications in the wake of issues identified at Biocon’s manufacturingplant. Earlier this year, an audit by French regulators found faults atthe Indian firm’s biological drug-product facility in Bommasandra,India (Generics bulletin, 14 July 2017, page 3).

Biocon had previously noted that resubmitting the filings wouldbe “part of the EMA procedural requirements” linked to a re-inspectionof the Bommasandra plant, which had also been the subject of 10 ‘Form483’ observations of deficiencies after a US Food and Drug Administration(FDA) inspection (Generics bulletin, 1 September 2017, page 21).

“Biocon has completed the corrective and preventive actions(CAPAs) outlined as a result of the audit observations,” Mylan stated.“The CAPAs will be confirmed during re-inspection, which will becompleted as part of the regulatory review process.”

Rajiv Malik, president of Mylan, said that “having gone throughinitial reviews of the applications and after completing the CAPAsfrom the EMA audit, we are even more confident with the strength ofour marketing authorisation applications”.

Additionally, Malik noted, “the voluntary action indicated (VAI)designation we received from the FDA gives us further confidence in thereadiness of the manufacturing site”. G


PRODUCT NEWS

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

Price WatchIndex

PharmacyProfit Index75.1 46.0

Monthly change -3.7 Monthly change +4.6

November 2017 November 2017

UK pharmacies saw an uplift in the dispensing profit that theyenjoyed for our typical basket of 20 popular generics in November,

reversing a trend that had been observed for several months inthe second half of 2017.

After a downward trend observed in September and Octoberthat saw the Pharmacy Profit Index fall to a low of 41.4 in October(Generics bulletin, 10 November 2017, page 14), November sawthe profit figure climb to £774.56 (US$1,041.53). However, thiswas still less than half the profit enjoyed when the Index was setat 100 in March 2016.

With a basket purchase price that fell from £1,677.15 in Octoberto £1,599.01 in November, the Price Watch Index fell by 3.7 pointsto 75.1. Meanwhile, the reimbursement price held fast at £2,373.57,lifting the profit enjoyed by pharmacies as the Pharmacy ProfitIndex rose by 4.6 points to 46.0. 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 PharmacyProfit Index is calculated on the same basis by applying Drug Tariff reimbursement prices to the basket.

November 2017

PRICE WATCH ....... UK

Basket Price Reimbursement Price Pharmacy Profit£1,599.01 £2,373.57 £774.56

ERECTILE DYSFUNCTION DRUGS

Pfizer takes Viagraon OTC path in UKMen in the UK will soon have OTC access to Pfizer’s Viagra

(sildenafil) blockbuster after an application to switch the erectile-dysfunction drug was given the green light by the country’s Medicinesand Healthcare products Regulatory Agency (MHRA).

Following a consultation,Viagra Connect sildenafil citrate 50mgfilm-coated tablets will be reclassified from prescription-only medicine(POM) to pharmacy (P) status, meaning they will be available froma pharmacist without a prescription for men aged 18 years or oldersuffering from erectile dysfunction. The maximum daily dose is onetablet, with a pack size of up to eight tablets.

The MHRA – which pointed out that other medicines containingsildenafil would still be available on prescription – confirmed to Genericsbulletin that generic 50mg formulations would remain prescription-onlyunless and until they successfully underwent a similar switch procedure.

Pfizer said it was “working on plans” to launch Viagra Connectas a non-prescription medicine in UK pharmacies “in the spring of 2018”.“In the interim,” the originator added, “the company will be implementingan extensive training and education programme with pharmacies.”

A UK supplementary protection certificate (SPC) linked to theEuropean sildenafil molecule patent EP0,463,756 expired in late June2013 (Generics bulletin, 28 June 2013, page 20). Generic film-coatedand chewable tablets are now widely available. G

AUTOIMMUNE DRUGS

Samsung Bioepis mustdisclose over BrenzysSamsung Bioepis must disclose to Pfizer details of its manufacturing

process for its Brenzys (etanercept) biosimilar, Australia’s FederalCourt has ordered. Pfizer had appealed against a lower court’s denialof a preliminary discovery order that the originator had sought todetermine whether three process patents were infringed (Genericsbulletin, 31 March 2017, page 10).

Pfizer had, on appeal, argued that it had reasonable grounds to thinkthat the upstream bioprocessing phase for Brenzys included processesin the three patents at issue: Australian patents 2005,280,034 and2005,280,036 describing the production of polypeptides and TNFR-Igfusion protein respectively; and Australian patent 2008,242,632 thatcovers the “use of low temperature and/or low pH in cell culture”.

Given the biosimilarity and “very similar glycosylation profile’of Brenzys to Pfizer’s Enbrel reference brand, the originator insistedthat it had reasonable cause to believe that both companies were usingthe same upstream bioprocessing procedures that would infringe thethree patents. Samsung Bioepis countered that biosimilarity did notimply that two products had been made using the same process, and alsopointed out that Pfizer had changed the production process for Enbrel.

Justice John Nicholas, of three judges on the federal panel, saidit was “more than a mere possibility or mere speculation” that SamsungBioepis or its supplier “may have used a method within one or moreof the broadly defined claims of the patents”.

Expert testimony offered by Pfizer scientist Neysi Ibarra, including onthe similarity of glycosylation profiles, “should have been given weight”by the lower court judge, he said. “Her evidence disclosed that she wasfamiliar with the patents and Pfizer’s manufacturing process, andthat she had the necessary technical knowledge and experience to giveprobative evidence relevant to that topic,” Nicholas stated.

Remanding the dispute, Nicholas said the lower court judge should“hear from the parties in relation to the scope of the preliminary discoveryto be ordered”, as well as on “preserving any confidentiality in thematerial to be produced”.

Australia’s Department of Health has just introduced measuresaimed at encouraging prescribers to favour Brenzys over Pfizer’s Enbrelreference brand (see front page). G

OPHTHALMOLOGY DRUGS

AAM weighs in on RestasisThe US Patent and Trademark Office’s (USPTO’s) Patent Trial and

Appeal Board (PTAB) should deny the Saint Regis Mohawk Tribe’smotion to dismiss inter partes reviews (IPRs) for six US patents shieldingAllergan’s Restasis (cyclosporine) based on the Tribe’s sovereignimmunity to such challenges, the Association for Accessible Medicines(AAM) has urged.

In an amicus brief filed in support of petitioners Akorn, Mylanand Teva, the AAM said the PTAB was “anything but hamstrung” fromexercising its authority to take a ‘second look at an earlier administrativegrant of a patent’, citing opinion from the US Supreme Court’s landmarkCuozzo decision concerning IPRs.

“The board had authority to institute proceedings with Allerganas a patent owner, and it retains discretion to complete its reviewnotwithstanding a transfer expressly calculated to prevent a final decision,”the AAM insists. G


PRODUCT NEWSAUTOIMMUNE DISEASE TREATMENTS

Pfizer faces dismissalof US infliximab suitPfizer’s US antitrust complaint accusing Janssen of using

anticompetitive tactics to unlawfully “maintain the dominance” ofJanssen’s flagship Remicade (infliximab) original in the US at the expenseof Pfizer’s Inflectra (infliximab-dyyb) biosimilar is at risk of beingthrown out, after the Johnson & Johnson subsidiary filed a motionto dismiss the case for failure to state a claim.

Filed in the US District Court for the Eastern District of Pennsylvania,Janssen’s motion insists that Pfizer has failed to plead facts showingthat it has suffered antitrust injury, and that Janssen’s rebate anddiscounting practices harmed competition.

Pfizer has accused Janssen in its antitrust suit filed in Septemberof using exclusionary contracts that “foreclose Pfizer’s access to anoverwhelming share of consumers” coupled with “anticompetitivebundling and coercive rebate policies designed to block both insurersfrom reimbursing, and hospitals and clinics from purchasing, Inflectraor other biosimilars of Remicade despite their lower pricing” (Genericsbulletin, 29 September 2017, page 13).

But Janssen first insists that Pfizer has thus far not pleaded factsshowing that Janssen’s discounts and rebates, “rather than Pfizer’sown unwillingness to offer lower prices on Inflectra or bundleddiscounts on Pfizer’s many profitable, billion-dollar products”, arethe cause of Inflectra’s “alleged poor record to date”.

“The complaint is silent on whether Pfizer has sought tocompete against Janssen by offering bundled discounts on its ownwide range of pharmaceutical products,” Janssen observes. “As oneof the world’s largest pharmaceutical companies, Pfizer certainlyhas the capacity to do so.”

Second, Janssen states, Pfizer has also failed to plead whether ithas actually offered a lower net price to payors on Inflectra than thenet price to payors that Janssen has offered on Remicade, “after alldiscounts and rebates are taken into account”. “It is…plausible thatPfizer’s failure to offer a lower net price is responsible for the allegedfailure of payors to prefer Inflectra over Remicade on their formularies,”Janssen insists.

In its antitrust suit, Pfizer noted that Inflectra was launched inNovember 2016 at a wholesale acquisition cost (WAC) 15% lowerthan Remicade, and said that Inflectra’s WAC had dropped to 19%lower than Remicade in the meantime. Pfizer also competes with Merck’sRenflexis (infliximab-abda) biosimilar that launched in July at a 35%discount to Remicade (Generics bulletin, 28 July 2017, page 1).

“The complaint says little to nothing about whether or to whatextent Pfizer has offered discounts and rebates sufficient to competewith Remicade to payors,” Janssen reiterates. Pfizer, Janssen says, hadattempted to “distract the court with the allegation that the ‘list price’for Remicade has increased”. “But as Pfizer is well aware, the pricesfor Remicade that Pfizer cites – whether in terms of the list price,known as the WAC, or the Average Sales Price (ASP) reported by thegovernment – do not take into account rebates or discounts to payors,who reimburse the providers.”

“As in the case of the complaint’s failure to address Pfizer’s effortsto offer competing ‘bundles’ of discounts and rebates, Pfizer’s failureto plead facts showing that it offered payors a lower net price requiresdismissal,” Janssen notes.

“Disappointed with the sales of its recently launched biologicInflectra, Pfizer now seeks to blame Janssen for the drug’s lack of successrather than its own apparently meagre efforts to compete.” Gn [email protected]

LANNETT has had its 505(b)(2) new drug application (NDA) forcocaine hydrochloride 4% and 10% topical solution accepted forfiling by the US Food and Drug Administration (FDA) under theproposed trade name Numbrino. The firm noted that the submissionwas supported by two Phase II, randomised, double-blind studies in“several hundred patients”, as well as a Phase I pharmacokineticstudy. Separately, Lannett has entered into an agreement with AralezPharmaceuticals to become “the exclusive distributor in the US”of the generic version of AstraZeneca’s Toprol XL (metoprololsuccinate) extended-release tablets. Aralez acquired the US rightsto the drug from the originator late last year (Generics bulletin, 14October 2016, page 14). The product, which is available in 25mg,50mg, 100mg and 200mg strengths, will be launched under Lannett’slabel “in the near future”. Financial terms of the deal were not disclosed.

DAIICHI SANKYO has launched its Lixiana OD (edoxaban) orally-disintegrating tablets in Japan. The anticoagulant is available in 15mg,30mg and 60mg strengths.

MYLAN has launched its Abevmy (bevacizumab) 100mg and 400mgbiosimilar in India, after the drug controller general of India (DCGI)approved the anti-angiogenic for all indications of originator Roche’sAvastin original biologic.

TELIGENT has received approval from the US Food and DrugAdministration (FDA) for its hydrocortisone butyrate 0.1% lotion.“As we were the first abbreviated new drug application (ANDA)applicant to submit an ANDA with a paragraph IV certification,”the company claimed, “Teligent is eligible for 180 days of genericdrug exclusivity.” The firm expects to launch the product by Marchnext year. Teligent has also obtained US approval for its betamethasonedipropionate 0.05% ointment.

CIPLA has secured approval from the World Health Organization(WHO) for its tuberculosis prophylaxis treatment, Q-Tib, whichwill be marketed by the firm globally. The Indian company notedthat Q-Tib would be available in a novel fixed-dose combinationin a single tablet, pointing out that “this was the first time thatsuch a combination had been made available in the world”.

DR REDDY’S – through its wholly-owned subsidiary PromiusPharma – has announced its fifth consecutive, first-cycle new drugapplication (NDA) for its Proprietary Products business unit, afterreceiving approval for its Impoyz (clobetasol propionate) 0.025%cream. The Indian company noted that Promius would work with itspartner Encore Dermatology “to bring this novel treatment to providersand their patients”.

AUROBINDO has received final approval from the US Food and DrugAdministration (FDA) for a generic version of AstraZeneca’sSeroquel XR (quetiapine fumarate) extended-release tablets,available in 50mg, 150mg, 200mg, 300mg and 400mg strengths. Citingdata from Iqvia, Aurobindo observed that the product had an estimatedmarket size of US$816 million for the year ended October 2017.

MITHRA has announced that it has successfully extended the shelf-life of its Tibelia (tibolone) synthetic steroid to 36 months, followinga decision by the UK Medicines and Healthcare products RegulatoryAgency (MHRA). The product is a generic of Mithra’s own Livialhormone replacement therapy. Other tibolone-based products have a 24-month shelf-life, the Belgium-based firm pointed out, citing a “uniqueformulation” for an “unstable active ingredient” developed by Mithra,for which an international patent application had been filed in May. G

IN BRIEF

PRODUCT NEWS


OTSUKA has become the first firm to get approval from the USFood and Drug Administration (FDA) for a pill incorporating a sensorthat digitally tracks whether patients have ingested the medicine. TheAbilify MyCite (aripiprazole) addition to the Japanese originator’soff-patent schizophrenia brand works by sending a message from thetablet’s senor to a wearable patch made by Proteus Digital Health.The patch then transmits information to a smartphone application thattracks compliance. Patients can also give physicians and caregiversaccess to information via web-based portals.

TITAN PHARMACEUTICALS has had its marketing-authorisationapplication (MAA) for Probuphine (buprenorphine) accepted forfiling by the European Medicines Agency (EMA) as a substitutiontreatment for opioid dependence. The US firm described its sub-dermalimplant as “the only six-month treatment for opioid dependence thatdelivers buprenorphine continuously”. In October, Titan receiveda notice of allowance from the European Patent Office (EPO) fora method-of-use patent that it says will protect until 2023 treatingopioid dependence with a sub-dermal buprenorphine implant. Thefirm is also using its ProNeura drug-delivery technology to developa ropinirole implant for idiopathic Parkinson’s disease.

PHYTON BIOTECH has received a US$400,000 grant from theBill & Melinda Gates Foundation to “fund research and developmentof an alternative method of producing artemisinin”. The Germancompany said it would use the funding to undertake a proof-of-conceptstudy to show that the malaria treatment – typically derived from theleaves of sweet wormwood plant – could be manufactured directlyfrom plant cell cultures using the firm’s plant cell fermentation(PCF) technology.

BIOPHARMX intends to present data at a scientific symposium thatshow its BPX-01 topical minocycline gel “may exhibit relevantantimicrobial and anti-inflammatory properties for the treatment ofacne”. The data from animal models in mice will be presented at aconference in Philadelphia, US, hosted by the American Societyfor Cell Biology (ASBC) and the European Molecular BiologyOrganization (EMBO).

INDIVIOR has obtained approval from the US Food and DrugAdministration (FDA) for Sublocade, “the first and only once-monthlyinjectable buprenorphine formulation to treat moderate to severeopioid-use disorder”. The company intends to make the extended-releasesubcutaneous formulation available to US patients during the firstthree months of next year. Citing its ‘opioid blockade’ study, Indiviorsaid Sublocade 300mg – previously known as RBP-6000 – had “fullyblocked the drug-liking effects of hydromorphone” for a full monthin most patients. Commenting on the approval, FDA CommissionerScott Gottlieb said the agency would issue two guidance documents,one on guidelines for approving depot formulations of buprenorphine,and the other on establishing additional endpoints to “facilitate thedevelopment of better treatments” for opioid dependence.

PROMIUS PHARMA says its Zembrace SymTouch (sumatriptan)3mg injection achieved its primary and secondary endpoints in apost-approval clinical trial in 268 subjects. The wholly-owned subsidiaryof Dr Reddy’s has marketed the migraine treatment in the USsince April last year.

OREXO has obtained a pan-European centralised authorisation forits Zubsolv (buprenorphine/naloxone) sublingual tablets. The Swedishfirm has licensed European marketing rights for the opioid-dependencetreatment to Mundipharma. G

VALUE ADDED MEDICINES - IN BRIEFOPHTHALMIC DRUGS

Formycon sets 2020US ranibizumab dateBiosimilars developer Formycon is preparing to launch in 2020 its

FYB201 alternative to Genentech’s Lucentis (ranibizumab) brandupon patent expiry in the US. The German company believes FYB201is the only biosimilar of the ophthalmic agent worldwide that is currentlyundergoing a Phase III clinical trial for highly regulated markets.

“Alongside advanced clinical testing,” the Munich-based firmcommented, “Formycon is working intensively and in close consultationwith the respective regulatory authorities on the preparation of thefiling documents.”

The German group says it is developing “an innovative applicationsystem, underpinned by the company’s own patent applications”.Furthermore, the firm claims to have “created additional tools for ahighly promising positioning of FYB201 on the market”.

In partnership with the Bioeq joint venture between Poland’sPolpharma and Germany’s Santo Holding, Formycon is conductinga global, pivotal Phase III clinical trial of FYB201. According to anentry in the US clinicaltrials.gov database, Bioeq is currently recruitingpatients aged 50 or over with neovascular age-related macular degeneration(AMD) for its ‘Columbus-AMD’ study. The primary outcome measureis the change from baseline in foveal centre point (FCP) retinal thicknessby spectral domain optical coherence tomography (SD-OCT) at month one,and the estimated primary completion date is March 2020.

Formycon pointed out that it had developed the trial in consultationwith both the US Food and Drug Administration (FDA) and the EuropeanMedicines Agency (EMA). The company intends to launch FYB201in Europe upon Genentech’s patent expiry for Lucentis in 2022.

For its second treatment for neovascular AMD, the German firm’sFYB203 biosimilar of Regeneron’s Eylea (aflibercept), Formycon saysit is “completing its final measures to establish a highly efficient biosimilarmanufacturing process”. Having submitted several formulation patentapplications, the firm believes FYB203 is “in a highly promising positionfor its market launch following the expiry of the reference product’slegal protection in the US in 2023”.

The German group is also optimising “a suitable manufacturingprocess” for its FYB202 biosimilar candidate for Stelara (ustekinumab).Earlier this year, Formycon signed a term sheet to jointly develop withSanto the psoriasis and Crohn’s disease treatment, with the formerbearing up to 30% of development costs in return for up to 30% ofglobal marketing proceeds (Generics bulletin,11 August 2017, page 22).

For the firm’s undisclosed FYB205 project, “work has been steppedup on the development of a suitable cell line”. G

ONCOLOGY DRUGS

Mylan links up with AspenMylan has launched in the US the Myleran branded generic rival

to Otsuka’s Busulfex (busulfan) 60mg/10ml single-dose vials forwhich South Africa’s Aspen received final approval from the US Foodand Drug Administration (FDA). Mylan said the leukaemia drug hadUS sales of US$97 million in the 12 months ended September 2017.

In the next few weeks, Mylan expects to extend its injectablesoffering to US hospitals with four strengths of heparin sodium multi-dose vials for which it has just obtained FDA clearance. And the firm hasalso just secured FDA approval for the first generic alternative to Akorn’sCapastat (capreomycin sulfate) 1g vials. G

15GENERICS bulletin

PRODUCT NEWS

8 December 2017

OTC MEDICINES

Mutual and Reckittsettle over MucinexSun’s URL Pharma and fellow Indian firm Mutual have ended US

litigation with Reckitt Benckiser over the originator’s Mucinex(guaifenesin), following a settlement reached between URL and Reckitt.The litigation had revolved around a previous settlement agreement– that the originator allegedly refused to honour – which involvedsupplying Mutual with a US authorised generic of Mucinex 600mgextended-release tablets once the first generic version of the OTCcough and congestion remedy became available (Generics bulletin,13 March 2015, page 15).

URL and Mutual had claimed that “both Mutual and consumersof extended-release guaifenesin products” had been harmed after Reckitt“expressly repudiated any obligation to supply Mutual with suchtablets” after Perrigo introduced the first US generic more than fouryears ago (Generics bulletin, 5 April 2013, page 12).

“In the absence of Reckitt’s breach, Mutual’s earlier market entrywould have substantially benefitted Mutual in its competition withPerrigo,” the lawsuit elaborated. But “as a result of Reckitt’s conduct”,Mutual was put at “a significant disadvantage”. Furthermore, Reckitt’sconduct “prevented the development of a broad and vibrant genericmarket to compete with Reckitt’s 600mg Mucinex product”.

Noting that URL and Reckitt had reached a settlement, a Pennsylvaniadistrict court ordered that the lawsuit be dismissed in its entirety withprejudice, but gave no further details of the settlement terms.

Mutual had originally claimed that the financial harm suffered bythe firm was “at least on the order of tens of millions of dollars”. Ithad sought treble ‘actual’ damages, direct and indirect damages “flowingfrom Reckitt’s breach of the settlement agreement”, a ruling orderingthat the originator honour the settlement, and fees. G

RESPIRATORY DRUGS

Glenmark’s Seretiderival nears in NordicGlenmark expects to obtain shortly national marketing authorisations

for partner Celon Pharma’s generic version of GlaxoSmithKline’s(GSK’s) Seretide Accuhaler (fluticasone/salmeterol) dry-powder inhalerin Denmark, Finland, Iceland, Norway and Sweden, after successfullyclosing the decentralised registration procedure for the respiratory productin the Nordic region.

Responding to a Generics bulletin query on projected dates forreceiving the national marketing authorisation approvals in order tobegin commercialising the product, a Glenmark spokesperson notedthat the approval timelines would “vary from country to country”.

Meanwhile, the Indian firm says commercialisation is also dependenton obtaining substitution and pricing approvals in the Nordic markets.

Under a development and licensing agreement signed two yearsago, Glenmark gained semi-exclusive marketing and distribution rightsfor the asthma and chronic obstructive pulmonary disease (COPD)treatment in 15 European markets (Generics bulletin, 6 November 2015,page 17). These include Germany and the UK, as well as Belgium, Italy,the Netherlands and Romania, and the aforementioned Nordic markets.

Glenmark also told Generics bulletin that the proposed Seretide rivalhad been filed in all 15 markets, “as per the strategic deal with Celon”.

As well as being the first approval stemming from the Celonagreement, Glenmark pointed out, the generic Seretide Accuhaler wasalso Glenmark’s first inhaled respiratory product approval in Europe.

Glenn Saldanha, Glenmark’s chairman and managing director,pledged that the company would continue to develop respiratory products,“especially devices in Europe”. Meanwhile, closing the registrationprocess in developed markets “reinforces Glenmark’s capability anddetermination towards the respiratory segment”, Saldanha added.

Discussing potential competition for generic Seretide in Europe,Glenmark identified Sandoz’ AirFluSal Forspiro (fluticasone/salmeterol),which the firm currently offers in Nordic markets including Denmarkand Sweden, as well as Teva’s Airexar Spiromax and Aerivio Spiromaxsalmeterol xinafoate/fluticasone propionate inhalers, both of whichare similar hybrid alternatives to Seretide.

Meanwhile Elpen also offers its Rolenium (fluticasone/salmeterol)Elpenhaler in multiple Nordic markets. Concerning the metered-doseinhaler formulation, Cipla recently said it planned to launch the firm’sSereflo (fluticasone/salmeterol) product in Sweden and Finland in the“coming quarters” (Generics bulletin, 17 November 2017, page 5).

In a brief statement, Glenmark also confirmed that it has plans todevelop generic fluticasone/salmeterol for the US market, where thereference product is marketed by GSK under the Advair name. G

AUTOIMMUNE DISEASES TREATMENTS

Janssen opposes on RemicadeAUS district court should dismiss Celltrion and Pfizer’s motion for

an interlocutory appeal against an earlier order from the same courtdenying the firms’ motion to dismiss, for lack of standing, patent-infringement litigation over Janssen’s US cell-growth media patent7,598,083, the originator has urged. The ‘083 patent relates to Janssen’sRemicade (infliximab), which Celltrion and Pfizer have rivalled withtheir Inflectra (infliximab-dyyb) biosimilar since late last year (Genericsbulletin, 16 December 2016, page 1).

Janssen had filed the patent-infringement complaint in late May,the third time that the originator had sued Celltrion and Pfizer forinfringing the ‘083 patent (Generics bulletin, 9 June 2017, page 17).

At the end of October, Massachusetts District Judge Mark Wolfdenied Celltrion and Pfizer’s motion to dismiss litigation, after findingthat Janssen had not, as they had argued, assigned rights to the ‘083patent “to more than 200 other companies” in a series of “employeesecrecy agreements”, including parent company Johnson & Johnsonand its subsidiaries and affiliates. Janssen was the sole owner of the‘083 patent, Wolf found, and therefore the firm was not required tojoin any other party to litigation and had standing to bring the case.

In their motion to certify an interlocutory appeal, Pfizer and Celltrionhave also moved to stay proceedings in the event Wolf certifies the appeal.

“After succeeding in delaying trial for over one year by makinga belated and ultimately unsuccessful challenge to Janssen’s standing,defendants seek further delay,” Janssen insists. G

GENITOURINARY DRUGS

Apotex adds PBS dutasterideApotex has had an alternative to GlaxoSmithKline’s Avodart

(dutasteride) 500µg capsules added to Australia’s Pharmaceuticalbenefits Schedule (PBS). The Canadian company has also securedsimilar reimbursement listings for allopurinol 100mg and 300mgtablets, for gabapentin 300mg and 400mg capsules, for gabapentin600mg and 800mg tablets, and for terbinafine 250mg tablets.

Meanwhile, Sandoz has expanded its roster of PBS-listed centralnervous system (CNS) drugs with entries for escitalopram 10mg and20mg tablets, as well as for lamotrigine 25mg and 50mg tablets. G


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APPOINTMENTS

AAM supports Azar asUS health secretaryThe US Association for Accessible Medicines (AAM) has thrown

its support behind Alex Azar’s nomination as secretary of Healthand Human Services (HHS). Association head Chip Davis said that theformer Eli Lilly executive’s “previous professional experience” – includingsix years with the HHS department, four as general counsel – providedhim with a “unique background and the expertise necessary to addressthe nation’s healthcare challenges”.

However, members of the Democratic Congressional ProgressiveCaucus organisation raised concerns regarding Azar’s nomination, andasked that his proposed appointment not be confirmed until pendinginvestigations into Lilly’s pricing for insulin drugs in the US – relatingto a time when Azar was Lilly’s US president – “are fully resolved”.“Mr Azar played a key role in raising drug prices, many by doubledigits, across many of their products, including the life-sustaining insulin,”the members said of Azar’s decade in senior management positionswith the US-based originator.

The contrasting views on Azar’s proposed appointment coincidedwith Azar’s nomination hearing before the Senate Health, Education,Labour and Pensions Committee, in which he proclaimed that drugprices were too high and that his experience helping to implement theMedicare Part D federal programme “can help us address these issues”.

The price of drugs was among four “critical areas” on which Azarpledged to focus his efforts, as well as making healthcare “more affordable,more available and more tailored to what individuals want and need intheir care”, and “shifting the focus in our healthcare system from payingfor procedures and sickness to paying for health and outcomes”.

Azar is in line to take on the role of HHS secretary after US PresidentDonald Trump last month nominated him to be a permanent replacementfor current acting HHS secretary Eric Hargan (Generics bulletin, 17November 2017, page 11). Following the resignation of Trump’s originalpick, Tom Price, earlier this year (Generics bulletin, 13 October 2017,page 24), Don Wright stepped into the role on an acting basis, beforebeing replaced by Hargan in October.

Meanwhile, Andrei Iancu also presented during his nominationhearing to be under secretary of Commerce for Intellectual Propertyand director of the US Patent And Trademark Office (USPTO). Iancu –currently serving as managing partner of US law firm Irell & Manella– was nominated by Trump to the position in early September. G

INDUSTRY ASSOCIATIONS

Stoller joins Pro GenerikaChristoph Stoller, who earlier this year became the general manager

of Teva’s operations in Germany and Austria, has joined the boardof German industry association Pro Generika as deputy chairman. Hewill work alongside Hexal’s chairman and head of strategy, portfolioand market development, Wolfgang Späth, who has just been re-electedas Pro Generika’s chairman.

Späth pledged to work with his colleagues in the association to“campaign on the concerns of the generics companies that guarantee eachday the security and affordibility of medicines provision in Germany”.

Other members of the association’s board are Mylan’s Heike Streu,Aliud Pharma’s Ingrid Blumenthal and Fresenius Kabi’s Boris Bromm,as well as Josip Mestrovic from Zentiva and Martin Schwarz fromAurobindo’s Puren Pharma. G

APPOINTMENTS

Wavelength appointsSeri as company headFormer head of Sun Pharma’s active pharmaceutical ingredients

(APIs) operation Iftach Seri has been named as chief executiveofficer of Wavelength Pharmaceuticals, the APIs business that privateinvestment firm SK Capital recently acquired from Perrigo forUS$110 million (Generics bulletin, 1 December 2017, page 2).

Seri was among four “highly-experienced Israeli pharmaceuticalexecutives” that SK Capital had said would be joining Wavelength’sboard when announcing the deal, alongside Itzhak Krinsky, MeronMann and Arik Yaari (Generics bulletin, 1 September 2017, page 3).

Wavelength noted that Seri was previously the chief executiveofficer of Israeli drugstore chain New Pharm, “and held numerous andvaried roles at Teva Pharmaceutical, providing him a broad perspectiveand skillset across the global API industry”.

Meanwhile, Wavelength has appointed Tami Cohen as chief financialofficer. Cohen previously served as chief financial officer and corporatecontroller of beverages firm SodaStream’s manufacturing subsidiary.“Tami brings a strong technical and financial skillset to Wavelengthand will be a key partner to Iftach and the broader organisation acrossboth tactical and strategic initiatives,” Wavelength added.

Principal of SK Capital, Stephen d’Incelli, said the appointmentwould “drive Wavelength’s organic and acquisitive growth and continuedevolution into a customer-centric API solutions provider G

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