company news eu asksusfor gmp reciprocal recognition · manufacturing facility located outside the...

3 June 2016

Three elements will help Jubilant to grow 2Saneca stays strong despite Suir sell-off 2Sun faces questions over 3prices in the USRemedica deal gives Ascendis a platform 3Torrent to invest to 4file up to 20 ANDAsCipla aims to focus on 15-20 countries 5Aurobindo’s actions give profit in Europe 5

MARKET NEWS 6

Alifar sets agenda for Latin America policy 6Dutch central buying would 6not cut costsUK implements cuts on pharmacy prices 8EU Parliament votes for SPC manufacture9Sandoz strikes back over 9BPCIA pathway

PRODUCT NEWS 12

Canada rejects deal in gatifloxacin fight 12Sandoz’ rituximab is 12accepted by the EMASamsung Bioepis has 13nod on EU infliximabEnoxaparin appeal queries safe harbour 13Hospira and Sun get EU bortezomib nods 14Dutch court denies injunction on Sandoz 15US Remicade rival is in 15sight for Samsung

FEATURES 16

Consolidation continues to 16shape the global hierarchy

Lupin counts on US pipeline 19

REGULARS

Events – Our regular listing 8Price Watch UK – UK pricing trends 12People – Valeant’s Stolz steps 20down from company

COMPANY NEWS 2

PPUUBBLLIISSHHEEDD WWEEEEKKLLYYNext issue – 10 June 2016

Standards of good manufacturing practice (GMP) and related inspections could bemutually recognised between European Union (EU) and US authorities for facilities

worldwide, under plans set out in an “EU proposal for an annex on medicinal products”as part of Transatlantic Trade and Investment Partnership (TTIP) bilateral negotiations.Removing “duplications of inspections of manufacturing facilities” could be achieved“through the mutual recognition of their manufacturing facilities inspections”.

The proposed annex states: “A party shall accept a certificate – or corresponding USinformation – of GMP compliance issued by a competent authority of the other party, asdemonstrating that the manufacturing facility that is covered by the certificate and located inthe territory of that party complies with GMP, or corresponding US information.” Moreover, theannex also states that “a party may accept a certificate of GMP compliance – or correspondingUS information – issued by a competent authority of the other party with respect to amanufacturing facility located outside the territory of any of the parties”.

The proposal calls on the EU and US to collaborate on “strengthening, developing andpromoting the adoption and implementation of internationally agreed scientific or technicalguidelines” and to “promote dialogue on scientific matters and exchange of information betweentheir competent authorities”, including for generics and biosimilars. This includes exchangingregulatory information – “including confidential and trade secret information” – related toauthorising and supervising medicines, including data on GMP inspections and pharmacovigilance.A working group to monitor regulatory co-operation is envisaged to review progress annually.

The annex also urges the EU and US to “further harmonise their respective requirementsand procedures applicable to the authorisation of medicinal products”.

The European Federation of Pharmaceutical Industries and Associations (EFPIA) welcomedthe “opportunity to strengthen the transatlantic pharmaceutical marketplace”. Noting the “goodprogress made to date in advancing a mutual-recognition agreement on GMP inspections”,EFIPA however said “we fail to see additional and necessary regulatory proposals that wouldallow TTIP to deliver ambitious outcomes once it enters into force”. G

EU asks US for GMPreciprocal recognition

UK authorities should cut National Health Service (NHS) expenditure by introducing bothgeneric and therapeutic substitution, the country’s Pharmaceutical Services Negotiating

Committee (PSNC) has proposed in a counter-proposal to government plans for communitypharmacies that include a £170 million (US$249 million) funding reduction (see page 8).

Allowing community pharmacists to substitute cheaper generics for prescribed brands onthe basis of a nationally agreed list would, the PSNC acknowledges, require pharmacists toreassure patients to ensure they accepted the dispensed medicine and adhered to the therapy.A similar substitution list introduced in Ireland in 2013 (Generics bulletin, 7 June 2013, page12) had generated “significant savings”, it observed.

Primary-care providers in the UK are obliged to dispense the brand if specified on theprescription. However, according to the latest government figures for prescriptions dispensedin England, 84.1% of prescriptions in 2014 were written by international non-proprietary name(INN), as this is considered to be good practice and is the default setting for most prescribingsoftware. Thus, pharmacy substitution would have a limited effect.

On therapeutic substitution, the committee is proposing that pharmacists recommend alternativeproducts to prescribers, “based on a list of ‘costly’ medicines with suitable alternatives”. G

UK pharmacists seek substitution

Gen 3-6-16 Pg. 1_Gen 18/11/05 Pg. 1 01/06/2016 17:39

Slovakian active pharmaceutical ingredients (APIs) specialist Sanecainsists the entry into provisional liquidation of its Suir Pharma

contract-manufacturing subsidiary in Clonmel, Ireland, will have“minimal impact on Saneca’s growing business in Hlohovec, Slovakia”.Suir’s management met with the firm’s 134 employees on 17 May toadvise them that the company had gone into liquidation due to itsfinancial insolvency (Generics bulletin, 27 May 2016, page 3).

“The insolvency has been caused by a number of issues, startingwith a significant and unexpected downturn in sales to Suir Pharma’skey US customer over the last year and recent quality issues relatedto a key raw material which stopped the firm’s ability to continue tosupply certain European customers in recent months,” Saneca explainedto Generics bulletin. “These events, coupled with the very competitivecontract-manufacturing environment that is present worldwide andongoing price pressure from existing customers, have all contributedto this unfortunate situation.”

“After investing significant amounts of money since acquisitionof the site in Ireland and based on the ongoing expected future losses,the shareholder was forced to withdraw any future funding, as SuirPharma did not have a viable future,” Saneca added. Liquidator MichaelMcAteer from Grant Thornton is seeking a buyer for the Clonmel siteand for Suir’s assets, including its raw materials and finished goods.

“Saneca Pharmaceuticals operates independently and has a strongtrack record of profitability and an impressive pipeline of business withvarious new and existing customers,” the Slovenian company stressed.“The Hlohovec plant has a strong future with its leading position inopiates and broad offerings of services to the pharmaceutical industry.” G

COMPANY NEWS

2 GENERICS bulletin 3 June 2016

3 June 2016 Issue 265

Editor: Aidan FryDeputy Editor: DavidWallaceAssistant Editor: Dean RudgeProduction Controller: Debi MinalProduction Editor: Jenna MeredithDirector of Subscriptions: Val DavisGroup Sales Manager: Rob CoulsonAwards Manager: Natalie CornwellManaging Director: Mike Rice

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BUSINESS STRATEGY

Saneca stays strongdespite Suir sell-off

Generics and radiopharmaceuticals launches are among threeelements that are set to drive growth for Jubilant Life Sciences’

Pharmaceuticals business during its financial year ending March 2017.The Indian firm is also anticipating growth in its Rest of the World

business, and plans to “ramp up” operations at its sterile injectablesand oral-solid contract-manufacturing facilities.

In Jubilant’s financial year ended 31 March 2016, Pharmaceuticalssales rising by 14% to Rs30.6 billion (US$457 million) helped the firmto avoid a turnover decline, as Life Science Ingredients sales slid by13% to Rs27.5 billion (see Figure 1). More than seven-tenths ofJubilant’s Pharmaceuticals sales came in the US and Canada. In the US,Jubilant submitted one filing and obtained eight approvals during itsfinancial year. The firm currently has 28 abbreviated new drugapplications (ANDAs) pending approval.

Jubilant’s earnings before interest, tax, depreciation and amortisation(EBITDA) climbed by 76% to Rs12.9 billion on lower expenses. G

BUSINESS STRATEGY/ANNUAL RESULTS

Three elements willhelp Jubilant to grow

Business Annual sales Change EBITDAsegment (Rs millions*) (%) margin (%)

US/Canada 21,890 +11 –Europe/Japan 4,400 +14 –India 1,420 +16 –Rest of World 2,840 +35 –Pharmaceuticals 30,550 +14 29.1

Life Science 27,480 -13 16.3

Jubilant Life Sciences 58,480 ±0 22.3**

* rounded to nearest Rs10 million** includes Rs450 million of unallocated corporate expenses

Figure 1: Breakdown by business segment of Jubilant Life Sciences’ sales andearnings before interest, tax, depreciation and amortisation (EBITDA) margin inits financial year ended 31 March 2016 (Source – Jubilant)

MEDICINES FOR EUROPE has joined the global ‘Fight the Fakes’anti-counterfeiting campaign, teaming up with over 30 partners.G

IN BRIEF

Gen 3-6-16 Pgs. 2-20_Layout 1 01/06/2016 17:38

Ascendis Health says its Pharma-Med pharmaceuticals divisionwill be transformed into an “international pharma player” after

striking a deal worth up to C335 million (US$374 million) for Cypriotgenerics developer Remedica.

Founded in 1960, Limassol-based Remedica currently “suppliesmore than 300 products from over 200 active pharmaceutical ingredients(APIs)” to around 100 countries, representing around 2,500 marketingauthorisation licenses worldwide.

The firm manufactures these products from a campus of fivelocal facilities that “in aggregate span over 40,000 sq m”, includinga “newly-constructed C15 million oncology facility”.

The Cypriot firm’s portfolio includes “a wide range of therapeuticcategories”, such as anti-infectives and analgesics, as well ascardiovascular, diabetes, central nervous system and gastrointestinaldrugs. Remedica’s manufacturing capabilities moreover cover dosageforms including tablets, capsules, creams, ointments, aerosols,pessaries, suppositories, liquid syrups and oral powders.

“Remedica has a strong pipeline of products,” Ascendis added,“particularly oncology and HIV products, which are expected to belaunched over the next three years.” The Cypriot firm had achieved a“solid financial performance with an earnings before interest, tax,depreciation and amortisation (EBITDA) margin of over 25% in 2015”.

The South African firm has agreed to pay an initial fee of C260million for Remedica, comprising C170 million up front and a furtherC90 million that is deferred for three years. The value of the deal couldreach C335 million, however, with up to C75 million payable basedon [Remedica’s] “average EBITDA achieved for the three financialyears post completion” of the transaction.

The proposed transaction comes after Ascendis revealed earlierthis year that it was evaluating opportunities to acquire “platformcompanies” in Europe, as well as in Australia (Generics bulletin,18 March 2016, page 5). The Johannesburg-based firm had establishedan overseas presence, and forayed into Europe, last year by payingZAR210 million for a 49% stake in Spanish generics and OTC playerFarmalider (Generics bulletin, 1 September 2015, page 4).

Shortly after, Ascendis expanded its domestic presence throughan agreement to acquire the pharmaceutical business of South Africa’sAkacia Healthcare (Generics bulletin, 9 December 2015, page 2).The deal recently received the green light after “all outstandingconditions” were met (Generics bulletin, 22 April 2016, page 3).

“Remedica provides a credible platform for furtherinternational expansion and growth in the generic pharmaceuticalindustry in both Europe and emerging markets,” Ascendis commented,“through its existing product portfolio and pipeline, as well as itsmanufacturing capabilities.” These will offer “opportunities forimportant synergies, which will be leveraged” from the Akacia andFarmalider acquisitions.

“With [Remedica’s] diversified portfolio of products, markets andclients, strong pipeline of new products, and synergies with theAscendis Pharma business in South Africa and Spain,” Ascendis added,“Remedica is well positioned to deliver strong earnings growth.”

In a separate transaction, Ascendis has also struck a deal worthup to C170 million for sports nutrition firm Scitec, a global player “thatsells its products in nearly 90 countries worldwide”.

Discussing the transactions together, Ascendis said that it had nowestablished a “sizeable European platform”, which would “supportfurther international growth and expansion into new geographies”. G

COMPANY NEWS

3GENERICS bulletin3 June 2016

MERGERS & ACQUISITIONS

Remedica deal givesAscendis a platform

Annual sales Change Proportion(Rs millions) (%) of total (%)

US 135,170 -1.5 48India 72,538 +8.9 26Emerging Markets 35,843 -4.0 13Rest of World 21,618 -7.3 8Formulations 265,169 +0.3 94

Bulk Drugs 14,025 +41.5 5

Others 3,503 – 1

Sun Pharma 282,697 +3.2 100

Figure 1: Breakdown by region and business of Sun Pharma’s sales in itsfinancial year ended 31 March 2016 (Source – Sun Pharma)

Sun Pharma has received a subpoena from the US Department ofJustice’s (DoJ’s) antitrust unit seeking documents “relating to

corporate and employee records, generic pharmaceutical products andpricing, communications with competitors and others regarding thesale of generic pharmaceutical products”.

Noting in a disclosure to the Bombay Stock Exchange (BSE) thatit was “currently responding to the subpoena”, the Indian firmcommented that the summons was “unlikely to have an material adverseimpact on the consolidated operations or consolidated financial resultsof the company”. “We have given a notice to the stock exchange, andI do not think at this current stage we have anything more to share withyou than that,” Sun’s managing director, Dilip Shanghvi, told investorsas the firm reported its full-year financial results for the year ended31 March 2016. A clear timeline could not yet be established, he said.

Sun joins companies including Mylan (Generics bulletin, 8 January2016, page 12) and Valeant (Generics bulletin, 15 April 2016, page 2)to face questioning over the pricing of its generic drugs in the US.

Meanwhile, Shanghvi said moves to integrate Ranbaxy were“on track”, and the firm moreover expected “to have one [of the fourdeficient] facilities offered for US re-inspection…sometime thisyear”. Sun is currently tackling US deficiencies at Ranbaxy’sIndian plants in Mohali, Dewas, Paonta Sahib and Toansa.

In Sun’s 2016 financial year the firm’s US sales slid by 1.5% toRs135 billion (US$2.00 billion), amounting to almost half of groupthat sales that advanced by 3.2% to Rs283 billion (see Figure 1). Thisfollowed ongoing supply problems arising from the firm’s deficientfinished-dose facility in Halol, India, along with pricing erosion.

Midway through last year, Sun issued a sales and profit warning,stating that it expected group turnover to stall or decline, while profitswould be “adversely impacted” by Ranbaxy integration costs(Generics bulletin, 7 August 2015, page 8). The firm reported apre-tax profit that was 5.7% higher at Rs67.7 billion.

During its 2016 financial year, Sun filed 22 abbreviated new drugapplications (ANDAs) and obtained 14 ANDA approvals. The firmnoted that it had 159 “product filings” awaiting FDA approval, whichincluded 13 tentative approvals.

Meanwhile, during its financial year ending March 2017, Shanghviforecasted, propelled by “traction in all parts of our business”, overallconsolidated sales would increase by 8-10%, while research anddevelopment costs would be approximately 9% of group sales as thefirm looked to build its US specialty business. G

PRICING & REIMBURSEMENT/ANNUAL RESULTS

Sun faces questionsover prices in the US

Gen 3-6-16 Pgs. 2-20_Layout 1 01/06/2016 17:38

COMPANY NEWS


Torrent says it will ramp up its research and development spendingas part of plans to file between 15 and 20 abbreviated new drug

applications (ANDAs) during its financial year ending March 2017.Noting that the Indian firm’s ANDA filings goal was currently

“on track”, Torrent’s executive director for international business,Sanjay Gupta, said Torrent’s research and development costs as apercentage of sales would rise to around 8% for 2017 – double theless than 4% reported for the firm’s 2016 financial year. “So if youlook at it in absolute numbers the research and development cost willgo up by around 40% compared to 2014-15,” forecasted Torrent’svice-president of finance, Sudhir Menon.

Torrent currently has 14 filings pending US Food and DrugAdministration (FDA) approval, holds six tentative approvals, and,moreover, has 121 pipeline projects under development.

Meanwhile, the firm is eyeing around 10 US launches during itscurrent financial year, including a generic version of AstraZeneca’sCrestor (rosuvastatin) blockbuster. The “bulk” of these proposedlaunches – which are all oral-solid dosage formulations – would beseen by the end of calendar 2016, Gupta noted.

Furthermore, Torrent revealed, the FDA last month had inspectedthe firm’s “flagship” manufacturing facility in Indrad, Gujarat, whichresulted in “two to three minor observations”. “Hopefully, we will getthe establishment inspection report (EIR) a few months from now,”

Gupta said. Production recently commenced at Torrent’s major newfacility in Dahej, Gujarat, after Torrent earlier this year obtained anEIR for the site (Generics bulletin, 25 March 2016, page 5).

In its 2016 financial year, Torrent’s group turnover climbed bymore than two-fifths to Rs66.8 billion (US$991 million) in the wake ofa significant sales spurt in the US. Turnover in the market more thantrebled to Rs26.7 billion, following five US launches during the year,including a rival to Otsuka’s Abilify (aripiprazole) blockbuster, astotal Unbranded Generics sales more than doubled to Rs34.5 billion.

Meanwhile, in Torrent’s domestic market turnover advanced by13% to Rs18.3 billion, as the firm in January launched an alternativeto Humira (adalimumab) under the fantasy name Adfrar. This risehelped offset lower sales in Brazil (see Figure 1) as total BrandedGenerics sales moved ahead by 3% to Rs26.3 billion.

Torrent’s earnings before interest, tax, depreciation and amortisation(EBITDA) soared by 129% to Rs29.3 billion. G

XELLIA PHARMACEUTICALS has begun building a centralisedlaboratory services building near its active pharmaceutical ingredient(API) manufacturing facility in Budapest, Hungary. The Danish anti-infectives specialist is investing US$10 million into the 3,000 sq msite, which is slated for completion “in summer 2017”, and throughwhich Xellia “intends to extend its highly-skilled team with up to 80new roles in manufacturing, product testing and quality assurance”.

INDOCO REMEDIES has obtained an establishment inspectionreport (EIR) from the US Food and Drug Administration (FDA) forits Goa plant II sterile and solid dosages facility, pursuant to aninspection by the agency in July last year. Earlier this year, the USagency issued an EIR for another of the Indian firm’s manufacturingfacilities in Goa – its plant I solids, semi-solids and liquids site –following an inspection in October 2015 (Generics bulletin, 1 April2016, page 2).

BASF has agreed to sell its Kollicoat immediate-release coatingsystems product line to US-based specialty excipients providerColorcon. Subject to “review of the Brazilian competition authorities”,the transaction includes the “current customer business, inventoryand relevant know-how”. “Both BASF and Colorcon look forwardto the opportunity to expand the cooperation between both companiesin the film-coating area,” the firms said, noting that they had initiallyallied over the German chemical producer’s Kollicoat line inOctober 2014.

COHERUS BIOSCIENCES is looking to raise up to US$63 millionthrough a public offering of 3.5 million shares priced at US$18.00per share. The US pure-play biosimilars developer says it “intends touse the substantial majority of the net proceeds from this offeringto fund manufacturing and related activities for late-stage products”,while remaining proceeds will be used “for working capital and othergeneral corporate purposes”. Coherus became a public companythrough an initial offering of its shares towards the end of 2014(Generics bulletin, 3 October 2014, page 3).

TAI HENG has received a warning letter from the US Food andDrug Administration (FDA) against its active pharmaceuticalingredient (API) manufacturing facility in Shanghai, China. Currentgood manufacturing practice (cGMP) violations cited by the agencyfollowing its inspection in May last year include a failure to properlyinvestigate out-of-specification results, to prevent unauthorisedaccess to data, and “to record activities at the time they are performed,and destruction of raw data”.

MICRO-MACINAZIONE – the Swiss active pharmaceutical ingredient(API) micronisation specialist – has bolstered its existing storagecapacity by establishing a 500 sq m warehouse at its base inMolinazzo di Monteggio, Ticino, “to meet the growing volume oforders”. Local regulator Swissmedic in May officially inspected thewarehouse, which “will hold incoming materials as well as alreadymicronised, highly-potent substances and cytotoxic products”.

VECTURA – the UK respiratory specialist – has agreed to collaboratewith US firm Propeller Health “to develop inhalers that combineVectura’s proven dry-powder inhaler technology with Propeller’sUS Food and Drug Administration- (FDA-) cleared digital healthplatform”. “The initial focus of the collaboration will be thedevelopment of an add-on sensor for Vectura’s lever-operated multi-dose inhaler,” the firms announced, revealing that they were “alsodiscussing additional connected strategies for other proprietaryrespiratory devices in Vectura’s pipeline”. G

IN BRIEFBUSINESS STRATEGY/ANNUAL RESULTS

Torrent to invest tofile up to 20 ANDAs

Annual sales Change Proportion(Rs millions*) (%) of total (%)

US 26,720 +221 40Others 7,730 +3 12Unbranded Generics 34,450 +118 52

India 18,250 +13 27Brazil 5,060 -16 8Others 3,020 -12 5Branded Generics 26,330 +3 39

Contract manufacturing/other 5,990 +17 9

Torrent Pharma 66,760 +43 100

* rounded to the nearest Rs10 million

Figure 1: Breakdown by region of Torrent Pharmaceuticals’ sales in its financialyear ended 31 March 2016 (Source – Torrent)

Gen 3-6-16 Pgs. 2-20_Layout 1 01/06/2016 17:38

Cipla intends to focus on 15 to 20 core countries as it looks torationalise its operations in Europe and emerging markets. “We

need to simplify the way we do business,” acknowledged the Indiancompany’s chief operating officer, Umang Vohra.

Vohra said Cipla was transitioning its operations in severalEuropean countries from a direct-to-market to a more profitablebusiness-to-business supply model. In emerging markets, the group’sfocus would, he said, be on reducing complexity and “prioritisinginvestments in markets where we are in a leadership position”. Cuttingout “fringe markets” that did not contribute material sales would makeit easier for the group to support its US operation that it expandedsignificantly in February this year by closing a US$550 million deal forInvaGen and Exelan (Generics bulletin, 26 February 2016, page 7).

Recent respiratory launches – including fluticasone in Germany,Hungary and Spain, fluticasone/salmeterol in the Netherlands,mometasone in Austria and Portugal, and ipratropium/salbutamolrespules in Belgium – helped Cipla to increase its European turnoverby 30% on a local-currency basis to US$92 million in its financialyear ended 31 March 2016.

Respiratory sales ahead by a fifth contributed to Cipla’sInternational business growing by 14% to US$523 million, or around aquarter of group turnover that advanced by 20.6% to Rs137 billion(US$2.04 billion). The firm said it had benefited from a “resurgencein partnership-led markets with 8% growth”. Growth of over 20%from its chronic obstructive pulmonary disorder (COPD) portfoliocontributed to 5.9% growth to Rs51.1 billion in Cipla’s domestic sales.

A 60% rise in tender sales, as well as a 14% sales increase in theprivate sector, propelled South African turnover up by 25% to ZAR3.27billion (US$209 million). Active pharmaceutical ingredient (API)exports climbed by 22.5% to Rs7.78 billion (see Figure 1).

Including around a 40-day contribution from InvaGen and Exelan,North American sales more than doubled to US$321 million as Ciplabenefited from supplying esomeprazole to Teva. Vohra said Cipla’srecent US launches under its own label, such as of celecoxib andnadolol, were performing strongly.

Noting that 78 of the 168 abbreviated new drug applications(ANDAs) that Cipla had filed to date were awaiting final approval,Vohra said the US operation would aim to file 20-25 ANDAs duringits current financial year and to launch around 15 products.

Cipla – which has just got US clearance to conduct a safety andtolerability study in healthy volunteers for its CBT124 bevacizumabbiosimilar – improved its pre-tax profit by 21.3% to Rs20.1 billion. G

COMPANY NEWS



Cipla aims to focuson 15-20 countries

Annual sales Change Proportion(Rs millions*) (%) of total (%)

Formulations 74,830 +38.0 55APIs 7,780 +22.5 6Exports 82,610 +36.4 61

India 51,110 +5.9 37

Others 3,060 – 2

Cipla 136,780 +20.6 100

* rounded to nearest Rs10 million

Figure 1: Breakdown of Cipla’s sales in its financial year ended 31 March 2016(Source – Cipla)

An “increased focus, product pruning and cost efficiencies” enabledAurobindo Pharma to return its European operations to profitability

in its financial year ended 31 March 2016. The Indian companyincreased its group turnover by 14.6% to Rs139 billion (US$2.07billion) as it received 58 final and tentative abbreviated new drugapplication (ANDA) approvals in the US.

When Aurobindo two years ago bolstered its presence in Europe bypaying C30 million (US$33 million) for Actavis’ generics operationsin seven countries (Generics bulletin, 3 February 2014, page 1), thefirm said it planned to use its manufacturing and active pharmaceuticalingredient (API) assets to return the loss-making operations to a profit.

In its 2015-16 financial year, Aurobindo – which claims to havevertical integration with in-house APIs for around three-quarters ofits finished-dose portfolio – reported European Formulations sales

down by 2.0% to Rs31.3 billion (see Figure 1). At the end of thereported period, on 31 March 2016, the European business obtaineda further 1,601 marketing authorisations from Actavis.

The 58 ANDA approvals in the US comprised 49 final and ninetentative authorisations. Of the final approvals, 20 were for injectables.

In the January-March 2016 quarter alone, Aurobindo secured 17final approvals, including for celecoxib, paricalcitol and rivastigminecapsules; for ibandronate, naproxen, norethindrone and valganciclovirtablets; and for injectable levetiracetam, pantoprazole and vancomycin.

Launching both oral-dose and injectable generics – as well asgrowth from the Natrol OTC operation that Aurobindo acquired inDecember 2014 – lifted the firm’s US Formulations turnover by 27.2%to Rs61.4 billion. During the 12-month period, the company filed 22ANDAs – 20 oral and two injectables – taking total filings to 398.

Formulations sales in Aurobindo’s Emerging Markets regionclimbed by just over a fifth to Rs6.91 billion, while global turnover fromthe firm’s antiretrovirals portfolio was up by a quarter to Rs12.0 billion.Total API sales increased by 6.6% to Rs28.8 billion, or a fifth of groupturnover, largely due to higher demand for non-betalactam bulk drugs.

A gross margin improvement of just over a percentage point to55.7% helped to offset a 38% rise in research and development costsas Aurobindo improved its pre-tax profit by 25.6% to Rs27.2 billion.

“Our focus remains on new launches in the US and improved costefficiencies in Europe,” stated managing director N Govindarajan. G


Aurobindo’s actionsgive profit in Europe

Business Annual sales Change Proportionsegment (Rs millions) (%) of total (%)

US 61,440 +27.2 44Europe 31,304 -2.0 23Emerging markets 6,914 +21.5 5Antiretrovirals 11,999 +24.5 9Formulations 111,657 +16.8 80

Betalactams 18,566 +3.5 13Non-betalactams 10,271 +12.6 7APIs 28,837 +6.6 21

Other/eliminations -1,533 – -1

Aurobindo 138,961 +14.6 100

Figure 1: Breakdown by business segment of Aurobindon Pharma’s sales in itsfinancial year ended 31 March 2016 (Source – Aurobindo)

Gen 3-6-16 Pgs. 2-20_Layout 1 01/06/2016 17:38

Introducing centralised purchasing of generics similar to New Zealand’s‘Kiwi model’ would not cut medicines costs in the Netherlands,

according to the Dutch foundation for pharmaceutical statistics, the SFK.In an article published in the Pharmaceutisch Weekblad journal,

the SFK argues that proposals by members of parliament LindaVoortman and Otwin Van Dijk to introduce a centralised purchasingsystem for generics are misguided. “Given the lowest-price guaranteesand other pricing agreements contained in contracts with healthinsurers, prices in the Netherlands are lower [than in New Zealand].”

With a generic substitution rate of 97.1% last year, the Netherlandsalready has one of the most efficient systems for off-patent drugs, theSFK maintains. The result, it says, is that generics accounted for 72.4%of prescriptions supplied through community pharmacies in theNetherlands during 2015, but made up just 16.5% of drug costs. Theaverage cost of the 167 million generics dispensed by Dutch pharmacistslast year – a rise of 6% – was C2.56 (US$2.86) per person per month,only a little over a third of the C6.50 average in 2005. G

MARKET NEWS


PRICING & REIMBURSEMENT

Dutch central buyingwould not cut costs

Stimulating competition, fighting against raised intellectual-property(IP) protections that would limit access, prioritising local

procurement, supporting biosimilar medicines, helping companies adaptto new regulatory standards and eliminating the “vertical concentration”of own-brand pharmacy chains are among the policy priorities thathave been identified by the Latin America Pharmaceutical IndustriesAssociation, Alifar. In a declaration following Alifar’s annual meetingin Brasilia, Brazil, in early May, the association has set out its agendaof policy recommendations for the region.

“Price controls that apply in some countries in the region distortthe market significantly,” Alifar points out, insisting that “the best policyto control prices is the promotion of free competition”. To this end,the association calls on Latin American governments to introducemeasures to stimulate competition.

Meanwhile, Alifar suggests that policy changes are needed to helpindustry adapt to “new standards and regulations, such as requirementsregarding good manufacturing practice (GMP) and product traceability”.Both “sufficient time” and investment will be needed to allow allactors in the supply chain to adapt to new regulatory standards, theLatin American association insists.

Another obstacle cited by Alifar is “the growing monopolistic andoligopolistic concentration of pharmacy chains in different countriesof the region”. Local governments should “reverse the current processesof vertical concentration of pharmacy chains and their own brands”,the association believes.

On IP, Alifar says it is speaking with Latin American governmentsparticipating in free trade deals “to encourage them to not accept newand higher standards of protection and enforcement of IP-infringingflexibilities in the World Trade Organization’s agreement on trade-related aspects of IP rights (TRIPS) and limiting access to medicines”.The association has previously been vocal in speaking out againstinflated intellectual-property protection to countries such as Chile,Mexico and Peru during Trans-Pacific Partnership (TPP) negotiations(Generics bulletin, 9 August 2013, page 15).

Urging governments to “implement patentability criteria froma public-health perspective”, Alifar suggests prioritising patentabilityguidelines and considering compulsory licensing. It is also recommendingthat Latin American governments “prioritise the acquisition of locally-produced products”.

Finally, Alifar warns of campaigns in the region aimed at “erodingthe prestige of biosimilar medicines” with the goal of restricting biologiccompetition and “monopolising the market”, including calls to reassessbiosimilars that have been marketed for “many years” with no safetyor efficacy problems. Alifar recently spoke out against a US Foodand Drug Administration (FDA) proposal that would require biologicaldrugs in the US to carry unique suffixes to their international non-proprietary names (INNs), dismissing it as having “no technical orscientific basis and lacking any public health justification” (Genericsbulletin, 6 November 2015, page 14). G

REGULATORY AFFAIRS

Alifar sets agenda forLatin America policy

Portuguese generics sales dipped slightly in volume in the first twomonths of 2016, according to data published by local medicines

agency Infarmed, with unit sales declining by 2.9% to 10.6 millionpacks. However, by value, sales in Portugal increased slightly, risingby 0.9% to C42.3 million (US$47.3 million).

The figures come against a backdrop of overall medicines salesdeclining by both value and volume in January and February, withturnover slipping by 0.4% to C195 million and unit sales falling by2.2% to 25.7 million packs. This gave generics a 41.4% of the totalmarket by volume, which Infarmed said translated to almost two-thirdsof the market available to generics. G

MARKET RESEARCH

Portugal selling less for more

Ameeting discussing extrapolation of indications for rheumatologybiosimilars will be held in London, UK, on 10 June as part of

the European League Against Rheumatism (Eular’s) annual congress.Organised by the Biosimilar Medicines Group (BMG) within Europeangenerics industry association Medicines for Europe, the educationalsymposium is titled ‘Biosimilar medicines for rheumatologists:understanding the science of extrapolation’. “Extrapolation of indicationsis a key element of the biosimilarity concept, while interchangeabilityis another ‘hot topic’ in this area,” the BMG explains. G

REGULATORY AFFAIRS

Extrapolation experts meet

EPO – the European Patent Office – says it is “giving the patentcommunity the opportunity to test and give feedback on the newonline procedure for registering unitary effect” through a ‘unitarypatent demo’ software plug-in. Feedback is open until 31 July. G

IN BRIEFIGDRP – the International Generic Drug Regulators Programme – said12 firms had submitted intentions to participate in its information-sharing scheme on European generics assessments by December2015. A total of 30 products are covered by the scheme. G

IN BRIEF

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PHARSAFER Full Pg 7-4-16_Layout 1 07/04/2016 11:43 Page 1

Reimbursement prices for generics paid to pharmacists in Englandand Wales have been cut by £12 million (US$18 million) per month

from the start of June. Drugs facing a cut of around a tenth includeaciclovir, candesartan, clopidogrel, lamotrigine and olanzapine.

The reductions of £48 million between June and September 2016for drugs in the Category M category of the Drug Tariff reimbursementprice list – covering multisource medicines that are “readily available”– are being made by the UK’s Department of Health in response tothe preliminary findings of a survey of medicines margins made bypharmacists in the financial year ending on 30 September 2016.

“Their intention is to reclaim excess margin that the Departmentbelieves was delivered to contractors in 2015/16 above the agreedallowed £800 million,” commented the Pharmaceutical ServicesNegotiating Committee (PSNC), which had previously agreed an annual£800 million purchasing profit margin for community pharmacistsas part of an overall £2.8 billion funding package (Generics bulletin,3 October 2014, page 9). “PSNC accepts that margin levels were highduring the period, but has not agreed to the reduction.”

‘Robust’ data supports reduction“The Department stated in a letter to PSNC that it felt the data was

robust enough to support at least a £12 million per month reduction,”the pharmacists’ body revealed, adding that the Department had pledgedto evaluate its position, in consultation with the PSNC, in Octoberonce final results from the margins survey were available. “Departmentprojections suggest that the October Drug Tariff is unlikely to see asignificant recovery,” the PSNC added.

The pharmacy reimbursement cuts come as the PSNC is battlinggovernment plans to cut the £2.8 billion annual funding package forcommunity pharmacies by at least £170 million to “no higher than£2.63 billion” in the financial year starting on 1 October 2016. Aspart of a counter-proposal, the PSNC is proposing both generic andtherapeutic substitution (see front page). G

MARKET NEWS


2-5 August

■ 3rd PharmaCon,Pharmaceutical Congress AsiaSingaporeThis is a two-day conference with pre- and post-conference workshops.There are four events hosted at the same location: PharmaceuticalRegulatory Affairs Asia, Market Access Asia, PharmaceuticalCompliance Asia and Clinical Trials Asia.

Contact: IBC Asia. Tel: +65 6508 2401.E-mail: [email protected]. Website: pharmaconasia.com.

7-8 September

■ GPhA Biosimilars Council ConferenceMaryland, USAThis is a two-day interactive conference looking at topics includingaccess, regulatory issues, reimbursement, interchangeability andthe legal landscape.

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

29-30 September

■ Biosimilars EuropeLondon, UKThis two-day conference will look at developments in thebiosimilar guideline framework and legislation in both Europe andthe US. Patent litigation, market access, pricing andreimbursement and emerging markets will also be covered.

Contact: SMi. Tel: +44 207 827 6000.E-mail: [email protected]. Website: smi-online.co.uk.

3 & 4-6 October

■ CPhI WorldwideBarcelona, SpainCPhI Worldwide is an exhibition and networking opportunity whichwill include the co-located events iCSE, P-MEC and Innopack.The event will be preceded by the Pre-Connect Congress whichwill look at the latest developments in the pharma industry.

Contact: UBM Information. Tel: +31 207 081 637.E-mail: [email protected]. Website: cphi.com

24-26 October

■ GPhA Fall Technical ConferenceMaryland, USAThis is a three-day event organised by the Generic PharmaceuticalAssociation (GPhA). There will be speakers from the industry andthe US Food and Drug Administration (FDA). Topics covered willinclude regulatory and technical issues affecting the industry.There will be a variety of networking opportunities available.

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

Cocktail Reception and Awards PresentationCocktail Reception and Awards Presentation4 October 20164 October 2016

Hotel Porta Fira, The Gran Via complex, Barcelona, SpainHotel Porta Fira, The Gran Via complex, Barcelona, SpainContact: [email protected]: [email protected]

EVENTS – August, September & October

SAVE THEDATE...

PRICING & REIMBURSEMENT

UK implements cutson pharmacy prices

Arecord 12 applications to authorise biosimilar medicines werereceived by the European Medicines Agency (EMA) in 2015,

compared to just three filings in 2014, according to the regulator’sannual report. However, during 2015 the EMA issued a single positiveopinion for a biosimilar – Benepali (etanercept) in late November(Generics bulletin, 9 December 2015, page 1) – having in 2014 giventhree such opinions.

Among the 2015 highlights listed by the agency in its annualreport is the biosimilars workshop for healthcare professionals, patientsand consumers held on 5 March last year. The event “explored howto bridge the scientific evaluation with clinical reality and publicacceptance of biosimilars”.

Within the framework of the planned Transatlantic Trade andInvestment Partnership (TTIP), the EMA said it had supported theEuropean Commission in making progress “on the mutual reliance ofgood manufacturing practice (GMP) inspections, biosimilars andpaediatric medicines” (see front page). The agency raised its numberof GMP inspections by 35% to 567. G

REGULATORY AFFAIRS

EMA biosimilar filings boom

Gen 3-6-16 Pgs. 2-20_Layout 1 01/06/2016 17:38

Sandoz has hit back at Amgen in the latest step in long-runninglitigation between the two firms over the US Biologics Price

Competition and Innovation Act (BPCIA). The generics firm has askedthe US Supreme Court not to grant a petition filed by the originatorasking the court to either review in full a previous decision in the matteror reject outright Sandoz’ petition for a writ of certiorari (Genericsbulletin, 1 April 2016, page 1).

Having previously requested that the Supreme Court review aFederal Circuit appeals court ruling that held that the generics firmwas unable to give Amgen the BPCIA’s statutory 180-day notice ofcommercial marketing before it obtained US Food and DrugAdministration (FDA) approval for its Zarxio (filgrastim-sndz)biosimilar (Generics bulletin, 26 February 2016, page 11), Amgenfiled an opposition brief and conditional cross-petition.

This brief and conditional cross-petition insisted that, should theSupreme Court review this part of the appeals court ruling, it shouldalso review the appeals court’s decision to back Sandoz’ argumentthat it did not need to disclose details of its manufacturing processand dossier to Amgen under the BPCIA.

Amgen brings state-law claimsIn making the allegation that Sandoz had violated the BPCIA by

withholding details of its application – and instead subjecting itselfto the risk of immediate patent litigation – Amgen “did not invoke anycause of action under the BPCIA itself”, according to Sandoz. Nordid it “claim any right to an injunction under that federal statute”.Instead, the generics firm’s filing asserts, “Amgen brought state lawclaims, alleging that Sandoz’ alleged violations of the BPCIA providedbases for state-law injunctive remedies under California’s unfaircompetition law and the common law of conversion”.

“For Amgen to succeed on the state law claims at issue in itsconditional cross-petition,” Sandoz insists, “Amgen would have toestablish that the Federal Circuit erred both in its interpretation of thefederal BPCIA statute and in its conclusions that Amgen’s claims failedfor separate reasons of California law. Amgen can establish neither.”

“In contrast to the questions presented by Sandoz’ petition – whichchallenge the Federal Circuit’s creation of a federal injunctive remedydirectly under the BPCIA to enforce its notice of commercialmarketing provision – the cross-petition’s arguments could supportat most an advisory opinion on the meaning of the BPCIA’s disclosureprovisions,” Sandoz believes. This was “unless [the Supreme Court]were to take the unusual step of reaching questions of state law”.

Amgen’s conditional cross-petition “presents a singularly poorvehicle for review”, Sandoz argues. “This court does not typicallygrant certiorari to resolve state law questions”, the generics firmobserves, “and Amgen does not even attempt to explain why the courtshould take that extraordinary step here.”

“By contrast, the portion of the Federal Circuit’s judgementchallenged by Sandoz’ certiorari petition presents none of thesecomplications,” the generics firm points out. “Amgen is therefore wrongin asserting that if the court grants Sandoz’ petition it also should grantAmgen’s conditional cross-petition. Each petition must meet this court’scertiorari standards on its own, and Amgen’s does not.”

“Moreover,” Sandoz concludes, “Amgen’s choice to file only aconditional cross-petition – as well as the lack of any amici supportingit – suggests its question presented is not sufficiently important towarrant this court’s consideration.” G

MARKET NEWS


REGULATORY AFFAIRS

Sandoz strikes backover BPCIA pathway

FGL – Sweden’s generics industry association – has published adocument outlining its views on “procedures for social andenvironmental responsibility” imposed throughout the supply chain.Criteria should be “clear and easy to measure” and written in English,FGL suggests, with harmonised requirements that do not distinguishbetween different procurement regions. Timing should also betransparent, the association recommends, to give the sometimes longchain of sub-contractors time to assemble necessary documentation.

FDA – the US Food and Drug Administration – says it has “not yetresolved” issues relating to a citizen petition submitted by UnitedAuto Workers Retiree Medical Benefits Trust on biosimilar labelling.Responding to the petition that was submitted in November lastyear – requesting that all prescription drug labelling for biosimilarand interchangeable products follow the ‘same labelling’ approachused for Sandoz Zarxio (filgrastim-sndz) – the agency says the petition“raises complex issues requiring extensive review and analysis”.

POLAND will be the “most rapidly developing market” in centralEurope’s generics market between 2016 and 2021, according to areport by market researcher PMR. Overall sales in the region willgrow by 3%-6% over the period, the report states, as Poland andHungary implement “very severe” cost-containment policies andBulgaria introduces generic prescribing. G

IN BRIEF

A‘single market strategy’ for the European Union (EU) that includesa waiver allowing generics firms to manufacture during the

supplementary protection certificate period (SPC) – as well as outliningproposals for the possible creation of a unitary SPC to accompanythe unitary patent framework – has been endorsed by the EuropeanParliament in a majority vote.

In April, the Parliament’s committee on internal market andconsumer protection had adopted its report on the single market strategy(Generics bulletin, 29 April 2016, page 7) following its publicationlast year (Generics bulletin, 6 November 2015, page 1).

“In their report,” noted European generics and biosimilarsassociation Medicines for Europe (MfE), “members of the Parliamenturged the European Commission to introduce and implement before2019 an SPC manufacturing waiver.” This, MfE said, would “boostthe competitiveness of the European generic and biosimilar medicinesindustries in a highly competitive global environment, which willcreate additional jobs and growth in the EU”.

“The European Parliament’s strong support for the creation ofpharmaceutical manufacturing jobs in Europe through an SPCmanufacturing waiver is clear,” said MfE director-general Adrian vanden Hoven. “Now we expect the Commission to quickly introducethis strong trade stimulus to spur high-tech job creation and economicgrowth in Europe.”

According to MfE, exporting generics and biosimilars tounprotected markets during the SPC period will “stimulate investmentin Europe, support the creation of highly-skilled jobs and increaseaccess to high-quality medicines in third countries, without changingthe equilibrium between the originator and the generic and biosimilarmedicines industries in the EU”. G

INTELLECTUAL PROPERTY

EU Parliament votesfor SPC manufacture

Gen 3-6-16 Pgs. 2-20_Layout 1 01/06/2016 17:38

Recognising the best in the global genericsand biosimilars industries

Presented by GGeenneerriiccss bbuulllleettiinn in association with IMS Health

Cocktail Reception &Cocktail Reception &Cocktail Reception &Awards PresentationAwards PresentationAwards Presentation

Tuesday 4 October 2016Tuesday 4 October 2016Tuesday 4 October 2016Hotel Porta Fira,

The Gran Via complex, Barcelona, Spain

Sponsor, Enter, Join us!Find out more about sponsoring or

entering an award and joining us on the night:Visit: www.generics-bulletin.com

Email: [email protected]: +44 1564 777550

GGB16 DPS1 3-6-16 V2_Layout 1 31/05/2016 15:53 Page 1

The Third AnnualGlobal Generics & Biosimilars AwardsMMaakkee ssuurree yyoouurr oouuttssttaannddiinngg bbuussiinneessss aacchhiieevveemmeennttss aarreecceelleebbrraatteedd bbyy tthhee gglloobbaall ggeenneerriiccss aanndd bbiioossiimmiillaarrss iinndduussttrriieess..

Presenting ...

Presented by:

In association with:

Sponsored by:

● Company of the Year

● Company of the Year, Americas

● Company of theYear, Asia-Pacific

● Company of the Year, EMEA

● Acquisition of the Year

● Leader of the Year

● Innovation of the Year

● Business Development of theYear

● API Supplier of the Year

● Biosimilar Initiative of the Year

● Patent Litigation of the Year

● Regulatory Achievementof the Year

● Industry Partner of the Year

● Corporate Social Responsibility(CSR) Initiative of the Year

Awards Entry Deadline – Friday 15 July 2016

The Awards ...

The tremendous work done by executives inthe global generics and biosimilars industriesduring the past year will be recognised bythe Global Generics & Biosimilars Awards2016, presented by Generics bbuulllleettiinn inassociation with IMS Health.

Now in their third year, these Awards willreward ‘best practice’ in the generics andbiosimilars space,while encouraging andsupporting all that's good in the sector.

Strategic initiatives – such as throughcorporate acquisitions and alliances,

innovative product development, cleverlicensing deals or smart legal manoeuvres –are at the heart of the Global Generics &Biosimilars Awards 2016.

Awards will also go the best executivesand leading companies that haverecorded outstanding achievementsduring the past 12 months.

The Awards will be presented on4 October at the Hotel Porta Fira,The Gran Via complex, Barcelona, Spain.

GGB16 DPS1 3-6-16 V2_Layout 1 31/05/2016 15:53 Page 2

Sandoz’ marketing authorisation application for a biosimilar versionof rituximab has been accepted for evaluation by the European

Medicines Agency (EMA).Noting that it was “seeking approval for the same indications as

the reference product”, Roche’s MabThera, Sandoz observed that theproduct was used to treat non-Hodgkin’s lymphoma – includingfollicular lymphoma and diffuse large B-cell lymphoma – as well aschronic lymphocytic leukaemia and autoimmune diseases such asrheumatoid arthritis. “Sandoz’ submission includes data from multipleclinical trials with over 800 patients,” the firm emphasised.

“In addition to analytical, functional and pre-clinical data,” Sandozexplained, “the submission includes data from two pivotal confirmatorysafety, pharmacokinetic/pharmacodynamic and efficacy studies thatinvolved 629 follicular lymphoma and 173 rheumatoid arthritis patients”.

The EMA’s acceptance of the application represented the “sixthmajor biosimilar file acceptance in less than one year” for Sandoz, thecompany observed. These included EMA and US Food and DrugAdministration (FDA) applications for etanercept and pegfilgrastim,as well as a subcutaneous route of administration for the nephrologyindication of its Binocrit (epoetin alfa) biosimilar, which was grantedin April (Generics bulletin, 15 April 2016, page 8). Epoetin andadalimumab filings with the FDA are forecasted for 2016, with USrituximab and European adalimumab filings to follow in 2017. G

PRODUCT NEWS


PRICE WATCH ....... UK

Up to the minute live retail market pricing is availablefor 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: [email protected].

Flecanide gets concessionsPrice concessions on flecanide tablets have been granted to UK

pharmacists by the country’s Department of Health (DoH)following price rises that have been recorded in May, according tothe latest figures provided by WaveData.

Comparing UK trade prices between the periods 1-30 April2016 and 1-31 May 2016, the average trade price for a 60-tabletpack of the 100mg strength rose by 16% to £11.44 (US$16.75),despite the lowest available offer remaining stable at £4.62, basedon averages calculated from at least 43 data points. The DoH granteda price concession of £10.73.

Concessions continue to be offered for nitrofurantoin tablets,with a concession price of £12.25 granted for the 100mg strength.According to WaveData, 28-tablet packs saw an average price riseof more than 30% in May, increasing to £11.72 as the lowestavailable price leapt from £1.99 to £7.50.

Price rises continued to persist for isosorbide tablets, with56-count packs of the 10mg, 20mg and 40mg strengths seeing theiraverage prices increase severalfold.

Meanwhile, duloxetine 20mg and 40mg enteric-coated capsulessaw their average prices drop by more than a quarter to £4.04 and£7.70 respectively. Pioglitazone 15mg, 30mg and 45mg continuedto experience declines similar to those seen earlier in the month(Generics bulletin, 27 May 2016, page 13). G

BIOLOGICAL DRUGS

Sandoz’ rituximab isaccepted by the EMA

Canada’s Federal Court of Appeal has overturned a lower court’sfinding concluding that Apotex and Allergan had reached a

settlement in litigation over Canadian gatifloxacin patent 1,340,316that expired in January this year.

In March last year, Federal Judge Roger Hughes found that thetwo firms had reached a settlement. He based that decision on an initialexchange of three letters and an e-mail sent in April 2012, followedby an exchange of e-mails in January and February 2014.

But a panel of three appeal judges said Hughes’ holding on theApril 2012 “suffers from several errors that warrant our interference”.Hughes “appeared to have been distracted by Allergan’s subjectiveview of the importance of certain terms that had to be negotiated out,rather than keeping to an objective assessment of the matter from thestandpoint of a reasonable businessperson,” the panel said. Concernsabout the scope of restrictions to be placed on Apotex were not minor,as Allergan had contended, but were rather an “essential term”, theappeal judges stated.

Turning to the correspondence in 2014, the appeal panel pointedout that Apotex had never acted on advice from its counsel to settle.“Examining all of the remaining communications between the parties,I find that at no time was there a matching offer and acceptance onall essential terms,” stated Justice David Stratas in a lead opinion forthe Court of Appeal. G

ANTIBIOTICS

Canada rejects dealin gatifloxacin fight

US rivals to UCB’s Vimpat (lacosamide) tablets could hit the marketseveral years ahead of patent expiry after the US Patent and

Trademark Office (USPTO) granted Argentum’s petition to institutean inter partes review against all claims of reissued patent RE38,551.The ‘551 patent is the sole remaining Vimpat patent listed in the USFood and Drug Administration’s (FDA’s) Orange Books, and shieldsthe anticonvulsant until 17 March 2022.

A final decision on patentability in the review was “due within oneyear”, Argentum stated, noting that the inter partes review trial wouldbe conducted by three specialist patent judges within the USPTO’sPatent Trial & Appeal Board.

“The PTO concluded that Argentum has established a ‘reasonablelikelihood that it would prevail in showing that claims 1-13 of the'551 patent are unpatentable’,” the generics firm commented.

Meanwhile, Argentum has also filed an ex parte re-examinationrequest “against this same patent that raises additional grounds ofunpatentability”. The re-examination request for the ‘551 patent isdue “no later than 29 July 2016”.

Just under 18 months ago, in January 2015, seven firms – Actavis,Amneal, Aurobindo, Breckenridge, Sandoz, Sun and Vennoot – sawdenied by the USPTO a request to conduct an inter partes review ofthe ‘551 patent, according to Argentum. Of these seven firms, Actavis,Aurobindo and Sun all currently hold final FDA approval forlacosamide 50mg, 100mg, 150mg and 200mg tablets, along withAlembic, MSN Labs and Mylan.

The anticonvulsant brand attracted at least 16 paragraph IV patentchallenges when the FDA began accepting generic filings three yearsago (Generics bulletin, 6 September 2013, page 24). G

EPILEPSY DRUGS

Vimpat patent to be reviewed

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The US Supreme Court must re-examine a ruling that foundAmphastar’s use of a patented analysis method for its enoxaparin

to fall outside of US Bolar safe-harbour rules, the firm has urged ina petition for a writ of certiorari that it has submitted to the court.

Last year, a US appeals court ruled that Amphastar’s use of thepatented analysis method – which is claimed by US patent 7,575,886,assigned to Momenta for its own generic version of Sanofi’s Lovenox(enoxaparin) – was not “reasonably related” to the development ofquality-control information submitted to the US Food and DrugAdministration (FDA) by Amphastar (Generics bulletin, 20 November2015, page 21). The decision vacated and remanded a district courtjudgement that said Amphastar’s use of the patent fell within the ‘safeharbour’ provisions (Generics bulletin, 3 September 2012, page 16).

Having earlier this year failed to convince the appeals court tohold an en banc rehearing of the decision (Generics bulletin, 26February 2016, page 13), Amphastar has now urged the Supreme Courtto consider the question of “whether the safe harbour protects a genericdrug manufacturer’s bioequivalence testing that is performed onlyas a condition of maintaining FDA approval and is documented inrecords that must be submitted to the FDA upon request”.

The Supreme Court should correct the appeals court’s “overlynarrow interpretation” of the Hatch-Waxman safe harbour, Amphastarargues, by examining the wording approved by Congress. Noting thatthe Supreme Court had already examined the safe harbour “twice since1990”, the firm says it “each time rejected the [appeals court’s]attempts to impose atextual restrictions on the safe harbour’s scope”.

While the appeals court had “eschewed the statutory language infavour of a new restriction, excluding so-called ‘routine’ uses”, it had“made no attempt to locate in the safe harbour’s text” this provision,Amphastar pointed out. “Indeed, the [appeals court’s] scant analysisof section 271(e)(1) of the federal Food, Drug, and Cosmetic Act(FDCA) and its implementing regulations barely cites the text at all,and nowhere locates the exclusion of “routine” submissions within it.”

The court had taken the view that Amphastar’s activity “does notinvolve the ‘development’ of information and the testing is not‘reasonably related’ to the submission of information to the FDA”, thefirm pointed out. But, it said, this “fundamentally misunderstands howthe FDA-specified bioequivalence testing relates to the safe harbour”.

“Amphastar ‘develops’ new information through the testing,” thecertiorari petition insists. “It does not simply collect information thatis incidentally generated through the manufacturing process. It performsthe testing for the specific purpose of creating the information necessaryboth to the continued approval of the abbreviated new drug application(ANDA) and to the ability to market the generic drug.”

Ultimately, Amphastar concludes, the appeals court’s decision “putsat risk the ability of generic manufacturers to conduct FDA-requiredpost-approval testing necessary to maintain approval of an unpatenteddrug”, and allows competitors to “block market entry despite the lackof any product or manufacturing patent”.

Moreover, the firm maintains that the “exceptionally importantquestion” posed to the Supreme Court is of significance that “will onlygrow in light of the increasing prevalence of complex biosimilar drugs,for which the FDA’s bioequivalence-testing requirements are particularlysalient”. “Hijacking one of the required bioequivalence tests, as Momentahas done, creates a roadmap for blocking generic market entry incontravention of Hatch-Waxman’s purposes,” Amphastar argues,concluding: “Given these stakes, certiorari is warranted.” G

PRODUCT NEWS


REGULATORY AFFAIRS

Enoxaparin appealqueries safe harbour

Samsung Bioepis has obtained a pan-European centralised marketingauthorisation for its Flixabi (infliximab) biosimilar rival to Janssen’s

Remicade. The approval granted by the European Commission forrheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosingspondylitis, psoriatic arthritis and psoriasis followed a positive opinionthat the European Medicines Agency (EMA) issued earlier this year(Generics bulletin, 8 April 2016, page 8).

As with the joint venture’s Benepali (etanercept) that has beenlaunched in several European countries (Generics bulletin, 26 February2016, page 1), Biogen will be responsible for manufacturing andmarketing Flixabi as a rival to Remicade as well as to Pfizer’s Inflectraand Celltrion’s Remsima infliximab biosimilars.

Samsung Bioepis’ clinical data package for Flixabi included a54-week Phase III trial also used for a US filing (see page 15). G

BIOLOGICAL DRUGS

Samsung Bioepis hasnod on EU infliximab

Mylan has begun shipping the first generic version of MaynePharma’s Doryx (doxycycline hyclate) 200mg delayed-release

(DR) tablets in the US with 180 days of generic market exclusivity.The US firm’s launch comes pursuant to Mylan obtaining final USFood and Drug Administration (FDA) approval for its supplementalabbreviated new drug application (sANDA).

Citing IMS Health Data, the Netherlands-based firm said the USmarket for the 200mg formulation of the acne treatment was wortharound US$182 million for the 12 months ended 31 March 2016.

At the end of April, Mylan obtained final approval for its sANDAcovering doxycycline 80mg DR tablets – the only firm to hold suchan approval – based on its ANDA for generic Doryx 75mg and 100mgDR tablets. The firm also holds final FDA approval for its genericalternatives to the 50mg and 150mg strengths of the brand.

Doryx DR tablets are currently protected by two US patents –6,958,161 and 8,715,724 – which expire in December 2022 andFebruary 2028 respectively. However, in an FDA letter accompanyingthe 80mg approval in April, the FDA notes that Mylan had “notifiedthe agency…that no action for infringement was brought against Mylanwithin the statutory 45-day period” concerning either patent. G

ACNE TREATMENTS

Mylan rivals Doryx in the US

Agroup of 15 US House of Representatives Democrats have writtento US Trade Representative (USTR) Michael Froman, seeking

clarity on the US administration’s position of compulsory licensing forgenerics in Colombia. Several non-governmental organisations recentlymade a similar demand (Generics bulletin, 27 May 2016, page 12).

In the letter, the Democrats express concern that “US officials mayhave discouraged Colombian government officials from issuing acompulsory licence on a cancer medicine, Gleevec (imatinib)”. “Pressreports suggest that Colombian officials were left with the deeplytroubling impression that US$450 million in US funding to aid peaceefforts could be in jeopardy if Colombia failed to change course.” G

ONCOLOGY DRUGS

Democrats push on Colombia


Pfizer’s Hospira and Sun Pharma have each received positiveopinions for bortezomib 3.5mg powder for solution from the

committee for human medicinal products (CHMP) within the EuropeanMedicines Agency (EMA). The European Commission typicallydecides within 67 days whether to use such opinions as the basis forgranting centralised marketing authorisations that are valid throughoutthe European Union (EU).

The CHMP noted that as the antineoplastic agent for treatingmultiple myeloma and mantle-cell lymphoma was administeredintravenously and was 100% bioavailable, no bioequivalence studyversus Johnson & Johnson’s Velcade reference product was necessary.Studies had demonstrated the “satisfactory quality” of the two genericversions, the agency added.

Johnson & Johnson reported non-US Velcade sales down by 17.6%to US$1.33 billion last year. Intas’ Accord obtained a centralisedapproval for the oncology drug in July last year following a positiveCHMP opinion (Generics bulletin, 5 June 2015, page 25).

Separately, the CHMP has adopted a positive opinion on FreseniusKabi’s application for a generic alternative to Eli Lilly’s Alimta(pemetrexed) 100mg and 500mg powder for concentrate to make aninfusion solution. Again, no bioequivalence trial was required for theintravenous anti-folate agent that is used to treat mesothelioma andnon-small-cell lung cancer.

The committee has also, following a review, recommendedincluding advice on the outer carton and in the package leaflet ofGedeon Richter’s Levonelle (levonorgestrel) emergency contraceptiveto take double the usual 1,500mg dose when used with certain drugswith which it interacts. These drugs include efavirenz, ritonavir,St John’s wort and some epilepsy and tuberculosis treatments.

Levonelle was authorised in the EU through a mutual-recognitionprocedure, based on an initial authorisation granted by UK authorities,which referred to the CHMP a dispute between EU member states onhow to handle levonorgestrel’s interaction with efavirenz.

For AbbVie’s Humira (adalimumab) blockbuster, the CHMP hassupported adding an indication to treat uveitis in adults. G

PRODUCT NEWS


ONCOLOGY DRUGS

Hospira and Sun getEU bortezomib nods

US biosimilars developer Coherus BioSciences has been issued withthree US patents – numbered 9,340,611; 9,340,612 and 9,346,880 –

covering formulations of adalimumab, the active ingredient in thefirm’s CHS-1420 biosimilar rival to AbbVie’s Humira that is currentlyin Phase III clinical development. “The formulations described in thesepatents achieve stability without the need for polyols or surfactants,”the Californian firm stated.

Each of the patents issued by the US Patent and Trademark Office(USPTO) is entitled ‘Stable aqueous formulations of adalimumab’. Theyare said to cover “adalimumab compositions suitable for long-termstorage”. “These US patents, along with pending foreign counterparts –as well as the USPTO’s recent decision instituting our inter partesreview against AbbVie’s US patent 8,889,135 (Generics bulletin, 20May 2016, page 12) – validates our differentiated intellectual-propertystrategy,” insisted Coherus, which also has its CHS-1701 pegfilgrastimand CHS-0214 etanercept candidates in late-stage development. G

BIOLOGICAL DRUGS

Coherus patents adalimumab

PFIZER has licensed to Galenica’s Vifor Pharma certain UScommercialisation rights for its prospective Retacrit (epoetin alfa)biosimilar. The deal – for which no financial details were disclosed –covers the US kidney dialysis market. Pfizer’s Hospira submitted abiologics license application (BLA) for Retacrit to the US Food andDrug Administration (FDA) in December 2014 for treating renalfailure, anaemia associated with chronic kidney disease andchemotherapy-induced anaemia. The FDA is continuing to assessthe application.

TEVA will be able to market a generic version of Spectrum’s Folotyn(pralatrexate) injectable chemotherapy agent in the US from 1December 2022 under the terms of a patent-litigation settlementreached by the two firms. Spectrum – which is continuing its litigationagainst other generic filers Dr Reddy’s, Fresenius Kabi and Sandoz,with a trial set for 12 September this year in a Delaware districtcourt – has a US composition-of-matter patent that runs until 16July 2022, while two use patents covering peripheral T-cell lymphomaexpire on 31 May 2025.

AUROBINDO has obtained final US approval for zolmitriptan 2.5mgand 5mg tablets equivalent to IPR’s Zomig migraine remedy as wellas for fenofibrate 48mg and 145mg tablets equivalent to AbbVie’sTricor cholesterol-reducing agent. Launches are imminent. TheIndian company has also bolstered its US opioid analgesics rosterwith authorisations for hydromorphone 2mg, 4mg and 8mg tabletsand for oxymorphone 5mg and 10mg tablets. Aurobindo also expectsto launch by September this year the bupivacaine 0.25% and 0.5%multiple-dose vials for which it has just secured US approval.

SORRENTO THERAPEUTICS says its partner, Mabtech, hassuccessfully completed a combined Phase II and III clinical studyin China for the firm’s STI-004 biosimilar version of Xolair(omalizumab). “STI-004 met its primary endpoint in a multi-centre,randomised, double-blind, placebo-controlled clinical trial,” statedthe US firm. “The types and incidence rates of adverse eventswere similar” to those for Xolair, Sorrento added. Having licensedomalizumab along with basiliximab, cetuximab and infliximab froMabtech in August last year, Sorrento is targeting regions includingNorth America, the European Union (EU) and Japan, while Mabtechwill seek marketing approval for STI-004 in China.

MEDICINES FOR EUROPE has released an updated edition ofits biosimilar medicines handbook.

MARTINDALE PHARMA has obtained approval for its Prenoxad(naloxone) 1mg/ml injectable treatment for opioid overdoses inDenmark, Estonia, Finland, Ireland and Sweden through a Europeandecentralised procedure, using Denmark as the reference member state(RMS). The UK-based company has licensed “the world’s first take-home naloxone product” to Ethypharm for marketing in France, whereMartindale has just secured a temporary authorisation for its Noyada(captopril) oral liquid that will be distributed by local firm Cevidra.

CELLTRION has accused Janssen of mischaracterising the claimedinvention described in claim 1 of US patent 7,598,083 in the firms’dispute over infliximab. According to Celltrion, the proper constructionof ‘cell culture media’ is “chemically defined media” that are “freeof all proteins”. Janssen claims that the true construction should beany “nutritive media for culturing cells”. Massachusetts DistrictJudge Mark Wolf recently denied Janssen’s motion to stay litigationpending an appeal of an inter partes review of the ‘471 patent andordered the parties to discuss a settlement. G

IN BRIEF


Samsung Bioepis has had its application for a biosimilar versionof Janssen’s Remicade (infliximab) accepted for review by the

US Food and Drug Administration (FDA), marking “the first SamsungBioepis candidate submitted for review in the US”. The joint venturehas just had its Flixabi (infliximab) biosimilar approved throughoutthe European Union (see page 13), having launched its Benepali(etanercept) biosimilar in the region earlier this year (Generics bulletin,26 February 2016, page 1).

If its SB2 infliximab candidate is approved in the US, the companypointed out, marketing and distribution will be handed by Merck & Counder the terms of a partnership deal struck in 2013. Indicationscovered by the SB2 filing include rheumatoid arthritis, Crohn’sdisease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritisand psoriasis. The biologics license application (BLA) is based onPhase I and Phase III clinical studies.

“In a 54-week Phase III clinical study,” Samsung Bioepis noted,“SB2 showed comparable safety and equivalent efficacy to Remicade,as evidenced in an American College of Rheumatology 20%improvement (ACR20) response rate of 65.3% in the SB2 arm versus69.2% in the Remicade arm at week 54.” This “fully supported”30-week study results of 64.1% and 66.0% respectively, the firm said.Samsung Bioepis’ study included 584 patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy across 73sites in 11 countries.

Celltrion recently indicated that its own Remsima version ofinfliximab “is going to enter the US market soon” (Generics bulletin,27 May 2016, page 6). The South Korean company received FDAapproval for the biosimilar in April (Generics bulletin, 8 April 2016,page 1), and local marketing partner Hospira has suggested that itcould launch Remsima as early as 30 June (Generics bulletin, 22 April2016, page 1). The firms remain engaged in litigation with Janssenover patents protecting the originator’s Remicade brand. G

PRODUCT NEWS


BIOLOGICAL DRUGS

US Remicade rival isin sight for Samsung

Acourt in the Netherlands has denied Leo Pharma an injunctionagainst Sandoz marketing its recently launched generic version of

the originator’s Dovobet (calcipotriol/betamethasone) psoriasis treatment.Judge EF Brinkman found that there was “a good chance” that theinvoked claims of Leo’s European patent EP2,455,083 would be foundinvalid during opposition proceedings.

Sandoz in April this year obtained a listing for its calcipotriol/betamethasone 50µg/500µg per gramme ointment in the country’sG-Standaard reimbursement database and launched its generic at aroundthe same time. The generic uses oleyl alcohol as its solvent, ratherthan the Arlamol-E solvent employed for the Dovobet original.

Shortly beforehand, in March, Leo had written to Sandoz claiminginfringement of the ‘083 patent, which is entitled ‘Pharmaceuticalcomposition for dermal use comprising calcipotriol and betamethasone’and expires in January 2020. But Sandoz insisted the patent was invalidand launched at-risk, causing the originator to seek an injunction.

In arguing for an injunction and a recall of the generic, Leomaintained that combining calcipotriol and betamethasone in a singleproduct was not obvious and produced a “synergistic effect”.

But Sandoz countered Leo’s argument by claiming that such asynergy was not “plausible” in light of the ‘083 patent or the studieson which it was based. In any case, Sandoz added, such an effectwas at best “a bonus effect of a non-inventive measure.”

No trace of synergistic effectBrinkman ruled that there was “no trace” of support for a synergistic

effect in the ‘083 patent and agreed with Sandoz that any improvementin Psoriasis Area Severity Index (PASI) score for Dovobet could bedue to better patient compliance as a combination product. Combiningthe two ingredients into an ointment would have been obvious to askilled person, he added.

Addressing novelty, Brinkman said there was a question whetherkey claims of the ‘083 patent could derive priority from Danish patent56,199 or the WO 00/64450 patent application that would otherwisetake away the novelty of the claims. Various technical boards of appealof the European Patent Office (EPO) had failed to reach a consensuson the matter, he observed.

The EPO is due to hold oral proceedings on the ‘083 patent on7 July this year after Mylan, Pentafarma, Sandoz and Teva broughtopposition proceedings. G

DERMATOLOGY DRUGS

Dutch court deniesinjunction on Sandoz

References to ‘conditions’ contained in three US patents that coverthe simultaneous administration of the antihistamine azelastine and

the corticosteroid fluticasone should be read as referring to ‘disease(s)or illness(es)’, as Apotex had suggested, Delaware District JudgeLeonard Stark has ruled following a claim-construction hearing.

Cipla and its co-plaintiff Meda had insisted that the mention of‘conditions’ in US patents 8,163,723, 8,168,620 and 9,259,428 mustbe read as referring to “diseases or illnesses resulting in or causingallergic reactions”. But Stark preferred Apotex’ “plain and ordinarymeaning”, stressing that “neither the intrinsic nor extrinsic evidencesupports a narrower construction of ‘conditions’”. G

ALLERGY DRUGS

Apotex’ construction accepted

Dr Reddy’s has agreed to buy six OTC brands from Ducere Pharmathat the Indian company will market in the US. The “eminent

portfolio” includes the analgesics Bufferin (aspirin), Doan’s (magnesiumsalicylate), Myloflex (trolamine salicylate) and Nupercainal (dibucaine),as well as Cruex (Bonicel probiotic) nail gel and the Comtrex(paracetamol/dextromethorphan/phenylephrine) cold treatment.Financial terms of the deal were not disclosed.

“These legacy products enjoy strong brand equity built overseveral decades,” said Dr Reddy’s US chief Alok Sonig. “We areextremely excited,” Sonig said, to be strengthening Dr Reddy’s existingpresence in the OTC market through products such as Habitrol(nicotine). The firm would build its presence in the branded consumerhealth arena through the acquired brands and “embark upon the nextavenue of growth for our OTC business in the US.”

Sonig said Dr Reddy’s would build on existing sales and marketingefforts for the brands and “continue to focus on their expansion intoexisting and new market channels”. Ducere had recently been successfulin “revitalising the brands through improved distribution andpromotional efforts”, Sonig recognised. G

ANALGESICS

Dr Reddy’s strikes OTC deal


While interest rates and the cost of borrowingremain low, it is perhaps unsurprising thatconsolidation continues apace in the global

generics industry. Nevertheless, the US$40.5 billiondeal that Teva expects to complete later this monthfor Allergan’s Actavis generics business sets a newbenchmark for the size of deals in the sector.

European antitrust authorities have already madetheir demands for substantial divestments as a conditionfor approving the transaction, including the sale of mostof Actavis’ operations in Iceland, Ireland and the UK(Generics bulletin, 18 March 2016, page 1). But asGenerics bulletin went to press, the US Federal TradeCommission (FTC) was still negotiating with the twofirms over what they would have to sell to maintainsufficient competition in the US generics market.

As can be seen from Figure 1, Teva remains theworld’s leading generics player by turnover, accordingto the latest Generics bulletin rankings, with annualgenerics, biosimilars and OTC sales of US$9.79 billionlast year. On top of that total, the US$19.7 billion Israeligroup generated another US$748 million from sellingactive pharmaceutical ingredients (APIs) to third parties.

By taking over Allergan’s Actavis operation, Tevawill remove from the rankings the fourth-largest player

in the generics space. However, given the sizeable scaleof the divestments needed to secure antitrust clearance,the width of the gap to second-placed Sandoz is unlikelyto grow in 2016 by as much as a pro forma calculationmight suggest.

And while the deal is far smaller, Teva’s US$2.3billion acquisition of Rimsa at around 10-times theMexican generics player’s annual sales strengthenssignificantly the group’s presence and platform in LatinAmerica (Generics bulletin, 23 October 2015, page 3).

With Sandoz hampered by adverse exchange-ratefluctuations – the Novartis generics division reported7% constant-currency growth, including its US$580million bulk anti-infectives business – third-rankedMylan was able to close the gap. Mylan benefitted fromclosing its US$6.31 billion takeover of Abbott’s specialtyand branded generics business in developed markets atthe end of February last year. That transaction precededMylan completing in November 2015 the Jai Pharmawomen’s healthcare business of Famy Care for up toUS$800 million.

Teva and Mylan were far from alone in announcingsizeable consolidation deals last year. Among the mostnotable were Pfizer’s US$17 billion move for injectablesspecialist Hospira; Endo’s US$8.05 billion takeover of

COMPANIES


A wave of mergers

and acquisitions

is reshaping the

global generics and

biosimilars industries,

with several familiar

names being swallowed

up. Aidan Fry reviews

which players are

emerging on top.

Consolidation continues toshape the global hierarchy

Sanofi Generics (7)

Teva

Sandoz

Mylan

Allergan (1)

Sun (4,5)

Sawai (4,17)

Fresenius Kabi (7,8)

Perrigo (2,3)

Aspen (11,12)

Valeant (10)

Dr Reddy’s (4,5)

Zydus Cadila (4,5,13)

Endo

Lupin (4,5)

Cipla (4,5)

Stada (7,9)

Krka (7)

0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 18,000 20,000 22,000 24,000

Generics/Biosimilars/OTC APIs Prescription Brands Other

(1) Includes Actavis Generics reported as a discontinued business(2) Financial year ended 27 June 2015(3) Generics, biosimilars and OTC total comprises Prescription Pharmaceuticals,

Consumer Healthcare and Branded Consumer Healthcare business segments(4) Financial year ended 31 March 2016(5) Reported in Indian rupees; converted at US$1 = Rs64(6) Generics, biosimilars and OTC total comprises Sterile Injectable Pharmaceuticals

and Biosimilars business segments(7) Reported in euros; converted at US$1 = C0.90(8) Generics, biosimilars and OTC total is Intravenous Drugs product segment(9) Branded products segment is aggregated between generics, biosimilars, and OTC

sales and Prescription Brand sales(10) Generics, biosimilars and OTC total is Emerging Markets segment(11) Financial year ended 30 June 2015(12) Reported in South African rand; converted at US$1 = ZAR12.75(13) Group sales divided based on nine-month figures(14) Financial year ended 25 September 2015(15) Reported in Hungarian forints; converted at US$1 = HuF279(16) Generics, biosimilars and OTC total is Pharmaceuticals sales excluding Esmya

(ulipristal acetate)(17) Reported in Japanese yen; converted at US$1 = ¥121

Turnover (US$ millions)

Hikma

Mallinckrodt (14)

Figure 1 (above) and Figure 2 (right): Generics companies which reported annual global generics/biosimilars/OTC turnover of more than US$1 billion (above) and more than US$225million (right). Figures have been quoted for the 2015 calendar year where possible, showing total growth compared with the previous year. Results not reported in US dollarshave been converted at the rates shown, but growth figures are as reported. Business breakdowns are mostly according to companies’ own definitions (Source – Company reports)

Aurobindo (4,5)

-3%

-4%

+22%

+62%

+16%

+13%

-14%

+3%

+37%

+21%

+4%

+27%

+6%

+22%

-2%

+14%

+15%

-3%

+61%

+15%

+3%

+11%

Pfizer Established (6)

Glenmark (4,5)

Gedeon Richter (15,16)

Nichi-Iko (4,17)

+3%

+13%

+17%


US generics rival Par; Hikma’s US$1.6 billion deal withBoehringer Ingelheim for Roxane in the US; Lannett’sUS$1.23 billion acquisition of UCB’s Kremers UrbanUS generics unit; and Lupin’s strengthening of its USpresence by buying Gavis and Novel for US$880 million.

The effects of such transactions on our rankingwere defined not only by the scale of the acquired sales,but also by the timings of the deals. For example,Canada’s Concordia Healthcare completed its US$3.5billion takeover of UK-based Amdipharm too latelast year for the group to make it onto our list.

Privately-owned players excludedExcluded from our rankings are: privately-owned

companies for which no detailed sales figures arepublicly available; state-owned entities for whichtransparent financial data is lacking; and corporationsthat group any generics operations into a wider maturebrands or established products segment within whichgenerics sales are not delineated from those of off-patent brands.

Thus, the likes of privately-owned Alvogen, Apotex,Chemo and Polpharma are not present in the rankings.State-owned Chinese firms that operate largely in theirdomestic market are also excluded, as are groups suchas Abbott that do not separate out generics-ledbusiness – such as Abbott’s 2014 acquisitions of CFR inLatin America and Veropharm in Russia – from theirbrands-focused established products divisions.

Pfizer, by contrast, qualifies by virtue of providinggranularity not only on sales of its off-patent or close-to-expiry brands, but also of its injectable generics and

biosimilars, including the former Hospira business. Off-patent and expiring brands are, where possible, excludedfrom our ‘Generics, biosimilars and OTC’ figures.

Perrigo is placed fifth, ahead of Sun Pharma andPfizer, by virtue of both its prescription genericsdivision and its consumer healthcare segment that isbuilt largely on non-prescription abbreviated new drugapplications (ANDAs) in the US.

Sanofi remains in our top-10 players this year, butwill surrender that place if the French group decides todivest its Zentiva generics operation in Europe that hasan annual turnover of around C1.0 billion (US$1.1billion). The company is continuing to weigh its options,but has made it clear that generics are not core to itsstrategy (Generics bulletin, 20 November 2015, page 3).

The top-10 firms in our rankings all have annualgenerics, biosimilars and OTC turnover in excess ofUS$2 billion. And on the same basis, 25 firms meet theUS$1 billion sales threshold for an entry into Figure 1,with Japan’s Nichi-Iko and Sawai making the cutfollowing double-digit advances in their domestic market.

US-based Akorn tops Figure 2 with turnover ofjust under US$1 billion following a recent acquisitionspree that includes Hi-Tech Pharmacal and VersaPharm.

A notable new entrant ranked towards the top ofFigure 2 is Alkem, which went public through aninitial public offering (IPO) of shares at the end of 2015(Generics bulletin, 8 January 2016, page 5). This ledthe Indian company – which also operates under theAscend label – to report group turnover of Rs49.9billion (US$780 million) in its financial year ended31 March 2016. G

COMPANIES


0 200 400 600 800 1,000 1,200 1,400 1,600

Generics/Biosimilars/OTC APIs Prescription Brands Other

Turnover (US$ millions)

Wockhardt (4,5)

Torrent (4,5)

Lannett (11)

Strides Shasun (4,5)

Impax

Aceto (11)

Jubilant (4,5,24)

PT Kalbe (21)

Cinfa (7)

Hypermarcas (18)

Intas (5,19)

Orion (7)

Towa (4,17)

Celltrion (22)

Akorn

Aché (18)

Pharmaniaga (20)

Sopharma (23)

Ipca (4,5)

Alkem (4,5)

Julphar (25)

Adcock (11,12)

+77%

+44%

+7%

+22%

+33%

+9%

+44%

±0%

+15%

+3%

+3%

+28%

±0%

+4%

+4%

±0%

+49%

+6%

-9%

+6%

+25%

+10%

(18) Reported in Brazilian reals; converted at US$1 = BRL3.33(19) Financial year ended 31 March 2015(20) Reported in Malaysian ringit; converted at US$1 = MYR3.90(21) Reported in Indonesian rupiah; converted at US$1 = IDR13,400(22) Reported in South Korean won; converted at US$1 = KRW1,130(23) Reported in Bulgarian lev; converted at US$1 = BGN1.76(24) Generics, biosimilars and OTC total is Pharma business segment(25) Reported in Emirati dirham; converted at US$1 = AED3.67(26) Reported in Mexican pesos; converted at US$1 = MXN15.86Sagent

Genomma (26)

Ajanta (4,5)

-4%

+17%

+7%


All that’s happening inconsumer healthcareWritten by OTC specialists from an OTC industry perspectiveThe best decision-makers in the OTC industry don’t have the time to go looking forgood information. They let it come to them. They subscribe to OTC bulletin.

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BUSINESS STRATEGY


Since acquiring Dutch specialty drug-delivery firmNanomi a little over two years ago (Genericsbulletin, 14 February 2014, page 5), India’s Lupin

has completed a number of acquisitions that havebolstered its portfolio and pipeline, and also directlyexpanded its presence outside of its domestic market.

By far Lupin’s largest deal came in July lastyear when the firm agreed to pay US$880 million forNew Jersey-based Gavis Pharmaceuticals and its NovelLaboratories affiliate. The deal – which gave the Indianfirm its first manufacturing site in the US – closed inMarch (Generics bulletin, 18 March 2016, page 3).

Described at the time of its announcement byLupin’s chief executive officer, Vinita Gupta, as a“pivotal acquisition”, the Gavis deal is chief among anumber of contributing elements that Lupin expects toraise its group turnover from around US$2.0 billion atpresent to US$3.5 billion by March 2018.

“We believe, based on the initiatives that we haveexecuted, the acquisitions that we have made, ourorganic growth efforts, and the pipeline that we havefor the US, Japan, India, and other parts of the world,that we can get to $3.5 billion or thereabout [by 2018],”Gupta told investors.

Founded just nine years ago, Gavis has benefittedLupin immediately by adding 28 products to its USportfolio, bringing Lupin’s total US basket to 124. Thisalso includes the addition of nine controlled-substancedrugs and one dermatology product.

“We see the potential of expanding share on thegeneric side of the portfolio [through Gavis],” Guptaobserved. “Gavis had reasonable share but we have astronger reach and stronger relationships with thecustomers, which should enable us to expand share.”

But combined with the timing of the Gavisacquisition is Lupin’s ongoing strategy of establishingby 2018 generics platforms for niche, high-valueproducts, including for complex injectables, dermatologyand respiratory drugs.

Including Gavis, Lupin’s US pipeline numbers 163filings pending US Food and Drug Administration(FDA) approval. Of these, almost two-thirds – or 64% –represent oral-solid or oral-liquid formulations. Butthrough Gavis, which has added 58 filings to the pipeline,Lupin has also obtained several niche filings, includingfor dermatology and topical and controlled-substanceproducts (see Figure 1).

However, within the firms’ combined pipeline of256 in-development projects – of which Gavis hasadded 66 – the percentage of oral solids and oral liquidsfalls to just over half (see Figure 2). The next largestcategory is injectables, representing 15% of pipelinecandidates, which Lupin gained the capabilities todevelop when it acquired Nanomi.

Development projects also include respiratorydrugs, totalling 6% of candidates, as Gavis added a“highly-skilled US research organisation” thatcomplements Lupin’s research and development centrefor respiratory drugs in Coral Springs, Florida. Lupinrevealed last month that it was conducting a clinicaltrial for a metered-dose inhaler, and moreoverexpected a clinical trial for a dry-powder inhaler to

begin during its current 2017 financial year.As a result of this strategy, Lupin’s research and

development spending soared by 46.0% to Rs16.0 billionin its financial year ended 31 March 2016 (Genericsbulletin, 27 May 2016, page 5), equivalent to 11.7%of group sales that advanced by 8.7% to Rs137.0 billion.“We believe that [research and development spending]will be somewhere between 12% and 15% [of groupsales] for our financial year ending March 2017,” Lupin’sexecutive vice-chairman Kamal Sharma revealed.

“Research and development is the lifeline of ourbusiness,” he insisted, “and we will continue to deliveron the pipeline, and evolve the complex generics andthe specialty pipeline over time,” he noted.

Lupin’s expansion plans in the US face achallenge from its deficient manufacturing plant inGoa that received nine observations from the FDA inMarch (Generics bulletin, 18 March 2016, page 6),having received the same amount of observations inJuly last year. Around 30% of Lupin’s 105 filings inthe US are from the Goa site.

“We have responded to the [Goa] observations andwe have provided an update thereafter,” Sharma said.

Moreover, Lupin has just obtained establishmentinspection reports (EIRs) approving its Indian facilitiesin Aurangabad and Mandideep following FDA auditsin January and February this year respectively. G

Wrapping up its

US$880 million

acquisition of Gavis

in March has greatly

expanded and

diversified Lupin’s

US pipeline.

Dean Rudge reports.

Lupin counts on US pipeline

Oral solids/Liquids64%

Derm/Topical16%

Controlledsubstances

8%

Oral contraceptives6%

Ophthalmics4%

Inhalers1% Others

1%

Oral solids/Liquids54%

Injectables15%

Derm/Topical10%

Controlledsubstances

9%

Inhalers6%

Ophthalmics6%

Figure 1 (top): Breakdown by dosage form and category of Lupin’s163 filings currently pending US Food and Drug Administration(FDA) approval. Figure 2 (bottom): Breakdown by dosage formand category of Lupin’s pipeline of 256 products currentlyunder development in the US (Source – Lupin)

“Research and

development is the

lifeline of our business

and we will continue

to deliver on

the pipeline”


Valeant’s senior vice-president of neurology, dentistry and generics,Brian Stolz, has stepped down from the Canadian company

“to pursue other opportunities”.Stolz, who officially departed on 30 May, had been with Valeant

since July 2011, joining the company as executive vice-presidentof administration and chief human capital officer before taking onhis most recent responsibilities 11 months ago. Valeant offered nofurther comment on his resignation.

Separately, the Canadian firm has appointed Tyco International’scontroller and chief accounting officer, Sam Eldessouky, as seniorvice-president and corporate controller. In his new role, Eldessoukywill report directly to chief financial officer Robert Rosiello.

Controller joins after misstatementsEldessouky’s appointment comes shortly after Valeant admitted

that “improper conduct” by senior executives had caused the firmto misstate recent financial results. This led to delays in mandatoryfinancial filings (Generics bulletin, 25 March 2016, page 3).

Joe Papa, Valeant’s chairman and chief executive officer, saidfinancial reporting remained a “key area of focus” for the firm, “andwe look forward to Sam’s contributions as we enhance and bolster ourreporting structure and policies, and rebuild trust among investors”. G

PEOPLE


RESIGNATIONS

Valeant’s Stolz stepsdown from company

Michael Raya, chief executive officer of Hikma’s West-WardPharmaceuticals US subsidiary, has been welcomed onto the

board of the US Generic Pharmaceutical Association (GPhA).Described by GPhA president and chief executive officer Chip

Davis as a “proven industry leader”, Raya has been with Hikma since1992, taking on roles of increasing responsibility before being appointedto his current position with West-Ward eight years ago.

Raya’s appointment brings the GPhA’s board membership up to17. Mylan’s chief executive officer, Heather Bresch, chairs the board,having taken over from Momenta’s Craig Wheeler earlier this year(Generics bulletin, 26 February 2016, page 16). G

INDUSTRY ASSOCIATIONS

West-Ward CEO joins GPhA

KRKA has appointed Joze Mermal as the president of its supervisoryboard from 7 July. He replaces Matej Pirc, who has resigned. Atthe same time, Anja Strojin Stampar will become the board’sdeputy president.

SUN PHARMA’S Kathryn Jones has been nominated as a “risingstar” in the Global Counsel legal awards. Based in the US, she waspreviously director of intellectual property for Ranbaxy before itstakeover by Sun. Medichem’s general counsel, Ana Marti, isnominated in the regulatory category, while Mylan’s JenniferSunderland and Rimsa’s Aida Rendon each have a nominationin the intellectual property list.

BOGIN – the generics and biosimilars industry association in theNetherlands – is recruiting a policy manager. Candidates will beexpected to have an excellent command of written and spokenDutch and English as well as knowledge of the pharmaceuticalindustry, with expertise in regulatory affairs being an advantage.

COHERUS BIOSCIENCES has appointed Patrick O’Brien as itssenior vice-president of investor relations. O’Brien had previouslyserved in a similar role with US originator Gilead Sciences. “2016 isa transformational year for Coherus, as we prepare our productregistration filings and accelerate our second wave of products,”commented president and chief executive officer, Denny Lanfear.

VERNALIS – the UK-based drug-development specialist – has namedSandy Sommer as president and chief operating officer of its VernalisTherapeutics affiliate in the US. Sommer spent 24 years atAstraZeneca, most recently as president of the originator’s Colombianoperations. “Sandy’s depth of experience in sales and marketing, aswell as in general management, make him ideally qualified to lead ourUS operations through this critical period of multiple product launchesand rapid growth,” said Vernalis’ chief executive officer, Ian Garland.

JUBILANT LIFE SCIENCES said independent director ShardulShroff had resigned from the Indian firm’s board of directorswith immediate effect.

ANI PHARMACEUTICALS has hired former Shire and Mallinckrodtexecutive Mark Ginski “to help lead the advancement” of the firm’s“most exciting pipeline opportunity, the re-commercialisation ofour corticotropin new drug applications (NDAs)”. The US firmbought the corticotropin assets from Merck & Co for US$75 millionlast year (Generics bulletin, 2 October 2015, page 23). G

IN BRIEF


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