3 February 2017

Early US generic competition to Teva’s 40mg/ml thrice-weekly Copaxone (glatirameracetate) has inched closer after a US district court invalidated four patents shielding the

multiple-sclerosis brand. The Israeli group plans to launch an “immediate appeal”.In consolidated litigation involving abbreviated new drug application (ANDA) filers Amneal,

Dr Reddy’s, Mylan, Sandoz and Synthon, Delaware District Judge Gregory Sleet ultimatelyconcluded that US patents 8,232,250, 8,399,413, 8,969,302 and 9,155,776 were invalid dueto obviousness. All four patents – of five listed in the US Food and Drug Administration’sOrange Book, also including US patent 9,402,874 – expire on 19 August 2030.

Responding to the development, Teva noted it had in December last year also sued ANDAfilers over the ‘874 patent. Meanwhile, the firm added, Teva had recently filed suit overchallenges to US patent 9,155,775, which is not listed in the Orange Book and expires on 28January 2035 (Generics bulletin, 27 January 2017, page 9).

Sleet’s ruling comes months after the US Patent and Trademark Office’s (USPTO’s) PatentTrial and Appeal Board invalidated the ‘250, ‘413 and ‘302 patents following successful interpartes review proceedings launched by Amneal and Mylan (Generics bulletin, 9 September2016, page 16). Pointing out that the decision had been reaffirmed in December last year, Mylansaid a PTAB ruling on its challenge to the ‘776 patent was anticipated by 16 May 2017. G

Teva fails in US Copaxone case

COMPANY NEWS 2

Sun refuses to deny plans to divest Ohm 2Endo to slash 90 jobs as part of restructure 2Wockhardt sees path on 3remediation effort

Beximco and BioCare have deal in Malaysia 3Ajanta denies reports of FDA import block 4

Alembic has plans to grow 4its US pipelineSandoz delays adalimumab filing in US 5Biocon wins contract for Malaysian insulin 6

MARKET NEWS 7

UK seeks continuity after leaving the EU 7Mechanisms needed to enact TRIPS rule 7EU report lauded by 8Medicines for Europe

PRODUCT NEWS 9

Three firms receive positive CHMP nods 9US court bars Mylan on mesalamine rival 9Teva inhalers receive approvals 10from FDAMylan finds no cure in 11Acetadote appeal

Sandoz cancels filing for EU pegfilgrastim11Reddy’s faces lawsuit over 13cGMP practices

Teva settles Barr case over 13US ciprofloxacin

FEATURES 14

Akorn unveils its plans as 14its sales pass US$1 billionA healthy pipeline of imminent launchesand a focus on alternate dosage-formsare among the key elements of Akorn’sstrategy as it becomes a billion-dollar firm.Aidan Fry reports.

REGULARSEvents – Our regular listing 8Price Watch UK – UK pricing trends 9Pipeline Watch – Olmesartan 12People – Pfenex’ Liang resigns 16for board misconduct

Issue No.294

Amgen has secured the first positive opinion from the committee for human medicinalproducts (CHMP) within the European Medicines Agency (EMA) recommending

granting a marketing authorisation for a biosimilar rival to AbbVie’s Humira (adalimumab).The European Commission typically acts on the CHMP’s recommendations within 67days. Amgen’s ABP 501 adalimumab candidate – which was endorsed by the CHMP undertwo proprietary names, Amgevita and Solymbic, each in both 20mg and 40mg presentations –had been recommended for “all available indications”, the company pointed out.

These indications include rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis,axial spondyloarthritis, chronic plaque psoriasis, hidradenitis suppurativa, non-infectiousintermediate, posterior and panuveitis, Crohn’s disease and ulcerative colitis. The CHMPopinion also recommends approval for the treatment of certain pediatric inflammatory diseases,including Crohn’s disease, chronic plaque psoriasis and arthritis.

A “comprehensive data package” supporting Amgen’s submission to the EMA includedresults from two Phase III studies conducted in moderate-to-severe plaque psoriasis and moderate-to-severe rheumatoid arthritis patients. “The Phase III studies each met their primary endpointshowing no clinically meaningful differences to adalimumab,” Amgen noted, while “safetyand immunogenicity of ABP 501 were also comparable to adalimumab”. Data supporting “thetransition of adalimumab patients to ABP 501” were also included in the submission.

“The positive CHMP opinion for ABP 501 marks the first time an adalimumab biosimilarhas been recommended for approval in the European Union,” noted Amgen’s vice-presidentof research and development, Sean Harper. “This represents another significant milestone forour biosimilars portfolio and is an important step in our effort to develop high-quality biologicmedicines for patients suffering from chronic inflammatory diseases.” Amgen’s ABP 501biosimilar had previously been approved by the US Food and Drug Administration (FDA) asAmjevita (adalimumab-atto) last year (Generics bulletin, 30 September 2016, page 1). G

Amgen has first nod foradalimumab in Europe

Gen 3-2-17 Pg.1.indd 1 01/02/2017 17:29

2 GENERICS bulletin 3 February 2017

company news

Endo plans to slash around 90 jobs as part of a further restructuringprogramme “primarily” related to the firm’s corporate and US

Brands research and development functions in Malvern, Pennsylvania,and Chestnut Ridge, New York.

Part of the US firm’s ongoing “comprehensive organisationalreview”, the restructuring scheme follows a broad initiative unveiledin May last year concerning Endo’s US Generics business, whichincluded cutting approximately 740 jobs across two of Endo’s USmanufacturing sites and discontinuing more than 60 products fromwithin the firm’s legacy Qualitest US generics portfolio (Genericsbulletin, 13 May 2016, page 3).

Several months later, Endo had also introduced a unified operatingmodel that “streamlined our global supply chain organisation to bettersupport our branded and generics businesses”, pointed out presidentand chief executive officer Paul Campanelli.

The US firm said the latest restructuring programme would resultin a cash charge of approximately US$15-US$20 million, while Endoalso expected to realise annual pre-tax savings of around US$40-US$50million by the final quarter of this year.

“Endo expects to invest a portion of these cost savings in thecompany’s core product franchises and new product developmentprogrammes for both the branded and generic business segments,”the US-focused company noted. G

Business strategy

Endo to slash 90 jobsas part of restructure

Sun Pharma has declined to deny media reports that the firm isconsidering selling its Ohm Laboratories US business.Obtained through Sun’s US$4 billion takeover of Indian rival

Ranbaxy in March 2015, Ohm Laboratories manufactures bothprescription and OTC oral-solid dosage forms, and furthermore is alsoapproved by the US Drug Enforcement Agency (DEA) to manufacturecontrolled substances.

Indian media reports had suggested Sun was looking to sellOhm – which is based in New Brunswick, New Jersey – for aroundUS$100 million, as part of Sun’s ongoing consolidation plans in theUS following the Ranbaxy acquisition.

Responding to an enquiry from the Bombay Stock Exchange(BSE), Sun neither confirmed nor denied the reports. “Sun Pharmacontinues to evaluate its global operational footprint on an ongoingbasis,” the Indian firm said in a brief statement. “As and when there arematerial developments, if any, we will make the required disclosures.”

Midway through last year, Sun agreed to divest two US oral-solidmanufacturing units to local contract-manufacturer Frontida BioPharmas well as “15 related pharmaceutical products”, as part of “manufacturingconsolidation in the US”. Frontida agreed to continue manufacturingcertain products for Sun at the facilities – located in Philadelphia,Pennsylvania, and in Aurora, Illinois – on a “contract basis for a pre-determined period” (Generics bulletin, 10 June 2016, page 2). G

Manufacturing

Sun refuses to denyplans to divest Ohm

Gen 3-2-17 Pgs.2-16.indd 2 01/02/2017 17:30

3GENERICS bulletin3 February 2017

company news

Beximco Pharmaceuticals will take a 30% stake in a joint venturethat the Bangladeshi firm is setting up with Malaysian generics

and active pharmaceutical ingredients (APIs) company BioCareManufacturing. Financial details of the deal – Beximco’s “firstoverseas manufacturing collaboration” – were not disclosed.

Under the terms of the agreement, Beximco will provide “fulltechnical support” to BioCare to establish manufacturing facilitiesin Seri Iskandar, Perak, in Malaysia. BioCare – which has a “strongpresence in a range of key therapeutic segments in both governmentand private healthcare sectors in Malaysia” – will operate and fundthe specialised pharmaceuticals facility.

According to Beximco, an “international standard metered-doseinhaler facility” has been created as part of the “first phase of theproject”, and has already received good manufacturing practice approvalfrom the Malaysian Ministry of Health.

Although the venture’s first sales are expected to be made “during2017”, Beximco pointed out that it “does not expect a significantcontribution to its profits from the collaboration in the short term”.“However, the joint venture is an important testimony of the company’stechnical capability as a generics manufacturer,” Beximco stated.

Through the venture, dry-powder inhalers, ophthalmics, nasalsprays, and pre-filled syringes will be manufactured and supplied underthe Malaysian government’s ‘economic transformation programme’.Initiatives within the programme include “increasing investment inthe country’s pharmaceutical industry to provide dedicated drugmanufacturing facilities, improving generic drug capabilities, andpromoting local production”.

Beximco’s managing director Nazmul Hassan said the collaborationwas “in line with our aspiration to continue to strengthen our globalpresence”. The company recently struck a sales and distribution dealwith privately-owned US generics specialist Bayshore Pharmaceuticalsto launch the Bangladeshi company’s carvedilol 3.125mg, 6.25mg,12.5mg and 25mg tablets in the US under the Bayshore label(Generics bulletin, 18 November 2016, page 15).

Beximco increased its turnover by 14% to BDT7.63 billion(US$96.0 million) in its financial half year ended 31 December 2016.The firm saw its pre-tax profit rise by 18% to BDT1.46 billion, eventhough its gross margin declined by 0.8 percentage points to 46.5%.G

Mergers & acQuisitiOns/first-HaLf resuLts

Beximco and BioCarehave deal in Malaysia

Wockhardt says it has agreed a plan with the US Food and DrugAdministration (FDA) to address deficiencies at several of its

plants sequentially until all of them meet the US regulator’s requirements.At the end of last year, Wockhardt received a warning letter from

the FDA following an inspection at its Indian manufacturing facilityin Ankleshwar, Gujarat (Generics bulletin, 13 January 2017, page 3).The firm has also received FDA establishment inspection reports (EIRs)for three Indian units – one at Chikalthana and two at Waluj – that includecertain observations (Generics bulletin, 26 August 2016, page 3).

“We are in dialogue with the FDA, and we have agreed on theway forward in very clear terms,” insisted Wockhardt’s founder, chiefexecutive officer and chairman, Habil Khorakiwala. “We have decidedto do one plant at a time, and we hope that in the next three to fourquarters, we should see the light at the end of the long tunnel.”

In Wockhardt’s financial third quarter ended 31 December 2016,US sales slipped by 29% to Rs1.97 billion (US$28.9 million) “mainly

due to subdued business”, as group turnover fell by 8% to Rs9.95billion. Accounting for a fifth of Wockhardt’s sales, the US businessfiled two new abbreviated new drug applications (ANDAs) during thequarter. As of 31 December, 81 ANDAs were pending approval.

Wockhardt stated that a 5% increase to Rs3.55 billion in itsdomestic market – aided by three products launched in India duringthe quarter – was “in line with focused strategies on various therapiesand product launches”. Sales in Emerging Markets dropped by over atenth to Rs920 million, accounting for 45% of group sales whencombined with India (see Figure 1). International operations contributedover three-fifths of Wockhardt’s turnover, reaching Rs6.40 billion.

Sales in the UK decreased by 8% to Rs2.60 billion, whichWockhardt said was “mainly on account of a one-time opportunity”in the previous period. Excluding this, the company noted, the UKbusiness inched up by 2% measured in pounds. Khorakiwala addedthat the country’s ‘Brexit’ decision to leave the European Union (EU)had partly made an impact “because we had a significant UK businessand the translation loss in the pound is there”.

Continuing to focus on research and development in the quarter,Wockhardt spent Rs1.00 billion, or around 10% of sales, in this area.Khorakiwala said the company was outsourcing production to reviveits US business. G

Manufacturing/tHirD-Quarter resuLts

Wockhardt sees pathon remediation effort

Third-quarter sales Change Proportion(Rs millions*) (%) of total (%)

India 3,550 +5 36Emerging Markets 920 -12 9India/Emerging 4,470 +1 45

UK 2,600 -8 26Ireland 360 ±0 4France 150 +7 2Other 400 – 4Europe 3,510 -1 35

US 1,970 -29 20

Wockhardt 9,950 -7 100

* rounded to the nearest Rs10 million

Figure 1: Breakdown by region of Wockhardt’s sales in its financial third quarterended 31 December 2016 (Source – Wockhardt)

Mallinckrodt has agreed to divest the firm’s Intrathecal Therapyspinal column drug-delivery business to Piramal in a deal worth

around US$203 million. Subject to customary closing conditions, thetransaction is scheduled to close by the end of next month.

Intrathecal Therapy will bring to Piramal the Gablofen (baclofen)injectable – “the only US Food and Drug Administration (FDA)approved baclofen in pre-filled syringes and factory-sealed vials” – aswell as a higher Gablofen concentration “in late-stage development”.

Struck with the Indian firm’s Piramal Critical Care business, theagreed transaction includes a US$171 million fixed consideration, andcontingency payments of up to US$32 million based on the future grossprofit of Gablofen. The divested business had net sales of US$44.6million in Mallinckrodt’s financial year ended 30 September 2016. G

DivestMents

Mallinckrodt to sell Intrathecal

Gen 3-2-17 Pgs.2-16.indd 3 01/02/2017 17:30

4 GENERICS bulletin 3 February 2017

company news

3 February 2017 Issue 294

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

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

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

India’s Ajanta Pharma has moved to deny reports the firm hasreceived an import alert for its local formulations manufacturing

facility in Aurangabad after a batch of sildenafil citrate manufacturedby Ajanta was unlawfully sent to the US.

“We have no relations or connection to this dispatch of sildenafilto the US,” Ajanta confirmed, noting that the product – the activeingredient in Pfizer’s Viagra and Revatio brands – was sold by Ajantain India and certain emerging markets.

“US authorities have seized this product as it is not approved bythe US Food and Drug Administration (FDA). We once again clarifythat there is no import alert on our facility or any of our productsapproved by the FDA and we continue to supply products to the US.”

Ajanta’s clarification came as the firm reported group sales aheadby 12% to Rs5.33 billion (US$78.3 million) in its financial thirdquarter ended 31 December 2016.

Boosted by mid-teen sales growth for its dermatology andcardiology portfolio, alongside mid-single digit turnover rises for itsophthalmology and pain management drugs, Ajanta’s domestic salesclimbed at the same rate to Rs1.54 billion.

Meanwhile, an 8% sales rise to Rs2.11 billion in Africa, Ajanta’slargest export market by value, coupled with a turnover boom in theUS helped overcome sales plummeting in Asia as Ajanta’s total exportsturnover increased by 9% to Rs3.61 billion.

In the US, Ajanta’s sales soared from Rs40 million to Rs590million, as Ajanta revealed it held 16 final abbreviated new drugapplication (ANDA) approvals and had a further 14 pending FDAapproval, having submitted six filings during its current financial year.The Indian firm is targeting a total of 8-12 ANDA filings by the endof its financial year on 31 March.

Despite operating costs rising as a proportion of Ajanta’s sales –by two percentage points from 68% to 70% – the firm’s operatingprofit increased by 7% to Rs1.62 billion. G

Manufacturing/tHirD-Quarter resuLts

Ajanta denies reportsof FDA import block

Alembic intends to “rapidly expand the breadth and quality” of itsUS pipeline after the Indian firm’s International Formulations

sales dropped by over two-fifths to Rs3.03 billion (US$44.4 million)in its financial third quarter ended 31 December 2016. Group salesslipped by 17% to Rs7.76 billion, with the US adding Rs2.26 billion.

In the same period last year, Alembic’s US business had“outperformed” after launching rivals to Otsuka’s Abilify (aripiprazole)in 2015, which caused International Formulations sales to soar by248% to Rs5.21 billion (Generics bulletin, 29 January 2016, page 4).The company had at that time envisioned “a greater front-end presencein the US”, which Alembic said was now “in place”, with “26 productsalready launched” in the US. Meanwhile, Alembic commented thatits ‘ex-US’ business “remains driven by partnerships”.

The firm’s domestic branded formulations sales improved by 2%to Rs2.94 billion (see Figure 1). The firm’s active pharmaceuticalingredient (API) sales rose by 64% to Rs1.66 billion.

Alembic described its dermatology-focused joint venture withfellow Indian firm Orbicular – which was established in April lastyear under the name Aleor Dermaceuticals (Generics bulletin, 29April 2016, page 4) – as a 2016 ‘milestone’. G

tHirD-Quarter resuLts

Alembic has plans togrow its US pipeline

Third-quarter sales Change Proportion of(Rs millions) (%) total (%)

International Formulations 3,027 -42 39Indian Brand Formulations 2,941 +2 38APIs 1,663 +64 21Other 131 -35 2

Alembic 7,762 -17 100

Figure 1: Breakdown by region and business of Alembic’s sales in its financialthird quarter ended 31 December 2016 (Source – Alembic)

Gen 3-2-17 Pgs.2-16.indd 4 01/02/2017 17:30

5GENERICS bulletin3 February 2017

company news

Regulatory inspection requirements caused Sandoz to miss its goalof filing for biosimilar adalimumab approval in the US by the end

of 2016. “Based on discussions with the US Food and DrugAdministration (FDA) and ongoing capacity upgrades we are makingat our production site – and the timing of regulatory inspections thatwould be required – we have pushed the filing into the first half ofthis year,” stated Vas Narasimhan, chief medical officer and head ofthe newly created Global Drug Development (GDD) organisation atSandoz’ parent group, Novartis. There were “no issues with our clinicaldata”, he stressed.

Sandoz has also just announced that it will have to re-file laterthis year a pharmacokinetic study for its LA-EP2006 pegfilgrastimcandidate in the European Union (EU), with a similar re-submissionin the US scheduled for 2018 (see page 11).

A planned regulatory filing for Sandoz’ GP2017 adalimumabalternative to AbbVie’s Humira in the EU during the first half of thisyear is set to followed by a similar US submission during the secondhalf. The first half should also see an EU filing for the GP1111 biosimilarinfliximab acquired from Pfizer, followed by a US application forrituximab in the second half once progression-free survival data is ready.

Sandoz already has its GP2013 rituximab biosimilar under reviewby the European Medicines Agency (EMA) and anticipates a decisionin the second half of 2017, opening the door for a potential launchthis year, while the firm has also submitted a rituximab marketingauthorisation application in Japan.

“We will launch five big biosimilars [in the US and EU] betweennow and 2020,” Novartis’ chief executive officer, Joe Jimenez, toldinvestors. “The first two will be etanercept and rituximab in Europe.They have been filed and they are under review, and we are lookingforward to getting started with the big monoclonals.”

“Sandoz continued to build its portfolio of biopharmaceuticals,which now represents a US$1 billion-plus business, with roughly halfof that coming from the US,” Novartis stated. “In 2016, our biosimilarErelzi (etanercept-szzs) was approved in the US to treat the sameinflammatory diseases as the reference product, Amgen’s Enbrel, withits launch pending litigation. In addition, our biosimilar Binocrit(epoetin alfa) was approved in the EU for a new route of administration.We are currently evaluating options for an epoetin alfa filing in the US.”

With the US launch of Erelzi held up by Sandoz’ legal battle withAmgen, the company anticipates a regulatory decision on its GP2015etanercept filing in the EU during the first half of this year.

“The fact that we are so big in biosimilars, we are able to go intohealth systems around the world and talk to health ministers abouthow we can lower their costs, based on the big new monoclonalsthat are coming in biosimilars, while we make some headroom forinnovation,” Jimenez commented.

“Where we have had the most success as a company is in thepharmaceutical and generics/biosimilars framework,” he stated as herevealed that Novartis would “explore all options, ranging from retainingthe business to separation via a capital markets transaction such as aninitial public offering (IPO) or spin-off,” for its Alcon surgical devicesand contact lens division that accounted for 12%, or US$5.81 billion,of group turnover that fell by 2% to US$48.5 billion last year.

Sandoz made up just over a fifth of Novartis’ turnover in 2016with sales that rose by 1% as reported, and by 2% on a constant-currency basis, to US$10.1 billion as eight percentage points of volumegrowth more than offset six points of price erosion.

At constant exchange rates, Novartis pointed out, Sandozincreased its sales in most regions. “Sales rose by 7% in Centraland Eastern Europe, 3% in Western Europe, 1% in the US, 11% in

LatinAmerica and 6% in the Middle East and Africa. Sales in Asia-Pacific were comparable to the prior year.”

As Figure 1 shows, Sandoz’ total reported sales growth stemmedsolely from its Biopharmaceuticals business comprising biosimilars, itsGlatopa (glatiramer acetate) 20mg rival to Teva’s Copaxone blockbusterand biopharmaceutical contract manufacturing. Biopharmaceuticalssales up by 30% to US$1.00 billion following the US launches ofGlatopa in June 2015 and Zarxio (filgrastim-sndz) in September 2015more than compensated for a reported 1% slip in Retail Generics salesto US$8.62 billion that equated to 1% constant-currency growth.

Excluding turnover from finished doses under Sandoz labels, bulkAnti-Infectives sales to third parties declined by 11% to US$519million, “reflecting the discontinued low-margin products and weakflu season in the first quarter of 2016”.

Sandoz’ global gross margin dipped by a point to 42.5%, but thedivision increased its operating profit by 11% to US$1.45 billion,“driven by strong operating performance in 2016 and higher restructuringcharges and legal provisions in the prior year”. Sandoz improved itsoperating margin by 1.3 points to 14.2%, as a 4% rise in research anddevelopment spending to US$814 million was more than offset outby a 13% reduction to US$300 million in general and administrativecosts. Sales and marketing costs were flat at US$1.68 billion.

In the fourth quarter of 2016 – during which Sandoz suffered anunsatisfactory EMA inspection of a site in Germany “as the sponsorof a clinical trial” – the division improved its operating margin by2.6 points to 14.0% on global sales that rose by 2% to US$2.61 billion,including US$277 million from Biopharmaceuticals and US$356million from bulk and finished-dose Anti-Infectives.

On a constant-currency basis, sales rose by 3% to US$961 millionin the US (see Figure 2) “as continued strong performance inBiopharmaceuticals more than offset ongoing price erosion”. Turnoverin Western Europe advanced by 4% to US$715 million, “with stronggrowth in Germany, France and Italy”, while 16% growth to US$295million in Central and Eastern Europe was “largely driven by Russia,despite the continued impact of the negative macroeconomicenvironment in the region”. G

Business strategy/annuaL resuLts

Sandoz delays adalimumab filing in US

Fourth-quarter sales Reported Constant-currency(US$ millions) change (%) change (%)

Europe 1,113 +4 +6US 961 +2 +3Asia, Africa, Australasia 364 -6 -4Canada, Latin America 167 +6 +5

Sandoz 2,605 +2 +3

Established Markets 1,941 +3 +3Emerging Markets 664 ±0 +3

Figure 2: Breakdown by region of Sandoz’ sales in the fourth quarter of 2016(Source – Novartis)

Product Annual sales Reported Constant-currencyfranchise (US$ millions) change (%) change (%)

Retail Generics 8,623 -1 +1

Biopharmaceuticals 1,002 +30 +31

Anti-Infectives 519 -11 -10

Sandoz 10,144 +1 +2

Figure 1: Breakdown by product franchise of Sandoz’ sales in 2016 (Source – Novartis)

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6 GENERICS bulletin 3 February 2017

company news

Third-quarter sales Change Proportion of(Rs millions*) (%) total (%)

Small Molecules 3,900 +24 36Syngene Research Services 3,170 +17 29Branded Formulations 1,230 +18 11Biologics 1,200 +61 11Licensing 790 +148 7Other 630 +88 6

Biocon 10,920 +32 100* rounded to the nearest Rs10 million

Figure 1: Breakdown by business segment of Biocon’s sales in its financial thirdquarter ended 31 December 2016 (Source – Biocon)

Biocon has commenced commercial operations from the firm’sUS$250 million insulin manufacturing facility in Johor, Malaysia,

after being awarded a three-year supply contract by Malaysia’s Ministryof Health for recombinant human insulin cartridges and re-usableinsulin pens produced at the site.

Falling under the Malaysian government’s ‘Off-Take Agreement’initiative, which encourages local manufacturing of new pharmaproducts, the supply contract is worth MYR300 million (US$67.7million) over the initial three-year period, and includes an option toextend for an additional two years, subject to government approval.

The Indian firm said it would distribute its insulin productsthrough local player CCM Pharmaceuticals, which boasts an “extensivesupply chain network to service primary healthcare clinics andhospitals across Malaysia”. “Recombinant human insulin is the firstproduct from Biocon’s Malaysian facility approved by [the country’s]National Pharmaceutical Regulatory Authority (NPRA), whichcertified Biocon’s facility first in 2015,” the firm pointed out.

“Strong growth” of Biocon’s portfolio of insulin products helpedto increase sales of the Indian group’s Biologics segment, comprisingbiosimilars and novel biologics, by three-fifths to Rs1.20 billion(US$17.6 million) in its financial third quarter ended 31 December 2016.

Achieved several milestonesBiocon also achieved several ‘milestones’ for its burgeoning

biosimilars business in developed markets, including acceptance ofits filing for an alternative to Sanofi’s Lantus (insulin glargine)in Europe and, last month, for its biosimilar rival to Roche’s Herceptin(trastuzumab) in the US (Generics bulletin, 20 January 2017, page 10).Both filings stemmed from the firm’s co-development partnership withMylan, which is composed of three insulins and six biologics.

Meanwhile, turnover from Biocon’s Small Molecules segment, thefirm’s largest by value, climbed by a quarter to Rs3.90 billion (seeFigure 1), following “strong demand” for Biocon’s rosuvastatin activepharmaceutical ingredient (API) in the wake of generic versions ofAstraZeneca’s Crestor brand flooding the US market last year (Genericsbulletin, 22 July 2016, page 8). FDA approval for its own genericrosuvastatin tablets during the quarter represented the first approvalin the US for Biocon’s generic formulations business, the firm said.

With Branded Formulations and Syngene Research Services salesalso climbing, coupled with income from licensing deals more thandoubling to Rs790 million, Biocon’s group sales grew by 32% to Rs10.9billion. The firm’s pre-tax profit soared by 71% to Rs2.45 billion.G

Business strategy/tHirD-Quarter resuLts

Biocon wins contractfor Malaysian insulin

MALLINCKRODT has completed the sale of its nuclear imagingbusiness to IBA Molecular for around US$690 million, comprisingan upfront payment of US$574 million, around US$39 million oflong-term debt being assumed by IBA, and around US$77 million“contingent consideration”. The deal – struck in late August lastyear (Generics bulletin, 9 September 2016, page 6) – includes twomanufacturing facilities and more than 800 employees worldwide.

PORTON FINE CHEMICALS – the Chinese contract developmentand manufacturing organisation – has struck a deal through its USsubsidiary to acquire New Jersey-based contract chemistryorganisation J-Star Research “for no more than US$26 million incash”. Employing 47 staff, J-Star “offers all of the necessary servicesto support early-phase clinical development of small-moleculeactive pharmaceutical ingredients (APIs), with core business coveringcustom synthesis, process research, crystallisation research anddevelopment, and analytical services”, Porton said.

JUBILANT LIFE SCIENCES has announced that it has now received‘Responsible Care 14001:2013 certification’ for its corporate officein Noida, India, and its manufacturing unit in Gajraula, India, underthe American Chemistry Council’s Responsible Care programme.“The certification is a demonstration of Jubliant’s continuedcommitment towards sustainable business operations,” the firm said.

SUNSHINE BIOPHARMA is reviewing 23 additional generics forin-licensing to market and sell under its own label, which will takethe firm’s generics portfolio up to 27 upon completion. The Canadiancompany’s current portfolio comprises generic rivals to AstraZeneca’sArimidex (anastrozole) and Casodex (bicalutamide), Novartis’Femara (letrozole) and Merck’s Propecia (finasteride). SunshineBiopharma said it was “moving forward” with the procurement ofdrug identification numbers (DINs) for these products and a drugestablishment license (DEL) for a new facility secured through thefirm’s recent strategic alliance agreement with a “major pharmaceuticalcompany” (Generics bulletin, 8 July 2016, page 10).

DR REDDY’S has renamed its Dutch OctoPlus research centreto ‘Dr Reddy’s Research and Development BV’ with “immediateeffect”. Having acquired OctoPlus in 2013 following a public offerfor the Dutch drug-delivery specialist (Generics bulletin, 2 November2012, page 6), Dr Reddy’s said OctoPlus had “became a fully-integrated centre of excellence” for the Indian firm’s complexinjectables. “The renaming of our legal entity reflects ourtransformation from an external service provider into a seamlesslyintegrated research and development centre for Dr Reddy’s,” statedRoger Friedrichs, general manager and site head of Dr Reddy’sResearch and Development BV.

ONCOBIOLOGICS has announced it has closed the sale of US$1.65million senior secured notes and warrants to buy 379,500 sharesof its common stock, bringing the total amount issued to US$10.0million senior secured notes and warrants to buy an aggregate of 2.3million shares. The pure-play biosimilars developer said it had useda “portion of the proceeds” on debt, and that it would use the remainder“for working capital purposes as it pursues strategic opportunities”.

DECHRA PHARMACEUTICALS says its group sales for the sixmonths ended 31 December 2016 increased by approximately 34%at constant exchange rates. Sales through the Putney veterinarygenerics business acquired by Dechra last year (Generics bulletin,18 March 2016, page 6) “have benefitted post-integration from thesales and marketing efforts of the enlarged Dechra team”. G

In BRIeF

Gen 3-2-17 Pgs.2-16.indd 6 01/02/2017 17:30

7GENERICS bulletin3 February 2017

maRket news

Find out more: www.generics-bulletin.comEmail: awards@generics-bulletin.com

Call: +44 1564 777550

Sponsor, Enter, Join us!

Cocktail Reception & Awards PresentationTuesday, 24 October 2017Frankfurt Marriot Hotel, Frankfurt, Germany

Recognising the best in the global generics and biosimilars industriesPresented by Generics bulletin

@GGB_AwardsTwitter LinkedIn

The UK wants to maintain the “closest possible relationship” withthe European Medicines Agency (EMA) following the country’s

‘Brexit’ decision to leave the European Union (EU), the UK’sSecretary of State for Health, Jeremy Hunt, has insisted in a healthcommittee meeting.

Stating that he did not expect the UK to remain under the ambitof the EMA following Brexit – and that it was “likely that EU countrieswill want the EMA to move out” of the UK from its current Londonbase – Hunt said he hoped for a working partnership with the EUthat is “as close as what we currently have”.

“I am very hopeful that we will continue to work very closely withthe EMA,” Hunt commented. Furthermore, he said the UK would not“rule out an agreement with the EU over the mutual recognition ofmedicines and medical device approvals”.

Meanwhile, Ireland’s Minister for Health Simon Harris hasannounced that the country’s government has endorsed his request forthe EMA to relocate to Dublin in the aftermath of Brexit (Genericsbulletin, 18 November 2016, page 13).

Harris in late January visited the EMA’s London headquartersto meet with the agency’s executive director, Guido Rasi. It was“essential to minimise the impact of a relocation” on the EMA, Harrissaid. In particular, he added, it was key to find “a solution thatmaximises retention of existing staff”. G

reguLatOry affairs

UK seeks continuityafter leaving the EU

Rules and procedures must be implemented to help exporters andimporters to take advantage of a recent amendment to the World

Trade Organization’s (WTO’s) agreement on trade-related aspects ofintellectual-property rights (TRIPS), the South Centre intergovernmentalorganisation of developing countries has recommended.

In late January, an amendment to TRIPS entered into force allowingexporting countries to grant compulsory licences to generics suppliers“exclusively for the purpose of manufacturing and exporting neededmedicines to countries lacking production capacity” (Generics bulletin,27 January 2017, page 1). Interest in making use of this mechanismwas “likely to rise”, the South Centre suggested.

“With the number of essential medicines, including biologics, underpatent protection expected to increase, countries without manufacturingcapacity should explore all means available to increase affordableaccess to medicines for their people,” the South Centre recommended.“This will require the adoption, at the national or regional level, bothby potential exporting and importing countries, of streamlined, easyto follow rules and procedures that ensure legal certainty.”

Referring to a recent United Nations high-level panel on access tomedicines (Generics bulletin, 23 September 2016, page 1), the SouthCentre said this panel had also “highlighted the importance of designinglegislation that allows for quick, fair, predictable and implementablecompulsory licences for legitimate public-health needs”. G

inteLLectuaL PrOPerty

Mechanisms neededto enact TRIPS rule

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8 GeneRIcs bulletin 3 February 2017

maRket news

13-15 februaryn GPhA 2017 Annual Meeting

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

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

2-3 Marchn 2nd Business Development & Innovation

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

22-23 Marchn 13th Legal Affairs Conference

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

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

23-24 Marchn 15th Biosimilar Medicines Conference

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

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

29-30 Mayn EuroPLX 64

Vienna, AustriaThis meeting provides an opportunity to discuss and negotiateagreements, development, in-licensing and marketing, promotionand distribution.

Contact: raucon. tel: +49 6221 426296 0.e-mail: meetyou@europlx.com. Website: europlx.com.

EVENTS – February, March, April & May

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

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

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

An ‘initiative report’ published by the Environment, Public Healthand Food Safety Committee within the European Parliament

“places generic, biosimilar and value-added medicines at the heart ofthe debate on access to medicines”, according to off-patent industryassociation Medicines for Europe. The report “is expected to beadopted in plenary in March”, the association noted.

“The report underlines that generic medicines are a cornerstoneof European healthcare, biosimilar medicines offer tremendousopportunity for access to biotherapies and that value-added medicinescan help to address major healthcare challenges,” Medicines forEurope stated. Moreover, it also confirms that “the European Union(EU) is serious about improving access to medicines for Europeanpatients”, according to the industry association.

“Specifically, the initiative report calls for member states toencourage competition from generic and biosimilar medicines byremoving barriers and adopting uptake measures,” Medicines forEurope reports. “These proposals are also echoed in the June 2016health council conclusion on balanced pharmaceutical markets,” theassociation noted (Generics bulletin, 24 June 2016, page 5).

“Together with the June 2016 European Council conclusions,”Medicines for Europe insisted, “this report provides the Commissionwith a clear mandate to encourage more competition from genericand biosimilar medicines and recognises the importance of assessingthe worth of value-added medicines.” This, the association believes,“should translate into concrete support measures for member statesto help remove barriers and stimulate uptake, for example in theEU semester country-specific recommendations”.

“Medicines for Europe calls on the Commission to rapidlyintroduce these proposals into its policies that support member statehealthcare sustainability,” the association urged.

“After many debates,” observed Medicines for Europe directorgeneral Adrian van den Hoven, “the parliament is aligning with theEuropean Council to make competition from generic, biosimilar andvalue-added medicines a high priority in policies to support accessto medicines.” The Commission “should now take action to ensure thatthese proposals are translated into real measures so that all patientsacross Europe get the access they need”, he urged. G

reguLatOry affairs

EU report lauded byMedicines for Europe

Flynn Pharma has failed to obtain an injunction suspending an ordermade by the UK’s Competition and Markets Authority (CMA) to

reduce its prices for phenytoin sodium capsules (Generics bulletin,16 December 2016, page 9).

“Whilst it is clear that reducing its margins and prices as required isdeeply undesirable to Flynn, I am not convinced that it is eitherimpossible or impracticable,” stated Peter Freeman, chairman of theUK’s Competition Appeal Tribunal.

“The claimed effect on Flynn’s business and other products lookshighly speculative. The same goes for the claims that any price risewould be irreversible,” Freeman adjudicated. “The harm to the publicfrom allowing the continuation of higher prices for this productoutweighs the harm to Flynn that this may cause,” he said, noting thatFlynn could still appeal against the CMA’s decision. G

Pricing & reiMBurseMent

UK denies Flynn injunction

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9GeneRIcs bulletin3 February 2017

pRoduct news

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: cjoynson@wavedata.co.uk.

Quetiapine rises and dropsAverage UK trade prices for quetiapine tablets saw mixed trends

in January, according to the latest figures from WaveData.Comparing UK trade prices between the periods 1-31 December

2016 and 1-31 January 2017, the average prices for 60-tablet packsof immediate-release quetiapine rose by 32% to £2.18 (US$2.72) forthe 100mg strength, by 38% to £3.69 for 200mg tablets, by 38% to£3.47 for the 150mg presentation and by 41% to £5.79 for the 300mgstrength, based on averages calculated from at least 54 data points.

Meanwhile, modified-release quetiapine in packs of 60 tabletssaw declines for the 50mg strength of 31% to £13.30; of 29% for200mg tablets to £21.42; of 26% for the 400mg version to £43.99;and of a quarter for the 300mg presentation to £33.94.

No price concessions for quetiapine were included among thosegranted by the UK’s Department of Health (DoH) towards the endof January. A concession price of £19.54 was maintained for30-count packs of buspirone 5mg tablets (Generics bulletin, 27January 2017, page 8), which saw their average price increase bymore than half to £19.32 as the lowest available offer almostquadrupled to £9.50.

And metformin 500mg tablets in packs of 28 saw theiraverage price more than double, rising by 138% to £0.59. G

pRIce watcH ....... uk

Mylan’s proposed generic version of Shire’s Lialda (mesalamine)1.2g delayed-release tablets infringes a key US patent protecting

the originator’s brand, a US district court has decided in litigationover the inflammatory bowel disease treatment.

Following a four-day bench trial in September last year, FloridaDistrict Judge Charlene Edwards Honeywell said Shire had “met itsburden to prove by a preponderance of evidence” that Mylan’sabbreviated new drug application (ANDA) product met all aspects ofclaim 1 within US patent 6,773,720, which expires on 8 June 2020.Therefore, Honeywell ruled, Mylan’s proposed mesalamine delayed-release tablets literally infringed the patent. Mylan’s proposed productalso literally infringed claim 3, the court found.

Meanwhile Honeywell also sided with Shire’s allegation ofinduced infringement, pointing out that asserted patent claims covereduses of the brand approved by the US Food and Drug Administration(FDA). “Mylan seeks to ‘piggyback’ on the FDA approval of Lialdawith the same active ingredient and a drug dissolution profile coveredby the asserted claims,” she commented.

And on the issue of contributory infringement, Honeywellconcluded that Mylan’s knowledge of the ‘720 patent ahead of filingits ANDA showed that “Mylan’s product is ‘especially made’ for ‘usein practicing the patented process’ that is a ‘material part of theinvention’”. “In light of the undisputed evidence of the identicalindications for the drugs and the properly construed asserted claims,no substantial non-infringing uses exist,” she ordered.

Dismissing Mylan’s claims of invalidity with prejudice, Honeywellbarred the US firm from receiving approval for its ANDA until the‘720 patent expires on 8 June 2020.

Mylan’s failure to work around the ‘720 patent puts it alongsideTeva’s Actavis, which was last year knocked back by a Florida districtcourt on both infringement and validity (Generics bulletin, 8 April2016, page 11). However, Zydus Cadila was later in 2016 able toconvince a Delaware district court that its proposed mesalaminedelayed-release tablets did not infringe the patent (Generics bulletin,23 September 2016, page 12). The originator has appealed this ruling.

Shire also faces additional court proceedings over Lialda in lightof additional ANDA submissions from several firms, including Amnealand Lupin. The US Patent and Trademark Office’s (USPTO’s) PatentTrial and Appeal Board (PTAB) did, however, recently uphold as validthe ‘720 patent following earlier inter partes review proceedings(Generics bulletin, 14 October 2016, page 16).

Global sales of Lialda, known as Mezavant or Mezavant XL inEurope, reached US$570 million in the first nine months of 2016.G

gastrOintestinaL Drugs

US court bars Mylanon mesalamine rival

Hospira, JensonR+ and Therakind have secured positive opinionsrecommending granting pan-European marketing authorisations

from the committee for human medicinal products (CHMP) within theEuropean Medicines Agency (EMA), covering two generics and onehybrid medicine. The European Commission typically decides within67 days whether to convert the committee’s positive opinions intopan-European centralised marketing approvals.

The CHMP said Hospira should be given a centralised marketingauthorisation for its daptomycin generic, which will be available asa 350mg and 500mg powder for solution for injection or infusion. Usedto treat complicated skin and soft-tissue infections, right-sided infectiveendocarditis and staphylococcus aureus bacteraemia, DaptomycinHospira is “administered intravenously and is 100% bioavailable”,meaning a bioequivalence study against the reference product, Merck,Sharp & Dohme’s Cubicin, was not required.

JensonR+’s Yargesa (miglustat), a generic rival to ActelionPharmaceuticals’ Zavesca, also obtained a positive opinion from theCHMP. Available as 100mg capsules, Yargesa is indicated to treatgaucher disease in patients “for whom enzyme replacement therapy isunsuitable”. The CHMP proposed Yargesa “be prescribed by physicianswho are knowledgeable in the management of gaucher disease”.

Meanwhile, the CHMP also recommended authorising TheraKind’shybrid medicine Jylamvo (methotrexate) 2mg/ml oral solution, whichis used to treat rheumatological disorders, psoriasis and acutelymphoblastic leukaemia. G

antiBiOtics

Three firms receivepositive CHMP nods

Pfizer’s Hospira has filed petitions seeking inter partes reviews of twoUS patents protecting Roche’s Herceptin (trastuzumab) by the US

Patent Trial and Appeal Board (PTAB). The two patents – US patents7,846,441 and 7,892,549 – cover methods of using trastuzumab incombination with certain other agents to treat cancer. The petitionsnoted that the ‘549 patent was “within the same family” as Europeanpatent EP1,037,926, which was recently declared invalid in the UK(Generics bulletin, 9 December 2016, page 11). G

BiOLOgicaL Drugs

Hospira challenges Herceptin

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pRoduct news

The Medicines Patent Pool (MPP) has signed a licensing agreementwith Johns Hopkins University to develop tuberculosis (TB) drug

candidate sutezolid. Describing the antibiotic as a “promisinginvestigational treatment”, the group said sutezolid, if developed incombination with other drugs, “could be used to more effectively treatboth drug-sensitive and drug-resistant TB in patients”.

Johns Hopkins University is granting the MPP an “exclusive,royalty-free licence covering all countries that currently have patentsissued or pending for a combination therapy comprising sutezolidand two additional compounds used to treat TB such as pretomanid,delamanid, bedaquiline, rifampicin and moxifloxacin”. Accordingto the MPP, the patent for the base compound sutezolid expired inAugust 2014, but the patent for the use of sutezolid in combinationtherapy for TB – held jointly by Pfizer and Johns Hopkins University –is valid until August 2029 in the countries in which it was filed.

Last October, the MPP reorganised its group into three divisionsfocusing on HIV, hepatitis C and tuberculosis (Generics bulletin, 21October 2016, page 16), after broadening its remit beyond antiretroviralsin late 2015 (Generics bulletin, 20 November 2015, page 16).

“We are proud to work with Johns Hopkins University toencourage the further development of sutezolid, a potentially importantcomponent of new TB regimens,” stated Greg Perry, the MPP’sexecutive director. “Faster acting, better therapies to treat TB are aparticularly urgent global public health priority.” G

tuBercuLOsis Drugs

Patent Pool gets first TB deal

ENDO has received US Food and Drug Administration (FDA)approval for Corphedra (ephedrine sulfate). The injectable forhypotension in surgical settings – submitted to the agency as ahybrid 505(b)(2) application – is packaged in cartons of 25 single-use 50mg/1ml vials and will begin shipping this month. CitingQuintilesIMS data, Endo said the ephedrine sulfate injection marketwas worth US$177 million in the year ended 30 November 2016.

PHARMAC – New Zealand’s Pharmaceutical Management Agency– has struck a deal with Baxter to list the firm’s glucose withpotassium chloride and sodium chloride intravenous fluids intwo presentations. They will be available in hospitals from the startof March 2017.

SANDOZ’ US Supreme Court battle with Amgen over the BiologicsPrice Competition and Innovation Act (BPCIA) requires briefs tobe submitted by mid-April, according to a briefing schedule that hasbeen adopted by the court. Opening briefs in the case – which dealswith the BPCIA’s requirements on the 180-day notice of commercialmarketing that must be provided to the brand company, as well asoriginator access to abbreviated biologic license applications (Genericsbulletin, 20 January 2017, page 1) – must be submitted by Sandoz onor before 10 February and by Amgen on or before 10 March tosupport their petitions, with response briefs due by 31 March and by14 April. Meanwhile, amicus briefs must be submitted in support ofSandoz’ petition by 17 February and for Amgen’s petition by 17 March.

HOSPIRA has issued a voluntary US recall for a lot of vancomycinhydrochloride for injection, “due to the presence of particulatematter within a single vial”. If administered to a patient, Hospirawarns, “it may result in local swelling, irritation of blood vessels ortissue, blockage of blood vessels and/or low-level allergic responses”.A customer report had confirmed the presence of particulate matter.

UK CANCER DRUG PRICES – including for generics – have insome cases risen by more than 1,000% between 2011 and 2016,according to researchers from the University of Liverpool. Researchpresented during the European Cancer Congress 2017 highlightedsteep rises in the cost of treatments such as busulfan and tamoxifen.“We have found that some companies take over the supply of somegeneric cancer medicines and then raise the price progressively,”stated lead researcher, Andrew Hill.

AMNEAL has launched generic rivals to Lotronox (alosetron)0.5mg and 1mg tablets in the US. Hikma’s West-Ward holds theonly other generic approval for the irritable bowel syndrometreatment. Amneal has also just secured the first US approval fora generic rival to Namzaric (donepezil/memantine) 10mg/14mgand 10mg/28mg extended-release capsules.

SANDOZ CANADA has introduced a generic equivalent toAdderall XR (amphetamine salts) extended-release capsules.

COHERUS BIOSCIENCES has filed four petitions for inter partesreview by the US Patent and Trademark Office (USPTO) of thevalidity of AbbVie’s US patent 9,085,619, which covers formulationsof adalimumab that do not contain a buffer. “The ability of proteinsto self-buffer has been known for decades,” insisted the US-basedpure-play biosimilars developer.

TEVA has been sued by Aralez in a Texas district court for infringingfour US patents protecting Yosprala (aspirin/omeprazole)325mg/40mg and 81mg/40mg delayed-release tablets. G

In BRIeF

Teva has expanded its respiratory portfolio after the US Food andDrug Administration (FDA) approved the firm’s fluticasone

propionate and fluticasone propionate/salmeterol RespiClick inhalers.Both asthma therapies are delivered through Teva’s proprietaryRespiClick breath-actuated, multi-dose dry powder inhaler.

ArmonAir RespiClick (fluticasone propionate) has approvedstrengths of 55µg, 113µg and 232µg doses, while AirDuo RespiClick(fluticasone propionate/salmeterol) – a fixed-dose combination productcontaining the same active ingredients as GlaxoSmithKline’s (GSK’s)Advair – is available in 55µg/14µg, 113µg/114µg and 232µg/14µg doses.Both products are to be administered as one inhalation twice daily.

“As a company at the forefront of developing inhaler technologiesfor people living with asthma, we are very pleased to now have twoadditional RespiClick-delivered medicines approved for adolescentand adult patients in the US,” said Michael Hayden, Teva’s presidentof global research and development and chief scientific officer.

Last June, the FDA accepted for filing Teva’s 505(b)(2) hybridapplications for the RespiClick inhalers (Generics bulletin, 1 July 2016,page 10), “supported by data from Teva’s clinical developmentprogramme”, including “three Phase III trials which evaluated theefficacy and safety of the treatments in adolescent and adult patients”.

At around the same time last year, the Israeli firm obtainedpositive opinions from the committee for human medicinal products(CHMP) within the European Medicines Agency (EMA) for its AirexarSpiromax and Aerivio Spiromax salmeterol xinafoate/fluticasonepropionate inhalers, both of which are similar hybrid alternatives toGSK’s Seretide Diskus version of Advair in Europe. G

resPiratOry Drugs

Teva inhalers receiveapprovals from FDA

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11GeneRIcs bulletin3 February 2017

pRoduct news

In 2017 Efarmesis celebrating its30th anniversary

Efarmes is offering the following dossiers with BE studies:

Contact: generics@efarmes.es Visit: www.efarmes.com

Products subject to any patent in force in any country will not be offered and/ormade available for commercial purposes prior to the relevant patent expiry date.

n Olmesartan+Amlodipine+ n ModafinilHydrochlorothiazide n Rivastigmine

n Rasagiline n Deflazacortn Sildenafil n Pioglitazone

Mylan has failed to convince a US Court of Appeals that a USmethod-of-use patent shielding Cumberland’s Acetadote

(acetylcysteine) intravenous antidote to acetaminophen, or paracetamol,overdoses is invalid and thus not infringed by Mylan’s proposedgeneric version.

Towards the end of 2015, Illinois District Judge Rebecca Pallmeyerrejected Mylan’s allegations that US patent 8,399,445 – which coversmethods of administering formulations of acetylcysteine that are freefrom chelating agents such as edetate disodium (EDTA) – wasderived and obvious (Generics bulletin, 9 December 2015, page 21).

Pallmeyer was moreover not convinced by Mylan’s allegationsthat the ‘445 patent – which expires on 24 August 2025 – wasanticipated, although the issue was not discussed on appeal.

According to Mylan, Cumberland had derived the invention ofthe ‘445 patent from US Food and Drug Administration (FDA)employees who questioned the need for EDTA when first consideringCumberland’s application for an original EDTA-containing Acetadoteformulation. Meanwhile, Mylan insisted, the patent “would have beenobvious in light of certain prior-art communications from the FDA”,including a chemistry review and the reformulated Acetadote’sapproval letter, which were issued in January 2004.

Both allegations were rejected. The three-judge appeals panel firstfound that Mylan had not ‘carried the burden’ of proving that the‘445 patent’s inventor, Leo Pavliv, had derived “the specific idea toremove EDTA from Acetadote…and not add another chelating agent”.“The [district] court thus found that Mylan did not prove that an FDAperson conceived of that formulation, or communicated it to Cumberland,before Pavliv thought of it. The evidence supports the finding.”

Turning to obviousness, the appeals court said Pallmeyer’s priorfinding was “not clearly erroneous”. “Considerable evidence supportsthe finding that relevant skilled artisans believed that chelating agentswere necessary to sequester metal contaminants and prevent oxidativedegradation of acetylcysteine and that such artisans had no reasonableexpectation of stability without such an agent,” the appeals court said.

The FDA’s Orange Book lists five US patents against Acetadote,including the ‘445 patent, running until 2032.

Cumberland – which reported Acetadote sales totalling US$5.53million in the first nine months of last year – supplies Perrigo withan authorised generic of the brand, included in that total. G

antiDOtes

Mylan finds no curein Acetadote appeal

Sandoz has withdrawn its application for a biosimilar rival toAmgen’s Neulasta (pegfilgrastim) in Europe. The firm has notified

the committee for human medicinal products (CHMP) within theEuropean Medicines Agency (EMA) that it wishes to withdraw theapplication for its Zioxtenzo version of the neutropenia treatment,which was to be available as a 6mg/0.6ml solution for injection.

Prior to the withdrawal, the CHMP had “evaluated the initialdocumentation provided by the company and formulated a list ofquestions”. “The company had not yet responded to the questions atthe time of the withdrawal,” the CHMP added.

Despite Sandoz presenting studies to show Zioxtenzo’s similarityto Neulasta – including safety and efficacy studies – the CHMP saidit “was of the provisional opinion that Zioxtenzo could not havebeen approved as a biosimilar of Neulasta”.

Outlining two “main concerns”, the committee maintained thatthe “study results were not able to show that the concentrations ofpegfilgrastim in blood were the same after taking Zioxtenzo andNeulasta”. The CHMP was also concerned by the lack of a certificateof good manufacturing practice (GMP) for the medicine’s manufacturingsite. “An inspection of the site will therefore be needed before themedicine can be approved,” the committee outlined.

Data not available in timeSandoz told the committee it had discontinued its application

because it “will not be able to provide the additional data required bythe CHMP within the regulatory timeframe allowed for the procedure”.“Sandoz will continue to collaborate with the EMA to make thisproduct available to patients in the European Economic Area (EEA),”the firm explained in its withdrawal letter, “and intends to resubmitthe application as soon as the outstanding information is available,”by the end of 2017 (see page 5). The firm added that the withdrawal“does not impact ongoing clinical trials”.

At the end of June last year, Sandoz received a complete responseletter from the US Food and Drug Administration (FDA), outliningproblems with the firm’s regulatory filing for its LA-EP2006 biosimilarpegfilgrastim candidate in the US (Generics bulletin, 22 July 2016,page 9). The firm acknowledged that such applications were “complexfilings where we have different elements we need to work through”.

Noting in October that it was in discussions with both the FDAand the EMA on pegfilgrastim, Sandoz said it planned to submit datafrom an additional study to address the FDA’s concerns outlined in thecomplete response letter (Generics bulletin, 28 October 2016, page 1).

Gedeon Richter recently also withdrew from the EMA itsmarketing authorisation application for its proposed pegfilgrastimbiosimilar, owing to a data issue that meant that the firm’s supportinginformation was insufficient for the CHMP to conclude a positiverisk-benefit assessment (Generics bulletin, 6 January 2017, page 16).

Coherus BioSciences had a marketing authorisation applicationaccepted for review by the EMA late last year, and the firm insistedthe filing “provides the basis for good partnering opportunities for[the CHS-1701 pegfilgrastim candidate] in European markets in thefirst half of 2017” (Generics bulletin, 9 December 2016, page 9).

Coherus also believes it will have “the first [US] biosimilarpegfilgrastim to be approved and to complete with Neulasta” after itsmarketing authorisation application for CHS-1701 was accepted forreview by the FDA with an action date of 9 June 2017 (Genericsbulletin, 14 October 2016, page 17). G

BiOLOgicaL Drugs

Sandoz cancels filingfor EU pegfilgrastim

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12 GeneRIcs bulletin 3 February 2017

pIpelIne watcH

SPC expiries in February

INN Country

Bosentan Norway, Switzerland *

Emtricitabine Czech Republic, Finland, Poland

Esomeprazole Estonia

Factor Willebrand Denmark, Germany, Spain,Sweden, UK

Gadobutrol Portugal

Olmesartan Austria, Belgium, Czech Republic,Denmark, Finland, France, Germany,Greece, Hungary, Iceland, Ireland,Italy, Luxembourg, Netherlands,Norway, Portugal, Switzerland, UK

Olmesartan/Amlodipine Belgium, Finland, Italy, Luxembourg,Switzerland

Olmesartan/Hydrochlorothiazide Belgium, Finland, Italy, Luxembourg,Norway, Switzerland

Olmesartan/Amlodipine/ Finland, Luxembourg, SwitzerlandHydrochlorothiazide

* EU countries have a 6-month paediatric extension to August 2017

Figure 1: Molecules for which supplementary protection certificates (SPCs) expire incertain markets in February 2017 (Source – Ark Patent Ingelligence)

Data exclusivity expiries in February

INN Country/Region

Agomelatine European Union *

Aztreonam US

Betaine European Union

Cimicoxib Turkey

Collagenase clostridium histolyticum Turkey

Dabigatran Korea

Dapoxetine European Union *

Dasatinib Switzerland

Degarelix European Union *

Influenza (B/Brisbane/60/2008, European UnionH1N1, H3N2) (IDFlu)

Lasofoxifene European Union *

Prasugrel European Union *

Romiplostim European Union *

Spinosad Turkey

Tafluprost US

* This will be followed by two years of market exclusivity, where a generic will not beplaced on the market

Figure 2: Molecules for which data exclusivity expires in certain markets duringFebruary 2017 (Source – Ark Patent Ingelligence)

This monthly update of key patent, SPC and data exclusivity data is extracted from QuintilesIMS’ Ark Patent Intelligence ExpiryDatabase. Covering 130 countries and over 3,000 INNs, Ark Expiry Database contains watertightdata teamed with the ultimate in generic launch analysis.For further information, visit www.arkpatentintelligence.comor e-mail: hello@arkpatentintelligence.com.

February brings the expiry of supplementary protection certificate(SPC) protection for olmesartan in the majority of European markets,

affecting Daiichi-Sankyo’s Olmetec olmesartan medoxomilantihypertensive, known as Benicar in the US. The SPCs are basedon European patent EP0,503,785, which covers ‘biphenylimidazolederivatives, their preparation and their therapeutic use’.

Also affected are several olmesartan medoxomil combinationantihypertensives, including the Olmetec Plus olmesartan/hydrocholorothiazide brand, which is marketed in the US under thebrand name Benicar HCT.

The Sevikar amlodipine/olmesartan combination – in the USknown as Azor – will also be affected, along with the Sevikar HCTamlodipine/hydrocholorothiazide/olmesartan brand, which is sold asTribenzor in the US. “However,” comments QuintilesIMS, whichmonitors intellectual-property protection through its Ark PatentIntelligence database, “the latter two combination products arefurther protected by constraining patents.”

SPC protection for sole olmesartan will come to an end in 18European markets (see Figure 1) in February. For olmesartan/amlodipine/hydrocholorothiazide combinations, SPC expiries will affectFinland, Luxembourg and Switzerland, while olmesartan/amlodipineSPCs will expire in those three countries along with Belgium andItaly. And olmesartan/hydrocholorothiazide combination SPCs willcome to an end in the same five countries as well as Norway.

In Daiichi-Sankyo’s financial first half ended 30 September 2016,the Japanese firm reported European sales by its olmesartan franchise

that slipped by 6.7% to C209 million (US$224 million), as combinedsales of the Olmetec and Olmetec Plus olmesartan and olmesartan/hydrocholorothiazide brands together slipped by just under a tenth –8.8% – to C115 million.

Turnover from Sevikar in Europe dropped by 11.5% to C56 millionover the six-month period, according to Daiichi-Sankyo, while SevikarHCT sales climbed by 9.5% to C38 million in the financial first half.

SPC expiries for emtricitabine will occur in the Czech Republic,Finland and Poland in February, while an Estonian SPC foresomeprazole and a Portuguese protection certificate covering gadobutralwill also come to the end of their terms this month.

At the same time, SPCs covering Actelion’s Traceleer (bosentan)will see expiries in Norway and Switzerland in February, QuintilesIMSindicates, although European Union (EU) countries will have to waituntil August this year for a six-month paediatric extension to expire.

February also brings the expiry of US data exclusivity for Bristol-Myers Squibb’s Azactam (aztreonam) antibiotic, as well as Akorn’sZioptan (tafluprost) ophthalmic solution. And in Turkey, threemolecules – cimicoxib, collagenase clostridium histolyticum andspinosad – will see data exclusivity expiries this month, along withdabigatran in South Korea (see Figure 2).

Molecules lined up for data exclusivity expiries in the EU inFebruary include agomelatine, dapoxetine and degarelix, along withlasofoxifene, prasugrel and romiplostim. However, QuintilesIMSpoints out, “this will be followed by two years of market exclusivity,where a generic will not be placed on the market”. G

SPC expiry opens up olmesartan brands

Gen 3-2-17 Pgs.2-16.indd 12 01/02/2017 17:30

13GeneRIcs bulletin3 February 2017

pRoduct news

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Dr Reddy’s Laboratories is being sued in the US for US$310 millionin damages by a development partner, Korean biotech firm Mezzion

Pharma, for allegedly misrepresenting and concealing the state of itscurrent good manufacturing practice compliance with the US Foodand Drug Administration (FDA).

According to the suit filed in a New Jersey district court, the firmshad collaborated for around a decade to develop for the US a novelerectile dysfunction treatment, udenafil. Dr Reddy’s was responsiblefor manufacturing the active pharmaceutical ingredient (API) andfinished drug product, as well as Phase III clinical trials.

Around a year after the new drug application (NDA) was filed inDecember 2014, however, Reddy’s received a warning letter from theUS Food and Drug Administration (FDA) covering three productionplants in India (Generics bulletin, 20 November 2015, page 3).

“Reddy’s misstatements, omissions, and fraudulent conduct, whenexposed by the FDA, caused Mezzion to not receive FDA approvalfor the commercial marketing of udenafil, to be barred from usingthe planned Reddy’s production facilities or any Reddy’s data, andto suffer serious monetary losses and delays in working toward USsales of udenafil,” the Korean firm summarised.

Responding in a brief disclosure to the Bombay Stock Exchange(BSE), the Indian firm said that “as of now, [Dr Reddy’s] has not beenserved with any legal papers or legal processes in the matter”. G

erectiLe-DysfunctiOn Drugs

Reddy’s faces lawsuitover cGMP practices

Mithra Pharmaceuticals intends to submit its generic version ofMerck & Co’s NuvaRing (ethinylestradiol/etonogestrel) 0.015mg/

0.120mg vaginal ring for marketing approval in both Europe and theUS in the second quarter of this year. The Belgium-based femalehealthcare specialist said two studies involving 42 subjects confirmedits Myring alternative was bioequivalent to the reference brand.

“Following completion of successful bioequivalence studies inboth Europe and the US, we are on track to submit Myring for regulatoryapproval in both markets in the second quarter of 2017,” commentedValérie Gordenne, Mithra’s chief scientific officer.

Chief executive officer François Fornieri said the firm was “ontrack to sign a commercialisation deal in 2017, both in the US, as wellas in other territories”. “Additionally, this is great news for Mithra’scontract development and manufacturing organisation (CDMO), ourintegrated research and development and manufacturing platform, wherewe will be producing Myring,” he stated. “This fundamental step showsthat Mithra is successful in developing complex therapeutic solutions.”

NuvaRing is protected by US patent 5,989,581 – which is theonly patent currently listed against the brand in the US Food andDrug Administration’s (FDA’s) Orange Book – until 8 April 2018.G

cOntracePtives

Mithra plans rival to NuvaRing

Teva has reached a preliminary agreement worth US$225 millionto settle an antitrust class action lawsuit concerning a ‘pay-for-

delay’ deal involving Bayer’s Cipro (ciprofloxacin).Brought by a group of Cipro purchasers in California, the lawsuit

stems from a 1997 settlement agreement struck between Teva’serstwhile Barr Pharmaceuticals affiliate – which Teva acquired in2008 – and the German originator over the antibiotic brand.

Under the agreement, Barr agreed to abandon its challenge to aCipro patent expiring in 2003 in exchange for US$398 million. Inaddition to violating antitrust laws, the settlement also drove up pricesof ciprofloxacin, the purchasers claim.

Bayer also reached similar settlement deals allegedly blockinggeneric competition to Cipro with a group of legacy genericscompanies, including Hoechst Marion Roussel, The Rugby Groupand Watson. Purchasers in the case have already reached settlementagreements with these firms worth US$174 million.

“Just as Bayer reaped the benefits of a prolonged monopoly, sodid the generic defendants come out far better under the terms of theCipro agreements,” the plaintiffs claimed. “Barr received more insettlement than it could have reasonably expected to gain throughcompetition,” they insisted.

Antitrust complaints lodged against the Cipro settlements hadpreviously trundled through various courts in California since 2000before the latest settlement, which must now be ratified during arequested final approval hearing.

“If the court approves the US$225 million settlement with Barr,the class’ total recovery is US$399 million. The amount exceeds, byapproximately US$68 million, plaintiffs’ highest single damage estimate.It is an extraordinary result for the class,” the purchasers stated.

A Teva spokesperson told Generics bulletin the company was“pleased that this longstanding litigation has been resolved”. G

antiBiOtics

Teva settles Barr caseover US ciprofloxacin

Gen 3-2-17 Pgs.2-16.indd 13 01/02/2017 17:30

14 GeneRIcs bulletin 3 February 2017

BusIness stRateGy

A healthy pipeline of

imminent launches

and a focus on

alternate dosage-forms

are among the key

elements of Akorn’s

strategy as it becomes

a billion-dollar firm.

Aidan Fry reports.

Akorn unveils its plans asits sales pass US$1 billion

Outlining Akorn’s strategy to investors last month,the US-based company’s chief financial officer,Duane Portwood, admitted that he had faced a

steep learning curve during his first 15 months in thejob since joining in October 2015. “This is a toughbusiness, and it has been a tough year,” he told attendeesof JP Morgan’s 35th Annual Healthcare Conferenceheld in San Francisco, US.

Among the “operating and strategic difficulties” hecited for companies operating in the generics arena werethe impact of politicians’ comments on drug pricing,media headlines about Department of Justiceinvestigations and “daily price challenges that we getfrom our customers”, while accounting problems hadlargely overshadowed the firm’s growth story.

Furthermore, Portwood pointed out, ophthalmics andinjectables specialist Akorn faced the added challengeof operating sterile manufacturing facilities, one thathad been highlighted midway through last year when theUS Food and Drug Administration (FDA) issued several‘Form 483’ observations following an inspection in Junelast year of the firm’s US Grand Avenue plant in Decatur,Illinois (Generics bulletin, 28 October 2016, page 5).

Shortly after the deficiencies – which includedfailing to record or justify departures from writtenproduction and process-control procedures – becamepublic, chief executive officer Raj Rai admitted thatapproval for around 10 products could be delayed pendinga re-inspection of the site by the FDA (Generics bulletin,11 November 2016, page 5).

“It is our assumption,” Rai told investors, “that allpending abbreviated new drug application (ANDA)and new drug applications (NDA) approvals from ourDecatur facility will be held up until the re-inspectionhappens and the compliance status of the facility isdeemed acceptable.” This, he said, would affect “a handfulof ANDA filings”, as well as an NDA for injectableephedrine sulfate, an unapproved, ‘grandfathered’ versionof which accounted for 23% of Akorn’s US$284 millionturnover in the third quarter of 2016 (see Figure 1).

Any delays proved to be short-lived. Before the endof 2016, Akorn was able to announce that the Decaturplant had passed a re-inspection with no Form 483observations (Generics bulletin,6 January 2017, page 4).

With the compliance issuesat Decatur resolved, Portwoodtold the JP Morgan conference

that the company could receive between 10 and 20product approvals during the first quarter of 2017. As ofthe end of 2016, the firm had 92 ANDA filings pendingfinal approval, representing a total addressable marketvalued at around US$9.5 billion, based on QuintilesIMSdata. Included in these 92 pending ANDAs are 38injectable formulations, 28 ophthalmics and 14 topicalproducts (see Figure 2).

Portwood pointed out that eight of the 92 filingshad already received tentative approvals from the FDA,but final approval was being held up by patent issues.Seven of the eight tentative approvals had been pendingfor more than 36 months, he added (see Figure 3).

“Our strategy around patent challenges is that wegenerally do not target first-to-file opportunities, butinstead employ a flexible strategy in which we selectivelytarget paragraph IV opportunities when we generallyhave a clear path to challenge a patent,” Portwoodexplained. “We believe this strategy can reduce muchof the associated risk and can potentially result in lessvariability in our financial results.”

Nevertheless, Akorn recently enjoyed success inchallenging through an inter partes review the validity ofUS formulation patent 6,114,319 protecting Alcon’sDurezol (difluprednate) eye drops until 18 November 2019(Generics bulletin, 9 December 2016, page 11). “This isan exciting opportunity for our company as we believewe will be eligible for sole marketing exclusivity pendingreceipt of final FDA approval,” Rai commented at thetime. “This outcome will help us reach our goal ofachieving a leadership position in generic ophthalmicsand further solidifies our strategic focus on alternate dosageforms such as ophthalmics, injectables and topicals.”

“We believe our key strategic differentiator is ourfocus on alternate dosage-form products,” Portwoodtold the conference. “We have a broad and diverseportfolio of ophthalmic, injectable, topical, nasal sprayand oral liquid products. These products typically carryhigher profitability versus oral solids, because there aregenerally fewer competitors due to the need for specialistmanufacturing expertise.”

While Akorn had built up a considerable portfolioof alternate dosage forms, Portword insisted the firm

Division Third-quarter sales Change Gross(US$ millions) (%) margin (%)

Prescription Pharma 268.9 +11.6 60.7Consumer Health 15.2 -3.7 45.5

Akorn 284.1 +10.6 59.9

Figure 1: Breakdown by division of Akorn’s sales and gross margin in thethird quarter of 2016 (Source – Akorn)

0 5 10 15 20 25 30 35 40 45

1

2

3

4

Series1 Series2

Ophthalmic

Injectable

Topical

Other

0 5 10 15 20 25 30 35 40 45

Filed To be filed

28

38

14

12

1

1

US$5,101 mn

US$3,313 mn

US$842 mn

US$420 mn

Figure 2: Breakdown by dosage form of Akorn’s pipeline of filed and yet to be filed ANDAs inthe US, and their addressable market value (Source – Akorn)

Gen 3-2-17 Pgs.2-16.indd 14 01/02/2017 17:30

15GeneRIcs bulletin3 February 2017

BusIness stRateGy

had “plenty of room to expand our presence”. Takingthe example of ophthalmics, he said the companycurrently marketed 38 of the 90 molecules recorded inQuintilesIMS data, representing a market size of justUS$624 million out of the total US$7.5 billion ophthalmicssector in the US (see Figure 4).

“We sell our products across multiple addressablemarkets, spanning human generics, branded prescription,controlled substances, branded and private-label OTCproducts, animal health and institutional unit-of-useoral liquids,” Portwood remarked. As Figure 5 shows,among nine products that the firm had launched lastyear were generic rivals to Suboxone (buprenorphine/naloxone) sublingual tablets, Zometa (zoledronic acid)vials and Topicort (desoximetasone) ointment.

“Entering 2017, we have a number of approvedproducts being prepared for launch,” Portwood revealed.“We are closely monitoring the review status of severalpending filings and are staging materials in an effort toshorten the time between approval and launch.”

Portwood said Akorn was keen to expand its portfolioboth organically through research and development andinorganically through licensing deals and acquisitions.

Having invested around US$45 million in researchand development during 2016, Akorn last year filed 12ANDAs as well as three animal health dossiers withthe FDA. The US firm also recently opened a centrein Cranbury, New Jersey, to house up to 40 scientistsworking on formulating alternate dosage-form generics.

Mergers and acquisitions, Portword commented,would focus on tuck-in product deals for “alternatedosage form products, legacy brand products that areeither soon to be or already genericised, brandedophthalmics that can be detailed by our field salesforce,and health and wellness brands that can add to our growingbranded OTC portfolio”. “In terms of companies,” hecontinued, “we are looking to acquire companies withalternate dosage-form portfolios that are complementaryto our existing portfolio, and/or companies that havecapabilities to manufacture alternate dosage forms thatare new to Akorn and that have a path to continuedgrowth and a promising pipeline.”

Acquisitions, Portwood recalled, had beeninstrumental in Akorn’s rapid rise from a turnover ofjust US$45 million in 2009 to a billion dollar companytoday with 2,100 employees around the world, includingin India, where the firm hopes to have manufacturingfacilities operational by the end of next year. Inparticular, Portwood highlighted two transformative

deals in 2014 when Akorn paid around US$650 millionfor injectables and ophthalmics supplier Hi-TechPharmacal and US$445 million for dermatology specialistVersaPharm (Generics bulletin, 16 May 2014, page 1).

Since then, Portwood remarked, Akorn had beenusing its considerable operating cash flow to reduceits debt, including a US$200 million pre-payment madein February 2016. By the end of 2016, he said, thecompany had reduced its cash to net debt leverage toaround 1.2 times. Recent share repurchases and anundrawn US$150 million ‘revolver’ loan would, hestressed, help to ensure the firm had “plenty of drypowder” to fuel further accretive deals that wouldunderpin Akorn’s growth trajectory. G

1 2 3 4 5 6

Series1 Series2

0 to 6 6 to 12 12 to 18 18 to 24 24 to 36 Over 36

Months since filing

12 14

3

17

38

7

1

Filed Tentative

Pending: 84Tentative: 8

Figure 3: Breakdown by age of filing of Akorn’s pipeline of ANDAs filed with the FDA (Source – Akorn)

Figure 4: Breakdown by dosage form of the addressable market for Akorn’s alternate dosage forms(Source – Akorn/QuintilesIMS)

Generic name/ Brand Market value Number of Launchstrength (US$ millions) competitors date

Tobramycin injection 40mg/ml Tobramycin 5.7 4 Dec 2015Buprenorphine and Naloxone sublingual tablets Suboxone 188.0 4 Jan 2016Zoledronic acid 4mg/5ml vials Zometa 28.4 8 Feb 2016Cyclopentolate 0.5% ophthalmic solution Cyclgyl 0.8 1 Mar 2016Desoximetasone 0.25% ointment Topicort 13.7 5 Apr 2016Ropivacaine injection 5mg/ml 30ml Naropin 17.4 2 Jun 2016Ofloxacin otic solution 0.3% Ofloxacin 18.5 2 Aug 2016Gentamicin ophthalmic solution (veterinary) Gentamicin – – Sep 2016Levetiracetam oral liquid UD Keppra 11.2 2 Sep 2016Ibuprofen oral suspension (Rx) 100mg/5ml Ibuprofen 18.3 4 Nov 2016Azelastine ophthalmic solution 0.05% Optivar 14.6 4 Jan 2017

Figure 5: Selected launches by Akorn since December 2015 (Source – Akorn)

Gen 3-2-17 Pgs.2-16.indd 15 01/02/2017 17:30

16 GeneRIcs bulletin 3 February 2017

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Afreeze on hiring federal employees in the US must not prevent theUS Food and Drug Administration (FDA) from ensuring that

patients have timely access to medicines, the US Generic PharmaceuticalAssociation (GPhA) has insisted.

Responding to a memorandum from US President Donald Trumpordering that “no vacant positions existing at noon on 22 January 2017may be filled and no new positions may be created, except in limitedcircumstances”, the GPhA pointed out that there were currently “morethan 850 open positions within the FDA Center for Drug Evaluationand Research (CDER), which includes more than 150 open positionsfor generic drug reviewers”.

Emphasising that “a fully-resourced FDA is critical to reducingthe backlog” of “more than 4,000 pending generic drug applications”at the agency, the GPhA noted that “the agency itself has recognisedthe need for more resources to expedite the approval of generics andbiosimilars”. “Industry fees that will continue to be collected duringthe hiring freeze should be fully available for their dedicated uses,including hiring,” the industry association insisted.

Trump’s memorandum states that within 90 days of the hiringfreeze, a “long-term plan to reduce the size of the federal government’sworkforce through attrition” will be formulated by the Office ofManagement and Budget. When that is implemented, the memorandumexplains, the hiring freeze order will expire. G

reguLatOry BODies

GPhA cautions overfederal hiring freeze

Pfenex chief Bert Liang has resigned by mutual agreement afteran investigation revealed board-level misconduct.Having previously held the titles of president, chief executive

officer and company secretary, Liang has also vacated his seat onPfenex’ board of directors, which has subsequently slimmed to fivemembers. The US-based biosimilars developer confirmed a searchfor Liang’s replacement was underway.

On an interim basis, Pfenex has appointed the firm’s chief businessofficer, Patrick Lucy, to Liang’s former positions.

According to Pfenex, an independent investigation overseen bythe company’s audit committee revealed Liang had “not acted inaccordance with the company’s board approval process policy and codeof ethics and conduct in connection with certain board approvalprocedures for third-party contracts”. “Liang, together with the board,agreed that a leadership transition is appropriate at this time and in thebest interests of the company and all of its stakeholders,” Pfenex said.

A former Amgen and Biogen executive, Liang had served asPfenex’ chief executive officer and as a board member since thecompany’s inception as a spin-off of The Dow Chemical Companymore than seven years ago. Liang is also chairman of the BiosimilarsCouncil within the US Generic Pharmaceutical Association (GPhA),although the association did not immediately respond to a Genericsbulletin enquiry regarding his future in the role. G

resignatiOns

Pfenex’ Liang resignsfor board misconduct

Gen 3-2-17 Pgs.2-16.indd 16 01/02/2017 17:30