Biosimilar code change receives industry praise · US import alert lifted at Divi’s site in...

10 November 2017

Biosimilar code changereceives industry praise

COMPANY NEWS 2US import alert lifted at Divi’s site in India 2Ajanta’s local sales help 2boost turnoverTeva is hit by further 3US$408m impairmentTorrent is to acquire Unichem’s 3India unitJubilant’s sales rise as its LSI unit grows 4Wockhardt sees loss on 4% slide in sales 4Pfizer has strategy to combat 5US shortagesTwo of Lupin’s plants hit with FDA warning 5Akorn deal still valid insists Fresenius head6Mylan eyes Europe to 6follow US glatiramerPiramal places focus on sustaining quality 7Alembic expands in US by acquiring Orit 7Sanofi lines up a US version of Humalog 8Biocon’s sales muted after 8facility setbacksLannett’s board eyes Jerome Stevens deal 9Glenmark sees global markets 9for candidate

MARKET NEWS 10Guidance updated on 10FDA correspondencePro Generika offers solutions 10to shortagesFrench agency debuts 11 biosimilar groups11

PRODUCT NEWS 12US Uceris patent not infringed, 12court findsAlvogen claims a first on 13oseltamivir powderTeva and Mylan clear 13path for UK tadalafilSwiss and Dutch find Alimta infringement14Actavis wins appeal on US Staxyn patent14Orencia trial fails for 15Momenta and Mylan

REGULARSPrice Watch UK – Reimbursement falls14Events – Our regular listing 15People – Belgium’s FeBelGen 16outlines a new board

Issue No.329

The US Centers for Medicare & Medicaid Services (CMS) has announced it will reviseits policy on payment for biosimilars by separately coding biosimilars under Medicare

Part B, in a decision welcomed by industry. “The decision by CMS to shift biosimilarsreimbursement to unique codes will not only increase patient access to more affordablelife-saving medicine, but also lower overall federal prescription drug spending,” said theAssociation for Accessible Medicines’ (AAM’s) Biosimilars Council.

Under existing CMS policy, the same ‘J-code’ is assigned to all approved biosimilars tothe same reference biologic for reimbursement under Medicare Part B, grouping them in thesame calculation for determining an average price limit. But from 1 January 2018, “newly-approved biosimilar products with a common reference product will no longer be grouped intothe same billing code”. Having sought stakeholder feedback on payment arrangements forbiosimilars earlier this year (Generics bulletin, 28 July 2017, page 9) “CMS received numerouscomments on this issue”, and made the change “in response to concerns raised”.

The AAM’s Biosimilars Council has long called on the CMS to adopt unique billing andpayment codes for biosimilars, raising the issue prominently at its latest conference in Septemberand noting that the current policy was creating “a lot of uncertainty” for industry (Genericsbulletin, 22 September 2017, page 9). A Moran Company analysis endorsed by the AAMrecently found that the US would save US$11.4 billion over the next decade by adopting uniquebilling and payment codes (Generics bulletin, 29 September 2017, page 9).

“CMS believes that a solution that increases provider and patient choice is superior toexisting policy and may lead to additional cost savings over the long-term,” the CMS stated.“By encouraging innovation and greater manufacturer participation in the marketplace, webelieve that this policy change will result in the licensing of more biosimilar products, thuscreating a stable and robust market, driving competition and decreasing uncertainty about accessand payment.” Commenting on the timescale of the change, the CMS said that “carrying outthis policy change as early as possible, rather than waiting, is expected to bring more certaintyto the new and developing marketplace”. G

Celltrion and Baxter ally in USCelltrion and Baxter BioPharma Solutions have struck a manufacturing deal in the US through

which Baxter will act as Celltrion’s fill-finish partner for biosimilar infliximab. The Koreancompany told Generics bulletin that the deal had been agreed “to cover growing demand andensure stable supplies in the US”, where Celltrion’s Remsima biosimilar is marketed by Pfizerunder the Inflectra name. “The firm expects to meet local demand in a more flexible mannerby securing a manufacturing base in the US,” Celltrion explained.

Baxter’s BioPharma Solutions unit boasts “innovative filling line technologies” designed to“protect a biologic’s integrity and optimise yield of costly active pharmaceutical ingredient(API)”. In particular, the company cites “100% in-line non-destructive weight checking, advancedcold-chain filling, dual filling technologies and high-yield process design”.

Celltrion’s deal with Baxter comes shortly after the US Food and Drug Administration(FDA) revealed a ‘Form 483’ list of 12 good manufacturing practice (GMP) deficiencies atCelltrion’s plant in Incheon, Korea (Generics bulletin, 15 September 2017, page 4). However,the firm emphasised that complaints referred to in the Form 483 were “not received by theFDA for Inflectra beingmarketed in the US”, but related to the European market. G

2 GENERICS bulletin 10 November 2017

COMPANY NEWS

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Divi’s Laboratories has announced that an import alert issued to itsUnit II facility in Visakhapatnam, India, by the US Food and Drug

Administration (FDA) in March is to be lifted. Moreover, the Indianfirm said the agency was “moving to close out” the warning letterissued to the site earlier this year citing several procedural deficiencies(Generics bulletin, 19 May 2017, page 4).

In a filing to the Bombay Stock Exchange (BSE), Divi’s said theFDA was lifting the import alert under clause 66-40 that relates togood manufacturing practice (GMP) deficiencies.

Following an FDA inspection of the Unit II active pharmaceuticalingredients (APIs) site at the end of 2016, the facility was subjectedto an import alert under clause 66-40, as well as clause 99-32 thatcovers ‘detention without physical examination of products from firmsrefusing FDA foreign establishment inspection’ (Generics bulletin,31 March 2017, page 5). The import alert under clause 99-32 wasrecently lifted (Generics bulletin, 1 September 2017, page 2).

In its financial second quarter ended 30 September 2017, Divi’ssales dropped by a tenth to Rs9.24 billion (US$143 million). The firmsaid its turnover was hit by the import alert and the “time required forsetting up protocols and procedures for the release of export shipmentsas stipulated in the import alert”. “This has since been established,and shipments for the exempted products are being done as per theprotocols,” Divi’s added. G

MANUFACTURING/SECOND-QUARTER RESULTS

US import alert liftedat Divi’s site in India

Ajanta said that “satisfactory” growth in its Indian and emergingmarkets region helped to lift the firm’s group sales by 5% to

Rs5.40 billion (US$83.5 million) in its financial second quarter ended30 September 2017. The Indian company’s domestic turnover advancedby 13% to Rs1.78 billion, with Ajanta “seeing recovery” following therecent reform of India’s goods and services tax (GST).

African exports increased by 25% to Rs2.18 billion, and Ajantanoted that its institutional business grew in the quarter but would“shrink on an annual basis”. Turnover in Asia rose by 6% to Rs1.04billion, as group pre-tax profit climbed by 8% to Rs1.78 billion.

Pricing hits US exportsUS exports tumbled by more than three-fifths to Rs260 million,

due to “customer consolidation resulting in price pressure”. Ajanta saidit was “hopeful to improve performance” in this region with productlaunches. During the quarter, Ajanta received three US abbreviatednew drug application (ANDA) final approvals and filed four ANDAs.

During its current financial year, the Indian firm said it plannedto file a total of between 12 and 15 ANDAs in the US.

In April, Ajanta started commercial production at a formulationsfacility it is building in Dahej, India (Generics bulletin, 12 May 2017,page 4). The company said the second phase was due to be commissionedat its Guwahati, India, site by early next year. G

SECOND-QUARTER RESULTS

Ajanta’s local saleshelp boost turnover

3GENERICS bulletin10 November 2017

COMPANY NEWS

Torrent Pharmaceuticals has entered into a definitive bindingagreement to pay Rs36.0 billion (US$557 million) for Unichem

Laboratories’ branded formulations business in India and Nepal.“The transaction is a strategic fit for Torrent and will strengthen its

position in the key segments of cardiology, diabetology, gastrointestinalsand central nervous system therapies,” commented the Indian firm’schairman, Samir Mehta. “It is also expected to realise cost and revenuesynergies in Torrent’s branded business in India,” he added.

In the three months ended 30 September 2017, sales by Unichem’sdomestic formulations business increased by 17% to Rs2.66 billion.The unit accounted for just over three-fifths of group turnover that roseby 16% to Rs4.28 billion, including international formulations salesthat grew by 13% to Rs1.28 billion and global active pharmaceuticalingredient (API) turnover up by 2% to Rs250 million.

Unichem’s domestic business includes more than 120 brands inIndia and Nepal, as well as a manufacturing plant catering to localmarkets that is located in Sikkim, India. More than 3,000 employeeswill also move with the business, while Torrent said its distributionnetwork would be enhanced by adding around 2,000 stockists.

Torrent said it would become one of India’s top-five pharma playersby value, with a 3.4% market share, and would also move up from 14thto seventh in terms of prescription volumes, with a top-five positionin seven key therapeutic segments. It would also be “amongst the topthree players” in antihypertensives, antidepressants and tranquilisers.

Unichem’s leading brands include Losar (losartan), Ampoxin(ampicillin), Telsar (telmisartan) and Vizylac (lactobacillus). Torrentsaid the transaction – which it expects to complete by the end of thisyear – would also “open doors to enter into the OTC segment” throughUnichem’s Unienzyme digestive enzyme brand.

Provided it obtains shareholders’ approval for the deal, Unichemintends to focus on “complex biologics and specialised generics”.

Torrent’s domestic formulations sales climbed by 22% to Rs6.07billion in its financial second quarter ended 30 September 2017 (seeFigure 1). Turnover in Germany rose by almost a fifth to Rs2.21 billion,helping to compensate for a fall of nearly a quarter to Rs1.20 billionin Brazil as the firm took a one-time charge “for near-expiry inventoryand additional discounts to distributors”.

In the US, “continued price erosion and customer consolidation”contributed to a 21% sales slide to Rs2.55 billion as two abbreviatednew drug application (ANDA) filings took the number pending as of30 September to 29. Group turnover stalled at Rs14.3 billion. Gn [email protected]

MERGERS & ACQUISITIONS/SECOND-QUARTER RESULTS

Torrent is to acquireUnichem’s India unit

India 6,070 +22 43US 2,550 -21 18Germany 2,210 +19 16Brazil 1,200 -24 8Other 1,350 +7 9Contract Manufacturing 910 -36 6

Torrent Pharma 14,290 ±0 100

* rounded to the nearest Rs10 million

Figure 1: Breakdown by market of Torrent Pharmaceuticals’ sales in its financialsecond quarter ended 30 September 2017 (Source – Torrent)

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

Teva has been hit by further impairment charges in the third quarterof 2017. The Israeli firm recognised an “impairment of long-lived

assets” of US$408 million, of which US$351 million stemmed from“product rights and research and development assets primarily relatedto the Actavis Generics acquisition”.

Previously, Teva suffered a US$6.1 billion goodwill impairmentin the second quarter due to weakness in its US generics operation(Generics bulletin, 11 August 2017, page 1).

Reporting sales for the third quarter ahead by just 1% to US$5.61billion – despite the inclusion of a full quarter of sales from Actavis,compared to just two months in the prior-year period – Teva’s operatingprofit halved to US$378 million. At the same time, Teva revised downits full-year sales guidance for 2017 to around US$22.2-US$22.3billion, from August’s US$22.8-US$23.2 billion forecast.

President and chief executive officer, Kåre Schultz – who beganhis tenure at the start of November after being named in September(Generics bulletin, 15 September 2017, page 1) – said he was“confident that the promise of Teva’s specialist pipeline, coupled with

a disciplined focus on executing key generic launches and the strengthand scale of operations, will allow Teva to compete successfully asthe global pharmaceutical industry continues to evolve”.

Citing a “need to study Teva’s operation closely at firsthand”,Schultz also recognised “the significant debt burden that Teva is currentlyunder”, adding that it would be an “absolute priority for me to stabilisethe company’s operating profit and cash flow”.

Generics sales in the US slipped by almost a tenth in the thirdquarter (see Figure 1) as the region continued to suffer from worseningprice erosion. Specialty sales were hit by Mylan’s launch of a USrival to Copaxone (glatiramer acetate) 40mg/ml (Generics bulletin,6 October 2017, page 1). Meanwhile, active pharmaceutical ingredient(API) sales fell by a tenth to US$171 million, while Teva’s OTCturnover dropped by more than a fifth – 22% – to US$306 million.

Meanwhile, Teva has completed its divestments of Paragard toCooperSurgical for US$1.1 billion and contraceptive brands includingPlan B One-Step to Foundation Consumer Healthcare for US$675million. Along with deals such as the previously-announced sale ofthe remaining women’s health business to CVC Capital Partners, Tevaexpects to generate around US$2.3 billion from divestments, “as wellas additional asset sales to be executed by year-end 2017”. Gn [email protected]

THIRD-QUARTER RESULTS

Teva is hit by furtherUS$408m impairment

US 1,179 -9 -9Europe 985 +6 +1Rest of World 843 -18 +5Generic Medicines 3,007 -8 -2

Copaxone 987 -7 –Other 1,047 +6 –Specialty Medicines 2,034 -1 -2

Other 569 +122 +117

Teva 5,610 +1 +4

Figure 1: Breakdown of Teva’s sales in the third quarter of 2017 (Source – Teva)

Third-quarter sales Change Constant-currency(US$ millions) (%) change (%)


COMPANY NEWS

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Issue 329 l 10 November 2017

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Wockhardt posted a pre-tax loss of Rs279 million (US$4.32 million)on group turnover that fell by 4% to Rs10.2 billion in the Indian

firm’s financial second quarter ended 30 September 2017. In the prior-year quarter, the company made a pre-tax profit of Rs257 million.

The group’s gross margin dropped by around 10 percentage pointsto 54%, while a 9% rise in staff costs to Rs2.26 billion largely offsetreducing research and development spending by 22% to Rs770 million.

While Wockhardt acknowledged that remediating problems atmanufacturing facilities continued to be a drain on profitability, it said

the group’s “strategic focus on cost containments and rationalisation”was starting to bear fruit. Sales exceeded Rs10 billion for the first timesince the prior-year financial second quarter.

Four launches in India helped to lift local turnover by 5% toRs4.52 billion (see Figure 1), while sales in Emerging Markets edgedup by 2% to Rs860 million.

But static sales on a local-currency basis in the UK translated toa reported 7% decline to Rs2.54 billion, while Irish sales were 3%lower at Rs380 million on flat turnover measured by euros.

In the US, where the firm made one filing and received oneabbreviated new drug application (ANDA) approval during the quarter,turnover declined by 13% to Rs1.58 billion. G


Wockhardt sees losson 4% slide in sales

India 4,520 +5 44

UK 2,540 -7 25Ireland 380 -3 4France 140 -18 1Other 200 -37 2Europe 3,260 -11 32

US 1,580 -13 15

Emerging Markets 860 +2 9

Wockhardt 10,220 -4 100


Figure 1: Breakdown by region of Wockhardt’s sales in its financial secondquarter ended 30 September 2017 (Source – Wockhardt)

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

Jubilant Life Sciences said that higher demand and a “healthy priceenvironment” for its Life Science Ingredients (LSI) business helped

lift the segment’s sales by more than a quarter to Rs7.38 million(US$114 million) during the firm’s financial second quarter ended30 September 2017. The business unit produces pharmaceuticalintermediates, as well as human and animal nutritional ingredients.

A “strong performance” was also achieved in Jubilant’sPharmaceuticals business, which rose by 12% to Rs8.60 billion andmade up over half of group sales, which advanced by nearly a fifthto Rs16.4 billion (see Figure 1).

That growth was fuelled in large part by Injectables sales thatadvanced by 42% to Rs5.31 billion.

As of 30 September 2017, Jubilant had filed 85 abbreviated newdrug applications (ANDAs) for oral solids in the US, of which 29 werecurrently pending US Food and Drug Administration (FDA) approval.Two of three injectable ANDAs had been approved.

Looking ahead, Jubilant expects higher sales in its contractmanufacturing organisation (CMO) business in the Specialtypharmaceuticals segment. For generics, the firm anticipates addedcustomer approvals and an “execution of deferred sales orders” in itsactive pharmaceutical ingredient (API) business. G


Jubilant’s sales riseas its LSI unit grows

North America 6,720 +27 –Europe/Japan 860 -7 –India 300 -50 –Rest of World 720 -16 –Pharmaceuticals 8,600 +12 24.5

Life Science Ingredients 7,380 +27 17.7

Drug Discovery Solutions 440 +16 10.7

Jubilant Life Sciences 16,420 +19 20.2


Figure 1: Breakdown by region and business segment of Jubilant Life Sciences’sales and earnings before interest, tax, depreciation and amortisation (EBITDA)margin in its financial second quarter ended 30 September 2017 (Source – Jubilant)

Second-quarter sales Change EBITDA(Rs millions*) (%) margin (%)


COMPANY NEWS

Pfizer says it has a “robust action plan” in place to help combatlegacy Hospira product supply shortages in the US, after capacity

constraints and “technical issues” for sterile injectables contributed tothe US firm’s Essential Health division reporting a double-digit salesdecline in the third quarter of this year. Sterile injectable shortages willwipe “several hundred millions of dollars” from Pfizer’s top line in2017, the firm believes.

“When we acquired Hospira, we originally thought it would takeone to two years to integrate the manufacturing plants and resolve themajority of the supply-chain issues,” group chairman and chief executiveofficer Ian Read conceded before investors. Announcing Pfizer’saction plan, Read said the firm believed it would make “substantialprogress in 2018 towards reducing the sterile injectable shortages”.

In the third quarter, US Sterile Injectable Pharmaceuticals (SIP)sales plummeted by a quarter – 24% – to US$626 million, draggingglobal SIP sales down by 13% as reported, and 12% on an operationalbasis, to US$1.27 billion (see Figure 1). In turn, this decline led totalEssential Health turnover to drop by 12% as reported to US$5.05billion, worsened by sales of peri-loss of exclusivity (peri-LOE) products,notably Pristiq (desvenlafaxine) in the US, and Lyrica (pregabalin)Vfend (voriconazole) in developed Europe markets, dropping by morethan a fifth to US$794 million.

Moving forward, John Young, group president of Pfizer EssentialHealth, said Pfizer believed the business would in the medium termreturn to low- to mid-single-digit growth. “In the past, [we] didn’tspecifically put a timeline on that. But we framed that out as being overa three-to-four year period,” Young revealed.

“Although Essential Health declined by 11%, if you exclude theimpact of the Infusion Systems divestiture and also the impact ofLOEs, the business was actually flat in the quarter,” Pfizer said.

Meanwhile, the decline was partially offset by operational growthof 67% to US$141 million from global biosimilars sales, includingturnover of US$34 million from Inflectra (infliximab-dyyb) in the US.

Quizzed by an investor on Pfizer’s recent antitrust lawsuit againstJanssen over challenges to obtain US market share for Inflectra (Genericsbulletin, 29 September 2017, page 13), Read said the “solution” tocombatting such alleged anti-competitive conduct would come froma “societal view that biosimilars are there to provide access to patientsonce the patent has expired”, and the view that “enough is enough”.“Europe is obviously benefitting from biosimilars, so why isn’t theUS?” Read asked. Gn [email protected]

MANUFACTURING/THIRD-QUARTER RESULTS

Pfizer has strategy tocombat US shortages

Innovative Health 8,118 +11 +11

Legacy brands 2,681 -1 –Sterile injectables 1,273 -13 -12Peri-LOE products 794 -22 -22Pfizer CentreOne 161 +3 +3Biosimilars 141 +70 +67Essential Health* 5,050 -12 -11

Pfizer 13,168 +1 +1* prior-year total included US$281 million from divested Infusion Systems business

Figure 1: Pfizer’s sales by division in the third quarter of 2017 (Source – Pfizer)

Third-quarter sales Reported Operational(US$ millions) change (%) change (%)

Lupin has suffered a double manufacturing setback after two of itsIndian formulation manufacturing facilities were struck with a

warning letter from the US Food and Drug Administration (FDA).The firm’s Goa site and its Unit II facility in Pithampur, near Indore,were both included in the combined warning letter, which was issuedby the agency to Lupin on 6 November.

Earlier this year, the company’s Goa plant received three ‘Form 483’observations following an inspection in April (Generics bulletin, 5 May2017, page 4), while its Pithampur site was hit with six observationsin May. Lupin acknowledged it had “responded to all the observations”.

“We are deeply disappointed to have received this outcome,” theIndian firm commented. “While there will be no disruption of existingproduct supplies from either of these locations, there will likely be adelay of new product approvals from these two facilities.” Lupin saidit planned to “address the concerns raised by the FDA expeditiously”,adding that it would work with the agency to “resolve these issuesat the earliest [opportunity]”.

Following the news, Lupin’s share price on the Bombay StockExchange (BSE) dropped by around 18% to Rs860 (US$13.20).

Pithampur’s Unit I site passed FDA muster earlier this year(Generics bulletin, 11 August 2017, page 7). G

MANUFACTURING

Two of Lupin’s plantshit with FDA warning

MERCK has extended its strategic alliance with Samsung BioLogicsafter signing a memorandum of understanding (MoU) to collaborateon biopharmaceutical manufacturing and biologics process development.Building on a MoU signed in 2014, the agreement “encompasses along-term supply agreement where Merck would provide raw materialsfor biopharmaceutical manufacturing”. Merck said the alliance would“accelerate process development and clinical material productionat small biotech start-ups focusing on novel-drug development forwhich Samsung BioLogics acts as a contract manufacturer”. Merckwill provide process development and support technical training toSamsung, in addition to its Mobius single-use systems. Separately,Samsung BioLogics reported group sales of KRW128 billion (US$114million) in the third quarter of 2017, which increased by KRW64.3billion over the second quarter “due to full utilisation of Plant I and asignificant increase in utilisation of Plant II” in Songdo, South Korea.

LANNETT has responded to price-fixing allegations in an amendedcivil complaint concerning US generics. The company was one ofthe 12 that were recently added to the antitrust lawsuit (Genericsbulletin, 3 November 2017, page 11). Reviewing the complaint, theUS firm said it “believes the price-fixing allegations regarding thesingle product named in the complaint that Lannett sells are meritless”and “intends to vigorously defend the claims”.

NATCO PHARMA has invested Rs75 million (US$1.15 million) fora 7.50% share in OMRV Hospitals, which is located in Hyderabad,India, and focuses on tertiary care services in medical and surgicalfields including gastroenterology, oncology and urology. The Indiancompany reported an 8% sales decrease to Rs4.32 billion in itsfinancial second quarter ended 30 September 2017. Formulationssales slid by 4% to Rs3.40 billion, while bulk-drug turnover rose bymore than a fifth to Rs584 million as other income fell. G

IN BRIEF


COMPANY NEWS

Fresenius’ chief executive officer Stephan Sturm insists that thestrategic rationale for acquiring Akorn “remains as valid as ever”,

despite conceding that the US ophthalmics and injectables specialist’sfinancial results were “for sure, not what we had hoped for” following asteep sales and significant profit decline in the third quarter of this year.

Akorn’s sales dropped by 28.7%, or US$81.7 million, to US$202million, following a “significant decline” in sales of key products, andsupply disruptions. On top of losing exclusivity for ephedrine sulphatefor injection, Akorn faced increased competition on lidocaine ointment,and more significant than expected declines for Nembutal (pentobarbital),progesterone and clobetasol ointment. As a consequence, Akorn’soperating profit plummeted by 89% to US$9.42 million.

“In light of Akorn’s year-to-date performance, it appears likely the2017 base will be lower than assumed. And as a consequence, thestretch required to reach our 2018 expectations is clearly larger,” Sturmtold investors as Fresenius presented too its third-quarter financial results.

At the time the deal was announced, Fresenius projected 2018group sales from Akorn of US$1.035-US$1.085 billion and earningsbefore interest, tax, depreciation and amortisation (EBITDA) excludingintegration costs of US$380-US$420 million. “I’d clearly prefer Akornto show a stronger financial performance,” Sturm underlined. “But Ialso wouldn’t want to be sitting here trying to answer your questionsabout the implications of somebody else acquiring them.”

Pointing to Akorn’s 24 product approvals so far this year, Sturminsisted Akorn would further diversify Fresenius Kabi’s product portfolio,while it would also enhance Kabi’s market reach and strengthen itsstrategic position, therefore helping Kabi become “ever more relevantto the powerful purchasers on both the institutional and retail side”.

Meanwhile, Sturm said Kabi and Akorn had selected a buyer andsigned an asset-purchase agreement for the firms’ select overlappingproducts, as per US Federal Trade Commission (FTC) requirements.That document had now been submitted to the Commission forconsideration, Sturm revealed. “We are targeting to close this acquisitionby year end and are cautiously optimistic that we will receive FTCclearance to be able to do so,” Sturm commented.

Turning to the former Merck KGaA biosimilars business thatFresenius acquired from 1 September, Sturm said Kabi had made “goodprogress” on integration. “All clinical studies remain well on track,specifically adalimumab, where our European Union (EU) filing isimminent,” Fresenius’ chief revealed.

In the third quarter, Kabi’s total sales rose by 7% to C1.56 billion(US$1.81 billion) on an organic basis, and 3% as reported, driven byglobal Intravenous Drugs sales rising by 9% organically to C648 million.Taken by region, Kabi’s North American sales climbed by 7% to C549million, while in Europe turnover rose by 4% to C538 million, both onan organic basis. Concerning pricing pressure for US injectables, Sturminsisted Kabi was “not seeing anything out of the ordinary”, with priceerosion “very much in line with our experience from recent years”.

Meanwhile, Kabi’s earnings before interest and tax (EBIT) inchedahead by 1% – or 6% in constant currencies – to C283 million, excludingacquisition-related expenses of C15 million.

Confirming Kabi’s outlook for 2017, forecasting organic salesgrowth of 5-7%, Sturm said Kabi was “now even targeting the upperend of the range”. This would stem from “the blend of the regionalcontributions”, including at least 10% organic growth in emergingmarkets, Sturm commented. Gn [email protected]

MERGERS & ACQUISITIONS/THIRD-QUARTER RESULTS

Akorn deal still validinsists Fresenius head

Mylan is preparing to roll out in Europe a generic rival to Teva’sCopaxone (glatiramer acetate) 40mg/ml three-times-a-week

formulation. This will follow the firm’s recent introduction of 20mgand 40mg strengths of the multiple-sclerosis treatment upon approvalin the US (Generics bulletin, 6 October 2017, page 1).

Having in early October obtained approval through Europe’sdecentralised procedure for glatiramer acetate 40mg/ml, using theNetherlands as the reference member state, Mylan is currently obtainingnational clearances to launch the pre-filled syringes under brand namesincluding Copemyl and Glatiramyl. Through its alliance with Synthon,Mylan already markets once-a-day glatiramer 20mg in several countries.

Discussing uptake in the US, chief commercial officer Tony Maurosaid Mylan was pleased to have achieved a 16.2% share of newprescriptions, equivalent to around 8% of total prescriptions, in theweek ended 27 October, about three weeks after launch. Supportservices for the 40mg/ml version that included in-home injectiontraining and a 24-hour support centre had been well received, he added.

Group president Rajiv Malik revealed the company had receivedUS approvals for more than 20 injectables to date this year, whileover 70 more were in its pipeline or pending approval. Mylan hadresponded to a complete response letter (CRL) issued by the USFood and Drug Administration (FDA) for its generic version of Advair(fluticasone/salmeterol) inhaler, while the firm remained “on track”to submit an abbreviated new drug application (ANDA) next year fora generic of Symbicort (budesonide/formoterol) through a partnershipwith 3M. “Pivotal pharmacokinetic studies are now complete, withbioequivalence demonstrated for both low and high-strength products.”

Reviewing Mylan’s biosimilars pipeline, Malik said the firmplanned to respond to the FDA’s CRL on pegfilgrastim “in the nextfew weeks”, while it had also discussed with the agency “a clear pathforward to resolve issues identified in an inspection”. An FDA goaldate for trastuzumab was fast approaching on 3 December, he noted,while in Europe Mylan and its partner Biocon have resubmittedapplications for both trustuzumab and pegfilgrastim after addressingproduction concerns through “facility modifications”.

As Figure 1 shows, Mylan’s turnover in North America tumbledby 22%, or by US$333 million, to US$1.17 billion in the thirdquarter of this year. A US$245 million decline in EpiPen (epinephrine)sales was exacerbated by loss of market exclusivity for armodafinil.

An extra month’s contribution for the Meda acquisition completedin August 2016 helped boost European sales by 24% to US$1.04billion, as did a positive currency effect of US$45.5 million. Medaand exchange-rate fluctuations were also major factors behind 9%sales growth to US$743 million in Mylan’s Rest of World region.Gn [email protected]

BUSINESS STRATEGY/THIRD-QUARTER RESULTS

Mylan eyes Europe tofollow US glatiramer

North America 1,172 -22 49.1Europe 1,041 +24 27.9Rest of World 743 +9 18.0Other 31 +12 –*

Mylan 2,987 -2 10.6

* unallocated corporate expenses totalled US$684 million

Figure 1: Mylan’s third-quarter sales and operating margin (Source – Mylan)

Region Third-quarter sales Change Operating(US$ millions) (%) margin (%)


COMPANY NEWS

An emphasis on quality and “sustained reliability” will be a keyfactor in ensuring sustained growth for Piramal Pharma, along with

building on recent acquisitions and expanding into new areas of thevalue chain, according to the firm’s senior vice-president for activepharmaceutical ingredient (API) generics and nutrition, Anil Srivastava.

Speaking exclusively to Generics bulletin, Srivastava insistedthat Piramal was committed to “sustainability in providing qualitysolutions”. “I think the generics market is going through a churn,” heobserved, “and the people who are surviving will survive if they keepthe focus on the end patient, and everything flows from that into quality”.

“It boils down to the culture which you have,” Srivastava suggested.“I personally believe that everybody should become as compliant asthe US Food and Drug Administration [standards],” he stated, citingPiramal’s continuous improvement plans and quality complianceprogrammes across all sites.

“We are very aggressive in terms of maintaining quality,” Srivastavasaid, emphasising that this had “really helped us to stand out, and ishelping us maintain our growth”.

In its most recent financial year, Piramal Pharma enjoyed growthof more than 10% to Rs38.9 billion (US$602 million) for the 12 monthsended 31 March 2017 (Generics bulletin, 26 May 2017, page 2). “Weare looking at maintaining that,” Srivastava confirmed.

A series of acquisitions – including of high-potency API specialistAsh Stevens in 2016 (Generics bulletin, 26 August 2016, page 10) – hadcontributed to Piramal’s recent expansion. “Ash Stevens was an excellentacquisition from our standpoint because we moved into the high-potencyAPI space where we were not present,” Srivastava explained.

High-potency APIs are a key businessDescribing the business as “very niche”, he noted that Piramal was

“investing quite a lot of money into these new assets”, having recentlyunveiled a US$55 million expansion plan for sites in North Americaand Asia that included increasing its footprint at the US Riverview,Michigan plant that it acquired via Ash Stevens (Generics bulletin,20 October 2017, page 5). “Ash Stevens brings in a lot of relationshipsand excellent products,” Srivastava observed, “and that helps us incompleting our value chain.” High-potency APIs would be “a key partof the business going forward”.

Future acquisitions would be made “on a case by case basis”. WhilePiramal did not have a particular drive to acquire, Srivastava said, “wepick up things when they fit into the whole vision and can provide theright sort of culture and the right sort of infrastructure to fit in with us”.

Looking ahead, Srivastava would not be drawn on specific plansfor the company to move into finished-dosage forms, but revealed that“we do have a strategy on which we are working, and we will look atthat when we cross that bridge”. “It is a logical culmination of whatwe do,” he acknowledged.

With FDA-approved formulations facilities including plants inPithampur, India, and Morpeth, UK, “the entire value chain” was opento Piramal, Srivastava pointed out. However, there were no immediateplans for Piramal to market its own products.

“We don’t want to compete with our customers,” Srivastavanoted. “We can start out-licensing some of the products we havedeveloped, but we are not looking at competing with our own productsin the generic market space directly.” Nevertheless, he maintained,“it is a market which is a logical forward integration”. Gn [email protected]

BUSINESS STRATEGY/MANUFACTURING

Piramal places focuson sustaining quality

Alembic Pharmaceuticals has increased its “breadth and capabilitiesin the US” after completing its acquisition of Okner Realty’s Orit

Laboratories. Financial details of the transaction were not disclosed.Pranav Amin, Alembic’s managing director, said the acquisition

of Orit Laboratories “expands our basket of product offerings to ourcustomers, shows our commitment to be a long-term player in the USgenerics industry, and will help us have a powerful research anddevelopment footprint in the US”.

Established in 2005 by chief executive officer Satish Patel, NewJersey-based Orit has an 800 sq m research and development and pilotmanufacturing facility, and is focused on developing and filing oralsolid and liquid products.

Orit has seven approved abbreviated new drug applications(ANDAs) and four dossiers pending approval. Along with these ANDAs,Alembic noted, the US firm would add “complementary skill sets insoft-gelatin based oral solids and oral liquids to Alembic with a teamof eight highly-experienced scientists”.

“This tuck-in acquisition marks our first cross-border transaction,”commented Alembic’s chief financial officer R K Baheti, “especiallyreflecting our ambition to grow Alembic’s US generic business.”

In Alembic’s financial second quarter ended 30 September 2017,the company’s Formulations sales slid by a tenth to Rs6.47 billion(US$99.5 million), accounting for over four-fifths of the group total.International Formulations turnover fell by more than a quarter toRs2.62 billion (see Figure 1), with the firm’s US Formulations business“continuing to face price erosion on some key products”. Alembicinsisted that concluding the Orit acquisition would “strengthen ourpresence in the US market”.

Although the Indian firm’s domestic Formulations sales lifted by6% to Rs3.85 billion, Amin stated these “numbers are not strictlycomparable due to goods and services tax (GST) treatment”, referringto the revised framework recently introduced in India. “The Indiabranded business is showing signs of recovery,” he added. Activepharmaceutical ingredient (API) turnover suffered a 13% slide to Rs1.42billion, as Alembic’s group sales dipped by 10% to Rs7.89 billion.

Alembic’s research and development spending was 12% lower atRs980 million, helping the firm’s pre-tax profit to rise by 3% to Rs1.61billion. During the quarter, the company submitted three ANDAs, takingits cumulative US filings to 104, of which 62 have been approved.

US approvals received by Alembic during the quarter includedgeneric versions of Aqua Pharmaceuticals’ Monodox (doxycycline)capsules, Daiichi Sankyo’s Azor (amlodipine/olmesartan) tablets andBoehringer Ingelheim’s Pradaxa (dabigatran) capsules (Genericsbulletin, 11 August 2017, page 21). Gn [email protected]

MERGERS & ACQUISITIONS/SECOND-QUARTER RESULTS

Alembic expands inUS by acquiring Orit

India 3,850 +6 49International 2,620 -26 33Formulations 6,470 -10 82APIs 1,420 -13 18

Alembic 7,890 -10 100


Figure 1: Breakdown by business segment of Alembic Pharmaceuticals’ sales inits financial second quarter ended 30 September 2017 (Source – Alembic)

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


COMPANY NEWS

Sanofi is hopeful of obtaining “in the next few months” finalapproval from the US Food and Drug Administration (FDA) for its

Admelog (insulin lispro) hybrid alternative to Eli Lilly’s Humalograpid-acting insulin analog. In early September, the agency grantedtentative approval for Sanofi’s 505(b)(2) application, noting that itcould not give final approval because a statutory 45-day period in whichLilly could respond to Sanofi’s paragraph IV patent challenge had notended. Sanofi said that 45-day period had since expired, without Lillyhaving filed a suit that would have triggered an automatic 30-monthstay on final approval (Generics bulletin, 8 September 2017, page 17).

Acknowledging that Sanofi does not expect “to have significantcoverage” with Admelog in 2018 because payer contracts for nextyear were largely in place already, Sanofi’s chief executive officer,Olivier Brandicourt insisted that “we believe we can make a compellingoffer to provide choice with Admelog in this market”.

Brandicourt observed that the US rapid-acting insulins marketwas essentially split between Lilly and Novo Nordisk. “Payer contractsare largely exclusive, because products are seen as relativelyinterchangeable,” he said, adding that the firm assumed that the FDAwould classify basal insulins as interchangeable from 2020.

Bringing an alternative to Humalog to the US market would helpSanofi to compensate for pressure on its blockbuster Lantus (insulinglargine) brand. In the third quarter of this year, US Lantus sales fellby 25.4% to C608 million (US$706 million) as the diabetes brand wasexcluded from formularies at CVS and United Health. Sanofi recentlysued both Merck and Mylan in a bid to hold off 505(b)(2) rivals.

Despite global Lantus turnover down by 15.5% to C1.12 billionamid biosimilar competition in Europe, Sanofi’s group turnover edgedup by 0.3% to C9.05 billion as the acquisition of Boehringer Ingelheim’sConsumer Healthcare business outweighed generic competition toRevela/Renagel (sevelamer) in the US, to Plavix (clopidogrel) in Japan,and to Lovenox (enoxaparin) from biosimilars in Germany and the UK.

Sanofi’s third-quarter Generics sales declined by 4.4% as reportedto C433 million. On a constant-currency basis, the fall was 0.9% (seeFigure 1), including a 7.1% drop to C183 million in Europe, whereSanofi is looking to divest its local Generics operation by the end ofnext year (Generics bulletin, 17 February 2017, page 2). Gn [email protected]

BUSINESS STRATEGY/THIRD-QUARTER RESULTS

Sanofi lines up a USversion of Humalog

Figure 1: Breakdown by business unit of Sanofi’s sales in the third quarter of 2017(Source – Sanofi)

Established Products 2,264 -10.7 -6.5Diabetes, Cardiovascular 1,675 – -9.1Specialty Care 1,633 – +12.5Consumer Healthcare 1,132 +43.1 +48.5Vaccines 1,916 +6.3 +11.0

Emerging Markets 186 – ±0.0Europe 183 – -7.1US 41 – +13.2Rest of World 23 – +22.7Generics 433 -4.4 -0.9

Sanofi 9,053 +0.3 +4.7

Third-quarter Reported Constant-currencysales (Cmillions) change (%) change (%)

Manufacturing setbacks, pricing pressures in its active pharmaceuticalingredient (API) business, and regulatory and tender delays for

biosimilars in emerging markets are among the factors that “muted”Biocon’s performance in its financial second quarter ended 30 September2017, according to the Indian firm.

“In particular, plant modifications undertaken to comply withregulatory requirements led to production disruptions,” the Indian firmexplained. For this reason, Biocon noted, sales in its Biologics division –comprising biosimilars and novel biologics – remained flat at Rs1.56billion (US$24.2 million) during the quarter. However, its insulinsbusiness “maintained its robust year-on-year growth momentum”, ledby “increased uptake in key emerging markets” and aided by salesin Malaysia and Mexico.

Biocon’s Branded Formulations rose by 29% to Rs1.76 billion,offsetting a 13% decrease in its Small Molecules segment, whichdropped to Rs3.51 billion due to “a lower offtake of certain products as

a result of pricing pressure faced by some of our clients”. Group saleslifted by 3% to Rs10.2 billion (see Figure 1).

Biocon pointed out that its Indian API manufacturing facility inVishakhapatnam, Andhra Pradesh, recently completed a US Food andAdministration (FDA) inspection with zero ‘Form 483’ observations.The firm also commissioned its first solid oral-dosage formsmanufacturing facility during the quarter to support filings in developedand emerging markets, particularly for highly-potent drugs (Genericsbulletin, 11 August 2017, page 9).

Moreover, Biocon during the quarter launched its generic versionof AstraZeneca’s Crestor (rosuvastatin calcium) tablets in the US.

Through Biocon’s co-development partnership with Mylan todevelop a broad biosimilar portfolio, the US company submitted to theFDA a regulatory submission for insulin glargine under the 505(b)(2)pathway. “Our dossier for this product is also under advanced stagesof review in some of the other developed markets,” Biocon added.

Mylan and Biocon recently received a complete response letter(CRL) from the FDA informing the firms that Mylan’s biologics licenseapplication (BLA) for a biosimilar version of Amgen’s Neulasta(pegfilgrastim) was not yet ready for approval (Generics bulletin,13 October 2017, page 1). Biocon noted that the application wouldbe resubmitted after it had “been updated with data from ongoingfacility requalification activities”. The partners have just refiledapplications for both pegfilgrastim and trastuzumab with the EuropeanMedicines Agency (EMA). Gn [email protected]


Biocon’s sales mutedafter facility setbacks

Figure 1: Breakdown by business unit of Biocon’s sales in its financial secondquarter ended 30 September 2017 (Source – Biocon)

Small Molecules 3,510 -13 34Branded Formulations 1,760 +29 17Biologics 1,560 ±0 15Syngene Research Services 3,350 +11 33Other 10 – –

Biocon 10,190 +3 100

* rounded to nearest Rs10 million

Business Second-quarter Change Proportion ofunit sales (Rs millions*) (%) total (%)


COMPANY NEWS

Glenmark’s chairman and managing director Glenn Saldanha saysthe firm has a “multi-prong strategy” behind the company’s

GSP 301 mometasone/olopatadine intranasal formulation candidate,with plans eventually to sell the combination product in multipleregulated markets outside of the US, as well as emerging markets.

As announced earlier this year, Glenmark plans in early 2018to submit a hybrid 505(b)(2) new drug application (NDA) to the USFood and Drug Administration (FDA), after the agency confirmed thatdata from a Phase III clinical trial was sufficient to support filing.

“While the primary focus is to get this [GSP 301] launched in theUS next year, we will also be able to have significant gains comingout of GSP 301 in the rest of the world, including regulated marketslike Japan and Australia,” Saldanha revealed, “and some other emergingmarkets, where these kinds of products are very exciting.” This non-USstrategy would “start kicking in” towards the end of 2018, Saldanhanoted, “and it will play out over the next three-to-four years”.

Meanwhile, Saldanha reiterated the potential of switchingmometasone/olopatadine to OTC status. Discussing potential pricingopportunities in the US, Saldanha noted that the “benchmark” wouldbe Mylan’s Dymista (azelastine/fluticasone) – the “closest competitor”for a steroid and an antihistamine combination to treat seasonalallergies – which has annual sales of around US$160 million.

Glenmark’s ‘USA Formulations’ sales fell by 5.7% to Rs7.27 billion(US$113 million) during the Indian firm’s financial second quarterended 30 September 2017. Robert Matsuk, president of Glenmark’sNorth America and global active pharmaceutical ingredients (APIs)business, revealed that price erosion in the US caused by customerconsolidation was more severe than initially forecasted – 13%, asopposed to 10-12% – and moreover that the “challenging environment”for prices would persist “for at least the next two years”.

As Figure 1 shows, USA Formulations sales made up just undera third of group sales that inched ahead by 1.5% to Rs22.5 billion,with Glenmark’s total turnover buoyed by mid-to-high single-digitsales rises for the firm’s India Formulations and API businesses, as wellas turnover in Europe that leapt by just under half to Rs2.00 billion.

“During the quarter, we expanded our footprint to the Nordic regionin Europe,” Glenmark revealed. “We launched buprenorphine in Sweden,and won the tender for desloratadine and escitalopram.”

Including an additional Rs297 million of licensing and otherincome, Glenmark’s pre-tax profit declined by 13.4% to Rs2.73 billion,caused by higher costs associated with inventory changes. Gn [email protected]

BUSINESS STRATEGY/SECOND-QUARTER RESULTS

Glenmark sees globalmarkets for candidate

US 7,271 -5.7 32India 7,107 +5.3 31Africa/Asia/CIS 2,521 -0.7 11Europe 2,000 +48.5 9Latin America 1,047 -21.7 5API 2,366 +6.9 10Licensing/other 254 -26.0 1

Glenmark 22,566 +1.5 100

Figure 1: Breakdown of Glenmark Pharmaceuticals’ sales in its financial secondquarter ended 30 September 2017 (Source – Glenmark)

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

Lannett chief Arthur Bedrosian has revealed that two members ofthe firm’s board of directors members in “recent weeks” met with

senior executives at Jerome Stevens Pharmaceuticals, ahead of thefirm’s distribution arrangement covering three of Jerome Stevens’products expiring in March 2019.

Through an agreement signed with Jerome Stevens in 2004 –which was extended four years ago through to 2019 (Generics bulletin,6 September 2013, page 23) – Lannett holds exclusive distributionrights in the US to the firm’s butalbital/aspirin/caffeine/codeine capsules,digoxin tablets and levothyroxine sodium tablets.

Sales of Lannett’s levothyroxine were around US$45 million inthe firm’s financial first quarter ended 30 September 2017, chieffinancial officer Martin Galvan has just revealed, amounting to around29% of the firm’s group turnover that fell by 4.1% to US$155 millionduring the three-month period. Galvan acknowledged that the product was“one of the strongest players amongst all the prices that are increasing”.

Pointing out that he had not anticipated discussions over a possiblerenewal “until next year”, Bedrosian stated: “It is my understandingconversations will continue.” “They’ve been dealing with us here atLannett, both contractually and without the contract, over 15 years,”Bedrosian noted. “I suspect [the partnership] will continue,” he forecasted.

Meanwhile, Bedrosian revealed, Lannett is looking to expand itsexisting partnership with China’s HEC Group to include development ofnew and innovative active pharmaceutical ingredients (APIs) throughthe US-based player’s Cody Laboratories API manufacturing operation.

Formed more than three years ago, Lannett’s partnership withHEC includes a distribution agreement currently spanning 11 of theChinese firm’s abbreviated new drug applications (ANDAs) that arepending US Food and Drug Administration (FDA) approval (Genericsbulletin, 16 May 2014, page 5). Meanwhile, the firms also have adistribution agreement in China, under which HEC has “committed”to acquiring rights to more than 20 of Lannett’s products.

Noting that he had recently met with HEC executives, Bedrosiansaid the Chinese firm had advanced its in-house API development, andtherefore “aligning the companies’ scientists” could only “strengthenmarketing opportunities”, including for Lannett introducing additionalHEC products in the US.

However, Bedrosian said the distribution agreement – currentlycovering 22 products – had been delayed due to “proposed changes”by China’s Food and Drug Administration related to bioequivalencetesting and marketing authorisation requirements.

Commenting on his own future with Lannett, following the board’sdecision to begin looking for a new chief executive officer at the endof September, Bedrosian said no “timetable” had been set to namethe new chief. “I expect to remain a member of the board through theend of my current term. The possibility exists that I will remain withthe company in a strategic advisory position, though such a role hasnot been formally defined or offered,” he disclosed.

Lannett reported an operating profit of US$40.7 million for itsfinancial first quarter, up from a US$20.3 million operating loss lastyear when Lannett was stung with a US$65.1 million asset-impairmentcharge. Meanwhile, the US firm has ramped up its full-year net salesforecast for its current financial year ending June 2018 – from US$655-US$665 million to US$710-US$720 million – as a result of the anticipatedlaunches of “a number of” FDA-approved products in the second halfof its financial year. Gn [email protected]

BUSINESS STRATEGY/FIRST-QUARTER RESULTS

Lannett’s board eyesJerome Stevens deal


MARKET NEWS

A Study Of Mail OrderAnd Internet PharmacyIn 17 European CountriesPlus Key LearningsFrom The US And China

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NEWFOR

2017

Comment has been invited on draft guidance on controlledcorrespondence between the US Food and Drug Administration

(FDA) and generics developers that has been published by the agency,to take into account ‘programme enhancements’ introduced as partof the reauthorised Generic Drug User Fee Amendments (GDUFA II).The revised guidance, when finalised, will replace similar guidanceon controlled correspondence published in September 2015.

Under the terms of GDUFA II, the agency agreed to review andrespond to 90% of standard controlled correspondence within 60 calendardays from submission; to do the same for complex controlledcorrespondence within 120 calendar days from submission; and toreview and respond to 90% of submitter requests to clarify ambiguitiesin the controlled correspondence response within 14 calendar days ofthe FDA receiving the request. For controlled correspondence relatingto one or more pending citizen petitions, the 60- or 120-day periodstarts on the date that the FDA responds to the last pending petition.

Standard controlled correspondence is defined by the GDUFA IIcommitment letter – and the updated guidance – as “correspondencesubmitted to the agency, by or on behalf of a generic drug manufactureror related industry, requesting information on a specific element ofgeneric drug product development”. It also covers “post-approvalsubmission requirements that are not covered by guidance on post-approval changes and are not specific to an abbreviated new drugapplication (ANDA)”.

Complex controlled correspondence, meanwhile, covers “evaluationof clinical content”, as well as “review of bioequivalence protocolsfor drugs that reference listed drugs with risk evaluation and mitigationstrategies (REMS) with elements to assure safe use (ETASU)”. It alsoincludes “evaluations of alternative bioequivalence approaches withinthe same study type – for example, pharmacokinetic, in vitro or clinical”.

Additional detail and definitionsOutlining the contents of the updated draft guidance, the FDA said

it provided additional detail and recommendations on what inquiriesthe agency considered to be controlled correspondence for the purposesof meeting its GDUFA II commitments; what information requestorsshould include in correspondence to facilitate the FDA’s considerationof the inquiry and the agency’s response; what information would beprovided by the FDA to requestors; and how requestors can submitfurther requests to clarify any ambiguities in the FDA’s responses.

The draft guidance includes detailed sections on inquiries that fallboth within and outside the scope of controlled correspondence, entitieseligible to submit inquiries through the controlled correspondenceprocess, and the application of the GDUFA II enhancements tocorrespondence that was submitted during the first GDUFA period.

Separately, the FDA has also published for comment draft guidanceon assessing user fees. The document “describes the type of feesauthorised by GDUFA II, the process for submitting payments to theFDA, the consequences for failing to pay generic drug user fees, andthe process for requesting a reconsideration of a user fee assessment”.

Under the fee structure for GDUFA II, companies submittingANDAs have from 1 October this year been required to pay overUS$100,000 more than they would have done in the previous financialyear, with the ANDA application fee set at US$171,823 for the yearending September 2018 (Generics bulletin, 8 September 2017, page 9).Annual programme fees have also been introduced. Gn [email protected]

REGULATORY AFFAIRS

Guidance updated onFDA correspondence

Three key ways to address medicines shortages in Germany are laidout in an advertising campaign run by local generics and biosimilars

industry association Pro Generika.From early November, posters displayed in Berlin’s government

quarter and Tegel airport, as well as “other selected locations nationwide”,are posing the question: ‘What is worse than any treatment? Notreatment.’ The posters – which bear the image of an infusion bagknotted in the middle – propose three ways in which clinics, hospitalsand health insurance funds can contribute to improving security ofdrug supplies. These are backed up by trade-press and online advertising,as well as social-media activities.

Firstly, Pro Generika suggests that supply deals awarded throughtenders be given to more than one generics manufacturer per molecule.“Insurance funds should no longer transfer responsibility for supplyingmedicines to their members onto a single pharmaceutical company,”the industry association insists.

Secondly, essential and life-saving medicines should not be subjectto tender processes, Pro Generika argues. Such procurement practiceshave historically led to supply shortages, it highlights.

And thirdly, the association appeals to hospitals to follow “sustainableprocurement behaviour”. By agreeing a ‘good buying practice’ withmanufacturers, clinical settings could move away from a “discounterprinciple that poses a serious danger to secure supplies for hospitals”.G

CAMPAIGNS

Pro Generika offerssolutions to shortages


MARKET NEWS

SANDOZ’ North American head of biopharmaceuticals, Sheila Frame,has called for “payers, policymakers, prescribers and patients tomake some changes to support a competitive biosimilars marketplace”. Citing a RAND Corporation report’s finding that US$54billion in savings could be achieved from biosimilars over the nextdecade (Generics bulletin, 3 November 2017, page 14), Frame saideducation was needed for both physicians and patients, and advocatedunique Medicare Part B reimbursement codes (see front page).

US SENATORS Amy Klobuchar and Chuck Grassley have introduceddraft US legislation under the banner of the Reducing Drug WasteAct aimed at curbing wasteful spending on unused and discardeddrugs. The statute would “require the US Food and Drug Administration(FDA) and the Centers for Medicare and Medicaid to develop a jointaction plan to reduce drug waste and better manage costs with respectto drug vial sizes and other drug delivery systems like eye-drops”.

UKRAINE is to establish a Supreme Intellectual Property Court,located in Kiev, following a decree by the country’s PresidentPetro Poroshenko.

PTAB – the Patent Trial and Appeal Board within the US Patentand Trademark Office – is permitting amicus briefs to be filed aspart of ongoing inter partes reviews (IPRs) relating to patentsprotecting Allergan’s Restasis (cyclosporine). The IPRs also involvethe Saint Regis Mohawk Tribe after Allergan transferred ownershipof the patents to the tribe through a controversial agreement inSeptember (Generics bulletin, 15 September 2017, page 13). Briefsof no more than 15 pages must be submitted by 1 December. FourRestasis patents were recently declared invalid by a Texas districtcourt (Generics bulletin, 20 October 2017, page 20).

GLOBAL sales of generics are expected to reach US$175 billionby 2025, according to a report by Grand View Research, which citesas a contributing factor patent expiries for drugs such as Novartis’Gilenya (fingolimod) multiple-sclerosis treatment.

I-MAK – the Initiative for Medicines, Access & Knowledge – claimsthat the US is “poised to incur US$55 billion in excess costsfrom pharmaceutical companies’ strategies to delay competitionon three drugs” over 15 years: Revlimid (lenalidomide), Sovaldi(sofosbuvir) and Gleevec (imatinib). This was due to “unmeritedpatents blocking generic competition”, I-MAK said in a report thatsets out detailed reasoning and cost analyses to support its claims.

THE UK’S National Health Service (NHS) is being “ripped off” byhaving to pay high prices for medicines that have been developedusing UK public money, according to a report co-authored bySTOPAIDS and Global Justice Now. “We must end the scandal ofthe public effectively paying twice for the same medicine – first todevelop it and then again to stock it,” said Tabitha Ha of STOPAIDS.“Patients in the world’s poorest countries are being ripped off too,even when generic versions are available at a tiny fraction of theprice. We need greater transparency and a radical rethink on howwe fund the development of new medicines.” Heidi Chow of GlobalJustice Now said firms were selling drugs developed with “substantialpublic money” back to the NHS at “extortionate prices”, referringto the behaviour as “nothing short of daylight robbery”.

FDA – the US Food and Drug Administration – has published forcomment revised draft guidance on abbreviated new drugapplications (ANDAs) relating to ‘pre-submission of facility informationrelated to prioritised generic drug applications’. G

IN BRIEF

Adecline in the number of patent-litigation settlements betweengenerics firms and originators “potentially involving pay-for-delay”

reverse-payment provisions has been reported by the US Federal TradeCommission (FTC) in an annual review.

Analysing data from the financial year ended 30 September 2015,the FTC said that of 170 final settlement agreements filed, just 14“potentially involve pay-for-delay because they contain both explicitcompensation from a brand manufacturer to a generic manufacturerand a restriction on the generic manufacturer’s ability to market itsproduct in competition with the branded product”. This compared to21 such agreements of a total of 160 in the year ended September 2014,and 29 deals of a total of 145 in the year before that.

Of the 14 potential pay-for-delay settlements, 10 includedcompensation “solely in the form of a cash payment for litigation fees”,while the remaining four included a promise by the brand manufacturernot to market an authorised generic for some period of time. One ofthese four was a settlement deal with a first-filer, and one of the fouralso included a cash payment for litigation fees.

The FTC said a further 10 settlements were characterised ascontaining “possible compensation” because it was not clear whethercertain provisions of the deals acted as compensation to the genericchallenger. Of the total 170 settlements, 126 restricted the genericmanufacturer’s ability to market its product but contained no explicitor possible compensation, while 20 contained no restrictions on genericentry. And “at least three” involved simultaneous resolution of aninter partes review or post-grant review initiated by the generics firm.The FTC also noted that 39 of the 170 deals involved first-filer generics.G

REGULATORY AFFAIRS

FTC notes pay-for-delay drop

Alist of ‘similar biologic groups’ designating equivalence categoriesfor biosimilars has been published by French medicines agency

ANSM, with 28 biosimilars listed alongside 11 different originalbiologics that act as reference brands. The groups’ reference productsinclude Humira (adalimumab), Lovenox (enoxaparin) and Eprex(epoetin), as well as Enbrel (etanercept), Neupogen (filgrastim) andGonal-f (follitropin alfa). Also included as reference brands are Remicade(infliximab), Lantus (insulin glargine) and MabThera (rituximab), alongwith Genotonorm (somatropin) and Forsteo (teriparatide).

At the same time, France’s health ministry has published anadministrative instruction on biosimilars and interchangeability. Aswell as asserting that biosimilars offer “the same efficacy, the samequality and the same safety as the reference biologic”, the documentsays “a biosimilar medicine can be prescribed at any point in treatment”,and not only for patients starting a course of treatment.

For patients in ambulatory care, the instruction suggests “systematicprescription of biosimilar medicines”. For molecules included in thereference groups, treatment should be initiated with a biosimilar inat least 70% of cases, the document urges, adding that switchingpatients from reference biologics to biosimilars “should be encouraged”.

In situations where two therapeutically-equivalent treatment optionsare available, there should be a preference for “the most efficientfrom a medico-economic point of view”, the instruction recommends,notably when an option includes treatment with a biosimilar. G

REGULATORY AFFAIRS

French agency debuts11 biosimilar groups


PRODUCT NEWS

CELLTRION’S Truxima (rituximab) biosimilar is comparable toits reference product – Roche’s MabThera/Rituxan – in terms ofefficacy, pharmacodynamics and safety profile, over a “sustainedperiod of time” after switching from the brand in patients withrheumatoid arthritis, according to new Phase III switching data offeredby the Korean firm. After completing treatment up to 48 weeks withTruxima, Celltrion noted, a total of 295 patients had participated inan extension to the original Phase III, randomised controlled trial.“Patients with rheumatoid arthritis in both groups during this mainperiod demonstrated equivalent efficacy and similar pharmacokineticand safety profiles,” the firm commented. The European Commissionapproved Truxima in February this year.

EAGLE PHARMACEUTICALS must now resolve “patent issues”in order to market the firm’s Pemfexy (pemetrexed) 505(b)(2)hybrid injectable product in the US after receiving tentative approvalfor the ready-to-dilute alternative to Eli Lilly’s Alimta (pemetrexed)chemotherapy agent from the US Food and Drug Administration(FDA). The US-based hybrid injectables specialist was sued in anIndiana district court in August this year for allegedly infringing theoriginator’s US patent 7,772,209, which covers a vitamin-dosageregimen until May 2022.

MSF – Médecins Sans Frontières – is celebrating securing dealsfor generic versions of Gilead Sciences’ Sovaldi (sofosbuvir) andBristol-Myers Squibb’s Daklinza (daclatasvir) “for as low asUS$1.40 per day, or US$120 per 12-week treatment course”. “In2015, MSF started procuring sofosbuvir and daclatasvir from Gileadand BMS through their ‘access programmes’ at a price of US$1,400to US$1,800 per 12-week treatment,” the humanitarian group noted.At the same time, the AIDS Healthcare Foundation (AHF) hasurged Gilead to “slash exorbitant sofosbuvir prices”, and called on“governments to take all possible measures, including issuing ofcompulsory licenses, to provide free hepatitis C virus treatment”.

PEDIAPHARM – a Canadian paediatric specialist – has receiveda notice of compliance, effectively a marketing authorisation, fromthe country’s Health Canada regulatory agency for its Cuvposa(glycopyrrolate) 1mg/5ml oral solution, which is indicated to reducechronic severe drooling in patients with neurological conditionsassociated with problem drooling, such as cerebral palsy.

PERRIGO has received tentative approval from the US Food andDrug Administration (FDA) for its abbreviated new drug application(ANDA) referencing a generic version of Leo Pharma’s Picato(ingenol mebutate) 0.05% gel. The US-based store brands specialistalready holds a tentative nod for a generic rival to the 0.015% strengthof the actinic keratosis treatment (Generics bulletin, 3 November2017, page 18). Both ANDAs are ‘first-to-file’ opportunities, withthe potential for 180 days of generic market exclusivity upon marketentry, according to Perrigo.

BOEHRINGER INGELHEIM has announced new switching datafrom its “pivotal” Voltaire-RA 48-week comparison Phase III clinicaltrial “showing that” the firm’s Cyltezo (adalimumab-adbm)biosimilar is “equivalent” to AbbVie’s Humira (adalimumab)original when treating patients with a form of rheumatoid arthritis.This included patients who switched from Humira to Cyltezo at week24 of the study, Boehringer insisted, “with no clinically meaningfuldifferences in efficacy, safety and immunogenicity to Humira inpatients with moderately-to-severely active rheumatoid arthritis”.Cyltezo received US Food and Drug Administration (FDA) approvalin August this year, but has not yet been launched. G

IN BRIEF

Teva’s Actavis and Alvogen have together received a favourabledecision from a US district court in patent-litigation proceedings

concerning the firms’ proposed generic versions of Valeant’s Uceris(budesonide) extended-release tablets.

Delaware District Judge Leonard Stark granted Teva and Alvogen’smotion for a judgement of non-infringement of US patent 8,784,888,which shields the ulcerative colitis treatment until 9 June 2020. However,Stark had not yet signed an order entering final judgement in favourof the generics firms as Generics bulletin went to press.

According to Teva, Stark’s court had in May this year found thatplaintiffs – Valeant and colon diseases specialist Cosmo – “did not meetthe threshold to establish infringement”. Stark’s memorandum opinion,explaining in writing the court’s findings, is currently under seal.

“Based on available information, Teva believes it is a ‘firstapplicant’ to file an abbreviated new drug application (ANDA) for thegeneric version of Uceris,” the Israeli firm noted. “Should its ANDAbe approved, Teva may be entitled to 180 days of generic marketexclusivity.” Citing QuintilesIMS data, Teva said Uceris had annualsales in the US of around US$191 million.

Alvogen allying with LotusAlvogen, meanwhile, is allying on its ANDA with its Lotus

Pharmaceuticals subsidiary, through its Alvogen Pine Brook arm inthe US. “The court determined that the asserted claims of this patentare not infringed, and therefore Alvogen US and Lotus will proceedwith ANDA-related preparations,” Taiwan-based Lotus commented.

Lotus said the ‘888 patent was the only remaining patent as partof a broader lawsuit, while Stark noted that plaintiffs had “at one timeasserted a number of patents and decided to drop the patents at variousstages of this litigation”. According to the US Food and DrugAdministration’s (FDA’s) Orange Book, Uceris extended-release tabletsare shielded by 10 patents, the latest of which expire in September 2031.

Moreover, Lotus acknowledged Teva’s potential 180-day exclusivityperiod, noting that it and Alvogen may receive ANDA approval afterTeva’s exclusivity lapses or is otherwise forfeited, subject to any appeal.

In a brief statement, Cosmo said it was “convinced of having a goodbasis for an appeal” and would continue to “strongly defend our patentrights on Uceris”. Lotus, in turn, says it is prepared for an appeal. G

GASTROINTESTINAL DRUGS

US Uceris patent notinfringed, court finds

Merck, Sharp & Dohme’s (MSD’s) Brenzys (etanercept) biosimilarmay be given preference over Pfizer’s Enbrel reference brand

for treatment-naïve patients, Australia’s Pharmaceutical BenefitsAdvisory Committee (PBAC) has stated.

Responding to a request to change prescribing software to favourthe biosimilar for naïve patients, the PBAC said this was a matter forthe Australian government, but clarified that “it did not have anyconcerns about encouraging prescribing of a biosimilar brand ratherthan the reference biological agent brand for treatment of naïve patients,including those though notes in the Pharmaceutical Benefits Schedule(PBS) and prescribing software changes”. Brenzys was added to thePBS reimbursement list earlier this year with an ‘a-flag’ substitutablestatus (Generics bulletin, 7 April 2017, page 11). G

ARTHRITIS DRUGS

Australia may favour Brenzys


PRODUCT NEWS

Alvogen says it is “first to market” in the US with a generic equivalentto Roche’s Tamiflu (oseltamivir phosphate) 6mg/ml powder for

oral suspension, developed with India’s Natco Pharma. The launchupon approval from the US Food and Drug Administration (FDA)follows the firm’s first-to-market introduction of oseltamivir capsulestowards the end of last year, also through a partnership with Natco(Generics bulletin, 16 December 2016, page 11).

Following the end, in February this year, of a six-month paediatricextension to US patent 5,763,483, there are no unexpired patents listedagainst Tamiflu powder or capsules in the FDA’s Orange Book.

Nesher holds a similar approvalWhile Alvogen is claiming to be first-to-market with the 6mg/ml

powder, it was not the first firm to secure FDA approval for thisformulation. That honour fell to Zydus Cadila’s Nesher unit in Septemberthis year. At the time, Zydus did not reveal its launch plans, but said itwould make the antiviral drug at Nesher’s US facility in St Louis, Missouri.

“Annual [US] sales for oseltamivir suspension amount to US$312million,” Alvogen stated, citing QuintilesIMS Midas data.

“Alvogen is one of the fastest-growing pharmaceutical companiesin the US market, and this launch further demonstrates our ability to befirst to market with new generic alternatives for US patients,” commentedthe company’s chairman and chief executive officer, Robert Wessman.G

ANTIVIRAL DRUGS

Alvogen claims a firston oseltamivir powder

Three key claims in Cialis (tadalafil) dosage patent EP1,173,181 areinvalid for obviousness, the UK’s Court of Appeal has ruled in

a decision that overturns a Patents Court verdict from last year. Thispotentially clears the way for generic versions of the erectile-dysfunctiondrug to enter the UK market after a supplementary protection certificate(SPC) based on molecule patent EP0,740,668 expires on 13 November.

Teva and Mylan had appealed against a ruling from August lastyear by Patents Court Judge Colin Birss to uphold the validity of thekey claims 1, 7 and 10 in the ‘181 patent that Eli Lilly licenses fromIcos (Generics bulletin, 26 August 2016, page 17). Claim 1 coversoral tadalafil doses of 1mg to 5mg, with a maximum daily dose of5mg. Claim 7 discloses such PDE5-inhibitor dosage forms for treatingsexual dysfunction, while Claim 10 is a Swiss-type claim describingtadalafil 1mg to 5mg dosage forms with the sexual dysfunction purposeand the 5mg daily maximum.

Having dismissed grounds of appeal including added matter andlack of novelty over a Stoner prior-art reference, the Court of Appealpanel – led by Lord Justice David Kitchin – described the obviousnessargument brought by Teva and Mylan on the basis of the Dauganprior-art reference as “a powerful one”. Daugan teaches the use ofPDE5-inhibitors for treating erectile dysfunction and specificallydiscloses tadalafil within doses of 0.5mg to 800mg per day.

Discussing differences between Daugan and the ‘181 patent’sclaims, Kitchin noted that, unlike Claim 1, the prior art did not specifya tadalafil 5mg tablet. And unlike Claims 7 and 10, Daugan did notspecify a tadalafil 5mg daily dose or that such a dose was an effectivetreatment for sexual dysfunction.

Kitchin summarised as the key question: “Was it obvious to theskilled but unimaginative addressee in light of the prior art and thecommon general knowledge to make a product or carry out a processfalling within the claim?” Claim 1, he said, was invalid because “itwas entirely obvious to develop such a composition in light of Daugan”.Similarly, Claims 7 and 10 lacked an inventive step. According toKitchin, Birss had “lost sight of the fact that, on his own findings, theclaimed invention lies at the end of the familiar path through theroutine pre-clinical and clinical trials process”.

Through a routine Phase IIb dose-ranging study, a skilled teamwould have identified the appropriate dose range, Kitchin noted. “Theskilled but uninventive team would find tadalafil an attractive second-in-class medicine to develop. Daugan made it obvious to do so and thesuccess of sildenafil made it very obvious, so it was entirely obviousfor the skilled team to take tadalafil forward,” he stated.

“The skilled team would very likely carry out a dose-ranging study,including a 5mg dose,” Kitchin continued. “If they did so, they wouldfind it was efficacious and had reduced side effects, and so they wouldtake it forward into Phase III. They would have arrived at the invention,”he concluded, noting that Lilly had not appealed against Birss’ findingthat European formulation patent EP1,200,092 was invalid. G

ERECTILE DYSFUNCTION DRUGS

Teva and Mylan clearpath for UK tadalafil

ABZENA and UGA Biopharma have partnered to develop anundisclosed biosimilar cell-line to treat multiple sclerosis. Theagreement “centred around the development of an NS0 murinemyeloma manufacturing cell-line, expressing a high-quality, fullybiosimilar antibody therapeutic”, Abzena stated. G

IN BRIEF


PRODUCT NEWS

Up to the minute live retail market pricing is available for theUK and Eire on Wavedata Live at wavedata.net.Alternatively, contact Charles Joynson at WaveData Limited, UK.Tel: +44 (0)1702425125. E-mail: [email protected].

Price WatchIndex

PharmacyProfit Index78.8 41.4

Monthly change ±0.0 Monthly change -6.4

October 2017 October 2017

The Price Watch Index is based on the actual average trade price according to WaveData of a representativebasket of 20 popular generic products in March 2016, when the Index was 100. The basket reflects recentofficial prescribing data for England and Wales and represents what an average pharmacy would pay forthe products, which were selected as being the top cash generators within pharmacy. The PharmacyProfit Index is calculated on the same basis by applying Drug Tariff reimbursement prices to the basket.

Dispensing profit enjoyed by UK pharmacies for our typicalbasket of 20 popular generics fell to a new low in October,

continuing the downward trend observed in September.A profit of just £696.42 (US$912.88) meant that pharmacists

were making barely two-fifths – 41.4% – of the profit they weremaking a year and a half ago when the Index was set at 100 inMarch 2016, and represented a 6.4-point decline from the previousmonth (Generics bulletin, 6 October 2017, page 8).

With a basket purchase price that was virtually unchanged – at£1,677.15 compared to September’s £1,678.28 – the Price WatchIndex remained static at 78.8. Meanwhile, the reimbursement valuefalling to a new low since the Index was set of £2,373.57 – from£2,483.02 in September – drove down the profit available to pharmacies.

These declines came against a backdrop of increasing pressurescaused by generic supply issues, including both shortages andpricing issues (Generics bulletin, 20 October 2017, page 12). G

October 2017

PRICE WATCH ....... UK

Basket Price Reimbursement Price Pharmacy Profit£1,677.15 £2,373.57 £696.42

ADelaware district judge “clearly erred” in finding that prior artdid not render obvious two key claims in a US formulation patent

protecting Bayer’s Staxyn (vardenafil) until December 2028, the USCourt of Appeals has stated in a ruling in favour of Teva’s Actavis.Two other US patents listed against the erectile-dysfunction drugexpire on 31 October 2018.

Actavis had appealed against district judge Gregory Sleet’s findingthat claims 9 and 11 of US patent 8,613,950 – which describe an oraldisintegrating tablet (ODT) formulation of vardenafil, with sorbitol andmannitol as excipients – were not obvious in light of prior art.

“The clear error in the district court fact-finding that there was nomotivation for formulate erectile-dysfunction drugs in ODT is that itconcluded that the record did not contain an indication that erectile-dysfunction drugs would be good candidates for ODT formulations,”the Court of Appeals stated, pointing to nine prior-art referencesprovided by Actavis.

Such references, the appeals panel said, were “highly relevant” towhether a skilled person would have had motivation to develop vardenafilODT. Furthermore, the panel added, six prior-art references that Sleethad disregarded identified erectile-dysfunction drugs as ODTformulations. And there was “an express motivation in the prior art” tousing sorbitol and mannitol as excipients, the appeals judges noted. G

ERECTILE DYSFUNCTION DRUGS

Actavis wins appealon US Staxyn patent

European patent EP1,313,508 protecting Eli Lilly’s Alimta(pemetrexed disodium) is valid and infringed by alternative salt

forms offered by Teva, courts in Switzerland and the Netherlands andhave found. A Dutch district court in The Hague reached a similarconclusion on Fresenius Kabi’s version of the oncology brand.

The ‘508 patent claims pemetrexed disodium administered incombination with vitamin B12 to inhibit tumour growth. Teva and Kabisought to circumvent the patent, which expires in June 2021, by obtainingauthorisations to market alternative salt forms of pemetrexed.

Switzerland’s Supreme Court found that the Amtiris (pemetrexeddiacid) branded generic introduced by Teva’s Actavis infringed the‘508 patent. In doing so, the Supreme Court reversed and remandeda declaratory judgement of non-infringement that the country’s federalpatent court had handed down in March this year.

Noting that Lilly had, during the prosecution of the ‘508 patent,narrowed its scope from antifolates, to pemetrexed and then further to‘pemetrexed disodium’, the Swiss Supreme Court said this had notcaused the patent holder to forego an infringement argument under adoctrine of equivalents.

In the Dutch preliminary injunction proceedings, the court rulingsof direct infringement in favour of Lilly followed Teva’s launch ofArmisarte (pemetrexed diacid) on 1 June, shortly after the generic wasentered into the country’s G-Standaard reimbursement list, while Kabialso introduced the diacid form in the Netherlands earlier this year.

Judge E F Brinkman found that a skilled person, having consideredthe ‘508 patent’s claims and specification, would have understood thatthe patent’s core inventive concept was adding vitamin B12 topemetrexed anions, thereby minimising toxicity and side effects.

Stressing the need to take “due account” of equivalents as outlinedin Article 2 of the Article 69 of the European Patent Convention (EPC),Brinkman insisted that “a literal reading of the patent claims makescircumventing the patent simple, indeed almost childish, whilenevertheless making use of the invention”.

While Brinkman said his findings were in line with similarinfringement rulings in Germany and the UK (Generics bulletin, 14July 2017, page 1), he recognised that other European judges – suchas in Italy (Generics bulletin, 13 October 2017, page 17) – had foundthere was no infringement of the ‘508 patent by other salt forms. “Suchdivergent decisions once again emphasise the desirability of a UnifiedPatent Court (UPC),” he maintained. G

ONCOLOGY DRUGS

Swiss and Dutch findAlimta infringement

Four key claims in a US patent protecting the use of Sanofi’s Multaq(dronedarone) tablets for preventing cardiovascular hospitalisation

are not invalid as obvious, Delaware District Judge Richard Andrewshas ruled in a verdict against Sandoz and Teva’s Watson. Furthermore,labelling in proposed generic versions of the cardiovascular drug wouldinduce infringement of the four claims, Andrews said.

Andrews found that Sandoz and Watson had failed to show that askilled person, as of the patent’s priority date, would have reasonablyexpected dronedarone to reduce the risk of cardiovascular hospitalisationin atrial fibrillation patients. Thus, US patent 9,107,900 – which expireson 16 April 2029 – was valid. G

CARDIOVASCULAR DRUGS

Multaq patent is upheld in US


PRODUCT NEWS

22 Novembern 1st Value Added Medicines Conference

Brussels, BelgiumThis event organised by Medicines for Europe will focus onopportunities presented by medicines that are repositioned,reformulated or combined.

Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: [email protected]. Register online atwww.medicinesforeurope.com/events.

27-28 Novembern euroPLX 65

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

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

24 Januaryn 11th Pharmacovigilance Conference

London, UKThis one-day Medicines for Europe conference will lookat implementing pharmacovigilance legislation and currentdevelopments within the industry.


25-26 Januaryn 17th Regulatory and Scientific

Affairs ConferenceLondon, UKThis conference will follow the Pharmacovigilance event at thesame venue. There will be updates on regulatory developmentsand representatives from competent authorities in attendance.


12-14 Februaryn Access! 2018 – AAM Annual Meeting

Florida, USAThis Association for Accessible Medicines event will look atregulatory topics and the challenges facing the US generics industry.

Contact: Association for Accessible Medicines. Tel: +1 202 249 7100.E-mail: [email protected]. Register online atwww.accessiblemeds.org/events.

1-2 Marchn 2nd OTC Innovation & Business

Development ConferenceLondon, UKOrganised jointly by the Pharmaceutical Licensing Group andOTCToolbox, this event will focus exclusively on businessdevelopment and innovation in the consumer healthcare/OTCmarket. The theme for this event is capitalising on change.

Contact: OTCToolbox. Tel: +44 121 314 8757.E-mail: [email protected]: plg-group.com/events/3rd-otc-event.

EVENTS – November 2017 – March 2018

Momenta head Craig Wheeler says it is too early to speculate onthe future of the development programme for its proposed

biosimilar version of Bristol-Myers Squibb’s Orencia (abatacept)with partner Mylan, after the candidate failed to meet its primarypharmacokinetic endpoints in a Phase I clinical trial.

“This was an unexpected result and we are disappointed with theoutcome of this pharmacokinetic study,” Wheeler commented. “Weare in the process of gathering the full data set and will work withMylan to fully analyse these data to better understand the study resultsand evaluate next steps for this programme.” The firms remainedcommitted to executing on their biosimilar portfolio, he insisted.

Initiated in November last year, the single-dose, subcutaneousadministration clinical study compared the pharmacokinetics, safety andimmunogenicity of the M834 abatacept biosimilar candidate, US-sourcedOrencia, and European Union- (EU-) sourced Orencia in 243 normalhealthy volunteers (Generics bulletin, 11 November 2016, page 12).

Addressing investors, Wheeler said the company would providemore information once it had had “adequate time to perform acomprehensive analysis of the full data set from the study”. “All we haveseen at this point is the top-line data, and so our technical teams arebeginning to dig in to the full data set,” he revealed.

Momenta and Mylan would be looking at “all aspects of trialconduct”, Wheeler said, “from the molecule itself to assay”. “So it’stoo early for me to say exactly what happened here. I don’t think thisimpacts the rest of our biosimilar portfolio,” he forecasted.

The partners are jointly developing the biosimilar under a globalcollaboration agreement signed at the beginning of last year (Genericsbulletin, 15 January 2016, page 1). Under the cost- and profit-sharingpartnership, the firms are allying on developing, manufacturing andmarketing six of Momenta’s biosimilar candidates, five of whichhave thus far not been disclosed.

Meanwhile, Wheeler told investors that Momenta and Sandoz hadidentified a potential alternative fill-and-finish vendor to supportmanufacturing for the firms’ proposed generic version of Teva’sCopaxone (glatiramer acetate) 40mg thrice-weekly formulation. Thisis in the event that current partner Pfizer is unable to remediatecompliance observations at its respective fill-and-finish facility followingan anticipated US Food and Drug Administration (FDA) re-inspection.

Pfizer’s facility in McPherson, Kansas – where the firms’ Glatopa(glatiramer acetate) 20mg and 40mg products are manufactured – hasbeen constrained by an FDA warning letter since February this year.

“We understand that Pfizer has made significant progress on theremediation of the majority of the observations cited in the warningletter and that the facility is prepared for re-inspection,” Wheeler said.“We believe a near-term positive outcome in the form of a lifting ofthe warning letter or a change to the voluntary action indicated (VAI)status could still allow for the approval or launch of Glatopa 40mg inlate 2017 or early 2018.”

Wheeler said the company had been “disappointed” to learn inearly October of Mylan’s US approval and subsequent launch of genericCopaxone 20mg and 40mg products, ahead of Momenta and Sandoz(Generics bulletin, 6 October 2017, page 1). But, he said, “given thesize of the market for Copaxone 40mg and Sandoz’ success in penetratingapproximately 40% of the 20mg market with our Glatopa 20mg product”,the firms believed there remained a “meaningful opportunity formultiple competitors in the glatiramer acetate market”. Gn [email protected]

AUTOIMMUNE DISEASE DRUGS

Orencia trial fails forMomenta and Mylan


PEOPLE

Belgian off-patent industry association FeBelGen has appointed itsboard for a three-year term running until 2020. Joris Van Assche

remains managing director of the association, while Jef Hus – managingdirector of Eurogenerics – retains his role as president of FeBelGen.

Teun Grooters, managing director of Teva Belgium, replaces asvice-president of FeBelGen Sandoz’ Vincent Verschraegen, who hasleft the board. Rebecca Guntern of Sandoz has joined the board asa director, while Mylan’s Maximilian von Wuelfing remains onFeBelGen’s board as a director. G

APPOINTMENTS

Belgium’s FeBelGenoutlines a new board

Siegfried has announced that the firm’s “longtime principal andsince 2003 honorary chairman” has died at the age of 83 “after an

extended illness”. Representing the fourth generation of the Siegfriedfamily, Bernard Siegfried joined the company in 1967 before beingelected a decade later to the board of directors and as chairman of theexecutive committee. In 1998, he became board chairman with executiveresponsibilities. These responsibilities were handed off in 2001 and heresigned as chairman of the board two years later. G

OBITUARIES

Obituary: Bernard Siegfried

Akorn director and chairman of the board, John Kapoor, hasresigned from both roles with immediate effect. Alan Weinstein –

who “qualifies as an independent director and has served on thecompany’s board since 2009” – will now serve as chairman.

Kapoor was recently charged in a Massachusetts court overaccusations of bribes and fraud relating to a fentanyl spray sold byInsys Therapeutics, of which Kapoor is founder. He has stepped downfrom Insys’ board. “I am confident that I have committed no crimesand believe I will be fully vindicated after trial,” Kapoor insisted.G

RESIGNATIONS

Akorn’s Kapoor hasresigned as chairman

SANDOZ’ global head of respiratory, Jan-Torsten Tews, has leftthe firm to join Belgium-based respiratory devices company Softhale.Prior to joining Sandoz, Tews was Teva’s European respiratoryhead. Sandoz did not comment on his replacement.

GLENMARK has announced the appointment of VS Mani as presidentand global chief financial officer with effect from 16 November,replacing P Ganesh. Mani’s previous roles have included chieffinancial officer of Cipla. G

IN BRIEF

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