tpp deal has minimum five years of exclusivity · 03/10/2015 · mallinckrodt division to see 20%...

23 October 201523 October 2015

Wockhardt passes inspection by MHRA 2Teva pays US$2.3bn for 3Mexico’s RimsaMallinckrodt division to see 20% sales hit 4Acino buys Ukrainian player 5Pharma SmartMylan says Perrigo has no better option 6Chemiphar controls itsVietnam venture 7Cipla finds deals forAlgeria and vaccines 8Swedish firm Xbrane strikes Primm deal 9

MARKET NEWS 10

India is ‘committed’ to EU trade dialogue 10FTC backs Mylan on US ‘product hopping’11South Africa misses ZAR4bn in savings 12TPP protection terms elicit 14mixed responseBGMA voices stance on secondary patents15FDA grants industry request on labelling 16

PRODUCT NEWS 21

FDA accepts Sandoz’ filing for etanercept 21Jordan leans on EMA 22biosimilar guidelinesItaly welcomes ruling onTuscan infliximab 23Sun drops US suit on FDA’s Ranbaxy nods24Glenmark halted on Indian Januvia rival 25Cinfa kicks off a trial for 26pegfilgrastim rivalOncobiologics’ rival toAvastin clears trial 27Actavis settles in US onAcorda’s Ampyra 29

FEATURES 32

Endo looks past Par deal 32to consider further targetsEndo has spent more than most on acquisitionsin recent years, and has just tied up its largestever deal, with an US$8.0 billion transactionfor Par. The US firm may not stop there,however. Dean Rudge reports.

REGULARS

PipelineWatch – Tiotropium 28Events – Our regular listing 30PriceWatch UK – UK pricing trends 31People – Roos replaces Anley 34at Pharma Dynamics

COMPANY NEWS 2

Aminimum of five years of biologics data exclusivity, the same as for otherpharmaceuticals, has been included in the Trans-Pacific Partnership (TPP) agreedon 5 October by 12 countries after more than five years of secret negotiations. US traderepresentative Michael Froman said the agreement recognised different approaches toconferring “effective market protection” for original biologics “through various mechanisms,including at least five years of data protection, plus other government measures that canachieve a comparable outcome”.

“Our goal, doing it one way or another, is to have a comparable outcome in terms ofincentivising innovation and at the same time enabling access to affordable medicines,” Fromanstated. He noted that in countries that offered five years of data protection – far shorter thanthe 12 years available in the US – regulatory and administrative measures such as clinical-trialrequirements or facility inspections meant that “it may take seven to eight years beyond thefive-year protection for various biosimilars to be approved”.

Froman acknowledged that biologics exclusivity had been “one of the most challengingissues” during the talks, but said the compromise was a “strong and balanced outcome”. “Thisis the first trade agreement in history to ensure a minimum period of protection for biologics,”he pointed out following the conclusion of negotiations in Atlanta, US.

Australian trade minister Andrew Robb insisted countries could “travel different roads” tooffer comparable protection without having to have “some hybrid single system”. His Chileancounterpart, Heraldo Muñoz, said the deal would allow the country to retain its current data-protection rules. Negotiators from Australia, Brunei Darussalam, Canada, Chile, Japan,Malaysia, Mexico, New Zealand, Peru, Singapore, the US and Vietnam will now finalise theTPP text before presenting it to their parliaments and the public.

A purported TPP intellectual-property chapter dated 5 October published on the WikiLeakswebsite lays down a minimum five years of data protection for all pharmaceuticals, as well as “atleast three years” for “new clinical information” covering new indications, formulations andmethods of administration. Biologics are to benefit from at least eight years of “effective marketprotection” or five years plus “other measures” that will deliver “a comparable outcome in themarket”. Exclusivity periods are to be reviewed after 10 years. G

For reactions to the TPP agreement, turn to page 14.

TPP deal has minimumfive years of exclusivity

Sandoz won the global Company of the Year Award at the Global Generics & BiosimilarsAwards 2015 that were held on 13 October in Madrid, Spain.Novartis’ generics division also picked up prizes during a cocktail reception co-hosted by

Generics bulletin and Ark Patent Intelligence for Biosimilar Initiative of the Year for securingapproval of Zarxio (filgrastim-sndz) in the US, and for Regulatory Achievement of the Year inobtaining US clearance for Glatopa (glatiramer acetate), the first generic rival to Copaxone.

Richard Francis, global head of Sandoz, commented: “We are truly proud to receive thistriple recognition. These awards are further evidence that we are succeeding in our goal of addingreal and sustainable value for patients and healthcare systems worldwide by driving globalaccess to affordable high-quality medicines, including biosimilars.”

Among the winners of 11 other Awards were Actavis, Alvogen, Amneal, EMP Pharmaand Intas, as well as Hikma, Medis, Piramal, Stada, Teva and Walgreens Boots Alliance. G

For details and photos of the winners, turn to page 17.

Sandoz is Company of the Year

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Ethypharm has acquired UK-based off-patent drugs distributorDB Ashbourne (DBA) for an undisclosed fee. The French firmsaid the deal would help it to “develop a direct commercial presencein key territories in Europe to market central nervous system products,with a particular focus on pain and innovative treatments for addiction”.

Established in 2009 by entrepreneur Dallas Burston, DBA suppliesa range of prescription-only medicines in the UK, “generatingsignificant savings for the National Health Service (NHS)”. Among thecompany’s portfolio of controlled-release branded generics are Abtard(oxycodone), Ebesque XL (quetiapine), Eppinix XL (ropinirole),Fencino (fentanyl) and Venlalic XL (venlafaxine).

“The know-how and expertise of both companies are totallycomplementary and synergistic, and DBA offers a great platform tolaunch products from our own pipeline,” commented Ethypharm’schief executive officer, Hugues Lecat. By combining DBA’s UKpresence with its own commercial operations in France and Germany,Ethypharm expects to generate an annual turnover of more than C240million (US$269 million), an increase of around 40% from the C167million that the French group reported for 2014.

The French sustained-release specialist – which is backed byprivate-equity firm Astorg Partners – currently generates nearly half ofits sales in its home market, and more than a quarter in the rest ofEurope. China makes up a tenth of turnover, and North America 8%. G

COMPANY NEWS

2 GENERICS bulletin 23 October 2015

Developing generics. [email protected]

MERGERS & ACQUISITIONS

Ethypharm acquiresUK’s DB Ashbourne

Wockhardt says its L-1 formulations plant in Chikalthana, India,has passed an inspection by the UK’s Medicines and Healthcareproducts Regulatory Agency (MHRA) with “no critical observations”.

Earlier this year, the Indian company announced plans to resumeshipments to the UK from the Chikalthana plant near Aurangabad,which has MHRA clearance for tablets, capsules and sachets. This cameafter the UK agency restored the plant’s certificate of compliance withgood manufacturing practice (GMP) that it had previously withdrawn.

Managing director Murtaza Khorikawala told investors that drugssupplied from Chikalthana had generated annual sales of £10-£15million (US$15-US$23 million) before the MHRA imposed restrictions(Generics bulletin, 1 September 2015, page 12).

Wockhardt also recently responded to ‘Form 483’ observationsmade by US Food and Drug Administration (FDA) auditors followingan inspection of the Chikalthana site, which was the subject of animport alert imposed just under two years ago (Generics bulletin, 6December 2013, page 3).

Separately, Wockhardt has refuted media reports suggesting thatit had received FDA notification that it could export to the US productsmade at its facility in Waluj, India. The US agency had in 2013 imposedan import alert against drugs made at the site (Generics bulletin, 7June 2013, page 5). At the end of May this year, Wockhardt said theFDA had completed an inspection of the Waluj facility. G

MANUFACTURING

Wockhardt passesinspection by MHRA

Gen 23-10-15 Pgs. 2-9_Layout 1 21/10/2015 18:24 Page 2

IGI Laboratories has agreed to acquire Canadian generic injectablesspecialist Alveda Pharmaceuticals for C$47 million (US$36 million)in cash. The purchase price is almost three-times the C$16.0 millionturnover that Alveda expects to report for its financial year ended30 September 2015.

Through long-term partnerships with “reputable Europeancontract-manufacturing organisations”, Alveda currently markets 17molecules in 36 injectable presentations in Canada. That marketedportfolio includes lidocaine-based anaesthetics, antibiotics such aspiperacillin/tazobactam and antiemetics like dimenhydrinate.

Toronto-based Alveda – which was formed in 2006 through amanagement buy-out of Bioniche’s Canadian operations – also offersthe Caldolor (ibuprofen) intravenous analgesic and Euflexxa (sodiumhyaluronate) for osteoarthritis knee pain. Other marketed moleculesinclude acetylcysteine, epinephrine, furosemide and naloxone. IGIsaid Alveda was market leader for most of the products it offered.

IGI’s president and chief executive officer, Jason Grenfell-Gardner,said the acquisition – which the US-based company expects to completebefore the end of November – would extend IGI’s strategy of focusingon topical, injectable, complex-product and ophthalmic (TICO) markets.

“The Alveda management team has a strong track record withthe Canadian institutional supply chain, including group purchasingorganisations (GPOs), wholesalers and individual hospitals,”Grenfell-Gardner commented. “Alveda’s in-house regulatory team hasbeen productive and, as a result, Alveda has a pipeline of eight products,four of which are pending approval by Health Canada,” he added.

Striking a deal to buy Alveda came shortly after IGI agreed to payConcordia US$10 million in cash for three marketed US injectables –Fortaz (ceftazidime), Zantac (ranitidine) and Zinacef (cefuroxime). Thethree acquired brands had combined annual US sales of aroundUS$26 million, IGI noted.

Grenfell-Gardner said the purchase “accelerates our commercialentry into the sterile injectables market”. While the acquired drugswere branded, they competed in genericised markets, he pointedout, which “should allow us to leverage our existing value chain forsales, marketing and distribution for these products”.

The Fortaz and Zinacef antibiotics would bolster IGI’s hospitalanti-infectives offering, “a market segment we believe is best servedby a portfolio approach”, he noted. Zantac is used to treatmentgastrointestinal disorders, including duodenal ulcers.

To date, IGI has filed nine abbreviated new drug applications(ANDAs) in the US this year, bringing its total number of ANDAspending approval with the US Food and Drug Administration (FDA)to 31, excluding four partnered submissions. Grenfell-Gardner saidthe 31-drug pipeline pending FDA approval had “a combinedaddressable market of over US$1.5 billion”.

Having expanded beyond a topical products specialist to becomea broader-based niche generics player, IGI has just been approved forlisting on the Nasdaq exchange’s ‘Global Select Market’. Grenfell-Gardner said the firm’s move from the New York Stock Exchange(NYSE) would “improve the visibility of our stock, enhance tradingliquidity in our shares, and provide us with greater exposure to abroader base of institutional investors”.

In the first six months of 2015, IGI increased its turnover by 47%to US$19.7 million. However, the company saw its operating loss riseslightly to US$0.81 million as product-development expenses almostdoubled to US$6.07 million. G

COMPANY NEWS

3GENERICS bulletin23 October 2015


IGI agrees a deal tobuy Canada’s Alveda

Teva is aiming to become a “leading pharmaceutical company inMexico” by agreeing a deal worth around US$2.3 billion for localmanufacturer and distributor Laboratorios Rimsa, “along with aportfolio of products and companies, intellectual property, assets andpharmaceutical patents in Latin America and Europe”. Slated to closein the first quarter of next year, the transaction is expected to “yieldsubstantial and achievable synergies and [to] offer a platform forgrowth in the region”.

Founded in 1970, Mexico City-based Rimsa is “the leadingindependent Mexican pharmaceutical company”, with sales of US$227million in 2014, having achieved a compound annual growth rate(CAGR) of 10.6% over the past four years, fuelled in part by fixed-dose combination drugs. The agreed purchase price is around 10-timesRimsa’s annual turnover.

Led by chief executive officer Luis Pérez Juárez, Rimsa offersa broad portfolio of branded generics, including musculoskeletal, pain,gastroenterology and respiratory treatments, as well as a line ofhospital drugs such as its Biocilin (filgrastim) and Yelit (somatropin)versions, and anaesthetics such as propofol, ropivacaine and lidocainethrough an alliance with AstraZeneca.

Provides a platform for growth“Rimsa will provide Teva with a significant platform for growth

by combining: the strong Rimsa brand; licensed portfolio ofdifferentiated, patent-protected products; promising pipeline; significantrelationships with physicians, patients and healthcare providers; andits strong commercial presence,” summarised the Israeli firm’s presidentand chief executive officer, Erez Vigodman.

Siggi Olafsson, head of Teva’s Global Generic Medicines division,said the company would meanwhile look to “build on [Rimsa’s] brandreputation, successful salesforce model, well-established commercialfootprint and loyal customer base to introduce additional specialty andgeneric Teva medicines to patients in Mexico and across the region”.

Teva’s operations in Latin America already include an office inMexico, as well as locations in Argentina, Brazil, Chile, Curaçao, Peru,Uruguay and Venezuela. The Israeli firm employs around 3,500 peoplein the region, and has its regional headquarters in Miami, US. G


Teva pays US$2.3bnfor Mexico’s Rimsa

India’s Unichem Laboratories has denied local media rumours thatit is planning to divest its Domestic Formulations business. In a shortstatement issued to the Bombay Stock Exchange (BSE), the Mumbai-based company described the sell-off report in the Economic Timesnewspaper as “a rumour”.

According to the Economic Times report, the Indian firm hadenlisted investment bank Jefferies to seek bidders for its Indianoperations in a deal that could raise more than US$1 billion.

In its financial year ended 31 March 2015, Unichem’s DomesticFormulations sales slipped by 1% to Rs6.51 billion (US$100 million).The business – led by its Losar (losartan) and Ampoxin (ampicillin)franchises – accounted for three-fifths of group turnover that advancedby 4% to Rs11.0 billion. International Formulations contributed Rs3.13billion, and active pharmaceutical ingredients (APIs) the remainder. G

DIVESTMENTS

Unichem denies domestic sale


Biosimilars developer Mabxience has officially opened amonoclonal antibodies facility in León, Spain, following a C25million (US$28 million) investment.

Having paid around C11 million last year to acquire the formerGenhelix plant in León (Generics bulletin, 20 June 2014, page 3),Mabxience has since spent another C14 million on upgrading the16,000 sq m site to meet the needs of its biosimilars pipeline. Thisincluded installing single-use technology such as disposable bioreactorsto maximise the facility’s flexibility and eliminate the potential for cross-contamination. Furthermore, Mabxience says single-use technologyreduces consumption of water and cleaning agents by 80% and 90%respectively, as they are not required to clean bioreactors.

Within the 5,500 sq m of the site dedicated to development andproduction are 2,000-litre bioreactors, a pilot plant, research anddevelopment laboratories, quality-control laboratories and warehouses.

Since it was set up in 2009 as the biosimilars arm of Spain’sChemo Group, Mabxience has invested over C115 million in itsbiosimilars operations. These investments include setting up thePharmADN research and Sinergium production facilities in BuenosAires, Argentina, from which the firm launched its first biosimilarin Argentina, rituximab.

Other than rituximab, Mabxience is developing four othermonoclonal antibodies – biosimilar versions of Avastin (bevacizumab),Enbrel (etanercept), Humira (adalimumab) and Synagis (palivizumab) –along with a recombinant coagulation factor VIII.

The company has struck a wide range of strategic alliances,including with Alvogen in south-east Asia, with Apotex in severaladvanced markets, and with Libbs in Brazil. Towards the end oflast year, Mabxience opened negotiations with Stada over licensingadalimumab to the German group (Generics bulletin, 5 December2014, page 22). And more recently, the company obtained licensingrights to Epirus’ BOW015 infliximab candidate in Latin Americanmarkets (Generics bulletin, 22 May 2015, page 23). G

COMPANY NEWS


23 October 2015 Issue 240

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

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

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MANUFACTURING

Mabxience unveilsC25m biotech plant

Mallinckrodt says it expects its Specialty Generics sales to fallby between 15-20% in its financial year ending 30 September2016 as a result of both the fallout from the US Food and DrugAdministration’s (FDA’s) reclassification of its methylphenidateextended-release products to non-substitutable status, and continuedadditional generic competition “across the Specialty Generics portfolio”.

Addressing investors at a recent business update, president andchief executive officer Mark Trudeau said the impact of the FDA’sdecision regarding its generic version of Janssen’s Concerta brandcontinued to “drive tough year-on-year comparisons” for SpecialtyGenerics. “Given the overall volume losses and the relative size ofthat product in our portfolio, the impact is notable,” he commented.

In the company’s recently-announced third quarter results,Mallinckrodt’s Specialty Generics sales slipped by 6.5% to US$308million (Generics bulletin, 1 September 2015, page 11). This comparesto the 18.6% rise to US$1.20 billion reported in Mallinckrodt’s financialyear ended 26 September 2014, shortly after the FDA rescinded theAB-rating for therapeutic equivalence for methylphenidate (Genericsbulletin, 5 December 2014, page 11).

But with Specialty Brands sales anticipated to rise by 30% in its2016 financial year, Mallinckrodt expects group turnover to advanceby at least 10%. “In fiscal 2016, we will execute against our long-term plan, building our hospital and autoimmune and rare diseasesstrategic growth platforms in the Specialty Brands segment through abalance of organic growth and continued pursuit of strategic businessdevelopment and licensing opportunities,” Trudeau commented.

Meanwhile, quizzed on whether Mallinckrodt would, in light ofits negative forecast, “consider options” for its Specialty Genericsbusiness, including a divestment, chief financial officer MatthewHarbaugh said selling the unit would not be as “straightforward adecision” as was the recent sale of its global contrast media and deliverysystems (CMDS) unit (Generics bulletin, 7 August 2015, page 11).“Specialty Generics generates a ton of cash for us,” he stressed. G

RESULTS FORECAST/BUSINESS STRATEGY

Mallinckrodt divisionto see 20% sales hit


Swiss group Acino has furthered its strategy of expanding in“selected high-potential emerging markets” by acquiring Ukraine-based developer and manufacturer Pharma Start for an undisclosed sum.

The ninth-largest local pharma company in Ukraine, accordingto Acino, the Kiev-based firm had sales of around UAH271 million(US$12.7 million) in 2013, and has experienced a compound annualgrowth rate (CAGR) of 41% from 2011 through to last year.

With a focus on cardiovascular and central nervous systemtreatments centred on delayed- and extended-release formulations,Pharma Start brings to Acino a portfolio of around 35 branded genericsin 75 presentations, including Clivas (rosuvastatin), Diocor Solo(valsartan), Gabantin (gabapentin), Levocom (levodopa/carbidopa)and Quetiron (quetiapine). The Ukrainian firm says it exports to Belarus,Georgia, Kazakhstan and Uzbekistan, as well as to Russia.

“To leverage the full potential of this acquisition, Acino intendsto gradually roll out its existing portfolio in Ukraine,” the Swiss firmcommented, “and to expand the combined portfolio to Commonwealthof Independent State (CIS) countries such as Belarus, Kazakhstan,Russia, Uzbekistan and others.”

Acino noted that it already had a presence in the CIS throughMoscow-based marketing and distribution firm Copharm, which also“operates across the CIS through affiliates”.

Meanwhile, the Swiss firm said it would prioritise integrating theUkrainian company’s quality system into its own “in order to meetinternational good manufacturing practice (GMP) standards”.

“The acquisition will positively impact Acino’s revenue, profit andoperating margin,” the firm insisted, pointing out that Pharma Start’soperations covered registration, distribution and sales and marketing.

Acknowledging the “volatile political and economic situation inUkraine”, Acino commented that local manufacturers nevertheless“benefit from the current situation due to their affordable drug prices,as they are less dependent on currency fluctuations than foreignimporters”. “Localising is an important success factor in these marketsto provide high-quality medicines at affordable prices,” it added. G

COMPANY NEWS



Acino buys Ukrainianplayer Pharma Start

Canada’s health minister Rona Ambrose “acted for an improperpurpose” and was “procedurally unfair” when she last yearimposed an import ban against Apotex covering drugs from two of thefirm’s facilities in India, the Federal Court of Canada has concludedin overturning the ban.

Drugs made by the Canadian firm’s Apotex Pharmachem IndiaPvt Ltd (APIPL) and Apotex Research Private Limited (ARPL) affiliatesin Bommasandra, India, had for almost a year been prevented fromentry into the country after Health Canada – acting at the minister’sbehest – in September 2014 took action over the “unsatisfactoryprocesses and systems in place to assure Canadians of their qualityand safety” (Generics bulletin, 3 October 2014, page 3).

Last month, however, the agency allowed Apotex’ drugs to beonce again imported to Canada, subject to certain conditions it hadset out, following remediation activities undertaken by the company(Generics bulletin, 11 September 2015, page 2).

No evidence of health risks“There is no evidence to support the contention that the minister

was concerned about immediate health risks posed by the productssubject to the ban, nor that the situation was highly urgent,” JusticeMichael Manson ruled. Ambrose had “failed to provide any notice,”he said, “and thus denied Apotex an opportunity to be heard beforeunilaterally imposing the import ban on 30 September 2014.”

“The import ban was motivated by the desire to ease pressuretriggered from the media and in the House of Commons,” Mansonmaintained, noting that the Toronto Star newspaper had run a seriesof highly critical articles.

In addition to lifting the import ban, public statements issued byHealth Canada at the time were to be retracted, Manson ordered.“Statements released by the minister and Health Canada conveyingthe information to the public, which also contained statementspotentially harmful to Apotex, were invalid,” he found in awardingcosts to Apotex. G

MANUFACTURING

Canadian court findsban on Apotex unfair

Bird faeces and lizard occupancy within an active pharmaceuticalingredient (API) site have led the US Food and DrugAdministration (FDA) to issue a warning letter against UnimarkRemedies’ production plant near Ahmedabad, India. “Your qualitysystem does not adequately ensure the accuracy and integrity of datagenerated at your facility to support the safety, effectiveness, and qualityof the drug products you manufacture,” the FDA added.

Noting that Unimark’s responses following an inspection inMarch 2014 had been inadequate, the FDA listed current goodmanufacturing practice (cGMP) deficiencies including failures to entertest results for batches in production, a lack of access controls toprevent data being altered and incomplete quality records.

The FDA strongly recommended that Unimark “hire a qualifiedthird-party auditor/consultant with experience in detecting data-integrityproblems”. The agency demanded a detailed action plan to address thecGMP deficiencies and a “comprehensive investigation into root causesof the data-integrity problems”, as well as a risk assessment. G

MANUFACTURING

Unimark hit by FDA warningHovione has acquired a finished-dose formulations facility adjacentto its existing particle-engineering and active pharmaceuticalingredients (APIs) plant in Loures, Portugal. The purchase willhelp the Portuguese producer to develop and make both oral-doseand inhalation drugs, including those based on highly-potent APIs.

“Over the past decade, we have built great knowledge in developingfinal dosage forms in the area of dry-powder inhalation and oral dosageforms, and have installed state-of-the-art formulation equipment tosupport these activities,” commented Hovione’s vice-president ofresearch and development, Filipe Gaspar. “Adding to our drug-substanceand particle-engineering capabilities, this new plant expands ourintegrated offer and technological capabilities ... to our customers.”

Hovione is also more than doubling the size and capacity of itsUS facility in East Windsor, New Jersey, expanding it from 2,200sq m to around 5,050 sq m. The company will install a commercialspray-dryer unit that is designed to handle potent APIs. The expansionis scheduled to be completed by early 2017. G

MANUFACTURING

Hovione has formulations site


Perrigo’s shareholders are unlikely to get a better offer than Mylan’sUS$75 in cash and 2.3 Mylan shares for each Perrigo share,according to Mylan’s executive chairman, Robert Coury. “Severalmonths of a public process clearly have proven that there does notseem to be any other firm third-party interest in acquiring Perrigoat such a value,” he claimed.

Mylan told Perrigo’s investors that its offer currently implied anenterprise value for Perrigo of US$30.0 billion, or 19-times the store-brand specialist’s adjusted earnings before interest, tax, depreciationand amortisation (EBITDA). It said this was a high ratio in comparisonto other similar acquisitions, which was the reason why no ‘whiteknight’ rival bidder had emerged for Perrigo during the past six months.

Mylan acknowledged that the value of its offer was US$5.7billion less than the initial valuation based on Mylan’s closing priceon 7 April, the first day it proposed the offer, before Teva dropped itsbid for Mylan in favour of Actavis. However, it claimed that “Mylan’soffer has been supporting the Perrigo share price”, so the premiumit was offering remained attractive.

Combination would reduce Tysabri dependenceA combined company, Mylan asserted, would be far less dependent

on royalties from Perrigo’s rights to Tysabri (natalizumab), whichcould from 2017 face competition from Roche’s ocrelizumab.

Noting that its offer would expire on 13 November – two monthsafter it launched its takeover bid (Generics bulletin 11 September2015, page 3) – Mylan said its offer was dependent on at least 50%of Perrigo’s shares being tendered. In the event that Mylan gainedmajority control, but less than the 80% threshold that would triggercompulsory ‘squeeze-out’ provisions for minority shareholders underIrish law, Mylan stressed that it was “prepared to manage the businessas a controlled subsidiary.” G

COMPANY NEWS



Mylan says Perrigohas no better option

Danish active pharmaceutical ingredients (APIs) and intermediatesmanufacturer Chr Olesen Synthesis has raised C10 million (US$11million) by selling shares to US private-equity firm Signet HealthcarePartners. The privately-owned company plans to use the proceeds toincrease its manufacturing capacity and to “fund the developmentof hard-to-produce generic APIs”.

“Chr Olesen Synthesis is growing, and we are sure to benefit fromSignet’s experience in both funding and supporting the developmentof the company into the next level,” commented the Danish firm’schairman, Mads Olesen.

“We are impressed with the chemical-synthesis capability of thecompany and its ability to provide excellent service to customers,”commented Signet’s managing director, James Gale, who will joinChr Olesen Synthesis’ board. “With this investment, we believe thebusiness will have sufficient capacity to meet the demand for itsAPIs in the visible future.”

Among the API molecules offered by Chr Olesen Synthesis areamphetamine derivatives, codeine phosphate, hydromorphone,pramipexole, risedronate, terbinafine and tolfenamic acid. The firm alsomakes advanced intermediates for buprenorphine and tamsulosin.G

BUSINESS STRATEGY

Olesen gets funds to expand

TEVA has agreed to acquire for an undisclosed fee Gecko HealthInnovations, a privately-held company that develops software andsolutions to aid compliance in treating respiratory disease. The deal willgive Teva access to Gecko’s CareTRx cloud-based compliance tool.

DOPPEL FARMACEUTICI is now controlled by Trilantic CapitalPartners Europe after the private-equity firm bought a 90% stakein the Italian contract developer and manufacturer for an undisclosedfee. The vendors were a group of Italian entrepreneurs. GiuseppeCassisi has been installed as chief executive officer, while PaoloLanfranchi has moved from managing director to become the firm’schairman. Last year, Doppel achieved earnings before interest, tax,depreciation and amortisation (EBITDA) of C12.3 million (US$13.9million) on a turnover of C83.4 million.

ACETO has filed a universal shelf-registration statement withthe US Securities and Exchange Commission (SEC), potentiallyallowing the generics and active pharmaceutical ingredients (APIs)supplier to publicly offer shares or other securities valued at up toUS$200 million. The US-based group said the option to raisecapital would help it to explore potential acquisitions and othergrowth opportunities.

ONCOBIOLOGICS has raised gross proceeds of US$43 million froman investment round that included funds from Sabby Management.The US company plans to use the proceeds to develop and expandits BioSymphony platform for biosimilar monoclonal antibodies.

KILITCH DRUGS has formed a joint venture with an undisclosedlocal party in Ethiopia. The Indian company will own 97% of thepharmaceuticals and nutraceuticals manufacturing facility that itintends to build in the country.

UPM has opened a 370 sq m development facility for solidformulations. The Tennessee-based US company said the site washighly scalable, allowing batches to be produced from “a few hundredgrams” of active pharmaceutical ingredient (API).

ENDO has completed its ZAR1.6 billion (US$118 million)acquisition of a “broad portfolio” of around 60 branded and genericinjectables and established products – including pain, anti-infective,cardiovascular and other specialty drugs – in South Africa from localfirm Aspen. The deal was first struck in May (Generics bulletin,22 May 2015, page 4), shortly before the US firm’s Litha Healthcareaffiliate agreed to divest a roster of non-core products, such asvaccines and device products, in South Africa to a consortium oflocal investors. Endo said the acquired drugs had combined salesof US$28 million in Aspen’s financial year ended 30 June 2014.

AESICA wants to manage its contract-development andmanufacturing clients’ entire supply chain by acting as “the single,central point of customer contact” for several service providers.The UK-based company – which has launched a fresh brand identityfollowing its takeover by Consort Medical – claims its single-contactmodel will “guarantee on-time, in-full product delivery, optimiseefficiency, eliminate waste and supply shortages and achievesignificant cost savings”.

JHL BIOTECH is now publicly listed on the Taiwan EmergingStock Board with an initial capital value of around TWD1.89billion (US$58.4 million). The biosimilars developer, which is backedby several venture capital firms, said some of its shareholders hadsold part of their holdings to allow the public offering. G

IN BRIEF


COMPANY NEWS


South Africa’s Ascendis Health has greatly expanded its domesticpipeline by picking up a basket of 85 currently not marketeddossiers in South Africa from Sandoz for an undisclosed fee.

Details of the products were not disclosed, although Ascendis saidthe acquisition would allow it “future access to registered productsin new and rapidly emerging therapeutic areas, including oncology,women’s health and urology,” while “strengthening [our] currentposition within the anti-infectives and neurosciences areas”.

Karsten Wellner, Ascendis’ chief executive officer, noted that “thesuccessful development of the products will offer sustained organicand new-market growth opportunities for our Pharma-Med divisionas we unlock operational efficiencies and explore new markets,while at the same time strengthening our diversification strategyand foreign earnings position”.

Ascendis said it was maintaining its target of achieving 30% ofsales overseas “in the medium term”. Having earlier this yearestablished a footprint outside of South Africa by snapping up a 49%stake in Spanish generics and OTC player Farmalider (Genericsbulletin, 1 September 2015, page 4), Ascendis said its internationalfocus was trained on “platform companies for all business units andmainly target opportunities in Australia, Europe, the US and Africa”.

Meanwhile the firm noted that it would continue to aim for “bolt-on acquisitions across all divisions” in its homeland. “Operationally,the group’s priorities are to improve gross margins through increasedlocal and in-house production, strict cost control and focus onefficiencies,” the firm said.

In its financial year ended 30 June 2015, Ascendis’ Pharma-Medprescription drugs and medical devices turnover trebled to ZAR1.25billion following a raft of acquisitions over the last 12 months. Inaddition to Farmalider, Ascendis also bought in July, for ZAR17.9million, local firm Bioswiss, which “has access to innovativebiotechnological products to manage and treat diabetes”.

Ascendis’ Pharma-Med sales made up 44% of group turnoverthat advanced by 74% to ZAR2.82 billion, including “comparableorganic growth of 11%”. Of that group figure, around 9% of sales– ZAR259 million – came outside of South Africa, with overseasPharma-Med turnover totalling ZAR56.8 million.

The firm’s Consumer Brands division sales increased by morethan two-fifths to ZAR949 million, and Ascendis’ Phyto-Vet plantand animal healthcare business turnover rose by 13% to ZAR620million. At the same time, Ascendis’ operating profit leapt by morethan two-thirds to ZAR362 million. G

MERGERS & ACQUISITIONS/ANNUAL RESULTS

Ascendis acquires 85dossiers from Sandoz

Chemiphar plans to acquire all shares in its Vietnamese joint venturewith MST Pharm. The venture was originally set up betweenJapan’s Chemiphar and Vietnam’s MST with an ownership ratio of60% to 40% respectively in early 2015 (Generics bulletin, 16 January2015, page 7). The share transfer is expected to be completed by theend of this month.

The Nippon Chemiphar Vietnam Joint Venture was Chemiphar’sfirst major overseas undertaking, with an original capital investmentof US$7.50 million. The venture – located in Binh Duong province –intends to start construction on a manufacturing facility by the endof 2015, with building to be completed within around 12 months, andproduction to commence by March 2019.

Chemiphar believes taking full control of the venture will“accelerate decision-making and business expansion”, as well as providea “foothold for future Asian development” to capitalise on growingdemand for value-added generics and treatments for lifestyle diseases.

President and chief executive officer Kazushiro Yamaguchimaintained that “entry into overseas markets is essential” given thatJapan’s shrinking population meant “it is inevitable that the Japanesepharmaceutical market will move into a phase of decline”. While theobjective for the Vietnamese facility would be producing for Japanesedemand “for the foreseeable future”, it would in the longer term serve“as a stepping stone towards future expansion into supply for thelocal market and other emerging markets”.

Noting that Chemiphar was also set to import into Japan anunspecified product manufactured by Stada Vietnam (Genericsbulletin, 3 October 2014, page 4), Yamaguchi said combining full-scaleoperations at the Vietnamese facility with its recently-expandedTsukuba factory in Japan would almost double the company’s annualcapacity over four to five years from 1.1 billion to 2.0 billion tablets.

Having identified Asia as the focus for Chemiphar’s internationalstrategy, Yamaguchi noted that the company had obtained approval forpioglitazone in Hong Kong and was preparing to market the diabetesdrug. Furthermore, Chemiphar was working with local distributorsto sell several brands in China, South Korea and Thailand.

Turning his attention to the Japanese group’s domestic outlook,Yamaguchi said the Japanese government’s continued promotion ofusing generics – in pursuit of achieving ambitious penetration goals(Generics bulletin, 5 June 2015, page 1) – would result in “a growthtrend in the foreseeable future”. Chemiphar’s near-term domesticpipeline includes the molecules clopidogrel, montelukast, olmesartan,rosuvastatin and telmisartan. G


Chemiphar controlsits Vietnam venture

Fujian South Pharmaceutical (FSP) has passed its first inspectionby the US Food and Drug Administration (FDA). The Chinese bulkoncology specialist, which produces drugs including docetaxel andpaclitaxel, worked closely to achieve the FDA accreditation withRochem International, which acts as FSP’s US and European Union(EU) site agent, as well as the Chinese producer’s exclusive distributorand regulatory agent for drug master files (DMFs) and certificatesof suitability (CoSs). Over the past five years, the two companies haveworked closely on audits, on-site training and technical support. G

MANUFACTURING

Fujian South passes FDA auditChemWerth has expanded its distribution into Mexico and CentralAmerica by appointing Mexico’s Ideos Servicios y EspecialidadesQuimicas as its local sales agent for generic active pharmaceuticalingredients (APIs). Peter Werth, ChemWerth’s president and chiefexecutive officer, said adding Ideos’ president, Jorge Sosa, to thegroup’s sales team would give the firm “a springboard into Mexicoand Central America as we continue to expand our distribution andshare our vision of ‘One World, One Quality’”. US-based ChemWerthplans to expand its operations in South America early next year. G

STRATEGIC ALLIANCES

ChemWerth links with Ideos


Cipla has entered into a definitive agreement with Biopharma toestablish a joint venture in Algeria. The Indian company has alsoexpanded its collaboration with Serum Institute of India by agreeinga deal to supply vaccines in South Africa.

Earlier this year (Generics bulletin, 27 February 2015, page 2),Cipla said it would hold a 40% stake in the Algerian venture, whichwould focus on marketing the Indian firm’s respiratory portfolio andwould involve supplying funds to build a local manufacturing facility.At around the same time, Cipla struck a similar deal in Morocco.

In South Africa, Cipla is building on its existing relationship withSerum Institute with the aim of becoming a “significant player” inthe local vaccines market.

Under the agreement, Cipla’s Medpro unit will gain “exclusivity andfirst right of refusal to the Serum pipeline within South Africa”, and willalso “become the holder of all Medical Control Council (MCC)regulatory approvals”. Pointing out that Serum manufactured a widevariety of vaccine classes – including treatments for polio, diphtheria,tetanus, hepatitis B, and measles, mumps and rubella (MMR) – Ciplasaid “South Africa will be participating in the majority of these portfolios”.

“With a presence in 140 countries, and 1.3 billion dosesmanufactured and sold, Serum is an ideal ally for Cipla Medpro andthis partnership will be instrumental in addressing the national vaccinesshortage,” commented the firm’s chief executive officer, Paul Miller.

Cipla had at the end of last year signed an agreement with Serumcovering paediatric vaccines in Europe (Generics bulletin, 5 December2014, page 6), before striking an agreement for Serum’s flu vaccineNasovac-S (influenza vaccine) in India. Serum earlier this yearmooted a potential merger between two firms. G

COMPANY NEWS


CONCORDIA HEALTHCARE expects to close its US$3.5 billionacquisition of Amdipharm Mercury (AMCo) imminently. TheCanadian company has debt financing of US$2.84 billion in placewith several financial institutions, while it has raised gross proceedsof US$520 million from a public offering of 8.0 million shares. “Weare acquiring more than 190 products sold in over 100 countries,”pointed out Concordia’s chairman and chief executive officer,Mark Thompson. AMCo’s pipeline of around 60 planned new productlaunches would fuel organic growth, he said, adding that the morediverse combined company would generate only two-fifths of itsturnover in the US.

EPIRUS has added its BOW070 biosimilar version of Actemra(tocilizumab) to its development agreement with Livzon Mabpharmin Asian markets including China, Hong Kong and Taiwan. TheUS-based company will pay Livzon US$4.5 million to completepre-clinical activities. The two firms last year agreed a “royalty-bearing” alliance covering the development, manufacture andmarketing of “up to” five biosimilars (Generics bulletin, 3 October2014, page 17). Epirus has also agreed to divest to Sun’s Taro affiliatethe novel ‘Z944’ pain treatment candidate and “certain related assets”that it acquired through its merger with Canada’s Zalicus last year.The sale – which comes just a year after Epirus and Zalicus completedtheir merger (Generics bulletin, 2 May 2014, page 2) – forms part ofthe US-based company’s strategy to “devote additional resourceson developing its pipeline of biosimilar product candidates”.

VETTER – the German aseptic contract manufacturer – plans toinvest around C300 million (US$341 million) over the next fiveyears in expanding and upgrading its facilities. Vetter – which hasalso opened an office in Tokyo, Japan – believes the upgrades willhelp it to cope with “ever-more complex molecules, smaller batchsizes and increasing regulatory requirements”.

ANI PHARMACEUTICALS said its board had authorised a stockrepurchase programme for up to US$25 million of shares. Theauthorisation allows the US generics firm to buy shares on the openmarket or through private transaction through to 31 December 2016.

AMERISOURCEBERGEN has agreed to pay US$2.575 billion incash to Clayton, Dubilier & Rice for Pharmedium HealthcareHoldings, a privately-held provider of compounded sterilepreparations to US hospitals. The US healthcare distribution groupexpects to complete the deal by the end of this year.

JILIN ASYMCHEM – the custom manufacturer of bulk drugs –said its plant in Dunhua, China, had passed an inspection byAustralia’s Therapeutic Goods Administration (TGA).

MERCK MILLIPORE has linked up with fellow German companyCelares to offer pegylation services to companies developingbiosimilars and other protein-based therapeutics. The partners willoffer “feasibility studies, process and analytical development, andscale-up from milligram to gram quantities required for pilot andsubsequent commercial scale”. By working with privately-ownedpegylation specialist Celares, the Millipore unit of Merck KGaAintends to capitalise on its range of pegylated products “of differentmolecular weight and activation chemistry”.

TWi PHARMACEUTICALS has raised TWD2.83 billion (US$87.3million) by issuing global depository receipts to international investors.The Taiwanese firm plans to invest in product development, itsChinese subsidiary and expanding production lines in Taiwan. G

IN BRIEFSTRATEGIC ALLIANCES

Cipla finds deals forAlgeria and vaccines

Biocon has acquired a bulk-drugs production site in Visakhapatnam,India, from Acacia Lifesciences for an undisclosed fee. “This unitis presently manufacturing advanced intermediates of potent activepharmaceutical ingredients (APIs) useful to the company’s business aswell as for supply to third-party customers,” the Indian firm explained.

Acacia operates two blocks, each of just over 2,000 sq m in size,on a 28,000 sq m site in Vishakapatnam, Andhra Pradesh. The campushas been approved by the US Food and Drug Administration (FDA). G

MANUFACTURING

Biocon buys a bulk-drugs site

Including the impact of acquiring Hospira from 3 September is set tolift Pfizer’s turnover by around US$1.5 billion to US$46.5-US$47.5billion this year, the US-based originator anticipates. Under Pfizer’saccounting system, the group will benefit from around four monthsof sales by Hospira’s US business, and around three months ofturnover from the injectables specialist’s international operations.

However, restructuring, purchase-accounting and other acquisition-related expenses are set to deplete Pfizer’s reported diluted earningsper share by US$0.09 this year to between US$1.29 and US$1.38. G

RESULTS FORECAST

Hospira lifts Pfizer’s forecast


COMPANY NEWS


Siegfried has completed its C270 million (US$304 million)acquisition of three former BASF bulk-drug manufacturing facilitiesin France, Germany and Switzerland. The Swiss group said the threesites achieved a combined turnover last year of around SFr280 million(US$288 million), helping it to “reach the critical size to play a leadingrole in the supplier market as a recognised partner”.

“This acquisition,” the firm stated, “represents the final step inSiegfried’s targeted acquisition policy implemented in the past fiveyears.” The Swiss group followed its purchase of California-basedinjectables specialist AMP last year by taking over Germany’s HamelnPharma (Generics bulletin, 5 December 2014, page 1). Siegfriedhas also built a bulk-drugs production plant in Nantong, China.

Having now reached a pro forma turnover of around SFr600million and earnings before interest, tax, depreciation and amortisation(EBITDA) of about SFr100 million, Siegfried insists its has “nowreached the necessary size to remain a comprehensive and leadingsupplier in the ongoing consolidation process”. The group employsmore than 2,300 people at nine sites across three continents.

BASF will provide transitional services until late-2016, including asa non-exclusive distributor of the divested active pharmaceuticalingredient (API) portfolio. The German group will focus on its “coreexpertise in pharmaceutical excipients”, although it will continue tooffer “selected APIs” such as ibuprofen and polyethylene glycol. G

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Siegfried closes dealfor BASF bulk drugs

Swedish complex generics specialist Xbrane Bioscience has acquiredItalian injectables supplier Primm Pharma for an undisclosed fee.The Stockholm-based company has also signed an Iranian distributiondeal for Primm’s lead development product, Spherotide (triptorelin)with local company Pooyesh Darou. According to Xbrane, sustained-release injectables developer Primm Pharma will start to roll out itsSpherotide alternative to Ipsen’s Decapeptyl (triptorelin) prostate-cancertreatment in emerging markets “from mid-2017”.

“Primm Pharma has unique expertise in microsphere-based drugsand a lead product, Spherotide, that we believe will become the world’sfirst slow-release ‘biogeneric’ for a sizeable prostate-cancer andendometriosis drug,” commented Xbrane’s recently-appointed chiefexecutive officer, Martin Åmark.

Xbrane plans to offer Spherotide at about half the price ofDecapeptyl and says its current “cost-efficient” production capacityof 1 million triptorelin doses per year could be trebled if necessary.

By adding Primm’s five sustained-release candidates, Xbrane saysit now has eight development candidates targeting brands withcombined annual global sales of around US$10 billion.

Commenting on the distribution alliance with Pooyesh Darou,former Bain & Co executive Åmark – who took over the chief executiverole from chief operating officer Siavash Bashiri – described Iran as“as an ideal first market for our high-demand complex generics”. G


Swedish firm Xbranestrikes Primm deal


India remains committed to the India-European Union (EU) Broad-based Investment and Trade Agreement (BTIA) and is “interestedin taking this agreement forward”, according to the country’s secretaryof the department of commerce, Rita Teaotia.

Earlier this year, reports surfaced that talks between two partieson the planned free trade agreement had been shelved, due to India’sdisappointment regarding the EU’s decision to suspend hundreds ofmarketing authorisations obtained by dozens of generics firms on thebasis of clinical trials conducted by India’s GVK Biosciences (Genericsbulletin, 1 September 2015, page 16).

This action had been predicated by an inspection of GVK byFrance’s medicines agency, ANSM, in 2014, during which “seriousconcerns” regarding bioequivalence trials at GVK’s Hyderabad facilityhad been raised (Generics bulletin, 8 August 2014, page 15).

But speaking to Generics bulletin as part of a delegationrepresenting the India Brand Equity Foundation (IBEF), Teaotiadescribed as “a misapprehension” suggestions that talks had brokendown entirely. “The meeting that we deferred was a meeting of thechief negotiators merely to sit down and gauge the level of interest ingoing forward. Since we had already expressed interest in goingforward, it was a meeting of minor significance from India’sperspective,” she commented.

Teaotia acknowledged that India was unhappy after GVK’s “valid”request for a joint inspection was ignored, and instead a “decision[was] taken in the EU on the basis of a single inspector’s report”. “[Therequest] was to be followed within a week by this particular meeting;we thought that this could happen a little later because it had caused alot of discomfort for the government of India,” she stated, ultimatelycommenting that “I do not think we are linking the two things at all”.

Quizzed on how Indian authorities would look to reinforceperceptions of quality in the wake of such events, Teaotia insisted thatIndia was “more conscious than even regulated markets about qualityin the pharma industry”. “I do not think we need to reinforce[perceptions of quality]. This is a quality-conscious industry, so we area very quality-conscious regulator, both at the central government andat the state level.”

Meanwhile, the IBEF revealed that India would in December thisyear sign a partnership with Japan’s Pharmaceutical & Medical DevicesAgency (PMDA) as part of plans to further India’s presence in thelocal pharma market. “The PMDA is willing for the first time toopen an office outside of Japan, and would consider India as one of thedestinations,” the delegation revealed. G

MARKET NEWS


REGULATORY AFFAIRS

India is ‘committed’to EU trade dialogue

Guidance “providing information on the regulation, prescribing,dispensing and traceability of biosimilar medicines in Ireland” hasbeen launched by the country’s Health Products Regulatory Agency(HPRA). Primarily aimed at healthcare professionals “for the purposeof informing and assisting their decision-making processes”, theguidance covers topics including an explanation of the differencesbetween a biologic reference product and a biosimilar, biosimilars andsmall-molecule generics, regulatory requirements, and “how this takesaccount of specific nature of these medicines”.

The document also offers details on how biosimilars are developedand manufactured – as well as how they are regulated in the EuropeanUnion (EU) – followed by sections on extrapolating indications,traceability and interchangeability and substitution.

“The HPRA does not recommend that patients are switchedback and forth between a biosimilar and the reference medicalproduct,” the guidance says, advising a consultation betweenprescribers, pharmacists and procurement staff on which drug to use.

Welcoming the guidance, brand industry association the IrishPharmaceutical Healthcare Association (IPHA) said “continuingdevelopment of biologic medicines, including biosimilar medicines,creates choice for patients and clinicians, increased commercialcompetition and enhanced value propositions for individual medicines”.

Meanwhile, a report by an Irish cross-party parliamentarycommittee is calling for Ireland’s government to clarify whether itplans to introduce legislation on biosimilar interchangeability.

In its report, the Joint Committee on Heath and Children suggeststhat including biosimilars in the country’s High Tech Drug (HTD)scheme might help to control future drug costs. Furthermore, thegovernment should consider providing financial incentives forpharmacists to supply generics through the HTD scheme.

An online “reliable and accessible patient-focused resource” wouldhelp to tackle “misinformation on generic drugs”, the report proposes,while healthcare bodies should collaborate on an awareness campaignhighlighting the efficacy of generics. G

REGULATORY AFFAIRS

Ireland’s HPRA hasguide on biosimilars

Least developed countries (LDCs) must be granted a permanentwaiver from enforcing intellectual-property (IP) rules for medicines,US Senator and Democratic Presidential candidate Bernie Sandershas urged in a letter to the US chief trade representative.

Noting that the World Trade Organization (WTO) would decideby the end of October whether to grant such a waiver – and that thecurrent waiver was due to expire on 1 January 2016 – Sanders pointedout that Europe and the Vatican supported such an exemption.

The European Commission recently voiced its support for “anindefinite exemption” for LDCs from implementing IP rules forpharmaceuticals (Generics bulletin, 2 October 2015, page 15). Bysupporting LDCs’ call to be exempted from patent-term extensions, dataexclusivity and other IP provisions included in the WTO’s agreementon trade-related aspects of IP rights (TRIPS), the Commission sayssuch countries will have “easier access to cheaper medicines”.

As Generics bulletin went to press, no final decision had beenmade by the WTO’s TRIPS council. G

INTELLECTUAL PROPERTY

US is urged to back IP waiver

State legislation passed in California, US, on biologics has beenwelcomed by the US Generic Pharmaceutical Association (GPhA).“This bill allows for substitution of interchangeable biologics and avoidsmeasures that would hinder timely patient access to these medicines,”stated GPhA president and chief executive officer, Chip Davis.

Noting that 11 US states and Puerto Rico had in 2015 passedlegislation facilitating interchangeable biologic substitution at thepharmacy level, Davis said it was “vital to make sure that the legal andregulatory framework enables competition and timely access”. G

REGULATORY AFFAIRS

GPhA lauds law in California


AUS district court made “significant analytical errors” when itruled that Warner Chilcott and its partner Mayne Pharma didnot engage in “predatory conduct” to exclude generic doxycylinefrom the US market by repeatedly tweaking the formulation of theDoryx brand, according to an amicus brief filed by the US FederalTrade Commision (FTC).

As part of an appeal by Mylan against the ruling that was handeddown by the Pennsylvania district court earlier this year (Genericsbulletin, 24 April 2015, page 17), the FTC filed its brief insistingthat “in examining whether such conduct is unlawful, courts shouldaccount for the unique aspects of the pharmaceutical marketplace,including the nature of competition between branded pharmaceuticalproducts and their generic counterparts”.

Noting that originators could seek to avoid competition andpreserve monopolies by “combining minor product reformulations withefforts to damage or destroy the market for the original formulation”,the FTC insisted that such a ‘product hopping’ tactic could harmconsumers. “If a brand-name manufacturer tweaks its brand-nameproduct shortly before anticipated generic entry and begins eliminatingthe market for the original formulation,” the regulator observed, “itcan impede competition from would-be generic entrants.”

While emphasising that “the FTC takes no position on the ultimatemerits of this case”, the regulator took the view that “the district court’sbroad ruling effectively embraces a rule of nearly per se legality”.

“The district court held that a brand company may with impunitydestroy what is often the only means of generic distribution – automaticsubstitution – so long as generics remain hypothetically free to pursuenew and more costly distribution alternatives, such as directadvertising to physicians,” the FTC concluded. G

MARKET NEWS


REGULATORY AFFAIRS

FTC backs Mylan onUS ‘product hopping’

Terms of supplementary protection certificates (SPCs) in someEuropean Union (EU) member states could be extended by afew days after the Court of Justice for the EU (CJEU) confirmedthat SPC terms should be calculated from when an applicant wasnotified of a marketing authorisation being granted, not when theauthorisation was granted by a relevant authority.

A higher regional court in Vienna, Austria, had referred to theCJEU a case brought by Seattle Genetics over the correct durationof an SPC for Adcetris (brentuximab vedotin).

Austria’s Patents Office had set the SPC expiry date as 25 October2027, based on the European Commission’s implementing decisiongranting a marketing authorisation having occurred on 25 October 2012.But Seattle Genetics successfully argued that the expiry date shouldbe five days later on 30 October 2027, 15 years after its partner, Takeda,had been notified of the implementing decision on 30 October 2012.

Ruling that the ‘date of first authorisation’ identified in the SPCRegulation 469/2009 must be determined by EU rather than nationallaw, the CJEU said it was “clear that the holder of an SPC is entitledto market his product only from the date on which he is givennotification of the decision granting the marketing authorisation inquestion, not from the date on which that decision was adopted”.

Given the SPC Regulation’s objective of re-establishing “asufficient period of effective protection” to compensate for the timebetween patent filing and marketing the invention following regulatoryauthorisation, procedural steps between granting and notification of amarketing authorisation should not reduce the valid SPC term, the courtsaid, following the advice of its advocate-general (Generics bulletin,2 October 2015, page 16). Therefore, the Adcetris SPC should rununtil 30 October 2027. G


CJEU ruling may seeSPC term extended

Adecision by the health commission of Romania’s chamber ofdeputies to introduce a ‘differentiated calculation’ for generics ofthe country’s mandatory pharmaceutical clawback has been welcomedby local industry association APMGR. The draft law comes afterrepeated calls by APMGR to modify the clawback for generics firms.

Dragos Damian, president of APMGR, said the decision wouldmeet the needs of patients and local manufacturers while also helpingto prevent the disappearance from the Romanian market of affordablegenerics due to declining profitability. G

PRICING & REIMBURSEMENT

Romania eyes clawback move

South Africa’s Von Seidels has formed a joint venture with globalintellectual-property firm Rouse to create a joint venture offeringlegal services throughout Africa. Called Rouse Africa, the venturealready has an office in Namibia, and it is “working towards openinglocal offices in Cameroon, Nigeria, Kenya and other key Africancountries”. South Africa’s Von Seidels will continue to operate asbefore in its domestic market. G


Legal venture opens in Africa

Australia’s Department of Health is seeking feedback via an onlinesurvey on an implementation framework for its three-yearA$20 million (US$14.5 million) biosimilars awareness campaigndesigned to “improve awareness and confidence in biosimilarmedicines, for both health professionals and consumers”.

Reporting details of the framework for the campaign that was firstannounced earlier this year (Generics bulletin, 26 June 2015, page21), the Department of Health said that of the A$20 million infunding, A$6.5 million would be spent in 2015-16, A$6.7 million in2016-17 and A$7.1 million for the final 2017-18 financial year.

Noting that the project would be led by the Pharmaceutical BenefitsDivision (PBD), the department added that it was seeking understandingfrom stakeholders on topics including “their position on biosimilars”,“what they believe the issues and risks are for communication” and“what they believe the key messages for prescribers, pharmacistsand consumers should be”.

“The implementation framework will be used to inform thelonger-term development and implementation of the awareness project,”the Department of Health commented.

Meanwhile, Australia’s Therapeutic Goods Administration (TGA)has agreed to adopt European Union biosimilar product-specificguidelines on insulins, interferon beta and r-hFSH. G

REGULATORY AFFAIRS

Australia asks on awareness


South Africa is missing out on well over ZAR4 billion (US$300million) of annual savings by dispensing off-patent brands ratherthan generic alternatives, according to a study commissioned by SouthAfrica’s National Association of Pharmaceutical Manufacturers (NAPM).

Using claims data from more than 1 million medical-aid members,pharmacy benefit management organisation Mediscor assessed genericpenetration in South Africa as at 56%. However, originator drugs forwhich generic alternatives were available accounted for another 18%of the market, the study found.

“Based on data gleaned from IMS Health,” the NAPM pointedout, “every one percentage-point increase in the use of genericswould save consumers around ZAR270 million.” Converting allprescriptions for off-patent originals to generics would thus saveSouth Africa around ZAR4.86 billion.

Captured two-thirds of private maketIMS sales data, the association added, showed that generics

accounted for two-thirds of all items dispensed in South Africa’sprivate sector, but only two-fifths of the ZAR22 billion drugs bill.

Looking at a basket of the 200 medicines most commonlyprescribed within the private sector, the NAPM said generics’ discountto originals had risen to 56.1%.

“Since 2010, we have seen a steady increase in the cost advantageof generics over originator drugs,” commented the NAPM’s chiefexecutive officer, Vivian Frittelli. “Considering that production standardsand manufacturing costs for both original and generic medicines aresimilar, these findings are significant.”

The issue of generics pricing and discounts to brands had beenhighlighted by claims in a submission on private healthcare byDiscovery Health to South Africa’s Competition Commission thatalleged the price gap between generics and brands was “far narrower”in South Africa than in international markets at “around 33%”.

The NAPM noted that a recent Discovery Health publication hadfound that two-thirds of generics were priced at a 40% discount to thebrand, while “at least 48% of generics are priced at 50% or morebelow their originator equivalents”. G

MARKET NEWS


MARKET RESEARCH

South Africa missesZAR4bn in savings

Europe’s Unified Patent Court (UPC) could be hearing cases beforethe end of next year, the European Patent Office (EPO) haspredicted after seven member states – including France, Germany andthe UK – signed a protocol on provisionally applying an agreementon the institutional, financial and administrative provisions neededfor the court to operate.

According to the EPO, the protocol – which is set to be signedby other states in the near future – marks “another milestone towardsthe realisation of the UPC”. Moreover, it “clears the way to makeall the necessary legal and practical arrangements, including theappointment of judges for the court, well in advance”.

“This should ensure that the court is fully operational and readyto hear cases on the very day the agreement formally enters into force –expected towards the end of 2016,” the EPO stated, noting that theUPC being ready to operate was a pre-condition for Europe’s unitarypatent system to come into effect.

Benoît Battistelli, the EPO’s president, described the signing ofthe protocol as “great news for innovators, who will benefit from thissimplified and better-value patent system”. He noted that eight out ofthe required 13 member states had already ratified the UPC agreement,while several other countries were finalising the ratification process.

After Italy formally acceded to the unitary patent package on30 September, 26 European Union (EU) member states are nowparticipating in the unitary patent scheme. G


Unified Patent Courtis closer to fruition

Price cuts and reference-pricing measures in Italy are putting“unbearable” pressure on the generics industry, according to localindustry association Assogenerici. Along with pressure caused by arecently-introduced system of reference pricing based ontherapeutically-equivalent groups, the association says that price cutsare “jeopardising the economic sustainability of our industry and itsrole in creating market competition”. This, Assogenerici says, comes“despite the absence of significant increases in the use of generic drugs”.

“We need to make it clear,” said Assogenerici president EnriqueHäusermann, “that if we do not change course, Italy will become anunsustainable market for generics.” Margins were now “euro centsper pack”, he outlined. G


Italian group warns over cuts

Abiosimilars workshop hosted by the European Commission’sDirectorate-General for the Internal market, Industry,Entrepreneurship and Small to Medium Enterprises on 6 Octobermet with approval from all sides of the pharmaceutical industry.

In a joint statement, the European Generic and Biosimilar medicinesAssociation (EGA), the European Federation of PharmaceuticalIndustries and Associations (Efpia) and the European Association forBio-industries (EuropaBio) said the forum would “increase the levelof understanding” about the benefits of biosimilar competition. G

BIOLOGICAL DRUGS

EU industry hails workshop

Interested parties have until 18 November to register to participate ina public meeting that the US Food and Drug Administration (FDA)is hosting on 18 December to discuss re-authorising the Biosimilar UserFee Act (BsUFA) for the agency’s fiscal years from 2018 through to2022. The meeting will take place in Silver Spring, Maryland, US.

The current legislative authority for collecting BsUFA feesexpires in September 2017. Without new legislation, the agency willthereafter be unable to collect user fees to fund its biosimilars reviewprocess. Up to 19 January 2016, the FDA is inviting public commentson its BsUFA performance goals covering the biosimilar applicationprocess, including development meetings as well as reviews of dossiers.

The FDA said it wanted “to hear stakeholder views as we considerwhether to retain, change or discontinue the current BsUFAperformance goals in the next BsUFA” before the agency begannegotiations with industry on re-authorising the fee programme. G

REGULATORY AFFAIRS

FDA holds user fee meeting


MARKET NEWS


Proposed provisions for biosimilar reimbursement in the US shouldbe put on hold until the US Food and Drug Administration (FDA)has finalised regulations and the biosimilars market is “safe and stable”,according to a letter sent by 20 senators to the US Centers forMedicare and Medicaid Services (CMS).

Applauding the letter, the US Biosimilars Forum noted that abipartisan group of Representatives had sent a similar letter in July.“The House, Senate and countless stakeholders have now made cleartheir concerns that multiple biosimilars being grouped and issued thesame J-code for Medicare reimbursement purposes could result infewer biosimilars being introduced in the US,” warned the BiosimilarsForum’s policy advisor, Michael Werner. G

FDA – the US Food and Drug Administration – has issued finalguidance on controlled correspondence relating to generic drugdevelopment. Along with a definition of what inquiries are consideredby the agency to be controlled correspondence for the purposes ofmeeting its commitments under the Generic Drug User FeeAmendments (GDUFA), the document details the “information thatrequestors can include in a controlled correspondence to facilitateFDA’s consideration of and response to a controlled correspondence”.It also outlines information that will be provided by the FDA.

GERMAN potential generics savings described in an annualmedicines report released by leading local health insurance fundthe AOK are “from another planet”, according to Bork Bretthauer,managing director of German generics and biosimilars industryassociation Pro Generika. Bretthauer said the mooted savingspotential of C2.5 billion (US$2.8 billion) was greater than the entire2014 net ex-factory sales by German generics players of C2 billion.

EMA – the European Medicines Agency – is adopting a formalframework for interaction with industry associations. Theframework aims to facilitate the exchange of views and promotedialogue, improve delivery of efficient and timely communication,enhance understanding of the European Union medicines regulatoryframework by pharmaceutical companies and increase transparencyof the organisation’s engagement with industry stakeholders.

AUSTRALIA’s government has asked the country’s ProductivityCommission to undertake a 12-month public enquiry into theAustralian intellectual-property (IP) system. Initial submissionsfrom interested parties are due by 30 November, with the Commissionto produce its final report in August next year. In its wide-rangingreview, the Commission is to consider potential IP changes in lightof “incentives for innovation and investment”, as well as “Australia’sinternational trade obligations”.

HEALTH CANADA is implementing a three-year pilot scheme“to explore a step-wise review approach to complement thesubsequent-entry biologic (SEB) development process”. Duringthe pilot, a SEB sponsor may request a scientific advice meetingin order to receive advice from the Canadian regulator on itscomparability package early in the SEB development process.

GPhA – the US Generic Pharmaceutical Association – is urging thepassage of the Fair Access for Safe and Timely (FAST) GenericsAct in the US. Chip Davis, GPhA president and chief executiveofficer, believes the legislation will strengthen the Food and DrugAdministration’s approved Risk Evaluation and Mitigation Strategies(REMS), while simultaneously reducing abuse of REMS by brandfirms preventing generic firms from gaining access to samples.

EDQM – the European Directorate for the Quality of Medicines –has released a revised version of its certification policy documenttitled “content of the dossier for chemical purity and microbiologicalquality”. The aim of this document is to provide Certificate ofSuitability applicants guidelines for preparing the authorisation dossier.

FDA – the US Food and Drug Administration – has warned the USCongress that devoting resources to responding within statutorydeadlines to citizen petitions on pending generic, hybrid or biosimilarapplications is diverting attention from the agency’s other tasks. Itexpressed concern that the statute was “not discouraging the submissionof petitions that are intended primarily to delay the approval ofcompeting drug products and do not raise valid scientific issues”. G

IN BRIEF


Senators seek payment hold

Pro Biosimilars, the working group set up within Germany’s genericsand biosimilars industry association, Pro Generika, has held its firstexpert symposium in Berlin. Industry leaders were joined byrepresentatives from insurance funds and doctors, as well asmanagement consultants, to discuss the operating framework neededfor biosimilars to succeed. At the same time, the working group has setup a website at probiosimilars.de from which several publicationscan be downloaded. G

INDUSTRY ASSOCIATIONS

Pro Biosimilars makes strides

Intellectual-property provisions in the agreed Trans-Pacific Partnership(TPP) trade agreement have met with a general welcome fromgenerics and biosimilars associations in the signatory countries. Butoriginators’ bodies and humanitarian groups are far less impressed.

Australia’s Generic and Biosimilar Medicines Association (GBMA)welcomed “the news that Australia has not agreed to extend the data-exclusivity period for medicines” following a deal to require aminimum of five years of data protection for all pharmaceuticals,including biological drugs. But local originators’ body MedicinesAustralia called the agreement “a missed opportunity”.

The Canadian Generic Pharmaceutical Association (CGPA)praised assurances from the country’s government that the final TPPtext would not require changes to local intellectual-property laws forpharmaceuticals beyond existing trade-deal commitments.

In the US, the Generic Pharmaceutical Association (GPhA) andits Biosimilars Council applauded the TPP negotiators for balancinginnovation and access, but originators’ bodies PhRMA and BIOexpressed disappointment that US negotiators had not secured 12 yearsof exclusivity for biologics.

Despite the lack of 12-year biologics protection sought byoriginators, humanitarian group Médecins Sans Frontières (MSF)described the TPP as “the worst trade agreement for access to medicinesin developing countries” ever struck. And US-based lobbying groupPublic Citizen said supplementing a minimum five-year term withthree years of other exclusivities “will likely cost lives”. G

TRADE AGREEMENTS/INTELLECTUAL PROPERTY

TPP protection termselicit mixed response


Prescribing quotas and financial incentives are not appropriate meansto drive uptake of biosimilars in Europe, according to ‘policyprinciples for off-patent biologic medicines’ released by the EuropeanFederation of Pharmaceutical Industries and Associations (Efpia).

Discussing market mechanisms, the orignators’ body says: “Thereare a number of biosimilar uptake measures that have been implementedin Europe, such as quotas and financial incentives/sanctions, whereEfpia strongly opposes the way in which they have been implementedas they undermine two key principles outlined in this document.”

Firstly, the association argues, such measures restrict a physician’sability to determine which medicine a patient receives. And secondly,“they do not foster sustainable competition in a non-discriminatorymanner”. “Competition should be non-discriminatory and not createany bias towards either originator or biosimilar medicines,” it stresses,adding that this applies to information for professionals and patients.

“Purchasing and procurement practices must always involve amedical committee,” Efpia proposes, warning against tenders that focussolely on price or that include a winner-takes-all scenario.

Any uptake measures implemented should, the associationmaintains, “explicitly retain doctors’ freedom to prescribe” and createa “level playing field” between biosimilars and off-patent originaldrugs, with potential savings not being retained in the distributionchannel, but rather being “passed on to payers and patients”.

Furthermore, uptake measures should “propose a level of volumeshift in the market that is, at a maximum, in line with a policy ofnaive patient initiation”, while “clinical judgement” should alwaysprecede the “overall value proposition” of individual products whendetermining which treatment to use.

Efpia – which “fully supports the creation of competitive, efficientand sustainable off-patent biologic markets” – acknowledges that allbiological drugs, including biosimilars, approved by the EuropeanMedicines Agency (EMA) are “safe, effective and of high quality”.

In its principles, the industry association identifies three keycharacteristics that it says should shape policies on biologic drugs.Firstly, it argues, product-level traceability based on a minimum ofrecording the brand name, active substance and batch number areessential for pharmacovigilance. Secondly, “interchangeability and/orsubstitutability cannot be assumed for biosimilars”, as “little is knownto date about the potential long-term clinical consequences ofrepeatedly switching or substituting one biologic to another”.

Thirdly, the US$100-US$200 million and eight to 10 years requiredto develop a biosimilar should result in fewer market entrants and alower level of price erosion than in the small-molecule arena.

“Such features may limit the applicability in biologic markets ofso-called ‘demand-side measures’ that have been used to increasecompetition and generate price erosion in small-molecule markets,”Efpia maintains. The association supports making public list pricesof off-patent medicines, but insists “confidentiality of net prices mustbe preserved”. Doctors, it says, can “adopt ‘economic’ prescribingbehaviour without being forced to write prescriptions for biosimilars”.

“The prescribing physician should always have the option todesignate which biological product should be dispensed to the patient,”it argues, adding that “prescribing guidelines and electronic prescribingsystems should not undermine doctors’ freedom to prescribe”.

Prescribing by international non-proprietary name (INN) is “notan appropriate policy”, and pharmacy-level substitution is “not anacceptable practice”, for biologic drugs, Efpia maintains. G

MARKET NEWS


BIOLOGICAL DRUGS

Quotas and pay-outsare opposed by Efpia

The British Generic Manufacturers Association (BGMA) says it“stands ready to play its part” to resolve any “systemic issues” thatcurrently prevent generic manufacturers from marketing productsfor the non-patented indications of patent-protected brands, whilerespecting valid medical-use patents.

Speaking in light of UK National Health Service (NHS) guidanceissued earlier this year concerning Pfizer’s Lyrica (pregabalin) thatinstructs that the analgesic and epilepsy treatment should only beprescribed for neuropathic pain under the Lyrica brand name (Genericsbulletin, 13 March 2015, page 19), the BGMA insisted it was“inappropriate for patent holders to intercede with others in the supplychain in a way which may reduce the uptake of the generic medicinefor non-patented indications and so diminish the benefits whichwould otherwise be enjoyed by patients, the NHS and taxpayers”.

Meanwhile, the association noted that, under the EuropeanMedicines Agency’s (EMA’s) guidance on generics manufacturersdeleting patented indications from the summary of productcharacteristics (SmPC) and patient information leaflet (PIL), it wouldalso be “inappropriate for patent holders to use the inclusion ofsafety sections – even where they relate only to the patented indications– in the generic product’s SmPC as evidence of patent infringement”.

UK Justice Richard Arnold recently noted that the NHS mightchange its guidance concerning Lyrica after ruling that six key claimsof the UK part of Pfizer’s European method-of-use patent 0,934,961were invalid on the grounds of insufficiency (Generics bulletin, 2October 2015, page 27). G

REGULATORY AFFAIRS

BGMA voices stanceon secondary patents

Several positions adopted within policy principles on off-patentbiological drugs just published by the European Federation ofPharmaceutical Industries and Associations (Efpia) have beenchallenged by the European Biosimilars Group (EBG) affiliated withthe European Generic and Biosimilar medicines Association (EGA).

In its principles, Efpia maintains that “interchangeability and/orsubstitutability cannot be assumed for biosimilars”. “Little is knownto date about the potential long-term clinical consequences of repeatedlyswitching or substituting one biologic to another,” the originators’body claims, taking the position that biosimilars should only be givento naive patients (see opposite).

The EBG takes a different position. “Once approved astherapeutically equivalent, biosimilar medicines are interchangeablewith their reference products under the supervision of a healthcareprovider, taking into account individual patient factors,” it insists.

“Switching biological medicines is common and happens on a verylarge scale,” the EBG states. “Decisions on interchangeability have beenmade after thorough reflection by national competent authorities formedicines in Europe,” it points out, highlighting positions on switchingadopted by regulators in Finland, Germany and the Netherlands.

On pharmacovigilance, the EBG is keen to emphasise that thecurrent issue of identification and traceability is not related to thenaming of the biological medicines. “In over 90% of all adverse drugreaction reports, the name of the biological medicine is includedcorrectly,” it stresses, noting the importance of batch numbers. G

BIOLOGICAL DRUGS

EBG questions Efpia position


Abbreviated new drug applications (ANDAs) will now be approvedby t

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