20 January 2017

The US Supreme Court has agreed to review litigation between Sandoz and Amgen over thecountry’s Biologics Price Competition and Innovation Act (BPCIA), granting the generics

firm’s petition and the originator’s cross-petition for certiorari in the long-running disputeover Sandoz’ Zarxio (filgrastim-sndz). The case revolves around the BPCIA’s requirements on the180-day notice of commercial marketing that must be provided to the brand company, as wellas originator access to abbreviated biologic license application (aBLA) submissions. Havingrecently dismissed without comment a petition to review similar litigation between Apotexand Amgen over the BPCIA and Apotex’ proposed rivals to Amgen’s Neupogen (filgrastim)and Neulasta (pegfilgrastim) brands (Generics bulletin, 16 December 2016, page 6), theSupreme Court has granted Apotex a motion to file an amicus brief in the Sandoz case. G

For further details of the case, turn to page 7.

Supreme Court to hear BPCIA

COMPANY NEWS 3

Reddy’s anticipates a re-audit this quarter 3

Lupin sets out vision for biosimilars unit 3

Abbott and ChemDiv further 4their alliance

Akorn targets deals for 4alternate dosages

MARKET NEWS 5

US biologic suffixes must 5be meaningless

Biosimilars Council reacts to suffix plans 5

FDA releases a raft of industry guidance 6

Italian penetration is a 6fifth and on the rise

Top US court denies appeal 7on jurisdiction

BPCIA review follows 7solicitor general lead

UK needs clarity on future for regulation 8

ISPE publishes report on 8injectable shortage

UK government will back UPC from start 9

GPhA responds over 9Trump pharma policy

PRODUCT NEWS 10

FDA accepts filing on 10Mylan’s trastuzumab

UK sends SPC cases to European Court11

Alimta patent upheld in US 11court of appeal

CVS Pharmacy has Impax’ Adrenaclick 12

Momenta gets payoff on 13Humira rival deal

Actavis loses out on Concerta in Canada13

Zydus grabs a launch date 15for a Livalo rival

REGULARS

Events – Our regular listing 10Price Watch UK – UK pricing trends 14People – Sentencing date is set 16for Glazer and Malek

Issue No.292

Applications for US biosimilars to be designated as interchangeable “generally willinclude data from a [clinical] switching study or studies in one or more appropriate

conditions of use”, the US Food and Drug Administration (FDA) states in its long-awaiteddraft interchangeability guideline. The agency has set a 60-day period for comments onthe document, released shortly after a final guideline on biologics naming (see page 5).

Section 351(k) of the Public Health Service (PHS) Act – as amended by the BiologicsPrice Competition and Innovation Act (BPCIA) – requires that for a biosimilar to be deemedinterchangeable, the drug “can be expected to produce the same clinical result as the referenceproduct in any given patient” and that switching to the biosimilar carries no greater risk “interms of safety or diminished efficacy” than sticking with the reference brand.

The agency intends to weigh all product-specific factors to determine the level of dataneeded. For example, the guideline explains, “a clinically relevant, and thus meaningful,fingerprint-like characterisation may reduce residual uncertainty regarding interchangeabilityand may lead to a more selective and targeted approach to the clinical studies necessary todemonstrate interchangeability”. But post-marketing evidence alone is unlikely to suffice.“Our current thinking is that post-marketing data collected from products first licensed andmarketed as a [non-interchangeable] biosimilar – without corresponding data derived from anappropriately designed, prospective, controlled switching study or studies – generally wouldnot be sufficient to support a demonstration of interchangeability,” the FDA states.

Describing how to design and analyse switching studies, the FDA says trials may be informedby “clinical practice” and pledges to adopt a “flexible approach”. The impact of switchingon clinical pharmacokinetics and pharmacodynamics will typically be the most appropriateprimary endpoints, while the agency expects studies to “assess immunogenicity and safety”.Scientific justification for extrapolating data across indications is to cover mechanisms of action,as well as PK, toxicity and immunogenicity risk in different patient populations.

Unlike when demonstrating biosimilarity, using a reference product not licensed in the US“generally would not be appropriate” due to the potential for “subtle differences in levels ofspecific structural features”. Sponsors are encouraged to “contact the FDA early in the productdevelopment process to discuss the design of a switching study”, including any proposal toprovide “adequate scientific justification” to support using data from a switching study witha non-US-licensed comparator product. G

Switching studies neededfor US interchangeability

3GENERICS bulletin20 January 2017

company news

Dr Reddy’s Laboratories expects by the end of the current quarterthe US Food and Drug Administration (FDA) to re-inspect three

Indian production facilities that have been subject to a warning letterfor more than a year.

Addressing investors at the 2017 JP Morgan HealthcareConference in San Francisco, US, the Indian firm – which draws justunder half of its sales from the US market – said a re-audit had beenscheduled for the first quarter of this year, “assuming no unexpectedchanges in the current schedule”.

Problems with documentation practices and controls, laboratorytesting procedures, incident investigation practices and standardoperating procedures led the FDA in November 2015 to issuea warning letter against the three sites.

These were active pharmaceutical ingredient (API) facilities inSrikakulam, Andhra Pradesh and Miryalaguda, Telangana, as well asan oncology formulations factory operated by the firm in Duvvada nearVisakhapatnam, Andhra Pradesh (Generics bulletin, 20 November2015, page 3).

Clarifying information to the Bombay Stock Exchange (BSE)following local media reports, Reddy’s said it believed “that thescheduling of the audit by the FDA is a usual activity in the normalcourse of pharmaceutical industries’ business operations”.

Reddy’s also pointed out that the firm’s “participation and accessto the presentation material” in the conference was “already intimated”to the BSE several days prior to the media reports.

In August last year, Reddy’s told investors that it had “completedmost of the commitments” it had made in its response to the FDAwarning letter, and was “about to send out the letter with the requestfor re-inspection very soon” (Generics bulletin, 5 August 2016, page 3).All commitments had now been completed, Reddy’s revealed, notingthat it had also met with the FDA last month.

Reddy’s had hired Lachman Consulting Services to performindependent product quality assessments at the facilities, which togethergenerated around 10-12% of the company’s turnover at the time thewarning letter was issued.

Meanwhile, Reddy’s said it had “no comments to offer on shareprice movement” in the wake of the report. “The movement in theprice... is completely market driven,” the Indian firm said. G

Manufacturing

Reddy’s anticipates are-audit this quarter

Lupin has revealed plans to file applications for biosimilar versionsof Amgen’s Enbrel (etanercept) psoriasis and arthritis treatment

in Europe and the US within the next two years.Addressing investors at the 2017 JP Morgan Healthcare

Conference in San Francisco, US, the Indian firm said it was targetingfiling biosimilar etanercept with the European Medicines Agency(EMA) during its financial year ending March 2018, and with the USFood and Drug Administration (FDA) the year after.

By that time, Lupin also plans to submit to the US agency filingsfor biosimilar versions of Neupogen (filgrastim) and Neulasta(pegfilgrastim). The Indian firm already markets its Lupifil (filgrastim)and Lupifil-P (pegfilgrastim) biosimilars in India.

Further down the line, during its financial year ending March2021, Lupin is targeting filing a biosimilar alternative to Roche’sLucentis (ranibizumab) with both the EMA and FDA.

Revealing further details of the firm’s biosimilar pipeline, Lupinsaid a proposed alternative to Amgen’s Xgeva/Prolia (denosumab) wascurrently in the pre-clinical stage, while clone and process developmentwas currently underway for rivals to Roche’s Perjeta (pertuzumab)and Bayer’s Eylea (aflibercept).

Together, these seven biosimilar opportunities represented amarket opportunity of around US$30 billion, Lupin observed.

Respiratory filings to 2020Lupin also detailed a nine-strong US inhalation pipeline, comprising

one solution, five metered-dose inhalers, two dry-powder inhalersand one suspension, with targeted filing days through to the firm’s 2020financial year. The Indian group in 2015 bolstered its respiratorydevelopment capabilities by opening a Center of Excellence forInhalation Research at its US research operation in Coral Springs,Florida (Generics bulletin, 1 September 2015, page 8).

Fuelled by a pipeline of 137 pending abbreviated new drugapplications (ANDAs), including 21 first-to-file opportunities, andwith research and development capabilities covering further complexgenerics such as oral contraceptives, dermatology products,controlled substances and injectables, Lupin says it is aiming tobecome a leading global and generics player “with a significantcomplex generics and specialty business” by 2020 and beyond. G

Business strategy

Lupin sets out visionfor its biosimilars unit

Valeant has struck a deal to sell its outstanding equity interestsin Dendreon Pharmaceuticals to the Sanpower Group, “one of

the largest privately-owned conglomerates in China”, for US$820million. Upon completion of the deal – which is expected in the firsthalf of 2017, subject to customary closing conditions – Valeant willreceive a cash payment of US$820 million, which the Canadianfirm said it would use to repay debt.

“With this sale, we are better aligning our product portfolio withValeant’s new operating strategy by exiting the urological oncologybusiness, which is one of our non-core assets,” said Valeant chiefexecutive officer Joe Papa. “We are pleased to take this step forwardin our divestiture programme and are continuing to evaluate transactionsto simplify our business and strengthen our balance sheet.” G

DivestMents

Valeant is to divest DendreonMedicure has provided a secured loan of US$9.8 million to US-based

active pharmaceutical ingredient (API) services provider Apicore,to repay Apicore’s debt with Knight Therapeutics and Sanders MorrisHarris. The loan, which bears 12% interest and matures at the endof 2020, is secured by a charge over the US assets of Apicore.

Late last year, Canadian firm Medicure reached an agreement toincrease its holding in privately-owned Apicore by acquiring a “majoritystake” in the firm of up to 64% – or 60% on a fully-diluted basis – inexchange for US$33.25 million (Generics bulletin, 25 November2016, page 3). Medicure has just paid US$0.5 million to buy sharestaking its holding in Apicore to 61% on a fully-diluted basis. Moreover,Medicure has further option rights running until 3 July this year tofurther increase its share in Apicore. G

Business strategy

Medicure gives Apicore loan

4 GENERICS bulletin 20 January 2017

company news

20 January 2017 Issue 292

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

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

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

ISSN 1742-0784.

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

Abbott and global research organisation ChemDiv have achieved“several key milestones” concerning their partnership aimed at

developing and registering new branded generic products across “keytherapeutic areas for high-growth emerging markets”.

The firms have together progressed one product to a first marketauthorisation, submitted another for Phase III clinical studies, andalso selected “multiple prototype products for further development”.The last development triggered “multiple milestone payments”,according to ChemDiv.

“Other projects in the collaboration are progressing on scheduleand are on track to achieve further project milestones for whichChemDiv will receive additional payments from Abbott,” the US-basedcontract researcher commented, without disclosing details.

Partnership formed in 2012Abbott and ChemDiv’s research and development partnership was

first struck in July 2012 “to broaden therapeutic opportunities forpatients in Russia, and to contribute to building an innovative pharmaindustry in Russia”. Three years later, ChemDiv announced Abbotthad increased its investment and expanded manufacturing plants inIndia to cater to the local market as well as to exports.

Commenting on the latest development, ChemDiv’s chiefexecutive officer, Nikolay Savchuk, said the firm was “delighted to beable to register a number of successful joint developments with ourstrategic partner”. “This is an excellent validation of our researchand regulatory contribution to Abbott’s generics strategy, as furthermanifested by the recent expansion of the collaboration,” Savchukstated. “Our strategic relationship with Abbott is extremely importantand valuable to us.”

Sales of Abbott’s branded generic Established PharmaceuticalsUnit, including its CFR and Veropharm businesses, climbed to US$1.01billion in the first nine months of last year. G

strategic alliances

Abbott and ChemDivfurther their alliance

Companies possessing an alternate dosage formulation portfolio ora “promising pipeline” are among those being targeted by US

injectables and ophthalmics specialist Akorn as part of a dedicatedmerger and acquisition strategy. Addressing investors at the recent2017 JP Morgan Annual Healthcare Conference in San Francisco, US,the company said it was also seeking to acquire firms that could bringnew capabilities to Akorn’s operations.

Meanwhile, Akorn is looking to bolster its portfolio by identifyingboth generic and branded prescription pharmaceutical products foracquisition, including legacy and ophthalmology brands.

The US firm is also weighing up offers for branded OTC productsand animal health drugs.

Akorn’s roster of alternate dosages comprises 10 topical creams,ointments or gels, 38 sterile ophthalmics, 34 sterile injectables, 34 oralliquids, six nasal sprays or respiratory products and three otic solutions.

Turning to the firm’s pipeline of abbreviated new drug applications(ANDAs), Akorn noted that it had 92 filings currently pending USFood and Drug Administration (FDA) approval and “over 75 additionalANDAs in various stages of development”.

Akorn pointed out that it had replenished its pipeline of ANDAsduring 2016 by filing 12 applications with the FDA.

While Akorn expects to receive between 10 and 20 productapprovals by the end of the first quarter of this year, this figure ishowever down from a previous forecast of around 25 approvals, in thewake of a now completed FDA re-inspection of the firm’s manufacturingfacility in Decatur, Illinois. The US agency recently cleared the Decaturfacility following Akorn’s corrective action response to deficiencies(Generics bulletin, 6 January 2017, page 4).

Finally, Akorn told investors that group sales were anticipatedto surpass the US$1 billion mark for 2016. Turnover is set to climbfrom US$985 million in 2015 to a projected US$1.13 billion, when thefirm reports its 2016 annual sales in the coming weeks. G

Business strategy

Akorn targets dealsfor alternate dosages

5GENERICS bulletin20 January 2017

market news

Guidance on US naming conventions for biological drugs “standsto increase confusion, hinder biosimilar uptake and increase

systemic costs” if it applies proprietary names to interchangeablebiosimilars, according to the Biosimilars Council within the USGeneric Pharmaceutical Association (GPhA).

Reacting to the final US Food and Drug Administration (FDA)guideline – which affirms that biological drugs must carry a unique,meaningless four-letter suffix to their non-proprietary name (seeopposite) – Pfenex chief executive Bert Liang, chairman of theBiosimilars Council, said the guidance “lacks insight into a namingconvention for interchangeable biosimilars”.

“In order to facilitate the development of a robust biosimilarsmarket and increase patient access, it is essential that the FDA and itsregulatory counterparts demonstrate support for the safety of biosimilarproducts,” Liang stated. “While we are supportive of the FDA decisionto move forward with a naming convention that includes a suffixdevoid of meaning, we encourage the agency to consider the use of theinternational non-proprietary name (INN) for biosimilars determined tobe interchangeable to a reference product, underscoring support forbiosimilar use in the US and reducing the potential of confusion forphysicians and pharmacists.”

“Specifically, as noted by the Federal Trade Commission (FTC), theuse of proprietary names for interchangeable products may leadstakeholders to believe products have ‘clinically meaningful differences’which by the very definition of a biosimilar is untrue,” Liang stated.As part of comments submitted to the FDA in 2015, the FTC had urgedthe agency to reconsider its suffix plans in favour of “other meansto accomplish its purposes that are less likely to hinder competitionfrom biosimilars” (Generics bulletin, 6 November 2015, page 14).

Nevertheless, Liang said the guidance “demonstrates positivemomentum in creating a regulatory framework for biosimilar products”.

Meaningless suffixes harder to trackMeanwhile, separate US biosimilars association the Biosimilars

Forum said it was “disappointed in [the FDA’s] decision to applymeaningless suffixes in the naming convention for biological drugs”.

“Non-meaningful suffixes will certainly be more difficult forphysicians and patients to recall than meaningful suffixes,” theBiosimilars Forum said. “Additionally, they will likely lessen the abilityto carefully track the identity of the biologic drug administered topatients, thereby contrary to the stated purpose of having a suffix toenhance pharmacovigilance.”

Nevertheless, the group said it “appreciates the ongoing efforts ofthe FDA to provide guidance on outstanding biosimilar policy issues”.“We look forward to learning more about the FDA’s plans for renamingof biologics that are already approved, as well as for the namingconvention that will be implemented for interchangeable biologics.”

Further dissatisfaction with the suffix plans was voiced by theAlliance for Safe Biologic Medicines (ASBM), which also expresseda preference for a meaningful rather than meaningless suffix.

“It remains ASBM’s position that incorporating a suffix based onthe name of the initial manufacturer or marketing authorisation holderat the time of approval would promote the most meaningful, memorable,intuitive and informative method of distinguishing similar biologicproducts from their reference products and one another,” ASBM stated.“It would better promote accountability,” the group added, “by efficientlyassociating the product with the legal entity ultimately responsible.”G

regulatory affairs

Biosimilars Councilreacts to suffix plans

Biological drugs in the US, including biosimilars, must carry aunique, meaningless four-letter suffix attached to the end of their

non-proprietary name with a hyphen, the US Food and DrugAdministration (FDA) has affirmed in final guidance on non-proprietarynaming of biological products that has been released to industry.

Suffixes will not only be applied to newly-licensed biologics butalso retrospectively for previously-licensed biological products, as wellas related biological products. Draft guidance recommending a randomsuffix was first published by the agency in 2015 (Generics bulletin,11 September 2015, page 1).

In line with draft guidance from June (Generics bulletin, 10 June2016, page 1), the FDA said biosimilar and biologic applicantsshould “submit up to 10 proposed suffixes, in order of the applicant’spreference”, at the time of the biologics license application (BLA)or during the investigational new drug application phase.

According to the FDA, the naming convention “will facilitatepharmacovigilance for originator biological products, related biologicalproducts and biosimilar products containing related drug substanceswhen other means to track a specific dispensed product are not readilyaccessible or available”.

Non-proprietary names with distinguishing suffixes “can serve asa key element to identify specific products in spontaneous adverseevent reporting and to reinforce accurate product identification inbilling and claims records used for active pharmacovigilance”, theagency said. Other product-specific identifiers such as proprietarynames or national drug codes, it added, “may not be available orcould change over time”.

Distinguishable suffixes would “facilitate accurate identificationof these biological products by healthcare practitioners and patients”,the FDA said. Moreover, the agency insisted, “distinguishing suffixesshould help minimise inadvertent substitution of any such productsthat have not been determined to be interchangeable”.

For interchangeable products, the FDA said it was “continuingto consider the appropriate suffix format”.

Application of the naming convention should “encourage routineuse of designated suffixes in ordering, prescribing, dispensing, record-keeping and pharmacovigilance practices”, the FDA recommended,while “inaccurate perceptions of the safety and effectiveness of biologicalproducts based on their licensure pathway” should be avoided.

“In implementing the Biologics Price Competition and InnovationAct (BPCIA),” the agency said, “the FDA has carefully consideredthe appropriate naming convention to maximise the success ofbiosimilar products and interchangeable products, and to help ensurethe safety of patients receiving biological products.”

The FDA acknowledged that it had in the past designated propernames for biologics that include an identifier attached as a prefix todistinguish them from previously-licensed products. In 2012, Teva’sGranix (tbo-filgrastim) was approved as a novel biologic (Genericsbulletin, 14 September 2012, page 1).

Another example was the Kadcyla (ado-trastuzumab emtansine)brand, the FDA pointed out, which had a unique prefix “to minimisecertain medication errors and facilitate pharmacovigilance” bydistinguishing it from trastuzumab, licensed under a different BLA.“The FDA may continue such practices on a limited basis, whereappropriate,” the guidance states, “when the agency determines thatthe designation of a prefix, in addition to a suffix as contemplatedby this guidance, is necessary to ensure patient safety.” G

US biologic suffixesmust be meaningless

regulatory affairs

6 GENERICS bulletin 20 January 2017

MARKET NEWS

Three separate draft guidance documents – relating to 180-dayexclusivity, referencing approved drug products in abbreviated new

drug applications (ANDAs), and drug-device combination productssubmitted in an ANDA – have been published by the Center for DrugEvaluation and Research (CDER) within the US Food and DrugAdministration (FDA). At the same time, the agency has also outlinedits agenda detailing guidances that it plans to release in 2017.

The FDA’s draft guidance on 180-day exclusivity adopts aquestion-and-answer format. Individual sections cover the statutoryframework for 180-day exclusivity; ‘first applicant’ status; the interplaybetween 180-day exclusivity and patents, including Orange Book patents;the trigger for and scope of 180-day exclusivity; the relinquishmentand waiver of 180-day exclusivity; forfeiting 180-day exclusivity; andother procedural questions relating to determinations of 180-dayexclusivity by the FDA.

Meanwhile, the FDA’s draft guidance on referencing approveddrug products in ANDA submissions “provides information to potentialapplicants on how to identify a reference listed drug (RLD), referencestandard, and the basis of submission in an ANDA submission”.

“A variety of factors has led to confusion among stakeholders onwhat the terms RLD, reference standard, and basis of submission mean,and how ANDA applicants should use them,” the document explains.“The purpose of this guidance is to address this confusion by explainingwhat these terms mean and clarifying the differences among them.”

Starting this year, the FDA said it intends to modify its OrangeBook to “clarify which listed drugs are RLDs and which are referencestandards”, and to indicate which products in the ‘discontinued section’may be referred to as an RLD. Further recommendations include “howpersons can request FDA designation of an RLD, and how personscan request selection of a reference standard”.

Separately, draft guidance has also been published on “comparativeanalyses and related comparative use human factors studies for a drug-device combination product submitted in an ANDA”. Recommendations“generally focus on the analysis of the proposed user interface for thegeneric drug-device combination product” – including the deliverydevice and associated controls and displays, as well as labelling andpackaging – when compared to the user interface for the RLD.

“In the early stages of development, potential applicants shouldcarefully consider the design of the user interface of a proposed genericcombination product and seek to minimise differences from the userinterface for the RLD,” the document suggests, recommending thresholdanalyses to identify and assess design differences. “Depending on theresults of the threshold analyses discussed in this guidance,” the FDAstates, “submission of additional data may be warranted, such as datafrom comparative use human factor studies.”

According to the guidance agenda for 2017 that has just beenpublished by the CDER, two draft biosimilars guidelines are scheduledto be published this year, including “statistical approaches to evaluationof analytical similarity data to support a demonstration of biosimilarity”.The other, regarding interchangeability, has just been published bythe agency (see front page).

Expected draft guidelines for small-molecule generics includedocuments on complete response letters, prior approval supplements,meetings on complex products, and three-year exclusivity determinations.Furthermore, the CDER plans to issue a document helping companiesto determine whether to submit applications under the 505(b)(2)hybrid or 505(j) generics pathways. G

REGULATORY AFFAIRS

FDA releases a raftof industry guidance

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4.83.53.1

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Figure 1: Value and volume shares of Italy’s overall retail medicines marketenjoyed by generics between 2001 and 2015, and in the year ended September2016 (Source – Assogenerici)

Penetration by volume of Italy’s overall retail medicines marketby generics exceeded a fifth in the year ended September 2016,

according to the latest data published by the country’s genericsindustry association, Assogenerici. Volume penetration reached 20.5%in the 12-month period, compared to 19.9% in the whole of 2015 and19.1% in 2014. By value, generics captured 11.2% of the country’soverall medicines market in the year to September, compared to10.9% in the whole of 2015 and 10.4% in 2014 (see Figure 1).

Assogenerici said the Italian generics market for the 12-monthperiod was worth C1.21 billion (US$1.29 billion), with volume salesof just over 386 million packs. This compared to figures of C1.09billion and 348 million packs recorded by the association on a similarbasis for the year ended September 2015 (Generics bulletin, 22January 2016, page 9).

As a proportion of Italy’s overall medicines market, Assogenericireported – based on QuintilesIMS sell-in data at ex-factory prices forthe year to September 2016 – the off-patent market as a wholerepresented 55.3% by value. However, as generics barely captured afifth of this available market – 20.3% – this gave them just 11.2% ofoverall medicines sales. Off-patent brands that accounted for 79.7% ofoff-patent sales therefore enjoyed a 44.0% share of the overall market.

By volume, however, the overall medicines market was less evenlysplit, with patented brands accounting for just 27.9% of packs sold.While this left the remaining 72.1% open to generic competition,generics only captured 28.5% of this opportunity, translating to justover a fifth of the total market at 20.5%. Off-patent brands – whichenjoyed a 71.6% share of the off-patent market – therefore captured51.6% of overall medicines volumes.

Midway through last year, Assogenerici complained that marketentry for generics was continuing to be delayed in Italy, with thecountry standing as one of the last in Europe to maintain patent linkage(Generics bulletin, 26 August 2016, page 15). This was despite theEuropean Commission expressly declaring patent linkage to be contraryto Community law in its 2009 report on the pharmaceutical sector.

Assogenerici has previously urged Italy to adopt a sustainablehealthcare policy instead of using price cuts as a “fig leaf” to coverunderlying problems in part due to a “systematic curb” in the utilisationof generics and biosimilars identified by the industry association(Generics bulletin, 27 May 2016, page 8). G

MARKET RESEARCH

Italian penetration isa fifth and on the rise

VolumeValue

7GenerIcs bulletin20 January 2017

market news

Adecision by the US Supreme Court to review litigation betweenSandoz and Amgen over the Biologics Price Competition and

Innovation Act (BPCIA) has followed a recommendation from thecountry’s solicitor general that the court hear the case. The SupremeCourt – which has just granted Sandoz’ petition and Amgen’s cross-petition for certiorari in the dispute (see front page) – had previouslyinvited the solicitor general to submit briefs “expressing the viewsof the US” (Generics bulletin, 24 June 2016, page 10).

Sandoz had petitioned the Supreme Court to review the part ofan appeals court decision that held that the generics firm could notprovide Amgen with the statutory 180-day notice of commercialmarketing until it obtained US Food and Drug Administration (FDA)approval for its Zarxio (filgrastim-sndz) biosimilar (Generics bulletin,26 February 2016, page 11).

Meanwhile, Amgen had queried whether providing biosimilarmanufacturing and dossier details to originators was an optional partof the BPCIA framework (Generics bulletin, 3 June 2016, page 9).

Outlining his views in an amicus brief, solicitor general Ian HeathGershengorn said that Sandoz and Amgen’s “important questions”applied to “every biosimilar for which FDA approval of an abbreviatedbiologic license application (aBLA) is sought”, and were “recurringin other actions pending in various district courts” (Generics bulletin,16 December 2016, page 6).

Referring to Sandoz’ argument against the appeals court’s findingthat the 180-day notice of commercial marketing may only be providedby a biosimilar applicant after FDA approval, Gershengorn said theappeals court “erred in interpreting” the relevant BPCIA provision.

No ‘temporal restriction’ on notice“The text and purpose of [the] notice provision and the BPCIA’s

broader statutory context demonstrate that the provision permits anapplicant to give advance notice of the first commercial marketing ofits biosimilar before the FDA has licensed the biosimilar,” Gershengornasserted. Nothing in the framework “additionally restricts how soonthe applicant may provide notice after the applicant submits its aBLAto the FDA”, he pointed out. He suggested that the appeals court hadwrongly “inferred a temporal restriction” from a reference to a phrasereferring to the date of first commercial marketing for a biosimilar“licensed” under the BPCIA framework.

“Under the [appeals court’s] reading, the owner of a biosimilarwith an effective licence could be forced to wait 180 days after theFDA has authorised it to commence marketing, even if the sponsorhad no arguably valid infringement claim to warrant such delay,”Gershengorn observed.

“In any event,” Gershengorn stated, “no federal cause of actionexists under which a sponsor could obtain injunctive relief if theapplicant fails to give notice”, as “nothing in the BPCIA creates acause of action” to enforce the notice provision.

Referring to the section of the BPCIA outlining the requirementfor biosimilars applicants to provide to originators a copy of the aBLAand manufacturing-process information, Gershengorn said the BPCIAfurther stated that if applicants fail to provide the application andinformation to the brand company, the applicant’s submission of theaBLA is deemed to be “an artificial act of infringement”.

In this case, the originator “may bring a declaratory-judgementaction based on any patent that claims the biological product or ause of the biological product”, he pointed out. G

litigation

BPCIA review followssolicitor general lead

litigation

Top US court deniesappeal on jurisdiction

More than 30 new bioequivalence recommendations are among thelatest batch of draft product-specific guidelines for generics

published by the US Food and Drug Administration (FDA).The agency’s most recent update consists of 31 new product

recommendations, along with 17 revisions to existing guidancedocuments, for which the FDA is seeking feedback.

Included within the newly-added guidance documents arebudesonide as a powder for inhalation, epinephrine as an intramuscularsubcutaneous injection, and lidocaine as a topical ointment. Alsoamongst the 31 additions are adapalene/benzoyl as a topical gel,esomeprazole delayed-release capsules and perampanel oral suspension.

Updates to existing guidance cover presentations such as acyclovirtopical 5% cream, albuterol in an aerosol metered form for inhalation,and medroxyprogesterone intramuscular suspension. Guidelines havealso been revised for buprenorphine/naloxone sublingual film as wellas the product’s sublingual tablet form, divalproex delayed-releasetablets and delayed-release pellet capsules, and nepafenac 0.1% and0.3% ophthalmic suspension. G

regulatory affairs

FDA issues recommendations

AUS appeals court ruling that generics applicants can be sued inany state in which they market drugs will not be reviewed by the

country’s Supreme Court, after it denied Mylan’s petition for a writof certiorari. The case revolved around two district court decisionsallowing patent-infringement cases over Ampyra (dalfampridine),Onglyza (saxagliptin) and Kombiglyze (saxagliptin/metformin) toproceed in Delaware.

As part of the original dispute with originators Acorda, Alkermesand AstraZeneca, Mylan had argued that Delaware state and its courtscould not exercise personal jurisdiction over the company under the‘due process’ clause of the 14th amendment to the US Constitution.However, two district court judges found that Mylan had sufficientlinks to the state justifying litigating both patent disputes in Delaware.

Subsequently, the US Court of Appeals for the Federal Circuitaffirmed the ruling, holding that Mylan was subject to specific personaljurisdiction in the cases (Generics bulletin, 25 March 2016, page 1).

In the lead opinion, Judge Richard Taranto stated that it was “ofparticular importance” that the US firm planned to sell products inDelaware upon US Food and Drug Administration (FDA) approval.

Minimum-contacts standard metNoting that the US Supreme Court had stated that the due process

clause was not impinged if the defendant had “certain minimumcontacts” and “purposefully directed” activities at the forum forlitigation, Taranto had maintained that this standard was satisfied byMylan’s actions – its abbreviated new drug application (ANDA)filings – “for the purpose of engaging in that injury-causing andallegedly wrongful marketing conduct in Delaware”. Furthermore,Mylan was registered for doing business in Delaware and had litigatedseveral ANDA cases in the state, “including some that it initiated”.

In a concurring opinion, Judge Kathleen O’Malley maintainedthat registering to do business in a US state amounted to givingconsent to “general personal jurisdiction”. G

8 GenerIcs bulletin 20 January 2017

market news

Key recommendations for industry have been set out by theInternational Society for Pharmaceutical Engineering (ISPE) and the

Pew Charitable Trusts (Pew) as part of a joint study to “identify themultidimensional set of drivers behind shortages of sterile injectabledrugs in the US”.

Conducted with input from 50 executives across 10 manufacturersof branded, branded-generic and generic products in the US, the studyaimed to discover “whether the decisions companies made to reducerisks of future shortages were influenced by correlations betweendrug shortages and elements other than quality-focused factors”.

“The collaboration [study] included the exploration of elementsrelated to market uncertainties and product margins; supply chainnetwork design; demand forecasting; and relationships betweenmanufacturers and key stakeholders, including purchasing organisationsand regulators,” the ISPE and Pew noted.

Factors examined within the study included market forces, businesscontinuity planning and supply chain management. The ISPE and Pewacknowledged the study was “not designed to produce a statisticallysignificant sample”, but that the main objective was “to understandkey trends and identify the directional focus for future research”.

Based on discussions with executives and around 29 drug shortageexamples, 45% of which were generic, the study found that “qualityrelated compliance issues are not the only factors driving the highnumber of shortages”. Key elements identified by companies alsoinclude market withdrawals, issues with supply chain design andmanaging regulatory expectations, purchaser-manufacturer incentivesand limited market insights into future demands.

The study therefore concluded that drug shortages resulted from“multiple underlying factors”, with quality issues nevertheless“paramount”. Drug shortages could be “prevented or mitigated withspecific improvements”, the ISPE and Pew proclaimed within itsconclusions, offering five recommendations to combat shortages.

This includes advice that industry should develop systems toproactively identify and resolve quality issues, including current goodmanufacturing practice compliance risks as well as issues that mayarise when development or manufacturing processes are lacking.

Meanwhile, the report recommends companies have “systematicapproaches in place for evaluating the risks across their supply chainsand the ability to predict the amount of product needed”, as part ofunderstanding the risks across the supply chain. Furthermore, industry,regulators and purchasers “must begin working together to improvethe accuracy of the information related to the risks of a shortage thatthey collect and communicate”.

The final two recommendations suggest improving overallincentives between purchasers and manufacturers and improvingcollaboration with regulators. The former recommends that purchasinggroups offer incentives such as long-term, exclusive contracts orguaranteed orders to motivate companies to invest in backupmanufacturing facilities. The latter, meanwhile, recognises the needto continue identifying ways of addressing disconnect betweencompanies and regulators that limit the ability of the manufacturerto expand capacity or invest in new equipment.

According to figures cited within the report, “for the period 2011-2014, the US Food and Drug Administration (FDA) announced thatthere were 456 instances of drugs in shortage”. Drug shortages also“result in nearly US$230 million in additional costs annually forhospitals because of the higher costs of substitutable drugs”. G

Market research

ISPE publishes reporton injectable shortage

Aclear plan is urgently needed to set out the UK government’sexpectations for how regulatory processes – including those related

to medicines – will function in the wake of the country’s planned exitfrom the European Union (EU), according to a report by the Houseof Commons committee on exiting the EU.

In its report, the committee highlights that the European MedicinesAgency (EMA) is based in London, UK, along with the EuropeanBanking Authority. “Soon after the UK’s vote to leave the EU tookplace” – as a result of the so-called ‘Brexit’ referendum in June lastyear (Generics bulletin, 1 July 2016, page 1) – “there were reportsthat member states had started to ‘jockey’ for position to secure therelocation of the agencies to their jurisdictions,” the documentobserves. These have included countries such as Germany, Italy andIreland (Generics bulletin, 18 November 2016, page 13).

“We are not aware of a precedent for an EU agency such as theEMA being based primarily outside of the EU,” the report states. “TheUK’s future relationship with both agencies will be a matter to bedefined by negotiations over the UK’s future relationship with the EU.”Insisting that the bodies “perform an important regulatory functionfor EU member states”, the report emphasises that arrangements mustbe made “for their continuing operation on the day after Brexit”.

Contributing to the report, Virginia Acha of brand industry bodythe Association of the British Pharmaceutical Industry (ABPI)said the EMA was already working in co-operation with nationalregulators which contributed to the EMA network to provide theevaluation and review required. She was optimistic that “the precedentis there for co-operation, and indeed there is already a precedentof countries that are not members of the EU being able to workthrough that co-operation”.

“We would like, wherever possible, to be able to continue withthat global, regulatory agreed process and to keep that co-operationas part of the network in a bespoke way,” Acha commented.

“The UK has delegated a number of other regulatory functionsto EU agencies,” the report points out. “The extent to which the UKwishes to continue to co-operate with these bodies or continuemembership, duplicate their functions in the UK or dispense entirelyor partially with the function that they perform will be matters fordomestic political decision and negotiation with counterpartiesrepresenting the EU.”

While UK legislation is planned to ensure that the country remainscompliant with EU regulations after it leaves the union – in the formof a ‘Great Repeal’ Act – it remains unclear whether this status willbe recognised by other EU member states.

“It will be essential to provide clarity as soon as possible, andcertainly by the time the UK leaves the EU, about the government’spreferred option for the UK’s future participation in EU regulatorybodies,” the report concludes. “If it is decided, however, not to seekto maintain membership of these bodies then the government must setout the new arrangements it proposes to put in place to ensure thatthese functions are carried out in future.”

Commenting in the immediate wake of the ‘Brexit’ vote, theBritish Generic Manufacturers Association (BGMA) said Europe’ssingle-marketing-authorisation system should be maintained in theUK as part of negotiations to leave the EU (Generics bulletin, 1July 2016, page 5). More recently, the ABPI said it was key to have“an aligned framework in place for medicines regulation ‘from dayone’ of leaving the EU” to maintain availability and supply. G

regulatory affairs

UK needs clarity onfuture for regulation

9GenerIcs bulletin20 January 2017

market news

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Comments made by US President-elect Donald Trump about thecountry’s pharmaceutical industry and drugs market have been

acknowledged by local generics industry body the US GenericPharmaceutical Association (GPhA).

Speaking in advance of his inauguration, Trump described theUS drugs industry as “disastrous”. “They supply our drugs, but theydon’t make them here, to a large extent,” he commented. “They’releaving left and right. We’ve got to get our drug industry coming back.”

Moreover, Trump said, the US must “create new bidding proceduresfor the drug industry, because they’re getting away with murder”.“Pharma has a lot of lobbyists and a lot of power,” Trump said, “andthere’s very little bidding on drugs.” Describing the US as “the largestbuyer of drugs in the world”, he lamented that “we don’t bid properly”.“We’re going to start bidding,” he declared, “and we’re going to savebillions of dollars over a period of time.”

Responding to Trump’s comments, the GPhA said “we understandthe President-elect’s concerns about drug prices”. Pointing out that“study after study demonstrates that generic medicines drive downdrug costs through competition”, the association nevertheless said“more can be done”. “We look forward to working with the newadministration to reduce the backlog of generic drug applications atthe US Food and Drug Administration (FDA), and on initiativesthat bring more generic and biosimilar products to the market.” G

regulatory affairs

GPhA responds overTrump pharma policy

The UK government is keen to participate in Europe’s unified patentcourt (UPC) from its inception, according to Jo Johnson, minister

of state for universities, science, research and innovation. Johnsonrecently assumed responsibility for intellectual property from BaronessLucy Neville-Rolfe, who stated late last year that the UK wouldpush ahead with ratifying the UPC agreement (Generics bulletin, 9December 2016, page 5).

Giving evidence to a parliamentary committee on intellectualproperty, Johnson pointed out that the UPC “is not a European Union(EU) institution, and it is independent of our membership of the EU”following the country’s ‘Brexit’ decision to leave the EU.

“We believe it is important we participate in this framework. Ithas value to UK inventors and businesses, and we want to be there atits creation,” Johnson stated, noting that insufficient countries had todate ratified the agreement for the UPC to come into effect.

Pressed on whether the UPC agreement allowed participation ofnon-EU member states, Johnson said such questions would “form partof the bigger discussion around the Brexit negotiations”. Given thatLondon was set to host a central division branch for chemistry and lifesciences that would cover pharma patent disputes, Johnson said thegovernment wanted “to be there supporting this entity”. But he addedthat “location decisions following Brexit are going to form part of thebigger package of discussions relating to us leaving the EU”. G

intellectual ProPerty

UK government willback UPC from start

10 GenerIcs bulletin 20 January 2017

product news

7-8 februaryn World Affordable Medicines Congress

Barcelona, SpainThis event brings together two conferences – World Generic MedicinesCongress and Biosimilar Drug Development World. There will beinsights into commercial strategies, pricing, and development challenges.

Contact: health network communications. tel: +44 (0) 207 092 1000.e-mail: customerservices@healthnetworkcommunications.com.website: healthnetworkcommunications.com.

13-15 februaryn GPhA 2017 Annual Meeting

Orlando, USAThis conference, organised by the Generic Pharmaceutical Association(GPhA), will look at regulatory issues for the US generics industry.

Contact: gPha. tel: +1 202 249 7100.e-mail: jsoup@gphaonline.org. website: gphaonline.org.

2-3 Marchn 2nd Business Development & Innovation

Opportunities in Consumer Healthcare/OTCLondon, UKOrganised jointly by the Pharmaceutical Licensing Group andOTCToolbox, this event will focus exclusively on business developmentand innovation in the consumer healthcare/OTC market.Contact: otctoolbox. tel: +44 121 314 8757.e-mail: deborah.wilkes@otctoolbox.com.website: plg-group.com/events/2nd-otctoolbox-plg-otc-conference-and-networking-event/.

22-23 Marchn 13th Legal Affairs Conference

London, UKThis Medicines for Europe conference will cover legal andintellectual-property developments and sustainability. The eventwill be followed by the 15th Biosimilar Medicines Conference atthe same venue.

Contact: lucia romagnoli. tel: +44 7562 876 873.e-mail: events@medicinesforeurope.com. register online atwww.medicinesforeurope.com/events/13th-legal-affairs-conference/.

23-24 Marchn 15th Biosimilar Medicines Conference

London, UKThis Medicines for Europe event will look at market access andtrends, regulatory developments and legal and intellectual-propertyaspects concerning biosimilars.

Contact: lucia romagnoli. tel: +44 7562 876 873.e-mail: events@medicinesforeurope.com. register online atwww.medicinesforeurope.com/events/bios-2017/.

EVENTS – February & March

Save the date ...n Joint 23rd Medicines for Europe &

20th IGBA Annual Conference14-16 June 2017,Lisbon, Portugal

n Global Generics & BiosimilarsAwards 201724 October 2017,Frankfurt, Germany

Mylan and Biocon’s application for a US biosimilar rival to Roche’sHerceptin (trastuzumab) has been accepted by the US Food and

Drug Administration (FDA) with a goal date under the BiosimilarUser Fee Act (BsUFA) of 3 September 2017.

Referring to the filing as a “major milestone”, Biocon and Mylanpointed out that it represented the first US regulatory submission underthe firms’ joint global biosimilars development programme. When theysubmitted the biologics license application (BLA) for their MYL-1401Otrastuzumab candidate, the firms noted that it had “the potential tobe the first submission of a proposed biosimilar trastuzumab in theUS” (Generics bulletin, 11 November 2016, page 1).

Last year, Mylan and Biocon also had their application forbiosimilar trastuzumab accepted for review by the European MedicinesAgency (Generics bulletin, 9 September 2016, page 17).

Mylan said it had exclusive sales rights for the proposedtrastuzumab biosimilar in the US, Canada, Japan, Australia and NewZealand, as well as in the European Union (EU) and European FreeTrade Association countries. Meanwhile, Biocon has co-exclusivesales rights with Mylan for the product in the rest of the world.

Comprehensive data packageRajiv Malik, Mylan’s president, said that the US acceptance

“reinforces the strength of our collaboration” with Biocon. “We believethat our comprehensive package of analytical similarity, non-clinicaland clinical data submitted with the BLA will demonstrate similarityof the proposed biosimilar trastuzumab to the reference product.”

Efficacy and safety data from the ‘Heritage’ Phase III studycomparing Mylan and Biocon’s trastuzumab to Herceptin was firstrevealed last June (Generics bulletin, 10 June 2016, page 13), and wasrecently published in the Journal of the American Medical Association(Generics bulletin, 13 January 2017, page 8).

Arun Chandavarkar, Biocon’s chief executive officer and jointmanaging director, said the development “positions Biocon and Mylanamong the first companies to be able to address the critical need of USpatients for a high-quality biosimilar to treat certain HER2-positivebreast cancers in the near future”.

Through the collaboration – which was formed in June 2009(Generics bulletin, 8 July 2009, page 1) – Mylan and Biocon are“exclusive partners on a broad portfolio of biosimilar and insulinproducts”. Trastuzumab is “one of the six biologic productsco-developed by the two firms for the global marketplace”. G

Biological Drugs

FDA accepts filing onMylan’s trastuzumab

France has expanded its répertoire of generic equivalents followinga decision by local medicines agency ANSM. Mylan’s generic

atazanavir 150mg, 200mg and 300mg capsules have been listed in groupswith Bristol-Myers Squibb’s Reyataz brand as the reference drug.

At the same time, Biogaran, Inopharm and Mylan have had theiratenolol/nifedipine 50mg/20mg capsules listed in a group againstAstraZeneca’s Tenordate original.

Finally, Fresenius Kabi’s rivals to Eli Lilly’s Alimta (pemetrexed)100mg and 500mg powder for solution have been listed in newly-created reference groups within the répertoire. G

antiretrovirals

France adds to its répertoire

11GENERICS bulletin20 January 2017

product news

AUS district court did not err in finding certain claims of a USvitamin-dosing regimen patent shielding Eli Lilly’s Alimta

(pemetrexed disodium) valid and infringed by a proposed genericversion developed by Teva, a US Court of Appeals has decided.

US patent 7,772,209 covers a method of administering pemetrexedwith the requirement that a physician co-administers vitamin B12, andinstructs the patient to obtain and take folic acid to reduce the toxicitycaused by pemetrexed. To market its generic, Teva would thereforehave to include identical prescribing and patient information, to bothdoctors and patients, as outlined in the ‘209 patent.

Around three years ago, an Indiana district court rejected Teva’sallegations that asserted claims within the patent were invalid due toindefiniteness, obviousness or obviousness-type double patenting(Generics bulletin, 4 April 2014, page 17).

However, the issue of infringement was delayed pending theoutcome of a US Supreme Court ruling concerning the standard forinduced infringement involving a third party. Pursuant to the SupremeCourt ruling, the same district court, in August 2015, found that Teva’sproposed generic would induce infringement of the ‘209 patent(Generics bulletin, 11 September 2015, page 18).

On appeal, Teva argued that the district court’s validity conclusionsrelated to indefiniteness, obviousness or obviousness-type doublepatenting were all in error. But the appeals court was not convinced.

“We agree with Lilly that defendants’ arguments fail to raisereversible error with respect to at least the [district court] findingsthat a skilled artisan would not have been motivated to use vitaminB12 pre-treatment with pemetrexed, let alone the appropriate dosesof such vitamin B12 pre-treatment,” the appeals court ordered in itsdiscussion on the issue of obviousness.

No error on inducing infringementTurning to infringement, the appeals court found that the district

court “did not clearly err in concluding that defendants would induceinfringement of the asserted claims of the ’209 patent”. “In sum,evidence that the product labelling that defendants seek would inevitablylead some physicians to infringe establishes the requisite intent forinducement,” the appeals court determined.

According to Lilly, more than 10 abbreviated new drug applications(ANDAs) have been filed referencing Alimta, which had US sales ofUS$831 million in the first nine months of last year. The oncologybrand’s US molecule patent 5,344,932 expires on 24 January 2017,including a six-month paediatric extension.

Lilly’s ‘209 patent still faces the threat of being invalidated,however, after the US Patent and Trademark Office last year grantedpetitions by Neptune Generics and Sandoz seeking inter partes reviewof the patent. “The final written inter partes review decisions areexpected in mid-2017,” Lilly said, adding “several additional genericcompanies have filed petitions seeking to join in these proceedings”.

Moreover, Lilly has also sued Dr Reddy’s in response to itsnew drug application for a salt form of pemetrexed product dilutedin dextrose solution.

Lilly’s victory in US patent-litigation proceedings follows mixedrulings in European courts. Last year, UK High Court Justice RichardArnold ruled that pemetrexed trometamol/diacid vials that Actavis,now operated by Teva, had launched in the UK did not infringe thelocal part of Eli Lilly’s European Union vitamin-dosing regimenpatent (Generics bulletin, 19 February 2016, page 13). G

oncology Drugs

Alimta patent upheldin US court of appeal

UK patents judge Justice Richard Arnold has, in a pair of rulingsboth handed down on 13 January, referred disputes over

supplementary protection certificates (SPCs) covering Gilead’s Truvada(tenofovir/emtricitabine) antiretroviral agent and Abraxis’ Abraxane(nab-paclitaxel) cancer treatment to the Court of Justice for theEuropean Union (CJEU).

In the Truvada proceedings, Accord, Lupin, Mylan and Teva hadchallenged the validity of SPC/GB05/041 on the grounds that theEuropean patent on which the SPC relies, EP0,915,894 does not describeTruvada’s combination of tenofovir disoproxil fumarate 300mg andemtricitabine 200mg. The generics firms argued that CJEU case lawmade it clear that the SPC does not comply with Article 3(a) ofEurope’s SPC Regulation, which requires that the product to be coveredby an SPC “is protected by a basic patent in force”.

Noting that it was “common ground that emtricitabine is notmentioned or referred to in the [‘894] patent”, Arnold said the closestthat the patent got was a mention in Claim 27 of adding “othertherapeutic ingredients” as an option beyond the disclosed compoundssuch as tenofovir.

Arnold conducted a lengthy review of CJEU case law oninterpreting Article 3(a) of the SPC Regulation, but decided that “ thetest to be applied in order to determine whether a product is ‘protected’by a basic patent within the meaning of Article 3(a) remains unclear”.While it was clear that it was not sufficient that the protected productwould infringe at least one patent claim, it was not clear what morewas needed, he said.

Highlighting the divergent national attempts to apply the CJEU’sreasoning, Arnold concluded that it was necessary to pose to the CJEUthe same question he had referred to the European court in a disputebetween Actavis and Sanofi over an SPC covering the originator’sCoAprovel (irbesartan/hydrochlorothiazide) combination: “What arethe criteria for deciding whether ‘the product is protected by a basicpatent in force’ in Article 3(a) of the SPC Regulation?” (Genericsbulletin, 1 October 2012, page 17).

Abraxis had challenged a decision by the UK’s comptroller-general of patents to refuse an SPC for the firm’s Abraxane albumin-bound paclitaxel on the grounds that Abraxane was not the firstmarketing authorisation for paclitaxel. The originator had argued thatthe active ingredient was properly construed as nab-paclitaxel.Alternatively, Abraxis had maintained, the brand was a new andinventive formulation of a known active ingredient that qualified for anSPC under Article 3(d) of the Regulation.

Arnold identified two key problems. Firstly, he observed, the SPCRegulation did not define what constituted an ‘active ingredient’, andin particular, did not state a position on substances such as albuminthat helped an active ingredient to achieve a therapeutic effect.

Secondly, he said, Article 3(d) of the SPC Regulation did notclarify how to meet its requirement that the marketing authorisationrelied upon be the first authorisation ‘to place the product on themarket as a medicinal product’.

Following another detailed review of CJEU case law, Arnolddecided it was clear that paclitaxel was the active ingredient of Abraxaneas albumin was a carrier. What was less clear, he said in referring thedispute to the European court, was the extent to which the CJEU’sNeurim ruling – which permits SPCs for new therapeutic uses of oldactive ingredients – could also, as Abraxis contended, extend to newformulations of known ingredients. G

hiv Drugs/oncology Drugs

UK sends SPC casesto European Court

12 GENERICS bulletin 20 January 2017

product news

Impax’ authorised generic Adrenaclick (epinephrine) auto-injector isset to offer cheaper competition to Mylan’s EpiPen (epinephrine)

after the anaphylaxis treatment became available at US pharmacychain CVS Pharmacy at around a sixth the price of Mylan’s brand.

“Patients can now purchase the authorised generic Adrenaclickat a cash price of US$109.99 for a two-pack – the lowest cash pricein the market,” CVS announced, adding that it had “recognised theurgent need for a less-expensive epinephrine auto-injector”.

Mylan has been mired in controversy over the firm’s EpiPen brandfollowing reports that EpiPen’s price had risen by more than 400%in recent years to more than US$600 for a two-pen set, as well as newsof Mylan improperly classifying for a number of years the brand asa ‘non-innovator multiple source’ drug that qualifies for a lower rebateunder Medicaid (Generics bulletin, 7 October 2016, page 8).

This led Mylan to announce plans to launch an authorised genericversion of EpiPen at a wholesale acquisition cost of US$300 perepinephrine injection two-pack, a pledge the firm fulfilled at the endof last year (Generics bulletin, 6 January 2017, page 14).

Impax obtained the authorised generic Adrenaclick through thefirm’s US$700 million takeover of US generics player CorePharmaand its affiliates (Generics bulletin, 17 October 2014, page 1). G

allergy Drugs

CVS Pharmacy hasImpax’ Adrenaclick

AbbVie has failed to convince a panel of three UK appeal judgesto strike out applications made by Fujifilm Kyowa Kirin (FKB)

for declarations that the Japanese firm’s proposed biosimilar of Humira(adalimumab) was “old and obvious” at the priority dates of severalsecondary patents, and thus could not infringe those patents. TheCourt of Appeal also denied AbbVie’s appeal against FKB seeking aninjunction preventing the originator from starting patent-infringementproceedings over acts covered by such declarations.

The Court of Appeal’s decision came shortly after a lower courthad said the litigants’ dispute over the UK parts of three secondarypatents should proceed to trial as FKB tried to clear the path to launchonce a supplementary protection certificate (SPC) linked to AbbVie’sEuropean basic adalimumab patent expired on 15 October 2018(Generics bulletin, 13 January 2017, page 12).

Delivering the verdict of the appeal panel, Justice ChristopherFloyd noted that FKB was seeking protection through ‘Arrow’declarations from infringing dosage-regimen patents EP1,406,656,EP1,944,322 and EP1,737,491, but also from infringing AbbVie’sdivisional applications from those patents. “We do not consider thatthere is any issue of principle which prevents the granting of Arrowdeclarations in appropriate cases,” he stated.

AbbVie, Arnold declared, appeared to be “deliberately trying toshield the claims of its patents from scrutiny in the European PatentOffice (EPO) and in the national court”. “Had the patents not beenvoluntarily de-designated or revoked, FKB would have had theopportunity to seek findings of invalidity of granted patents in the usualway,” he pointed out, adding that granting the declarations sought would“provide FKB with a measure of useful commercial certainty”.Furthermore, he added, “an appropriately framed injunction may bean alternative to the declaration”. G

Biological Drugs

UK denies appeal on Humira

AJANTA has obtained final approval from the US Food and DrugAdministration (FDA) for its generic version of Eli Lilly’s Cymbalta(duloxetine) 20mg, 30mg and 60mg delayed-release capsules.

AUROBINDO plans imminently to launch its US generic versionof HQ Specialty Pharma’s levetiracetam injectable next month,after receiving approval from the US Food and Drug Administration(FDA). Available in 500mg/100ml, 1,000mg/100ml, and 1,500mg/100ml single-use bags, the epilepsy treatment will be available thismonth. According to QuintilesIMS data, the product had a marketworth US$32 million in the 12 months ended November 2016.

STADA has launched two new forms of atorvastatin in Spain.Atorvastatin Stadagen is now available as 30mg and 60mg tabletsin 28-count packs, extending from four to six the current range ofstrengths, which also includes the existing 10mg, 20mg, 40mg and80mg tablets.

LUPIN has been awarded final approval for its generic rival toDaiichi Sankyo’s Evoxac (cevimeline) 30mg capsules from theUS Food and Drug Administration (FDA). Citing QuintilesIMSdata, Lupin said the capsules – which are used to treat symptomsof dry mouth in patients with Sjögren’s syndrome – had US salesof US$40.8 million in the 12 months ended September 2016.Meanwhile, the Indian firm has also obtained final FDA approvalfor its desoximetasone 0.05% and 0.25% cream, rivalling Taro’sTopicort Emollient 0.05% cream and Topicort 0.25% cream.Both products are indicated for the relief of the inflammatory andpruritic manifestations of corticosteroid-responsive dermatoses.

AIFA – the Italian Medicines Agency – has announced a precautionarywithdrawal of certain batches of Mylan’s film-coated metformintablets. The withdrawn lots include 500mg and 850mg tablets in30-count packs and 1,000mg tablets in packs of 60. The actionfollows Portugal’s medicines agency, Infarmed, identifying non-compliance with good manufacturing practice standards at theproduct’s manufacturing site in India (Generics bulletin, 13 January2017, page 12). “[The withdrawal] is not related to safety or efficacyissues,” AIFA noted. “There have been no reports of adversereactions for medicinal issues that may be related to quality defectsnoted by the Portuguese [agency].”

BRECKENRIDGE – along with its development and manufacturingpartner, Natco Pharma – has received final approval from the USFood and Drug Administration (FDA) for an abbreviated new drugapplication (ANDA) for their generic version of Cephalon’s Treanda(bendamustine), available in 25mg/vial and 100mg/vials as a powderfor infusion. Privately-held Breckenridge intends to launch the genericon 1 November 2019, or “earlier based on certain circumstances”,under the terms of a settlement.

SLAYBACK PHARMA has launched a US generic rival to Valeant’sZovirax (acyclovir) 5% ointment for cutaneous use through itslicensee, Sandoz’ Fougera. Slayback developed the product andout-licensed the sales and marketing rights to Sandoz.

CAMARGO – the 505(b)(2) hybrid application specialist – says thenumber of US 505(b)(2) new drug application (NDA) approvalsin 2016 increased to a “13-year high of 48, up from 2015’s 44”. Thiswas in contrast to novel drug approvals, which had “decreaseddramatically from 2015”, Camargo observed. The rise continues atrend seen over recent years, with 43 approvals for 505(b)(2) NDAsin 2014, 39 in 2013 and 37 in 2012. G

In BrIeF

13GENERICS bulletin20 January 2017

product news

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2017

Momenta Pharmaceuticals will receive a “one-time asset returnpayment” of US$51.2 million from Shire to end the firms’

collaboration agreement on a proposed biosimilar version of Humira(adalimumab). Last year, Momenta struck a deal to regain developmentand commercial rights from Baxalta, following a “comprehensiveportfolio assessment” by Baxalta after Shire acquired the firm (Genericsbulletin, 7 October 2016, page 9).

Noting that it would use the payment “to fund the estimated coststhat would have been incurred by Shire through September 2017”,Momenta said it expected to file the biosimilar – which recently metits primary endpoint in a Phase III clinical study (Generics bulletin,9 December 2016, page 12) – in “mid-2017”.

Meanwhile, the US firm said a tentative approval “could be grantedat any time” for a 40mg version of the Glatopa (glatiramer acetate)rival to Teva’s Copaxone that it markets with Sandoz. And a finalapproval “could be granted following the expiration of Copaxone 40mgregulatory exclusivity on 28 January 2017”.

Following a district court trial that ended in October during whichfour of Teva’s five Orange Book-listed patents for Copaxone 40mgwere challenged, Momenta expects a decision in the first quarter of2017. Teva recently said rivals to Copaxone 40mg launching inFebruary could cost the Israeli company as much as US$1.2 billionin sales this year (Generics bulletin, 13 January 2017, page 1). G

Biological Drugs

Momenta gets payoffon Humira rival deal

Actavis has failed to prevent Janssen from obtaining an orderblocking Canada’s Minister of Health from issuing a notice of

compliance – effectively a marketing authorisation – for the genericsfirm’s version of the originator’s Concerta (methylphenidate)extended-release treatment for attention deficit hyperactivity disorder.

Federal Judge James O’Reilly described as unjustified Actavis’allegations that Canadian patent 2,264,852 – which covers the use ofcompositions that release methylphenidate in a “sustained-ascendingdose over time” – was invalid due to obviousness, lack of utility andclaims within the patent being overbroad.

Awarding Janssen costs, O’Reilly also found that Actavis’ proposedgeneric methylphenidate tablets would infringe the ‘852 patent.

Actavis had foremost fallen to Janssen on the issue of claimconstruction. O’Reilly sided with the originator’s interpretation of themeaning of the phrase “sustained-ascending dose over time”, agreeingthat the phrase “specifically distinguished” Concerta from olderimmediate-release formulations of methylphenidate, namely Ritalin.

O’Reilly explained that Ritalin needed to be taken either two orthree times a day, and required a responsible party to administer thetablets, which resulted in compliance problems in school children.Ritalin’s successor product, Ritalin sustained-release, “did not liveup to expectations”, as it “turned out to be effective only for a fewhours”. With this in mind, O’Reilly found that Concerta did notlack an inventive step, as Actavis contended, and thus the ‘852 patentwas not obvious.

“The skilled person would have been aware of the performance andshortcomings of the available drugs for treating attention deficithyperactivity disorder. In particular, he or she would have regardedadministration of Ritalin twice or three-times a day as the height of the art.”

“The inventive concept of the ‘852 patent is the use of a formulationthat delivers a sustained-ascending dose of active ingredient over timein order to address acute tolerance. This represented an advantageover the prior art, given the problems associated both with Ritalinimmediate-release and Ritalin sustained-release,” O’Reilly said.

Turning to utility, O’Reilly found that “utility was clearlydemonstrated” by way of two Janssen-developed ‘sipping studies’,which involved administering small amounts of methylphenidate tomimic the dynamics of various methylphenidate formulations, includingthe earlier Ritalin formulations. “The data from those studies wasprovided in the patent and support the inventors’ conclusions,” he noted.

O’Reilly also rejected Actavis’ allegation that claims withinthe patent were overbroad. A skilled person would not interpretthe inclusion of a “mere” 100ng dosage form of methylphenidatewithin the patent claims as claiming a sustained-ascending dosageof 100ng of methylphenidate as Actavis contended, he said.

Finally, O’Reilly ruled that Actavis’ generic product also infringedthe ‘852 patent, after labelling “questionable” an expert opinion offeredby Actavis on the release rate of methylphenidate in the generics firm’stablets in a variety of media. “The preponderance of evidence showsthat the Actavis product does release methylphenidate at a sustained-ascending rate over a sufficiently long period to regulate acute tolerance.Therefore, the Actavis tablets infringe the ‘852 patent,” O’Reilly decided.

O’Reilly’s ruling on the ‘852 patent comes after Teva’s NovopharmCanadian subsidiary obtained, around seven years ago, a notice ofcompliance for generic methylphenidate extended-release tabletsfollowing a positive decision on infringement of the patent (Genericsbulletin, 12 February 2010, page 14). G

attention Deficit hyPeractivity DisorDer treatMents

Actavis loses out onConcerta in Canada

14 GENERICS bulletin 20 January 2017

prIce watch ..............uk

Average prices for recently-launched generics were relatively stablein December, with only two products – eplerenone and rizatriptan

– showing double-digit changes (see Figure 1). But two older products –pregabalin and zolmitriptan – experienced massive average price risesin December of many times their November levels (see Figure 2).The gains were so huge that a 253% monthly average price rise wasnot enough to qualify pregabalin 100mg for our ‘biggest risers’ list.

Two six-tablet versions of zolmitriptan 2.5mg – standard andorodispersible, sugar-free tablets – were granted monthly priceconcessions by the Department of Health to ensure that pharmacistswere reimbursed a profitable amount. The price concession for theorodispersible presentation was £23.99 (US$29.11), considerably morethan the average price of £7.07 recorded by WaveData. However, the

concession of £13.70 for six standard tablets was comparable with theaverage price of £16.24 for the 12-tablet presentation. Pregabalin hadnot been granted any monthly price concessions by 22 December.

Five strengths of ropinirole were granted price concessions inDecember, but the average price of at least one of them – 12-tabletpacks of ropinirole 0.25mg – was starting rapidly to fall in December(see Figure 3). Nevertheless, the price concession of £5.70 for theproduct agreed closely with its average price of £5.47.

Pharmacists were tempted in December by an unusually largenumber of price offers for one-capsule packs of fluconazole 150mg(see Figure 4). Meanwhile, the flurry of offers for omeprazole duringOctober and November subsided somewhat in December, leavingatorvastatin as the most heavily promoted product as the year ended.G

Figure 1 (above): Comparison between the periods 1-30 November 2016 and 1-31December 2016 of UK trade prices of the most recently-launched generics listed incategory M of the Drug Tariff of pharmacy-reimbursement prices. Averages calculatedfrom at least 27 data points. Figure 2 (top right) and Figure 3 (centre right): Biggestaverage trade-price changes between 1-30 November 2016 and 1-31 December 2016.Averages calculated from at least 12 data points. Figure 4 (bottom right): Ranking offastest-moving products subject to the most price offers made to independent UKpharmacists (one strength per ingredient; offers recorded by 31 December). Data forFigures 2, 3 and 4 from a basket of about 750 commonly-dispensed generics. Recently-launched products in Figure 1 excluded from Figures 2 and 3 (Source – WaveData).

RECENT LAUNCHES

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

Aripiprazole tabs 10mg 28 £0.53 -21 £1.16 +2Benzydamine 0.15% 300ml £4.64 -5 £5.87 +4Carbimazole tabs 5mg 100 £51.68 -1 £64.71 +4Celecoxib caps 200mg 30 £0.83 -2 £1.46 +3Cilostazol tabs 100mg 56 £2.09 ±0 £3.61 +4Cyclizine tabs 50mg 100 £5.31 ±0 £7.44 -2Desogestrel tabs 75µg 84 £1.21 ±0 £1.78 -2Duloxetine caps 30mg 28 £0.88 +10 £1.97 +2Entacapone tabs 200mg 30 £3.16 -11 £5.14 -1Eplerenone tabs 25mg 28 £2.80 -3 £4.77 +13Escitalopram tabs 10mg 28 £0.26 +4 £0.80 +7Frovatriptan tabs 2.5mg 6 £8.39 -3 £10.88 +3Memantine tabs 10mg 28 £0.60 +18 £1.03 +1Mometasone furoate 0.1% 30g £1.24 +2 £2.06 -5Montelukast tabs 10mg 28 £0.97 -5 £1.58 -6Nortriptyline tabs 10mg 100 £25.64 +5 £36.73 ±0Oxcarbazepine tabs 300mg 50 £4.41 -10 £6.02 ±0Rabeprazole tabs 10mg 28 £0.67 ±0 £1.18 +8Raloxifene tabs 60mg 28 £2.52 -1 £3.39 +2Rasagiline tabs 1mg 28 £1.24 -8 £4.57 ±0Riluzole tabs 50mg 56 £10.33 -2 £15.14 -1Rizatriptan tabs 10mg 3 £0.75 ±0 £1.32 -11Sevelamer tabs 800mg 180 £29.00 -19 £58.46 +5Sildenafil tabs 100mg 4 £0.23 ±0 £0.51 +6Telmisartan tabs 80mg 28 £1.10 +18 £1.73 -5

FAST MOVERS

Price offers as at 31 December 2016Product/Strength/Pack size October November December

Atorvastatin tabs 10mg 28 105 85 103

Fluconazole caps 150mg 1 70 60 102

Omeprazole caps 20mg 28 146 155 101

Phenytoin tabs 100mg 28 75 59 98

Hypromellose eye drops 0.3% 10ml 66 55 96

Chloramphenicol eye oint. 1% 4g 69 48 93

Ferrous sulphate tabs 200mg 28 85 77 92

Mycophenolate caps 250mg 100 62 48 91

Hydrocortisone tabs 10mg 30 101 95 91

Co-codamol tabs 8mg/500mg 100 86 76 90

BIGGEST RISERSProduct/Strength/Pack size Lowest Change Average Change

price (%) price (%)

Zolmitriptan tabs 2.5mg 12 £1.90 +21 £16.24 +571

Zolmitriptan o/d tabs 2.5mg 6 £0.80 +5 £7.07 +494

Pregabalin caps 25mg 56 £1.03 +11 £15.67 +325

Pregabalin caps 25mg 84 £1.99 +15 £30.79 +307

Pregabalin caps 75mg 56 £1.49 +51 £15.53 +295Pregabalin caps 50mg 84 £1.29 -16 £24.52 +294

BIGGEST FALLERSProduct/Strength/Pack size Lowest Change Average Change

price (%) price (%)

Ropinirole tabs 0.25mg 12 £3.23 -7 £5.47 -23

Loprazolam tabs 1mg 28 £2.16 -33 £4.45 -20

Levetiracetam 100mg/ml 300ml £3.79 -11 £4.73 -20

Ramipril tabs 5mg 28 £0.44 +26 £0.94 -18

Ramipril tabs 10mg 28 £0.47 -15 £0.96 -15

Bicalutamide tabs 150mg 28 £3.29 +8 £5.68 -14

Pregabalin and zolmitriptan prices take off

Up to the minute live retail market pricing is available for the UK and Eire on Wavedata Live at wavedata.net.

Alternatively, contact Charles Joynson at WaveData Limited, UK.Tel: +44 (0)1702 425125. E-mail: cjoynson@wavedata.co.uk.

want more lIke thIs?

15GENERICS bulletin20 January 2017

product news

Eagle Pharmaceuticals is continuing to advance its pipeline of505(b)(2) hybrid new drug application (NDA) injectables after

submitting to the US Food and Drug Administration (FDA) the firm’sapplication for a ready-to-dilute pemetrexed injectable.

The US firm’s 500mg liquid alternative to Eli Lilly’s Alimta –which is administered as an intravenous infusion – is indicated for thetreatment of locally advanced or metastatic non-small cell lung cancer,as well as mesothelioma in combination with cisplatin. Scott Tarriff,Eagle’s chief executive, said the hybrid injectables specialist would“look forward to the FDA’s decision on this NDA this year, and tocontinuing to work closely with the FDA through the review process”.

Eagle’s portfolio of hybrid injectables in the US currently includesBendeka (bendamustine), a rapid-infusion alternative to Teva’s Treandathat is marketed by the Israeli firm through a deal with Eagle, as wellas a non-alcohol docetaxel formula, argatroban, diclofenac/misoprostoland the US firm’s Ryanodex (dantrolene).

Meanwhile, Eagle is also developing a ready-to-use version of TheMedicines Company’s Angiomax (bivalirudin) brand, as well as aready-to-dilute bendamustine alternative. G

oncology Drugs

Eagle submits Alimta hybrid

Zydus Cadila has agreed to settle US patent litigation with Japanesefirms Kowa Pharmaceuticals and Nissan Chemical Industries

over the originators’ Livalo (pitavastatin calcium) tablets.Under the terms of the agreement, the Indian firm will be able to

market its generic version of the cholesterol-lowering agent from 2May 2023, or “earlier under certain circumstances”. This date is morethan two years after Kowa and Nissan’s US substance patent, 5,856,336,expires on 25 December 2020, and less than 12 months ahead of thefirms’ drug product and method-of-use patents – 8,557,993 and7,022,713 – expiring on 2 February and 19 February 2024 respectively.Other details of the settlement were not disclosed.

According to the US Food and Drug Administration’s (FDA’s)Approved Drug Products database, Aurobindo is the only firm tocurrently hold final FDA approvals for generic versions of Livalo 1mg,2mg and 4mg tablets, following action from the FDA on 20 Decemberlast year. Litigation involving the ‘336 and ‘993 patents in a New Yorkand New Jersey district court had been dismissed, the agency noted.

Separately, Zydus will also be able to launch its generic versionof Upsher-Smith Laboratories’ Qudexy XR (topiramate) extended-release capsules in the US more than a decade ahead of patent expiryunder the terms of a further patent-litigation settlement.

Under the settlement, Zydus will obtain from Upsher-Smith alicence to market the firm’s rival to the anticonvulsant brand on 19March 2020, or earlier under “certain circumstances”. Further detailsremain undisclosed. According to the FDA’s Orange Book, Qudexyis shielded by three US patents – 8,652,527, 8,889,190, 9,101,545 –which all expire on 19 March 2033. Upsher-Smith already marketsan authorised generic version of its own brand, which is availablein 25mg, 50mg, 100mg, 150mg and 200mg strengths.

The FDA’s Approved Drug Products database does not currentlylist any tentatively approved or approved abbreviated new drugapplications (ANDAs) for generic versions of Qudexy XR. G

cholesterol-lowering Drugs/anticonvulsants

Zydus grabs a launchdate for a Livalo rival

IMPAX has filed an abbreviated new drug application (ANDA) withthe US Food and Drug Administration (FDA) containing aparagraph IV patent challenge for a generic version of Sanofi andGenzyme’s Aubagio (teriflunomide) 14mg tablets. Subject to newchemical entity (NCE) exclusivity, Aubagio’s earliest ANDAsubmission date was 12 September 2016 (Generics bulletin, 8 July2016, page 12). Sanofi and Genzyme subsequently filed suit forpatent infringement against Impax in a Delaware district court.

SUN PHARMA has reported successful Phase III results for Seciera(cyclosporine) 0.09% ophthalmic solution in a 12-week, randomised,multi-centre study. Used to treat dry eye disease, the novelacqueous solution was developed by Sun’s recently acquired OcularTechnologies (Generics bulletin, 4 November 2016, page 7).

LUPIN has launched a generic version of Purdue Pharma’sMS Contin ER (morphine sulphate) extended-release tablets afterreceiving approval from the US Food and Drug Application (FDA).Available in 15mg, 30mg, 60mg, 100mg and 200mg doses, the tabletswill enter a market that was worth around US$283 million annually,according to QuintilesIMS data. Impax recently released a USgeneric version of Kadian (morphine sulphate) extended-releasecapsules, available in 20mg, 30mg, 50mg, 60mg, 80mg and 100mgdoses (Generics bulletin, 13 January 2017, page 10).

WOCKHARDT has added to its UK portfolio by launching imatinib100mg and 400mg film-coated tablets in 30-count and 60-count packs.

AUROBINDO has obtained final approval from the US Food andDrug Administration (FDA) for its generic version of OakPharmaceuticals’ Xopenex (levalbuterol) inhalation solution, availablein 0.31mg/3ml, 0.63mg/3ml, and 1.25mg/3ml presentations. CitingQuintilesIMS data, the Indian firm said the bronchospasm andreversible obstructive airway disease treatment had US sales ofUS$130 million in the 12 months ended November 2016.

MERRIMACK PHARMACEUTICALS has agreed to divest to Ipsenits generic version of Doxil (doxorubicin) liposome injection, aspart of a wider agreement valued at up to US$1.03 billion, as wellas up to US$33 million in milestone payments. Subject to certaincustomary closing conditions – including Merrimack stockholderapproval and certain governmental regulatory clearances – thetransaction is set to close in the first quarter of 2017.

SANDOZ has launched the first US generic rival to Merck, Sharp &Dohme’s Emend (aprepitant) 40mg, 80mg and 125mg capsules.The antiemetic treatment is indicated for patients over 12 yearsold – in combination with other antiemetic agents to prevent nauseaand vomiting caused by certain chemotherapy medicines – as well asadults to prevent nausea and vomiting after surgery. According toQuintilesIMS data, US sales for Emend were approximately US$62million for the 12 months ended October 2016.

EGALET has announced that the US Food and Drug Administration(FDA) has approved its Arymo ER (morphine sulfate) extended-release C-II tablets in 15mg, 30mg and 60mg doses. “Arymo ER isthe first approved product developed using Egalet’s proprietaryGuardian Technology – a physical and chemical barrier approach toabuse deterrence without the use of an opioid antagonist – creatingtablets that are difficult to manipulate for the purpose of misuse andabuse,” Egalet stated. The FDA approval of Arymo ER triggeredUS$40 million in new funding to the firm, which expects to launchthe product in the first quarter of 2017. G

In BrIeF

16 GENERICS bulletin 20 January 2017

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Two former Heritage Pharma executives, ex-chief executive officerJeffrey Glazer and former president Jason Malek, have had

sentencing hearings scheduled after pleading guilty to criminal chargesbrought against them in December concerning illegal conspiraciesto raise the prices of two generics in the US.

Both are due to be sentenced on 10 April 2017 in an EasternPennsylvania district court for their roles in conspiring to “fix prices,rig bids and allocate customers” for the antibiotic doxycycline hyclatedelayed-release and diabetes drug glyburide. According to prosecutors,price-fixing activities for doxycycline occurred from April 2013, whilethe undertakings for glyburide began in April 2014. Both lasted untilat least December 2015 (Generics bulletin, 6 January 2017, page 1).

Attorneys general from 20 US states filed suit against six genericpharmaceutical players in December for their parts in conspiring toinflate prices and reduce competition for the two generics in the US.

Heritage – a subsidiary of India’s Emcure – was described in theantitrust complaint as the “principal architect and ringleader of theconspiracies”, while the lawsuit also named Aurobindo, CitronPharma, Mayne Pharma, Mylan and Teva, for their involvement.

The antitrust action involving the generics firms is the result ofa still ongoing investigation begun by the US state of Connecticutmore than two years ago into the “reasons behind suspicious priceincreases of certain generic pharmaceuticals”. G

LITIGATION

Sentencing date is setfor Glazer and Malek

AUSTRALIA’S Minister for Health, Sussan Ley, has resignedfrom the post following “intense media speculation” and “communityannoyance, even anger, with politician’s entitlements”. Greg Hunthas been named as her replacement.

VALEANT PHARMACEUTICALS has elected Dick DeSchutterto join its board of directors, which has increased to 13 members,12 of which are independent. Prior to his retirement, DeSchutterserved as the chief executive officer and chairman of DuPontPharmaceuticals from July 2000 until its acquisition by Bristol-Myers Squibb in October 2001. DeSchutter is also a director ofAuVen Therapeutics and Applied Silver.

DUANE MORRIS – the US law firm – has named Kevin Nelson asone of five new division heads within its intellectual property practicegroup. Nelson will serve as co-chair of the generic and biosimilarpharmaceuticals sub-group. Meanwhile, Patrick McPherson ischair of the newly-created inter partes review unit.

3SBIO – the Chinese biotech firm – has appointed Zhenping Zhuas president of research and development and chief scientific officer.

CELESIO has appointed president and chief operating officer BrianTyler to serve as management board chairman from 1 April 2017.Marc Owen is set to retire from the position on 31 March.

LOHMANN THERAPIE-SYSTEME – the transdermal system andoral films specialist – has announced that its chief executive officer,Wolfgang Hartwig, has retired. G

IN BRIEF