Generics bulletin 8 January 2016 · Operating under the Osmotica name, ... afully-integrated...

8 January 20168 January 2016

Zydus Cadila warned over Indian facilities 2Vertical-Trigen group to join 2with OsmoticaStada gets Argentine foothold viaVannier 3Sun’s Halol facility is hit by a US warning 3Mylan makes claims to Strides over Agila 4Endo to keep an eye on small acquisitions 4Valeant cuts prices withWalgreens deal 5

MARKET NEWS 6

US Senate considers expedited FDA path 6Problem settlements kept down in the EU 6BGMA and MHRA to collaborate 7on safetyFDA label rule will be published in July 7US biosimilars must mirror label of brand 8

PRODUCT NEWS 9

Sandoz advances its 9European etanerceptAccord clears path on UK bendamustine 9Biocad bevacizumab receives 10Russian nodAustralian ruling lets state 10claim damagesApotex appeals after US 11pegfilgrastim barRichter pegfilgrastim accepted 12by the EMAMerck and Samsung get 13Korean infliximabSpain’s Rovi is ready for enoxaparin in EU13Alvogen settles with 14Roche on oseltamivirEPO upholds Teva’s patent 14for Copaxone

REGULARS

Events – Our regular listing 15

People – Alvotech hands post 15to Schimmelpennink

COMPANY NEWS 2

Market entry of biosimilar epoetins and granulocyte-colony stimulating factors(G-CSFs) has reduced the price per treatment day by more than a quarter while

allowing greater volumes to be supplied to patients, a study conducted by IMS Healthfor the European Commission has found.

Examining 2014 data, IMS said biosimilar epoetins had captured 43% of the EuropeanUnion (EU) market versus their reference products, and 15% of the total market. The priceper treatment day had fallen by 28% versus the reference product and 27% versus the totalmarket prior to biosimilar entry, but total market volumes had increased by 16%.

Biosimilar G-CSFs secured just over four-fifths of the EU market versus their referencedrugs, as total market prices per treatment day tumbled by 28%. At the same time, the volumeof treatments supplied doubled when compared to the year before biosimilar entry. “Pricechanges per treatment day in the total market vary considerably across the different EuropeanEconomic Area (EEA) countries,” IMS observed, highlighting a span between just an 8%fall in the UK to a 72% reduction in Bulgaria, based on list prices and average invoiced prices.

Human growth hormones captured a third of the market versus their reference products,but the price reductions were just 7%. The 2014 data showed little impact to date of the recentintroductions of biosimilar follitropin, insulin and anti-tumour necrosis factor (Anti-TNF)biosimilars, but the Commission and IMS plan to update the report on an annual basis.

The study was published alongside a summary of a workshop on access to and uptake ofbiosimilars that the Commission held in October last year. “To date,” the Commission notesin its summary, “biosimilars account for less than 0.5% of the US$221 billion market ofbiological medicines worldwide.”

Pledging to “continue to foster dialogue among stakeholders at European level”, theCommission stressed that “multi-stakeholder dialogue and co-operation” was also crucial ata national level, as was “patient-oriented and patient-friendly information on biosimilars”. TheCommission intends to reconvene the workshop’s stakeholder group – including the EuropeanBiosimilars Group (EBG) within the European Generic and Biosimilar medicines Association(EGA) – in one year’s time. G

EU biosimilars cut costof treatment by quarter

Rebates that will be payable in the US from the first quarter of 2017 on generic drugs thatexperience price increases in excess of inflation would have saved the US at least US$1.4

billion if they had been in effect over the past decade, according to a report by the Office of theInspector General (OIG) within the US Department of Health and Human Services (DHHS).

Under the legislative provisions enacted at the start of November in the ‘Bipartisan BudgetAct of 2015’, manufacturers will be required to pay an additional rebate to the Medicaid healthinsurance programme if the price of a generic drug has increased faster than inflation(Generics bulletin, 6 November 2015, page 15).

While the total savings figure of US$1.39 billion would have been achieved between 2005and 2014, the OIG report found, for 2014 alone the additional savings would have amountedto US$465 million, which was almost twice as much as the actual rebates collected of US$246million. The OIG report covered the top 200 generic drugs by Medicaid reimbursement in eachyear, with 869 drugs appearing at least once over the decade. For the 1991-2004 period, the OIGobserved, the additional rebates received by Medicaid would have come to US$966 million.G

US prepares to reap rebate reward

NNOOWW PPUUBBLLIISSHHEEDD WWEEEEKKLLYYNext issue – 15 January 2016

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COMPANY NEWS

2 GENERICS bulletin 8 January 2016

Private-equity backed Vertical-Trigen – the holding company of USgenerics player Trigen Laboratories – is aiming to create a “fully-

integrated specialty pharmaceutical and generics company” by agreeingto merge with US-based drug-delivery specialist Osmotica. Financialdetails of the transaction or a scheduled closing date were not disclosed.

Operating under the Osmotica name, the combined entity will“utilise Vertical-Trigen’s strong front-end commercialisationcapabilities” to “leverage Osmotica’s portfolio of attractive approvedproducts, differentiated formulation technology, proven research anddevelopment function, and high-quality manufacturing facility toeffectively compete in the pharmaceuticals sector”.

Osmotica currently has two approved abbreviated new drugapplications (ANDAs) – for alternatives to Pfizer’s Procardia XL(nifedipine) and Janssen’s Ditropan XL (oxybutynin) extended-releasetablets – as well as a pipeline of “numerous ANDA programmes andseveral innovative neurology-based new drug application (NDA)programmes”. The firm’s NDAs approved through the hybrid 505(b)(2)pathway include venlafaxine and desvenlafaxine extended-release tablets.

“The new entity will continue to offer Vertical-Trigen’s fullportfolio of branded and generic products, as well as Osmotica’ssuccessful extended-release formulations upon achieving the requiredregulatory approval,” the firms explained.

Avista Capital Partners’ healthcare industry executive, BrianMarkison – who took the role of Vertical-Trigen’s executive chairmanwhen Avista acquired its majority stake in the firm at the end of 2013(Generics bulletin, 10 January 2014, page 31) – will lead thecombination in the role of chief executive officer. Meanwhile Osmotica’spresident and chief executive officer, Praveen Tyle, will become chiefscience officer and president of science and technology. “WithOsmotica’s formulation, development and manufacturing capabilitiesand Vertical-Trigen’s strong commercialisation arm and productportfolio,” Markison commented, “the combined firm has the makings ofa fully-integrated branded and generic specialty pharma company.”G

MERGERS & ACQUISITIONS

Vertical-Trigen groupto join with Osmotica

8 January 2016 Issue 244

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Deficiencies at two of Zydus Cadila’s Indian manufacturing facilitieshave led the US Food and Drug Administration (FDA) to issue

a warning letter. The letter covers the Indian firm’s formulations factoryin Moraiya, as well as its Zyfine oncology active pharmaceuticalingredients (APIs) plant in Ahmedabad.

“We will respond to the FDA to address the observations withinthe statutory time permitted in the letter,” Zydus Cadila stated. “Weare committed to resolve all the issues and revamp our quality systemsand processes as the top-most priority.”

As Generics bulletin went to press, the FDA had not yetpublished the warning letter on its website.

Disclosing the warning letter in a notification to the BombayStock Exchange, Zydus Cadila did not expand on the nature of theFDA’s observations. However, the company stressed, none of itsproducts marketed in the US used APIs produced at the Zyfine facility.

Three-and-a-half years ago (Generics bulletin, 3 August 2012,page 11), the FDA issued a close-out letter indicating that deficienciesat the Moraiya plant had been addressed.

The site in Moraiya near Ahmedabad is one of two FDA-approvedoral solids facilities the firm has in India, the other being in Baddi.The company’s Nesher Pharma subsidiary in the US operates acontrolled substances plant.

“We take quality and compliance matters very seriously and standby our commitment to fully comply with current good manufacturingpractice (cGMP) quality standards across all our facilities,” ZydusCadila stated. “The company is working hard to ensure that thecommitments made to the FDA are fully completed, and will continueto take all necessary steps to ensure that the FDA is fully satisfiedwith our remediation of the above facilities.”

In its most recent financial year ended March 2015, USFormulations sales of around US$550 million accounted for abouttwo-fifths of Zydus Cadila’s group turnover. The Indian companyclaims to rank eighth by generic prescriptions filled in the US. G

MANUFACTURING

Zydus Cadila warnedover Indian facilities

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Stada intends to gain a foothold in Latin America by agreeing topurchase Argentine privately-owned generics producer Laboratorio

Vannier. The German group will pay a maximum of US$13.0 millionincluding a “small performance-related component”. The transactionis scheduled to close early this year.

Buenos Aires-based Vannier recorded sales of ARS72.0 million(US$7.40 million) in its financial year ended 31 August 2015,representing growth of 43% in local-currency terms.

Vannier specialises in “niches which are subject to few priceregulations,” focusing on central nervous system, cardiology anddiabetes drugs. Its primary-care and hospital units offer both brandedand unbranded generics. The company’s production facility is certifiedto Argentine good manufacturing practice (GMP) standards.

Stada is planning to combine products from Vannier’s portfoliowith its own pipeline. Matthias Wiedenfels, Stada’s executive directorwho oversees business development and integration activities, said theGerman group would also “use the network, production and sellingpower of Vannier for OTC branded products from the Stada portfolio”.

Hartmut Retzlaff, Stada’s executive chairman, said the group was“strengthening our Generics segment in an emerging market, whichwill demonstrate growth potential after the current crisis”. He addedthat Vannier “was clearly profitable even during the crisis, and willbe part of the expected economic upswing”.

At present, Stada has a negligible presence in Latin America.In the first nine months of 2015, Western and Central Europeaccounted for 70% of the group’s C1.53 billion (US$1.66 billion)turnover (Generics bulletin, 20 November 2015, page 9), whileEastern Europe and the Commonwealth of Independent States (CIS)added another 23%. The remaining 7% of sales were generated inStada’s Asia-Pacific and Middle East and North Africa (MENA)region, where the German group has been expanding in countriesincluding Egypt and Vietnam. G

COMPANY NEWS

3GENERICS bulletin8 January 2016

MERGERS & ACQUISITIONS

Stada gets Argentinefoothold via Vannier

Teva’s joint venture with Takeda in Japan to “deliver Teva’s high-quality generic medicines and some of Takeda’s off-patent products

to patients and healthcare professionals” is set to be “established inor after April 2016”, the Japanese firm has revealed.

Under the “unprecedented partnership”, unveiled at the end oflast year (Generics bulletin, 9 December 2015, page 1), the Israelifirm will own a 51% stake, while Takeda will have the remaining49%. The two companies already collaborate on marketing Teva’sCopaxone (glatiramer acetate) in Japan.

The Japanese firm noted that the products it would transfer intothe new business – including Blopress (candesartan), Takepron(lansoprazole) and Basen (voglibose) – had total sales of around ¥125billion (US$1.05 billion) in Takeda’s most recent financial year ended31 March 2015. Moreover, the venture would also be “instantlyaccretive to Teva’s earnings per share in 2016 and beyond”.

A complex transaction involving Teva’s majority-owned Japaneseaffiliate Taisho Pharm will result in two companies entitled Teva-Takeda Pharma and Teva-Takeda Yakuhin, with the latter wholly-owned by the former. G

STRATEGIC ALLIANCES

Teva-Takeda JV set for April

Sun Pharma has received a warning letter from the US Food andDrug Administration (FDA) covering its deficient finished-dose

formulations facility in Halol, India. The Indian firm’s managingdirector, Dilip Shanghvi, said exports to the US from the Halol siterepresented “a high single-digit number in percentage terms for ourtotal sales”, with the facility being the only one from which Sun hadfiled injectable products for FDA review.

The FDA warning letter stems from an inspection at the site inSeptember 2014, which resulted in the facility at the end of that yearbeing issued with several ‘Form 483’ observations (Generics bulletin,5 December 2014, page 3). While Sun continued to ship drugs fromthe site to US customers, supply constraints resulted in the firm lastyear issuing a sales warning for its current financial year ending 31March 2016 (Generics bulletin, 7 August 2015, page 8).

“Our initial reading of the warning letter indicates that it isessentially based on the observations in the ‘483,” managing directorDilip Shanghvi told investors, insisting that there was “no doubt onthe safety of our products in the market”.

Specific violations of current good manufacturing practice (cGMP)listed in the FDA’s letter include: failing to establish and followappropriate sterilisation procedures; unjustified rejection of vialsduring media fill; failing to maintain floors, walls and ceilings suchthat they could be easily cleaned; and not investigating batchdiscrepancies or failures. The FDA also said Sun had “failed to establishand document the accuracy, sensitivity, specificity and reproducibilityof test methods employed by the firm”, while the agency highlightedissues with record-keeping and controls over computer systems.

“These examples are serious cGMP violations,” the FDAconcluded. “Your quality system does not ensure the quality, safetyand effectiveness of your drug products.”

Shanghvi said Sun was forming an “internal taskforce” to workalongside external consultants on an existing “robust remediationplan” for the Halol facility. Noting that the firm had already made“significant investments in automation and training to enhance itsquality systems”, he said Sun was “evaluating whether we need tosignificantly or materially augment our remediation plan”.

Pointing out that the FDA had withheld product approvals fromHalol following its September 2014 inspection, Shanghvi noted “thissituation will continue until all issues are resolved and the site comesback into compliance”. “I believe that customers will perceive potentialdisruption as a risk, and that may impact our ability to win long-termmarket share if we are not able to address this in a short period oftime,” he admitted.

“Post the inspection at Halol,” Shanghvi said “almost all our majorsites have been inspected by the FDA without any major observations.”

Separately, Sun has streamlined its US manufacturing operations byselling to Nostrum Laboratories for an undisclosed sum its FDA-approved liquids and semi-solids facility in Bryan, Ohio. US-basedNostrum – which picked up the facility’s employees and related products– said the deal would support its own plant in Kansas City, Missouri,along with its research and development centre in Mumbai, India.

Nostrum has also bought “additional products from Sun’s wholly-owned subsidiaries”, which Sun will manufacture for the firm aftertransferring sales and marketing responsibilities. The Indian firm’s chiefexecutive officer for its North America business, Kal Sundram, said Sunwould “benefit from the collaboration with Nostrum on product-development opportunities in the future”. G

MANUFACTURING/DIVESTMENTS

Sun’s Halol facility ishit by a US warning

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Mylan is looking to claim back a portion of the US$1.65 billionit paid Strides Shasun for the Indian firm’s Agila Specialties

injectables business, pursuant to US Food and Drug Administration(FDA) warning letters Mylan recently received covering three formerAgila manufacturing facilities, all located in Bangalore, India.

In a disclosure to the Bombay Stock Exchange (BSE), Stridesnoted that it had “received notifications of claims from Mylan…inrelation to certain provisions contained in the sales and purchaseagreement [for Agila] and in relation to certain regulatory concerns”.“The company believes it can successfully defend these claims andis in the process of evaluating each claim notified by Mylan,” theIndian company observed.

Nevertheless, Strides said it had doubled to US$200 millionprovisions allotted for “potential claims on warranties and indemnities”in relation to the Agila transaction. “In any event, the company isconfident that the ultimate claims will be within the escrowed amountsand will not result in unforeseen liabilities.”

Sites covered in those warning letters – which Mylan received inAugust 2015 (Generics bulletin, 1 September 2015, page 2) –include Agila’s special formulation facility in Bommasandra that wassubject to a warning letter in September 2013, three months beforeMylan completed its acquisition of the Agila business. The warningletter also covers Mylan’s OTL plant, which neighbours the site inBommasandra, and a sterile products division site in Bilekahalli. At thetime, the FDA informed Mylan that the firm was “on notice of theviolations” contained in the September 2013 warning letter.

When its agreement to buy Agila was first announced at thebeginning of 2013 (Generics bulletin, 8 March 2013, page 1), Mylanbrokered a deal worth around US$1.75 billion. But the warning letteragainst Agila’s special formulation facility in Bommasandra causedMylan to restructure terms and hold back US$250 million of the cash(Generics bulletin, 10 January 2014, page 3).

The US firm at the time noted that Strides would receive the fullamount “upon satisfaction of certain regulatory conditions relating tothe warning letter”, with Strides pledging to meet those requirements“sometime in 2014”. The Indian firm later settled on collecting US$150million from Mylan, thereby losing out on US$100 million incontingency payments (Generics bulletin, 3 October 2014, page 5). G

COMPANY NEWS


MANUFACTURING

Mylan makes claimsto Strides over Agila

Endo’s US generics business is at “critical mass” following itsUS$8.0 billion acquisition of Par, but the US firm remains interested

in opportunities to “bulk up” in niche areas where its presence iscurrently small, according to chief executive officer Rajiv De Silva.

“We are at scale, and we have true breadth and diversity ofproducts, as well as [in] our product pipeline. There is no real burningneed for us to do anything else for the sake of scale,” De Silva toldinvestors at the Piper Jaffray 2015 Annual Healthcare Conference heldin New York, US. Endo’s “priority” from an acquisition standpoint“is more likely to be on the branded or international side”, he noted,while continuing to integrate Par trumped any appetite for a furtherlarge generics transaction.

“But I think we would always be interested in doing small‘tuck-ins’ in areas we like,” De Silva commented, identifying injectables,topical, patches and thin films as some of the “unusual formulationsof high interest” to Endo. Following the completion of the Paracquisition (Generics bulletin, 23 October 2015, page 32), Endo“already has a starting point in most of those [areas]”, he pointed out.

Sales attributable to Par during the third quarter of last year,which included four total shipping days, totalled approximatelyUS$23.4 million, Endo disclosed via a ‘frequently asked questionsand answers” document posted to its website.

Few prospects from Teva-Actavis dealMeanwhile, De Silva noted, Endo was pessimistic regarding its

chances of picking up divested products in the wake of continuedmerger and acquisition activity, especially following the expectedcompletion of Teva’s US$40.5 billion deal for Actavis’ genericsbusiness this year. “While we remain interested and certainly hopewe can pick up one or two products, it is unlikely that we will be apreferred party because of our breadth,” he commented.

Separately, Endo has agreed to pay US$39 million to settle claimsthat its Qualitest generics unit unlawfully marketed multivitaminscontaining less than half of the claimed fluoride. “By mislabelling thestrength of its fluoride products, Qualitest caused healthcare providersto submit false reimbursement claims to Medicaid and various federalhealthcare plans,” remarked New York attorney general EricSchneiderman, who led the national investigation. G

BUSINESS STRATEGY

Endo to keep an eyeon small acquisitions

Samsung BioLogics anticipates becoming the “the world’s largestbiologics contract manufacturing organisation (CMO)” when it

commences operations at a large-scale manufacturing plant in Incheon,South Korea, on which it has just broken ground.

Set to be completed “by 2017”, ahead of operations beginning“in the fourth quarter of 2018 after validation”, the facility – Samsung’sthird in the Incheon special economic zone – represents an investmentof KRW850 billion (US$725 million). Once operational, the Koreanfirm believes the site’s capacity of 180,000 litres will help it reachannual sales of KRW2 trillion and KRW1 trillion in operating profits.

Through its Samsung Bioepis alliance with Biogen, the SouthKorean firm is developing biosimilars including adalimumab,bevacizumab, etanercept and trastuzumab. G

MANUFACTURING

Samsung builds biologics siteLannett expects cost savings of around US$40 million during the

first 12 months following the closing of its acquisition of KremersUrban Pharmaceuticals on 27 November, more than it had initiallyenvisaged. The US firm – which anticipates “additional savings in lateryears” – is “moving quickly to reduce overheads and streamline ourorganisation”, according to chief executive officer Arthur Bedrosian.

Alongside closing Kremers’ US-based corporate headquarters inPrinceton, New Jersey, Lannett is also planning to “eliminate duplicateadministrative functions, rationalise our product-developmentprogramme and optimise our manufacturing, distribution and researchand development operations”. Bedrosian said the US firm’s customershad pledged to replace some of the US$87 million in sales lost when aclient left Kremers (Generics bulletin, 20 November 2015, page 5). G

BUSINESS STRATEGY

Lannett shares savings plans

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Valeant claims it has “launched with Walgreens the first brandedgenerics programme in the US” by reaching a pricing and

distribution agreement with the 8,173-outlet drugstore chain.Under the terms of the deal, Valeant will match generics prices

for more than 30 of its off-patent US brands in the dermatology,ophthalmology, gastrointestinal, neurology and other therapeuticcategories from the second half of this year. The Canadian companysaid the price reductions of between 5% and 95% for brands such asAldara (imiquimod), Glumetza (metformin) and Tiazac (diltiazem)would amount to a weighted average cut of more than 50%. “Thisprogramme will be available to all patients, including those withgovernment coverage,” Valeant added.

Separately, Valeant has agreed to cut the wholesale list prices ofall its prescription and OTC dermatology and ophthalmology brandsby 10% over the next six to nine months. This applies both toWalgreens’ range of more than 8,000 retail outlets as well as toparticipating independent pharmacies.

Valeant will set the prices for patients and will pay Walgreens adistribution and pharmacy-fulfilment fee.

Once fully implemented, the two agreements with Walgreens will“provide up to US$600 million in annual savings to the US healthcaresystem”, noted Valeant, which has brought in management consultancyLeavitt Partners to evaluate its new distribution model. “We havelistened to what the marketplace is saying and we have taken positivesteps to respond,” insisted Valeant’s chairman and chief executiveofficer, Mike Pearson who is facing medical leave (see page 16).

In recent months, Valeant has seen its share price plummet afterinvestors and politicians voiced concerns over the company’s pricingpolicies and ties to specialty pharmacy Philidor that the firm has sincesevered (Generics bulletin, 6 November 2015, page 4).

Separating from Philidor as of 30 October 2015 is set to reduceValeant’s fourth-quarter turnover by around US$250 million. As itannounced the Walgreens deals, the Canadian firm revised its full-year 2015 sales forecast down from US$11.0-US$11.2 billion toUS$10.4-US$10.5 billion, but laid out for investors its strategicpathway for bouncing back.

Driven by “double-digit organic growth”, Valeant expects to recorda group turnover of US$12.5-US$12.7 billion in 2016. G

COMPANY NEWS


BUSINESS STRATEGY/RESULTS FORECAST

Valeant cuts priceswith Walgreens deal

SAGENT PHARMACEUTICALS has received board authorisationto proceed with the sale of its Chinese subsidiary, Sagent ChinaPharmaceuticals (SCP). The US injectables specialist will take apre-tax impairment charge of US$45-US$50 million on its sale ofSCP, which includes a Chinese manufacturing complex (Genericsbulletin, 1 September 2015, page 5).

STADA says its Serbian subsidiary Hemofarm has resolved its legaldispute with the insolvency administrator of local wholesalerVelefarm. The administrator has waived its claim against Hemofarmfor C54.2 million (US$59.0 million) in a Belgrade commercial court(Generics bulletin, 7 March 2014, page 5), while Hemofarm hasdropped a claim in the “single-digit million euro range” (Genericsbulletin, 15 October 2010, page 5).

ANI PHARMACEUTICALS plans to set up a “centre of excellence”to bring development of complex formulations in-house ratherthan relying on partners. President and chief executive officer ArthurPrzybyl told delegates to the Oppenheimer 2015 HealthcareConference held in New York, US, the US generics player would seekacquisitions as it aimed to follow recent launches of flecainide tabletsand nimodipine capsules by introducing eight products this year.

PAN PHARMACEUTICALS has seen its products banned from importinto the US after an import alert was issued by the US Food andDrug Administration (FDA) against the firm’s facility in Vadodara,India. This action is the latest in a series of escalating consequencesagainst Pan, which recently received a warning letter from the FDAdue to a series of good manufacturing practice violations, includingallowing pigeons access to equipment in a bulk-drugs facility inBaroda, India (Generics bulletin, 2 October 2015, page 8).

CELESIO will see its proposed acquisition of Sainsbury’s UKpharmacy business subjected to an “in-depth investigation” by theUK Competition and Markets Authority (CMA). Following an initialinvestigation of the proposed deal announced last year (Genericsbulletin, 7 August 2015, page 5), the CMA has “identified 78 localareas” in which competition may be reduced between Sainsbury’sand Celesio’s Lloyds pharmacies. After Celesio did not offeracceptable undertakings, the CMA referred the deal for independentreview by 13 June. Separately, the CMA says it is investigating a“suspected breach of competition law related to discounts offeredfor a pharmaceutical product”. The watchdog will decide by Maywhether to proceed with its probe into the product, no details ofwhich have been disclosed.

STERLING – the Italian hormone and steroid specialist – said itsMaltese active pharmaceutical ingredient (API) facility passed anaudit by the US Food and Drug Administration (FDA). The bulk-drug specialist also has a site in Italy and two years ago set up asubsidiary in the US.

CIPLA has seen its plan to spin-off its consumer healthcarebusiness into its newly-created Cipla Health subsidiary approvedby its board of directors. The Indian firm – which announced itsintention last year (Generics bulletin, 7 August 2015, page 4) –expects to complete the move by the end of March.

VERTICE PHARMA – the recently-formed US-based company thatis backed by Warburg Pincus and headed by former Sandoz and Endoexecutive Don DeGolyer – has completed the acquisition of Florida’sVistaPharm for an undisclosed fee (Generics bulletin, 9 December2015, page 27). G

IN BRIEF

India’s Alkem Laboratories has gone public by making an initialpublic offering (IPO) of almost 12.9 million shares equivalent to

around 10.75% of the firm’s share capital. Shares started trading onthe Bombay Stock Exchange on 23 December, having been offeredat Rs1,050 (US$15.76) for investors and Rs950 for eligible employees.

Following the IPO, Alkem’s ‘promoters’, or owner-operators,control just over 79 million, or around two-thirds, of the company’s120 million issued shares.

In its most recent financial year ended 31 March 2015, Mumbai-based Alkem increased its turnover by 21% to Rs37.9 billion. Three-quarters of that total was achieved in the Indian firm’s domestic market,while its US operations under the Ascend label accounted for the bulkof International sales that grew by a quarter to Rs9.57 billion. G

BUSINESS STRATEGY

India’s Alkem starts trading

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An “expedited review process at the US Food and DrugAdministration (FDA)” is needed for generics in cases where

there has been a price spike on off-patent drugs, according to commentsrecently made by Senators at a US hearing.

The Senate’s special committee on aging held a hearing on “suddenprice-hikes in off patent drugs”, during which co-chairman SenatorClaire McCaskill called for the review process for generics to beshortened so that rivals to off-patent brands with no competitorscould be “approved within six months”.

These comments echoed earlier statements by Senator TimKaine and Senator Joe Donnelly calling for suggestions on how to“better expedite the review for generics within the FDA”.

The committee specifically called out Retrophin, Rodelis, Turingand Valeant as companies which had “hiked the price of off-patentdrugs they recently acquired by 20, 30, or even 40 times the prior price”.These companies had previously been accused of ‘price-gouging’when the committee launched its investigation in November (Genericsbulletin, 20 November 2015, page 15). The hearing examined whatit called a “market failure” to provide generic alternatives to prevent“enormous” price hikes by those companies.

Among other solutions examined were a re-examination of patentlength, the use of compounding pharmacies, and efforts at priceregulation. The committee also highlighted brand industry tacticsthrough which specialty pharmacies were given sole access to specificdrugs in order to restrict distribution of the drug and prevent genericscompanies from gaining access to the product. Specifically, Turing’scontract with Walgreens’ specialty pharmacy was scrutinised as theonly access point for patients to acquire Daraprim (pyrimethamine).

Chip Davis, president and chief executive officer of the USGeneric Pharmaceutical Association (GPhA), echoed calls to “shortenFDA median generic drug approval timelines, which at the industry’sbest estimate, currently stand at 48 months”. He also appealed to theFDA to address the backlog of 3,800 generic drug applications thatare currently awaiting approval.

Must avoid ‘sweeping policies’Davis however warned that: “Congress must avoid addressing

outlier pricing actions taken by individual companies with sweepingpolicies that restrict patient access or invite other unintendedconsequences.” He also repeated his calls for Congress to “pass thebipartisan Fair Access for Safe and Timely (FAST) Generics Act tocurb some brand drug company abuses of FDA safety programmessuch as Risk Evaluation and Mitigation Strategies (REMS) used tokeep generics off the market” (Generics bulletin, 23 October 2015,page 14). This legislation would produce “an estimated savings ofUS$2.4 billion over 10 years”, according to Davis.

Other suggestions offered by Davis were “increasing genericutilisation among the low-income Medicare population” and “ensuringthat the framework for biosimilars – safe and effective alternatives tocostly brand biologic drugs – expands and expedites patient access”.

Davis also continued to argue for the repeal of Section 602 of thebipartisan Budget Act of 2015, whereby “single-source and innovatormultiple-source drugs [including generics] pay an additional rebateif the price of the drug has increased faster than inflation” (Genericsbulletin, 6 November 2015, page 15). He called the rebate increasefor generic drugs in the budget deal as “bad for Medicaid, bad forits beneficiaries and bad for taxpayers”. G

MARKET NEWS


REGULATORY AFFAIRS

US Senate considersexpedited FDA path

Only 12% of patent settlements concluded between generics firmsand originators in the European Union in 2014 were ‘problem’

settlements that contained both a limit on generic market entry anda “value transfer” from the originator to the generics firm, accordingto the latest monitoring report by the European Commission.

Following its sixth round of monitoring, the Commission foundthat the 12% figure – representing nine out of a total of 76 patentsettlements agreed during 2014 – indicated that such settlements, whichwould attract the highest degree of antitrust scrutiny, “have stabilisedat a low level”. The figure remained relatively unchanged from the11 that occurred in the previous year (Generics bulletin, 16 January2015, page 14).

Of the 76 patent settlements concluded, 49% – or 37 – did notinclude any limitation on generic market entry, while 39% – 30 –limited generic market entry but did not include a “value transfer”.It was also noted that 90% of settlements limiting generic entry butnot including a value transfer occurred in Portugal, where an originatormust initiate arbitration within 30 days of a generic company applyingfor a marketing authorisation. Putting aside settlements related toPortuguese law, such settlements only accounted for 7% of the total,or three in absolute terms.

The Commission disclosed that the number of international non-proprietary names (INNs) that had been the subject of settlements“increased significantly”, from fewer than 10 INNs between 2000and 2003 to 45 in 2014.

It was also found by the Commission that despite previousstatements from industry stakeholders – suggesting that theCommission’s approach would have the effect of “forcing companies tolitigate each patent dispute until the end” – the monitoring exercise had“not hindered companies from concluding settlements in general”. G

INTELLECTUAL PROPERTY

Problem settlementskept down in the EU

South Africa has announced plans to reform its healthcare systemafter releasing its white paper on National Health Insurance (NHI),

which aims to “lay the foundations for moving South Africa towardsuniversal health coverage”. The white paper proposes that “a centralisedfunction will be established to assume responsibility for facilitatingand coordinating all functions related to procurement of health-relatedproducts” which will include pharmaceuticals. The government believesthis policy has “the potential to save millions of rands every year”.

Plans to create a formulary of generic drugs listing their prices areset out within the document, along with standard treatment guidelinesthat will be established nationally. There will also be a national healthproducts list “with pre-determined facility or provider level which willgreatly streamline the procurement process for facilities”. The list will bereviewed “on a regular basis” in light of “product availability and pricechanges”. The NHI also aims to promote “greater provider competition”to control costs as well as establishing “selective contracting”.

“Accredited and contracted retail pharmacies will be able to orderdrugs and other health products from the nationally agreedpharmaceutical contracts and will be required to dispense drugs thatare procured at subsidised prices,” the paper explains. The NHI willreimburse the cost of subsidised drugs and other health products. G

REGULATORY AFFAIRS

South Africa sets out reforms

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Acollaboration between the British Generic ManufacturersAssociation (BGMA), 11 generics companies and the UK’s

Medicines and Healthcare products Regulatory Agency (MHRA) toproduce patient information has been undertaken as part of a scheme“aimed at removing unnecessary duplication and improving impactwhen contacting pharmacists, general practitioners and other healthcareprofessionals about safety information”. The BGMA claims theinitiative, which saw patient reminder cards distributed throughoutthe UK, is “the largest ever coordinated communication of its type”.

Under current regulations, when new safety information becomesknown about a product, all individual drug manufacturers are legallyrequired to communicate it to healthcare professionals.

“This results in multiple copies of the same information being sentto busy healthcare professionals” the BGMA observed, adding thatthe initiative with the generics firms and MHRA “replaces that witha single high-quality communication for generic products.”

The scheme saw the partners distribute “patient reminder cardsfor zoledronic acid specifically detailing the risks associated withosteonecrosis of the jaw” to 2,600 hospital pharmacies.

Paul Fleming, technical director of the BGMA, said the project“meant the regulator was not required to review separate applicationsand those receiving the mailings received one set of consistent, clearinformation.” The collaboration was “a great example of howpartnerships between the regulator and provider companies can be veryeffective in driving through a more streamlined, clearer process whichultimately is good news for patients,” he added.

MHRA deputy director Sarah Branch said: “Removing regulatoryduplication and improving the quality of communications to healthcareprofessionals and patients is an important priority. MHRA hopes thatthis will pave the way for similar opportunities.” G

MARKET NEWS


REGULATORY AFFAIRS

BGMA and MHRA tocollaborate on safety

Afinal rule on generic labelling will be published by the US Foodand Drug Administration (FDA) in July this year, the agency has

revealed. First announced more than two years ago (Generics bulletin,15 November 2013, page 1), the FDA’s proposed rule would requiregenerics firms to update safety information using the same ‘changesbeing effected’ (CBE) process as originators.

However, the agency has acknowledged that it is “consideringseveral alternatives described in comments submitted to the publicdocket established for the proposed rule”, as well as “evaluating theanticipated costs and benefits that would be associated with a final rule”.

Welcoming the FDA’s comments, the US Generic PharmaceuticalAssociation (GPhA) said it “continues to support the Expedited AgencyReview (EAR), a better way forward that strengthens the communicationof drug safety information without putting patients at risk”. Outlinedby the GPhA earlier this year – alongside brand industry associationPhRMA (Generics bulletin, 10 April 2015, page 9) – the EAR proposalwould require FDA approval of any proposed labelling change.

Rule would base labels on incomplete data“Current law requires brands and generics to carry the same label

to assure healthcare practitioners have consistent information to informtheir decisions and patient conversations,” the GPhA’s president andchief executive officer, Chip Davis, pointed out. However, the proposedrule “would change this by requiring generic manufacturers to updatelabels based on incomplete information without first receiving FDAapproval”. But, Davis emphasised, “no single manufacturer has accessto the full range of available data: the proprietary data from clinicalstudies or the data held by each individual applicant holder”.

Insisting that the FDA was “the only entity with all of the dataneeded to recommend a safety information change”, Davis noted thatthe EAR scheme instead “suggests time parameters for the FDA totake action and encourages the adoption of e-labelling for real-timeinformation-sharing, rather than continuing the reliance on paper labelchanges that take months or years to adopt”. The EAR scheme “alsotakes important steps to make sure that multiple different labels do notexist for products with the same active ingredients, safety and efficacy”.

“GPhA will continue to work with the agency and otherstakeholders committed to advancing and protecting patient health,”Davis concluded, “to ensure that any changes to labelling regulationsdo not put patient safety at risk and avoid causing provider confusion.”G

REGULATORY AFFAIRS

FDA label rule willbe published in July

Fear of drug shortages is among the concerns raised by Canadianlobbying group CPM over the introduction of draft legislation

proposing tenders in Quebec. Bill 81, introduced in the province’snational assembly, “aims at reducing the cost of certain medicationscovered by the basic prescription drug insurance plan by allowingcalls for tender” (Generics bulletin, 9 December 2015, page 12).

Citing recent drug shortages that have occurred in the province,the group believes tendering could exacerbate the problem. CPM alsoraised the concern that “centralising a drug’s volume in a singleplace and giving exclusive sales rights to one or two producers that mayoffer the lowest price threatens to adversely impact hundreds ofthousands of Quebecers by forcing them to change drugs”.

The patients’ organisation’s president, Paul Brunet, has urgedlocal authorities “to ensure its draft legislation includes initialnegotiation of lower prices for generic drugs directly with thecompanies, in order to obtain the best price first of all and letpatients continue to take the drug they are accustomed to and thatsuits them, as well as to lower the risk of shortages substantially”.

The group has also voiced concerns about “pharmacists losinganother aspect of their professional independence, namely the powerto select a drug that is appropriate for each patient’s needs”. G

PRICING & REIMBURSEMENT

Canada’s CPM fears tenders

The European Medicines Agency (EMA) is to be a “global referenceauthority for the regulation of medicines” according to plans laid

out by the EMA’s executive director, Guido Rasi. The plan to “reinforcethe EMA’s role as a global reference authority” was one of the five“building blocks” of Rasi’s vision for his five-year mandate.

“A commitment to transparency” was another of the goals laidout, as well as the need for “patient involvement” and making “thebest use of all available evidence”. A fifth ‘building block’ was to“steer research and development to unmet medical needs” withRasi expressing a desire “to engage in early dialogue in medicinedevelopment to guide them in focusing their resources”. G

REGULATORY AFFAIRS

EMA plans to have global role

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Biosimilars in the US should “have the same labelling as theirreference drugs”, according to a citizen petition submitted to the

US Food and Drug Administration (FDA) by a group of 15 industryinvestors. The group of institutions has also petitioned the FDA to“conduct a public hearing so that stakeholders can express theirviews, which will lead to a more comprehensive public record priorto any proposed rulemaking or draft guidance”.

The investors are calling for the FDA to continue labellingbiosimilars in the style that was adopted for the US’ first biosimilar,Sandoz’ Zarxio (filgrastim-sndz), the label of which contained thesame information as that of Neupogen, its reference product.

A public hearing is being requested by the investor group toaddress “the implications of labelling rules for biosimilar innovationand investment in the US”. They are calling on the FDA to consider“the European experience with biosimilars, including same labelling,patient tracking, and patient safety”. The investors have also askedthe FDA to consider stakeholder views on how different approachesto labelling may affect prescribing, dispensing and patients’ use ofbiosimilars and interchangeable biologic products.

It is noted by the investors that their proposals are in directopposition to AbbVie’s citizen petition “to require that biosimilar andinterchangeable biologic product labels include information about theclinical trials conducted by the biosimilar sponsor and the licensurepathway under which the drug was approved” (Generics bulletin,26 June 2015, page 19). The FDA recently answered AbbVie’s petition,delaying its response as it was “unable to reach a decision on thepetition because it raises complex issues requiring extensive reviewand analysis by Agency officials”.

The investor group points out the information asked for by AbbVieis already available from multiple sources, including the Purple Bookbiologics database, the FDA’s own documents and published peer-review literature. The institutions and funds believe their proposedapproach “is critically important in boosting investor confidence,signalling market certainty, and upholding the role of the FDA indetermining biosimilarity and interchangeability”. G

MARKET NEWS


LEGISLATIVE AFFAIRS

US biosimilars mustmirror label of brand

CGPA – the Canadian Generic Pharmaceutical Association – hasasked the government of Canadian province Quebec to maintain a“reasonable limit” on professional allowances paid to pharmacistsby generics manufacturers. Eliminating the cap altogether was “asolution that is neither viable, nor sustainable for financing theseservices”, the CGPA insisted.

GAO – the US Government Accountability Office – should carry outan assessment of the US Food and Drug Administration’s (FDA)regulatory pathway for reviewing generic versions of non-biologiccomplex drugs (NBCDs), according to members of the US Housecommittee of energy and commerce. The House committee seeksthe “GAO’s input on whether the current statutory pathway forgeneric NBCDs is adequate to guarantee patient safety”.

CFDA – the Chinese Food and Drug Administration – has rejected13 generic drug applications from 14 domestic companies. Amongthe problems listed by the regulatory agency were selective use ofdata, missing original records and incomplete analysis of test data.The CFDA is also initiating inspections of certain hospitals forfalsifying data and irregularities in clinical trials. These rejectionscome after the CFDA rejected drug applications for 11 othermedicines due to “untrue or incomplete data” in November.

FDA – the US Food and Drug Administration – must “increase andstrengthen” its biosimilars resources and capabilities to give“timely detailed feedback to manufacturers during the applicationprocess”, according to the US Generic Pharmaceutical Association’s(GPhA’s) president and chief executive officer, Chip Davis. “Animportant step that can be taken to expedite these alternative tocostly brand biologic therapies is to codify the currently outstandingbiosimilars regulations,” he added. The FDA recently held a publicmeeting on the Biosimilar User Fee Act (BsUFA) reauthorisation.

TGA – Australia’s Therapeutic Goods Administration – has introducedpilot changes in the pre-submission phase of registering prescriptionmedicines in Australia. The pilot changes – which will apply toapplications for new generic medicines, biosimilars and new chemicaland biological entities – come into effect on 1 February and will runfor “approximately six months”. Participation in the scheme will beoptional and the current registration pathway will remain available.

US doctors should “prescribe generic medications wheneverpossible as a way to improve adherence to therapy and clinicaloutcomes while containing costs,” according to the American Collegeof Physicians (ACP) in a paper published in the Annals of InternalMedicine. The study found patients were almost twice as likely to“abandon” prescriptions for branded drugs, which have “higher out-of-pocket costs” than for generics. Despite this, “clinicians oftenprescribe more expensive brand name drugs when equally effective,well proven, and less expensive generic versions are available”.

FRENCH pharmacy unions have failed to reach an agreement withthe country’s government over issues including performance-relatedremuneration for achieving generic substitution targets in 2016. Ameeting expected in mid-December 2015 to finalise a deal with localunions including FSPF, UNPF and USPO was delayed until thisyear. Noting that French health insurer CNAMTS had proposed asubstitution target of 87% of eligible prescriptions for 2016 and2017 – as well as changes to the way the remuneration is calculated –FSPF said the proposed deal could see every pharmacy lose C1,000(US$1,094) annually in its current state. “These objectives areclearly unattainable,” the union stated. G

IN BRIEF

Long-acting injectable (LAI) specialist Qrono has been awarded aUS$612,000 contract by the US Food and Drug Administration

(FDA) to investigate the viability of computer simulations versus thetraditional experimental approach to model generic long-actingmedicines. Qrono will “compare a computationally driven approach toa more experimentally intensive approach for the development ofcomplex LAI microspheres”, while the study will have “substantialfederal scientific or programmatic involvement”. Initial studies willmodel Risperdal Consta (risperidone) and Sandostatin (octreotide).

“Patients lack generic formulations of LAI products,” Qrono said,“due in large part to the high clinical and research burden to developthese generics and demonstrate bioequivalence”. The use of computersimulations could create generic versions of LAI drugs and “reducebillions of dollars in strain in the nation’s healthcare systems and allowa broader range of patients to benefit from medications that improveadherence, patient outcomes and overall quality of care”. G

REGULATORY AFFAIRS

FDA eyes long-acting models

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Sandoz’ marketing authorisation application for its biosimilar rival tothe Enbrel (etanercept) original marketed by Pfizer in the European

Union has been accepted by the European Medicines Agency (EMA).The Novartis subsidiary is seeking approval for all indications includedin the label for the reference product, which is used to treat a rangeof autoimmune diseases including rheumatoid arthritis and psoriasis.

Supported by two pivotal clinical studies – a pharmacokineticstudy in healthy volunteers and a confirmatory safety and efficacystudy in patients with chronic plaque-type psoriasis – the Europeanetanercept application will “provide clinical confirmation of similarityto the reference product established in extensive prior analyticalcomparability studies”, Sandoz believes.

The US Food and Drug Administration (FDA) accepted forfiling Sandoz’ biosimilar etanercept application in October last year(Generics bulletin, 23 October 2015, page 21).

Sandoz has also released Phase III trial data for its proposedbiosimilar version of Amgen’s Neulasta (pegfilgrastim), which showed“there were no clinically meaningful differences between the proposedbiosimilar pegfilgrastim and the reference product”. The global,randomised, double-blind trial involving 308 patients “met its primaryendpoints”. The FDA also recently accepted Sandoz’ regulatoryfiling for the proposed biosimilar pegfilgrastim (Generics bulletin,9 December 2015, page 17). G

PRODUCT NEWS


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BIOLOGICAL DRUGS

Sandoz advances itsEuropean etanercept

AGerman marketing authorisation issued to Astellas for Ribomustin(bendamustine) in 2005 means the originator’s 10-year European

market exclusivity for the chemotherapy agent has expired, UK HighCourt Justice Paul Morgan has ruled. Therefore, he said, the UK’sMedicines and Healthcare products Regulatory Agency (MHRA) hadbeen entitled to grant Intas’Accord Healthcare a marketing authorisationfor generic bendamustine on 24 November 2015.

Astellas argued unsuccessfully that the German approval issuedin July 2005 did not amount to a first marketing authorisation underthe terms of European Union (EU) Directive 2001/83/EC. Rather, theoriginator insisted, the first EU marketing authorisation that triggeredthe 10-year exclusivity period was granted in France under the Levactbrand name in July 2010.

Morgan said Astellas had put forward two reasons. Firstly, thefirm said German approval had come under national law and did notcomply with the EU Directive. Secondly, the originator claimed itsappeal against part of the German approval process had suspendedthe local authorisation. Astellas, the judge pointed out, had not disclosedto the court or to Accord its German dossier, so he could not concludethat the dossier was incomplete and did not comply with the Directive.

Noting that Germany had through its re-registration orNachzulassung procedure in 2005 approved Ribomustin for non-Hodgkin’s lymphoma and multiple myeloma – but not for chroniclymphatic leukaemia (CLL) – Morgan found that Astellas’ appeal overthe CLL indication did not suspend the authorisation for the other twoindications. A settlement of the appeal in 2011 could not retrospectivelyrevoke the marketing authorisation as if the authorisation had neverexisted, thereby removing the exclusivity trigger, he stated.

Recognising Accord’s desire to compete in “a number of imminenttenders”, Morgan said Astellas had on 26 November 2015 startedadministrative court proceedings seeking a judicial review of the MHRAdecision to approve Accord’s generic. Therefore, he said, referring thedispute to the European Court of Justice (ECJ) would be premature.

Noting that it had secured a ruling within four months of startingan action, Accord said its UK victory followed similar successes inAustria, Finland and Poland. G

ONCOLOGY DRUGS

Accord clears pathon UK bendamustine

Recommended study durations in a European Medicines Agency(EMA) guidance on clinical investigation of asthma medicines

have been revised after Mylan objected that some proposals could “bea hindrance to global development programmes”.

Mylan said some study durations corresponded neither to the drugs’pharmacology nor to US Food and Drug Administration (FDA)guidelines. “In order to facilitate global registration programmes and tolessen the risk of reduced access to medicines for asthma,” the firmmaintained, “it would be optimal if the European Union (EU) guidancecould be consistent with FDA guidance in terms of duration of pivotalstudies for efficacy.” Three-month studies could demonstrate efficacy“across the range of asthma-controller medicines”, Mylan contended.

Teva successfully sought clarification in the draft guidance over thedefinition of ‘exacerbation’ and on flexibility around the duration ofplacebo-controlled studies. G

RESPIRATORY DRUGS

Mylan affects asthma guide

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Biocad anticipates launching its biosimilar version of Roche’sAvastin (bevacizumab) in Russia in the first quarter of this year

after obtaining a marketing authorisation from the country’s Ministryof Health. Having announced its filing at the beginning of last year(Generics bulletin, 27 February 2015, page 25), the Russian developersaid it expected the biosimilar “to capture rapidly a ‘lion’s share’ fromthe original product in the very first year”.

Pointing out that that the official registered price for Roche’soriginal in Russia was RUB61,536 (US$890), Biocad said its versionwould be marketed with a 30% discount, retailing at RUB43,075instead. According to Biocad, this pricing strategy within Russia’sessential drugs list will “open up a new perspective for reconsideringthe cost/benefit ratio of anti-vascular endothelial growth factor (VEGF)therapies”. Currency depreciations also made Biocad’s bevacizumabversion – along with Roche’s reference product – “among the cheapestin Europe and the US”, the Russian firm commented.

Biocad recently overcame a patent-infringement suit brought byRoche over its biosimilar rival to the originator’s Rituxan/MabThera(rituximab) that it had launched in 2014 (Generics bulletin, 20November 2015, page 17). G

PRODUCT NEWS


BIOLOGICAL DRUGS

Biocad bevacizumabreceives Russian nod

Damages claimed against originators for obtaining interlocutoryinjunctions against generics firms that later are judged to be

baseless may be sought by the Australian Commonwealth, as well asby generics firms, according to a decision by the country’s FederalCourt. The case involved Sanofi and Pfizer’s Wyeth – as well asAlphapharm, Apotex, Generic Health and Sigma – and revolvedaround formulations of clopidogrel and venlafaxine.

Noting that Australian law required that a court cannot grant aninitial interlocutory injunction unless the applicant provides anundertaking as to damages, Federal Court Judge John Dowsett notedthat an amendment to the country’s Therapeutic Goods Act “enhancesthe entitlement to damages for the generic company and for theCommonwealth, states and territories”.

Dowsett observed that Sanofi and Wyeth had claimed the amendedTherapeutic Goods Act must also “limit the power to grant interlocutoryrelief, subject to the giving of an undertaking, at least to the extent thatit concerns loss suffered by the Commonwealth, or that theCommonwealth is precluded by those sections from seeking to enforcesuch an undertaking for its own benefit”.

But Dowsett said he found it “impossible to infer that parliamentintended to limit the power of the court to extract an undertaking asto damages, given the absence of any express statements to that effect”.Rejecting the suggestion that “the court cannot extract an undertakingin a form which would benefit the Commonwealth”, Dowsett said that“nothing in [amended] section 26C purports to limit theCommonwealth’s right to exploit the benefit conferred by it”. Twoother judges agreed that “if parliament intended by the enactment of[the amendments] to curtail the prescribed court’s power to make anaward”, then “we would expect it to have done so by express words”.G

CARDIOVASCULAR DRUGS/ANTIDEPRESSANTS

Australian ruling letsstate claim damages

Canadian consumers who used Pfizer’s Viagra (sildenafil) cannotsue the originator for being overcharged after a patent was found

invalid, the Court of Appeal for British Columbia has ruled.In a class-action suit, consumers had cited a 2012 Supreme Court

finding that Pfizer’s Canadian patent 2,163,446 was invalid forinsufficient disclosure (Generics bulletin, 23 November 2012, page 17).They claimed that the originator had unlawfully abused the patentsystem, thereby imposing monopoly prices on purchasers of Viagrabetween 2006 and 2012.

But the appeals court found that the consumers had no statutoryright to sue Pfizer for abusing Canada’s patent system. “It would makeno sense logically or from a policy perspective to allow consumersto claim disgorgement of profits from brand names when genericsare precluded from claiming the same, based on identical wrongfulacts,” the court stated. G

ERECTILE DYSFUNCTION DRUGS

Canadian Viagra claim fails

US-based developer Antares Pharma expects its partner Teva tolaunch the pair’s generic version of GlaxoSmithKline’s Imitrex

Statdose (sumatriptan) 4mg/0.5ml and 6mg/0.5ml injectable in Juneafter the US Food and Drug Administration (FDA) granted final approvalfor its abbreviated new drug application (ANDA). Indian playersDr Reddy’s and Sun hold similar approvals for the latter strength.

According to Antares, the approval for the migraine and clusterheadache treatment is the company’s “first ANDA approval of acomplex generic, and second product approved using the Vibex auto-injector platform [technology]”. Antares and Teva are also collaboratingon a generic epinephrine and exenatide pen, both of which are “underreview with the US Food and Drug Administration (FDA)”, as wellan undisclosed new drug application (NDA).

Under the firms’ agreement for the sumatriptan injectable reachedin November 2012, Teva will manufacture and supply the activepharmaceutical ingredient (API) to Antares, which will in turnmanufacture, assemble and package the device, before selling the finalproduct back to Teva.

The Israeli firm will distribute the product in the US, “and netprofits, after an allowance for a fixed percentage cost of distribution”will be split equally between the companies. Teva also has anoption for rights to the product in other territories. G

MIGRAINE TREATMENTS

Antares bags US sumatriptan

Sun remains on course to launch the first generic version of Novartis’Gleevec (imatinib mesylate) blockbuster leukaemia treatment in

the US after obtaining final US Food and Drug Administration (FDA)approval for its abbreviated new drug application (ANDA).

The Indian firm is entitled to launch the first generic Gleevec –which had sales of US$2.5 billion for the 12 months ended August2015, according to IMS Health data – on 1 February 2016 under theterms of a patent litigation settlement brokered last year (Genericsbulletin, 6 June 2014, page 21). Sun believes itself eligible for 180 daysof generic market exclusivity. Apotex holds a tentative approval. G

ONCOLOGY DRUGS

Sun is handed first imatinib

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PRODUCT NEWS


Apotex has responded to a US district court injunction requiringthe firm to provide Amgen with a 180-day notice of marketing

for its biosimilar rival to Neulasta (pegfilgrastim) before it can launchits version by immediately lodging an appeal against the decision. Theruling by a Southern Florida District Court came in response to arequest by Amgen for an injunction barring the generics firm fromlaunching its biosimilar without providing such notice.

Apotex’ pegfilgrastim – an application for which was acceptedfor filing by the FDA a year ago (Generics bulletin, 16 January 2015,page 1) – has not yet been approved by the agency.

“The only issue before the court,” District Judge James Cohnexplained, “is whether the Biologics Price Competition and InnovationAct (BPCIA) requires a company such as Apotex to give a companysuch as Amgen 180 days notice of its intent to market a licensedbiosimilar project, as Amgen claims – or whether, as Apotex argues,the BCPIA merely makes the 180 days notice provision optional atthe discretion of the applicant.”

Apotex had “informed Amgen that it will not notify Amgen whenand if it obtains US Food and Drug Administration (FDA) approval forits biosimilar product and it will not provide the 180 days commercialmarketing notice”, Cohn noted.

While the text of the BPCIA stated that applicants “shall providenotice to the reference product sponsor not later than 180 days beforethe date of the first commercial marketing of the biological product”,Cohn observed: “In the realm of statutory construction, ‘shall’ maysometimes mean ‘may’.”

Different from Sandoz caseWhile a recent ruling in a case involving Sandoz’ biosimilar

filgrastim (Generics bulletin, 7 August 2015, page 1) had seen anappeals court interpret the BPCIA pathway as requiring notice to begiven after FDA approval of a biosimilar, Cohn acknowledged, thatruling was “limited to situations where the applicant completely failsto provide its abbreviated biologics license application (aBLA) and therequired manufacturing information to the reference product sponsorby the statutory deadline”, which was not the case with Apotex’pegfilgrastim. Having provided its aBLA to Amgen, Apotex argued,the generics firm was not subject to the 180-day notice requirement(Generics bulletin, 20 November 2015, page 20).

“Apotex would have this court limit the Sandoz decision,” Cohnsurmised, in such a way as to make the notice of marketing optionalin instances where the aBLA and manufacturing information had beensupplied by the biosimilar applicant. But agreeing with a statementmade by a dissenting judge in the Sandoz case, Cohn insisted that“nothing in the statute supports this peculiar outcome”. Neither thestatute nor the Sandoz decision “condition the 180-day notice provision”on compliance with the aBLA and manufacturing informationrequirement, he concluded.

Addressing Apotex’ argument that the notice provision of theBPCIA “unfairly gives the reference product sponsor an additional180 days of exclusivity”, Cohn observed that “that extra 180 days willnot likely be the usual case, as aBLAs will often be filed during the12-year exclusivity period for other products”.

The injunction granted by Cohn would “maintain the status quo”by requiring Apotex to “notify Amgen when and if it receives FDAapproval and will prohibit Apotex from marketing the approved productfor 180 days after the notice is provided”, the judge outlined. G

BIOLOGICAL DRUGS

Apotex appeals afterUS pegfilgrastim bar

DR REDDY’S has relaunched its rival to AstraZeneca’s Nexium(esomeprazole) delayed-release capsules in the US following a“change in the capsule colour”. The Indian company had previouslybeen prevented from selling its version with a similar purple colourto the original after AstraZeneca obtained a temporary restrainingorder (Generics bulletin, 20 November 2015, page 16) but hadinsisted it had the right to market a purple version, having previouslymade the originator aware of the colour prior to a patent-litigationsettlement (Generics bulletin, 9 December 2015, page 16).

ACCORD HEALTHCARE has obtained a positive opinion from theEuropean Medicines Agency (EMA) for its caspofungin 50mg and70mg powder for concentrate. The intravenous antimycotic agentis equivalent to Merck, Sharp & Dohme’s Cancidas brand. The Intasaffiliate has also introduced mycophenolate mofetil 500mg powderin European countries including Spain, while in France the firm hashad atorvastatin, mitoxantrone, quetiapine and voriconazoleproducts added to the country’s répertoire of substitutable products.

PERRIGO will acquire US rights to generic Retin-A (tretinoin)from Matawan Pharma. Perrigo had previously acted as thedistributor of authorised generics of the topical acne treatment between2005 and 2013 before an agreement was terminated. The firm believesthe acquisition will add “net sales of greater than US$60 million”within a year of the deal closing.

MYLAN has seen Canada’s Federal Court of Appeal uphold alower court’s ruling that Eli Lilly’s Canadian patent 2,379,948should not prevent Mylan from getting a notice of compliance, ormarketing authorisation, for tadalafil. The appeals court said thelower court had been correct to find the’948 patent invalid as“obvious to try”. A year ago, Mylan failed to persuade a federalcourt that a Canadian patent protecting Lilly’s Cialis (tadalafil)erectile dysfunction brand until July 2016 was invalid (Genericsbulletin, 6 February 2015, page 19).

FDA – the US Food and Drug Administration – has dropped a riskevaluation and mitigation strategy (REMS) for rosiglitazone. Notingthat it had removed prescribing and dispensing restrictions forrosiglitazone in 2013 after data showed the drug carried no greater riskof heart attack than other treatments for type 2 diabetes, the agencysaid it had since “identified no new pertinent safety information”.

CREO PHARMA is claiming a “first to market” launch of genericfrovatriptan 2.5mg tablets in the UK. The company – which is usinga marketing authorisation held by Ireland’s Chanelle Medical –introduced the migraine remedy immediately upon the expiry of asupplementary protection certificate (SPC) protecting Menarini’sMigard original (Generics bulletin, 9 December 2015, page 22).

TWi PHARMA has seen the US Court of Appeals affirm a districtcourt ruling that US patent 7,101,576 protecting Par’s Megace ES(megestrol acetate) is invalid. Noting that it had been enjoineduntil the end of July 2015 from launching the weight-loss treatmentwhile Par appealed the district court’s ruling (Generics bulletin,7 August 2015, page 23), TWi pointed out that the Endo affiliatehad posted a US$16 million bond to cover the generics firm’slosses from wrongly being excluded from the market.

VISTAPHARM has introduced potassium chloride 10% oralsolution in the US in the form of 30ml unit-dose cups. The US firmhas just been acquired by newly-formed Vertice Pharma (Genericsbulletin, 9 December 2015, page 27). G

IN BRIEF

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Gedeon Richter has taken another step to introducing a biosimilarversion of Amgen’s Neulasta (pegfilgrastim) blockbuster in

Europe immediately upon patent expiry in 2017 after the EuropeanMedicines Agency (EMA) accepted for filing its marketingauthorisation application.

Under a licensing and distribution agreement reached last year,the Hungarian firm will co-market the biosimilar in Europe outsideof Russia with Stada (Generics bulletin, 1 September 2015, page 23).“Biosimilar pegfilgrastim is expected to be launched under both Richterand Stada labels,” the Hungarian company stated, noting that it was“seeking approval for the same indications as the reference product”.

Germany’s Stada made an upfront payment to Richter – whichretains its worldwide marketing and distribution rights to pegfilgrastim –upon the signing of the licensing agreement, and also pledged to makefurther payments “depending on the progress of the project”.

Separately, the EMA has accepted for filing Richter and Stada’srival to Eli Lilly’s Forteo (teriparatide) osteoporosis brand. G

PRODUCT NEWS


BIOLOGICAL DRUGS

Richter pegfilgrastimaccepted by the EMA

MYLAN has received a subpoena from the US Department of Justiceseeking information on the pricing, marketing and selling of itsgeneric doxycycline in the US. The company said it intended tocooperate fully with the Department, which also wants details of anycommunications Mylan had with competitors about such antibiotics.

SANDOZ has extended its lorazepam offering in Canada with a2mg/ml injectable formulation. The company already offers a 4mgversion of the anxiety and seizures treatment.

TEVA has seen its Copaxone (glatiramer acetate) 40mg/mlformulation recommended for use within the National HealthService (NHS) Scotland. The Scottish Medicines Consortiumnoted that the three-times per-week formulation cost the same asTeva’s once-daily 20mg version of the treatment for relapsingforms of multiple sclerosis.

TELIGENT has secured US approval for its Cefotan (cefotetan)injectable antibiotic. The approval is the first for a roster ofdiscontinued and withdrawn drugs acquired from AstraZenecaaround 15 months ago. The US firm is working with a manufacturingpartner to launch cefotetan 1g and 2g vials early this year, addressingmarket shortages.

MARTINDALE PHARMA has extended its Tapclob (clobazam)5mg/5ml and 10mg/5ml oral suspension line in the UK with 250mlbottles. Both the larger size and existing 150ml bottles now includea 5ml syringe and a 30ml dosing cup.

AMNEAL has released a lidocaine 5% ointment in a 35.44g tubefollowing final US approval, the first drug in its “new lidocaineproduct line”. The firm also expects to launch a transdermal patchupon final approval, underlining its “commitment to expand intonew, more complex dosage forms”.

BMWP – the Biosimilar Medicinal products Working Party (BMWP)within the European Medicines Agency (EMA) – says finalising arevised guideline on biosimilar low-molecular-weight heparinswill be on the agenda when it next meets on 7-8 March. The BMWPintends to finalise the guideline by the second quarter of 2016, ataround the same time as it releases for consultation a draft revisedreflection paper on biosimilar recombinant interferon alpha.

ELI LILLY has been told by an Indiana District Court that a statutory30-month stay on US approval for generic versions of its Effient(prasugrel) should not be extended during a stay on patent litigationpending the outcome of inter partes reviews of two US patents8,404,703 and 8,569,325.

BAXALTA and Momenta have succeeded in meeting the primaryendpoints of a pharmacokinetic study for their M923 proposedbiosimilar version of AbbVie’s Humira (adalimumab). The trialevaluated pharmacokinetics and safety, tolerability andimmunogenicity in comparison to Humira sourced in the US andEuropean Union. The study is intended to support regulatorysubmission in 2017 and a commercial launch in 2018.

ENDO has received the right to market a US authorised generic ofNovartis’ Voltaren Gel (diclofenac sodium) 1% topical gel underthe terms of a licensing agreement reached with the originator forthe osteoarthritis treatment that extends its exclusive rights to marketthe brand until 30 June 2023. Novartis’ Sandoz will continue tosupply the product to the US firm. G

IN BRIEF

Allergan and Perrigo have celebrated a “first-to-marketaccomplishment” by launching store-label rivals to Reckitt

Benckiser’s Mucinex D (guaifenesin/pseudoephedrine) 600mg/60mgextended-release tablets to retail and wholesale customers in the US.

Perrigo said the cough and cold brand had annual US sales ofapproximately US$46 million. Chairman and chief executiveofficer, Joe Papa, noted that the company would launch “the balanceof the range of five additional Mucinex-comparable products to theUS store-brand market” in the first half of 2016.

Separately, Perrigo has announced the temporary suspension ofsales of guaifenesin 600mg extended-release tablets “pending theresolution of challenges related to an excipient used in production”. G

OTC MEDICINES

Mucinex D receives US rival

Eli Lilly has halted its launch plans for its biosimilar Basaglar(insulin glargine) in Australia after the country’s Pharmaceutical

Benefits Advisory Committee (PBAC) proposed allowing pharmacy-level substitution with Sanofi’s Lantus.

“The regulatory and cost-effectiveness processes preceding the[PBAC] recommendation create yet-unresolved conflicts between theTherapeutic Goods Administration (TGA) and PBAC outcomes forBasaglar,” Lilly told Generics bulletin. Whereas labelling approvedby the TGA had required any substitution to be done under “strictmedical supervision”, the firm observed, PBAC was proposingswitching without the prescriber’s intervention.

Highlighting “unresolved concerns” over switching betweendifferent delivery devices “with a lack of functional equivalence”, Lillysaid its decision to stop the launch of Australia’s first biosimilar insulinglargine had also halted “tens of millions in savings” through mandatoryreimbursement price cuts upon biosimilar market entry. G

BIOLOGICAL DRUGS

Australian Basaglar is halted

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Laboratorios Rovi is preparing to introduce Europe’s first biosimilarenoxaparin this year. The Spanish company’s chief executive officer,

Juan López-Belmonte, told investors at a recent Jefferies HealthcareConference in London, UK, that “things are going as expected” ina European Medicines Agency (EMA) review that should result inapproval for its pre-filled syringes during 2016.

López-Belmonte told Generics bulletin that he foresaw nointellectual-property barriers to entering European markets followingEMA approval for its first-to-file biosimilar, for which an assessmentprocess started on 9 February last year following a validation phase.Discussions were continuing with several potential marketing partners,López-Belmonte revealed.

Rovi, he pointed out, had extensive experience with low-molecular-weight heparins, having established a leading position in Spain withbemiparin, which the firm is currently rolling out in Brazil and China.“Developing a biosimilar enoxaparin is difficult, but heparins arethe bread-and-butter of this company,” he stated, pointing out that thefirm was vertically integrated with its own raw-material supply.

To support the launch of biosimilar enoxaparin, the internationalexpansion of bemiparin and the capacity for contract manufacturing,Rovi last year acquired a production plant in in San Sabastián de losReyes, Spain, from Crucell. The site has an annual capacity of 120million syringes and 40 million vials.

Including any impact from enoxaparin, Rovi expects to increase itsturnover this year at a high single-digit or low double-digit rate. In thefirst nine months of 2015, the Spanish group increased its operatingturnover by 3% to C178 million (US$194 million), despite a 3% dropto C46.6 million in revenues from contract-manufacturing activities.

The Spanish group currently has injectable formulations of once-monthly risperidone and a quarterly letrozole in clinical development. G

PRODUCT NEWS


BIOLOGICAL DRUGS

Spain’s Rovi is readyfor enoxaparin in EU

Korea’s Ministry of Food and Drug Safety (MFDS) has approveda biosimilar rival to Janssen’s Remicade (infliximab) developed

through a collaboration between Merck, Sharp & Dohme (MSD) andSamsung Bioepis under the name Renflexis.

Indicated for the treatment of rheumatoid arthritis, ankylosingspondylitis, Crohn’s disease, ulcerative colitis, psoriatic arthritis andplaque psoriasis, the biosimilar is the second approved in Korea underthe collaboration, following approval of the pair’s Brenzys (etanercept)biosimilar version of Amgen’s Enbrel last year (Generics bulletin,2 October 2015, page 25).

MSD – which will market and distribute the infliximab biosimilarunder the terms of the firm’s partnership with Samsung Bioepis thatwas first established in early 2013 (Generics bulletin, 8 March 2013,page 23) – said it planned to launch Renflexis in the country in thefirst half of this year, providing “comprehensive education and supportservices for healthcare professionals, patients and their caregivers,including biosimilars education”.

Follows positive Phase III dataThe approval for Renflexis, as well as Brenzys, follows the

candidates meeting their primary endpoints in global Phase III studiesthat involved patients with moderate-to-severe rheumatoid arthritisdespite methotrexate therapy in June this year (Generics bulletin,26 June 2015, page 23).

Samsung Bioepis – the South-Korea based joint-venture ofSamsung and Biogen Idec – is responsible for developing andmanufacturing all of the biosimilars in its tie up with MSD, withthe partnership between the two firms also including versions ofadalimumab and trastuzumab, as well as insulin glargine (Genericsbulletin, 14 February 2014, page 17). G

BIOLOGICAL DRUGS

Merck and Samsungget Korean infliximab

Alopinavir/ritonavir combination antiretroviral may be manufacturedand sold throughout Africa by generics companies that obtain a

sub-licence from the Medicines Patent Pool (MPP), after the MPPagreed a non-exclusive, royalty-free licence with AbbVie. Theagreement, which was encouraged by the South African government,will allow generics companies to market “lopinavir/ritonavir throughoutAfrica, as well as combinations of ritonavir with other antiretrovirals,such as atazanavir and darunavir, as alternative second-line treatments”.

The MPP has stated it will work “swiftly” to grant licences togeneric manufacturers with “stringent regulatory approval”. Companiesthat already have regulatory approval in South Africa will be able todistribute in the country and the South African government will considerother manufacturing applications under its “fast track process”.

Greg Perry, executive director of the MPP, commented: “Whilemany African countries are currently able to purchase genericversions of these medicines from India, this licence will now enablemanufacturers in other countries where there are patents, such as Chinaand South Africa, to manufacture lopinavir/ritonavir and otherritonavir-based treatments for Africa, thus broadening the supplierbase for the entire continent.” In 2014, AbbVie and the MPP strucka deal covering paediatric versions of the drug. G

ANTIRETROVIRAL DRUGS

Patent Pool gets combinationNatco will be able to launch a rival to Celgene’s Revlimid

(lenalidomide) in the US before the drug’s last patent expires inApril 2027, after Celgene and India’s Natco Pharma along withNatco’s US partner, Allergan, settled litigation over Revlimid patents.

Celgene will provide Natco with a licence to Revlimid patentsrequired to manufacture and sell generic lenalidomide in the USbeginning on 31 January 2026. Natco will also receive a volume-limitedlicence to sell generic lenalidomide in the US from March 2022. Thevolume limit is “expected to be a mid-single-digit percentage of thetotal lenalidomide capsules dispensed in the US during the first fullyear of entry”, according to Celgene.

This volume limitation is expected to increase gradually each12 months until 2025 and is not expected to exceed one-third of thetotal lenalidomide capsules dispensed in 2025.

Natco’s marketing of its generic will depend on it obtainingUS Food and Drug Administration approval. The companies haveagreed to file consent judgements in the New Jersey District Courtthat “enjoin Natco from marketing generic lenalidomide before theexpiration of the patents-in suit, except as provided for in thesettlement”. Revlimid had sales of US$3.38 billion in the US marketfor the 12 months ended September 2015, Celgene stated. G

LITIGATION

Natco strikes Revlimid deal

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Alvogen and its development partner Natco have settled US litigationconcerning the Indian firm’s abbreviated new drug application

(ANDA) for a generic version of Roche’s Tamiflu (oseltamivir) 30mg,45mg and 75mg capsules.

Under the settlement, the Icelandic firm said it was entitled toroll out an alternative to the antiviral brand – which Roche licensesfrom Gilead – “before the expiration of the paediatric exclusivityperiod listed in the US Food and Drug Administration’s (FDA’s)Orange Book for US patent 5,763,483, which is 23 February 2017”.

Natco – which submitted its filing for generic Tamiflu aroundfive years ago (Generics bulletin, 8 April 2011, page 17) – has helda tentative approval for its ANDA since March 2014. Around that time,a US appeals court vacated and remanded for further proceedings aprior New Jersey district court ruling that had gone against Natco afterthe Indian firm successfully argued to the appeals court that the‘483 patent was invalid for obvious-type double patenting (Genericsbulletin, 2 May 2014, page 17).

Then, in March last year, Natco scored a further victory after theUS Supreme Court denied a petition launched by Roche and Gileadfor a certiorari review of the appeals court’s decision.

A further US patent – 5,866,601 – shields Tamiflu until 2 Augustthis year including six months of paediatric exclusivity, while USpatent 5,952,375 expired on 27 August last year. Tamiflu had US salesof SFr686 million (US$678 million) in 2014, amounting to aroundthree-quarters of global sales that reached SFr959 million. G

PRODUCT NEWS


ANTIVIRALS

Alvogen settles withRoche on oseltamivir

Teva has seen its European patent EP2,405,749 protecting itsCopaxone (glatiramer acetate) 40mg/ml formulation upheld by the

European Patent Office (EPO) in an oral hearing. The ‘749 patent –which is entitled ‘low frequency glatiramer acetate therapy’ anddescribes a method of alleviating symptoms of multiple sclerosisthrough three subcutaneous injections of glatiramer each week –expires in 2030.

Actavis, Mylan and Synthon had brought opposition proceedingsagainst the ‘749 patent “on various grounds”.

Noting that the EPO was expected to “issue a detailed writtendecision within a few weeks”, Teva acknowledged that the decisioncould be appealed. However, the Israeli company pointed out, anyappeal could take up to two years to be heard.

In 2014, the EPO upheld the validity of Teva’s European processpatent EP2,177,528 protecting its original Copaxone 20mg/ml until9 September 2025, following an attack by firms including Mylan andSynthon (Generics bulletin, 6 June 2014, page 17). G

MULTIPLE SCLEROSIS DRUGS

EPO upholds Teva’spatent for Copaxone

Eli Lilly and its partner Boehringer Ingelheim can begin rolling outthe first “follow-on insulin glargine treatment” in the US later this

year after the US Food and Drug Administration (FDA) granted finalapproval for the pair’s Basaglar (human insulin) 505(b)(2) hybrid.

Having held tentative approval for Basaglar since August 2014,Lilly and Boehringer last year resolved pending litigation with Sanofiover their alternative to the originator’s Lantus SoloStar diabetesblockbuster (Generics bulletin, 23 October 2015, page 25). Underthat settlement, which dismissed litigation from early 2014 concerningseven US patents with expiry dates running to March 2028, the firmsobtained the right to launch Basaglar on 15 December.

Sanofi also granted Lilly a royalty-bearing licence that allowsthe US originator to manufacture and sell Basaglar globally in theKwikPen pre-filled delivery device.

According to Lilly, the FDA’s approval “was based, in part, uponan extensive clinical development programme”, with the firms’ humaninsulin submission including results from pharmacokinetic andpharmacodynamic studies, as well as Phase III studies in people withtype 1 and type 2 diabetes comparing the safety and efficacy of Basaglarto US- and non-US-approved Lantus.

The US approval for its insulin glargine was the eleventhworldwide, Lilly noted. The originator recently said it was in “fulllaunch mode” in Europe – where it markets the product as Abasaglar –having followed initial launches in the Czech Republic and Slovakiawith shipments to Germany, Poland, Sweden and the UK. Lilly hasalso launched its insulin glargine in Japan. G

BIOLOGICAL DRUGS

Lilly’s Lantus rival approved

Coherus BioSciences has struck a “long-term” manufacturingagreement for its CHS-1701 biosimilar pegfilgrastim candidate

with KBI Biopharma. The pure-play biosimilars developer says theagreement will provide for manufacturing and delivery of the rivalto Amgen’s Neulasta brand “for the planned commercial launchand multiple years of commercial product sales”.

“Through this agreement, KBI has now allocated ample capacityfor Coherus to address the substantial market potential of CHS-1701,”president and chief executive officer Denny Lanfear commented.“We anticipate putting in place additional strategic manufacturingarrangements like this one for our other pipeline molecules.”

Further biosimilars in Coherus’ pipeline include its CHS-0214biosimilar etanercept candidate, which recently met its primaryendpoints in a two-part Phase III study evaluating the safety and efficacyof the proposed Enbrel rival in patients with moderate-to-severe chronicplaque psoriasis (Generics bulletin, 20 November 2015, page 18). TheUS-based firm is also developing an adalimumab biosimilar.

Meanwhile, plans to file a US biological license application (BLA)for its pegfilgrastim candidate have been pushed back to the secondquarter of this year after Coherus revealed it would initiate a follow-up trial in healthy volunteers to add to a recent pharmacokinetic/pharmacodynamic (PK/PD) study for the candidate.

Commenting that “the recent PK/PD study is acceptable to supportfiling the BLA”, the US-based developer said the follow-up study wasnevertheless “most prudent” given the “low cost” – estimated to bearound US$4 million – and “relatively short delay involved”. Coherushad previously disclosed plans to file during the first quarter of2016 (Generics bulletin, 11 September 2015, page 20).

Coherus said it was currently analysing “implicating factorsfor the key outliers” in the PK/PD study. “Given the stronganalytical profile, robust chemistry, manufacturing and control(CMC) package, and positive clinical performance of CHS-1701 inthe recent PK/PD study, we are confident the follow-on study willsupport our objective,” it said. G

BIOLOGICAL DRUGS

Coherus and KBI strike deal

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Alvogen’s sister biotech operation, Alvotech, has appointed formervice-president of Hospira’s Global Generics business, Eef

Schimmelpennink, as its chief executive officer.Bringing “over 18 years of global generic pharmaceutical

experience”, Schimmelpennink joins the Icelandic firm from Pfizer,where he had taken up the role of vice-president of global sterileinjectables after the US-based originator acquired Hospira in September(Generics bulletin, 11 September 2015, page 3).

Schimmelpennink – who spent nine years with Synthon prior tojoining Hospira in March 2011 – succeeds Andreas Herrmann, wholast year announced his intention to step down from the role.Herrmann will now join Alvotech’s scientific advisory board andbecome a consultant to the business. Schimmelpennink will besupported by Emmanuelle Lepine, who last year added the role ofdeputy chief executive officer to her position as Alvotech’s vice-president of business development.

Kristjansson oversees facility completionMeanwhile, interim chief executive Fjalar Kristjansson, who

serves as Alvogen’s technical director, would “continue to play aleading role at Alvotech”, including overseeing the completion andregulatory inspection of its new manufacturing facility, the firm noted.

Alvotech’s founder and chairman, Robert Wessman, saidproduction would soon begin at the biopharma site next to the Universityof Iceland in Reykjavik (Generics bulletin, 2 October 2015, page 31).G

PEOPLE


27 January

■ 9th EGA PharmacovigilanceLondon, UKThis European Generic and Biosimilar medicines Association (EGA)event will cover legislation, risk management and biologics.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: [email protected] online at www.egaevents.org/egaphvrac2016reg.htm.

28-29 January

■ 15th EGA Regulatory & Scientific AffairsLondon, UKThis conference will provide updates on regulatory developments.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: [email protected] online at www.egaevents.org/egaphvrac2016reg.htm.

10-11 February

■ World Generic Medicines Congress Europe 2016Barcelona, SpainTopics covered at this event will include legal and regulatorydevelopments, current market trends and future challenges.

Contact: Health Network Communications. Tel: +44 207 092 1210.E-mail: [email protected]: www.healthnetworkcommunications.com.

22-24 February

■ GPhA 2016 Annual MeetingFlorida, USAThis meeting, organised by the US Generic Pharmaceutical Association,will look at regulatory issues and opportunities within the industry.

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

3-4 March

■ Business Development & InnovationOpportunities in Consumer Healthcare/OTCLondon, UKOrganised jointly by the Pharmaceutical Licensing Group andOTCToolbox, this event will focus exclusively on businessdevelopment and innovation in the consumer healthcare/OTC market.Contact: OTCToolbox. Tel: +44 (0)121 314 8757.E-mail: [email protected]: plg-group.com/events/bdconsumerhealthcareotc/

6-7 March

■ EuroPLX 60Barcelona, SpainThis meeting provides an opportunity to discuss and negotiateagreements, in-licensing and marketing and distribution.

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

8-9 March

■ 12th EGA Legal AffairsBrussels, BelgiumThis conference will cover issues including the latest legal andintellectual-property developments regarding generics and biosimilars.

Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: [email protected] online at www.egaevents.org/laf/egalaf2016reg.htm.

EVENTS – January, February & March APPOINTMENTS

Alvotech hands postto Schimmelpennink

Momenta Pharmaceuticals has appointed former Biogen executiveMatt Ottmer as its chief operating officer overseeing strategic

product development, research, clinical development, pharmaceuticalsciences and commercial activities.

Ottmer – who was most recently Biogen’s senior vice-presidentof strategy and emerging businesses during a 16-year career withthe biotech firm – reports directly to the US generics and biosimilarsspecialist’s president and chief executive officer, Craig Wheeler. G

APPOINTMENTS

Momenta gains Biogen boss

Hexal’s Wolfgang Späth has been re-elected as chairman of Germangenerics and biosimilars industry association Pro Generika. He

continues to be supported by Teva’s Markus Leyck Dieken, whoserves as deputy chairman.

Newly elected onto Pro Generika’s board are Fresenius Kabi’ssenior vice-president Boris Bromm and Zentiva Pharma’s managingdirector Daniel Diesel, along with Actavis Deutschland’s managingdirector Martin Schwarz.

They join Mylan Dura’s country manager Heike Streu and StadaArzneimittel’s director of strategic management, healthcare policyand association engagement Anne Demberg on the association’sboard. Streu also acts as Pro Generika’s treasurer. G

INDUSTRY ASSOCIATIONS

Späth still leads Pro Generika

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Former Sandoz executive Nick Haggar will on 1 July take overas chief executive officer of Spain’s Chemo Group, affiliates of

which include biosimilars developer Mabxience.Haggar – who had until recently served as Sandoz’ head of

Western Europe, Middle East and Africa – will join the Spanishcompany’s board in April before taking over as chief executive fromincumbent Leandro Sigman. At that time, Sigman – whose familyowns the Chemo Group – will become chairman.

British national Haggar joined Sandoz in 2008 as head of WesternEurope, adding responsibility for the Middle East and Africa in 2011.He had also overseen Sandoz’ operations in Germany since 2014. Ina pharmaceuticals and healthcare career spanning around 30 years,Haggar has also held positions at Ranbaxy, Baxter and Glaxo.

He joined the board of the European Generic and Biosimilarmedicines Association (EGA) in 2006, before being elected theassociation’s president for a two-year term in October 2013 (Genericsbulletin, 18 October 2013, page 27). Last year, he handed over therole to Mylan’s Jacek Glinka and became the EGA’s treasurer(Generics bulletin, 26 June 2015, page 27).

Along with Mabxience, the group comprises branded women’shealth specialist Exeltis and bulk-drugs and finished-dose supplierChemo. Last year, Mabxience opened a monoclonal antibodies plantin León, Spain (Generics bulletin, 23 October 2015, page 4). G

PEOPLE


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APPOINTMENTS

Haggar to take leadwith Spain’s Chemo

The US Generic Pharmaceutical Association (GPhA) has hiredChris Bowlin as its senior vice-president of government affairs.

Bowlin brings to the position “over 25 years of leadership roles in theexecutive branch, Congress and the private sector”, having formerlyserved as chief health advisor to US senator John McCain. G

APPOINTMENTS

Bowlin takes role with GPhA

Valeant board member and former chief financial officer HowardSchiller has been appointed as the Canadian firm’s chief executive

officer on an interim basis after company head Mike Pearson was placedon medical leave having contracted a “severe case” of pneumonia.

Moreover, Valeant’s lead independent director, Robert Ingram,will take on Pearson’s responsibilities as chairman of the board, alsoon an acting basis.

Schiller’s appointment on 6 January comes nine days after Valeantformed a temporary ‘office of the chief executive officer’ – composedof general counsel Robert Chai-Onn, group chairman Ari Kellen andchief financial officer Robert Rosiello – to lead the company in Pearson’sabsence. The timing of Pearson’s expected return is “uncertain”. G

INTERIM APPOINTMENTS

Valeant’s Schiller isnamed interim chief

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