26 October 2018

Four adalimumabs compete in EUFour separate biosimilar versions of AbbVie’s Humira (adalimumab) are competing for market

share in the European Union (EU), after Amgen, Mylan, Samsung Bioepis and Sandoz alllaunched into European markets immediately after a key supplementary protection certificate(SPC) protecting the autoimmune treatment expired. Amgen, Mylan and Samsung Bioepissaid their respective Amgevita, Hulio and Imraldi biosimilars had launched in markets acrossEurope, including in Italy for Amgen. A Sandoz spokesperson told Generics bulletin thecompany – which has received approval under the Hyrimoz, Halimatoz and Hefiya labels – had“launched and supplied” its adalimumab in Germany and the UK, while it had placed tenderbids in the Netherlands and Ukraine.

The unprecedented multiple launch was preceded by a global patent-litigation settlementbetween AbbVie and Sandoz that provided guaranteed market entry dates (Generics bulletin,19 October 2018, page 19), following other deals struck by AbbVie with Amgen, Mylan andSamsung Bioepis. Generics bulletin understands that Boehringer Ingelheim – which has notpublicly announced a settlement with AbbVie, but which has European Medicines Agency(EMA) approval for its Cyltezo version – does not have immediate plans to launch.

Meanwhile, Fresenius Kabi andAbbVie have just announced a global resolution of Humirapatent disputes through a royalty-bearing deal that will grant Kabi a US licence starting on 30September 2023 and that also allows the firm to launch in the EU upon EMA approval. G

Global development pathproposed to ICH by FDAAset of “internationally harmonised guidelines on scientific and technical standards for

genericdrugs”shouldbedeveloped throughtheInternationalCouncil forHarmonizationof Technical Requirements for Pharmaceuticals for Human Use (ICH), according to aproposal that has been put forward by the US Food and Drug Administration (FDA).

“The idea is straightforward,” explained FDA Commissioner Scott Gottlieb. “Genericdrug developers should be able to implement a single global drug-development program andutilise common elements of applications to file for approval in multiple markets.” This would“make it easier for developers that would otherwise only seek generic drug approval in oneregion to also seek approval in the US, increasing competition in America”. At the same time,“it would also make it easier for developers that would otherwise only seek generic drugapproval in the US market to gain access to other markets”.

“The ultimate goal of this global harmonisation of scientific and technical requirementswould be the attainment of a single global generic drug-development program that can supportsimultaneous regulatory filings across multiple markets,” Gottlieb set out. Harmonising theserequirements was “foundational to achieving a future goal of enabling global approval”.

Pointing out that manufacturing specifications currently differed between countries, withdifferent tests required to support approvals, Gottlieb said the “lack of harmonisation acrosssuch basic components of generic drug development reduces the opportunities for generic drugdevelopers to use their data and information acrossmultiple applications in different jurisdictions”,resulting in “increased cost and complexity”. Harmonising development, he said, would alsoincrease global quality consistency, enhance regulatory oversight and bolster competition.

“We anticipate that the ICH will review the FDA’s proposal and that the ICH Assemblywill be invited to endorse the proposal at its next meeting in November 2018,” Gottlieb said,revealing that the agency had proposed developing a series of guidelines on standards fordemonstrating equivalence for both non-complex and complex dosage forms. G

COMPANY NEWS 3Teligent sole success in exiting price case 3

Akorn appeals ruling letting Kabi stop deal 3

WBA sees sourcing savings start sliding 4

Better API conditions boost Jubilant’s sales 4

US sale puts Sandoz on the ‘right track’ 5

Alembic’s derma pact passes FDA inspection 6

Abbott’s EPD unit is outpacing the market 6

Lupin’s inhalers plant gets five observations 7

Teva formalises plan for US headquarters 7

Idifarma attracts with spray-drying capacity 8

MARKET NEWS 9EU insurers seeking stockpiling on SPCs 9

Canadian competition hit by sample blocking 9

UK market working, Accord report claims 10

Maintain on-sale bar argues US industry 10

Israel consults over bio data exclusivity 11

Budget backlash on French substitution 11

Portuguese patients handle device switch 12

PRODUCT NEWS 13Apotex minutes late on potassium CGT 13

Mylan’s trastuzumab is greenlit by CHMP 13

English contracts to save up to £150mn 14

Teva sues FDA over Restasis exclusivity 14

Impurity issue stops Aurobindo irbesartan 15

Biosimilar infliximab US share only at 7% 15

Three blockbusters to face 2019 competition 16

Polpharma and SIFI ally on eye diseases 17

Ciclosporin SPC case sent to EU by France 17

FEATURES 20Canadian industry is seeking 20lower costs and improvements

REGULARSEvents – Conferences and meetings 12

Price Watch UK – Our regular listing 18

People – Ford’s Abbott named 24in chief operating role

Issue No.373

Gen 26-10-18 Pgs.1-24.indd 1 24/10/2018 16:00

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3bulletin26 October 2018

COMPANY NEWS

MERGERS & ACQUISITIONS

Akorn appeals rulingletting Kabi stop dealAkorn has appealed against a recent US court ruling that absolved

Fresenius Kabi of completing its US$4.75 billion merger with theUS-based ophthalmics and injectables firm. In its appeal to Delaware’sSupremeCourt,Akornhas filedamotionseekingexpeditedproceedingsand anticipates stating its appellate argument in an opening brief thatwill be “filed on a schedule set by the Supreme Court”.

AfterAkorn filed suit in order to compel Kabi to consummate thetransaction, Delaware Chancery Court Judge Travis Laster sided withthe German company following a five-day trial in July (Genericsbulletin, 5 October 2018, page 1). Laster ruled that Kabi had notbeen in material breach of its own obligations under the mergeragreement and had validly terminated it several months earlier, citinga multitude of “serious and pervasive data-integrity problems” atAkorn uncovered during an independent investigation (Genericsbulletin, 27 April 2018, page 1).

In a highly detailed decision that spanned almost 250 pages,Laster noted that closing the US$34-per-share transaction “was nota foregone conclusion”, but was rather conditional on “Akorn’srepresentations having been true and correct both at signing and atclosing”, unless any failure to be so did not represent a contractuallydefined ‘material adverse effect’. Furthermore, Fresenius was onlyobliged to complete the transaction ifAkorn “complied in all materialrespects” with its own obligations under the merger agreement, andif Akorn had not suffered a ‘material adverse effect’.

Shortly after agreeing the US$4.75 billion deal in April 2017,“Akorn’s business performance fell off a cliff”, reporting for thesecond quarter of 2017 “dismal results that shocked Fresenius” giventhat Akorn had reaffirmed its full-year guidance, Laster observed.And then in October 2017, an “anonymous whistle-blower” hadalleged to Fresenius that Akorn’s product-development processdid not comply with regulatory requirements. This prompted theGerman group to launch an investigation that “uncovered serious andpervasive data-integrity problems”, leading Fresenius in April 2018to give notice it was terminating the deal.

Addressing Akorn’s appeal against that termination notice, Lasterfound that “Fresenius validly terminated themerger agreement becauseAkorn’s representations regarding its compliance with regulatoryrequirements were not true and correct, and the magnitude of theinaccuracies would reasonably be expected to result in a materialadverse effect”.

Launching its appeal against Laster’s verdict, the US firminsisted that, “despite misleading allegations made by Freseniusthroughout the trial regarding Akorn’s regulatory compliancepractices and activities, Akorn takes data integrity and other US Foodand Drug Administration (FDA) compliance issues very seriously.”The company said it was working with the US agency “to evaluateand improve its practices and procedures to ensure compliance withFDA regulations”.

Having pushed aside the Akorn deal, Kabi has revealed thatit expects to reach “the top end” of its forecasted full-year organicsales growth of between 4% and 7%. Having increased its earningsbefore interest and tax (EBIT) outlook, the German firm now predictsbetween 1% to 3% growth in constant currencies, up from thepreviously anticipated range of a 2% decline to a 1% rise. Kabi saidthe profit rise was driven by “a strong development across all productlines and regions, with North America standing out”. Gn grace.montgomery@generics-bulletin.com

LITIGATION

Teligent sole successin exiting price caseTeligent has emerged as the only generics provider to succeed in

having a motion to dismiss class-action antitrust complaints overpricing granted by a Pennsylvania district court. While the US-basedtopicals and injectables specialist persuaded Judge Cynthia Rufe tothrow out accusations brought by direct purchasers, indirect resellersand end payers, on pricing for econazole – the only drug for whichTeligent was cited as a supplier in the case – a wide array of leadingindustry players met with far less success.

Rufe dismissed joint motions to dismiss class-action complaintsunder the US Sherman antitrust act on clobetasol, digoxin, divalproex,doxycycline, econazole and pravastatin brought collectively by around20 generics suppliers. She also rejected individual motions broughtby: Teva’s Actavis, Akorn, Perrigo and Wockhardt on clobetasol;Amneal’s Impax, Mylan, Endo’s Par and Hikma’s West-Ward ondigoxin; Dr Reddy’s, Mylan and Zydus on divalproex extended-release tablets; Actavis, Mayne Pharma, Mylan, Par and West-Wardon doxycycline; and Apotex, Glenmark and Sandoz on pravastatin.

In an accompanying opinion issued in the multi-district antitrustlitigation covering alleged unlawful schemes to fix prices for sixoff-patent active ingredients, Rufe noted that the US Judicial Panelon Multidistrict Litigation (JPML) had in August 2016 consolidatedseveral cases on prices for generic digoxin and doxycycline. TheJPML then in April 2017 expanded the scope of the litigation tocover allegations over price fixing, market allocation and other anti-competitive behaviour by the US generics industry.

“There are no allegations in the econazole complaints thatTeligent received subpoenas,” Rufe observed in her opinion, whereassubpoenas on the topical antifungal agent had been served on SunPharma and its Taro affiliate, while “search warrants were executed atPerrigo’s corporate offices”. Nor, she noted, was Teligent “alleged tohave been a regular member of any trade association”.

No opportunity to conspireAs a result, Rufe decided that the plaintiffs’ allegations “fall short

of making plausible” the contention that Teligent had an opportunityto conspire with the other defendants, particularly in light of thetiming of the firm’s econazole price increases “several months” afterrises by Perrigo or Taro and “given the absence of any allegation thatTeligent has received a subpoena or has been specifically touched bya government investigation”.

Although the plaintiffs, with the exception of doxycycline, reliedon circumstantial rather than direct evidence on anti-competitivepractices, Rufe found that their allegations of “parallel conduct” –effectively mirroring each other’s pricing levels and changes – weresufficient to proceed with the litigation against all defendants otherthan Teligent. Noting that her opinion related only to six ‘Group 1’active ingredients, and not to six other molecules each in Groups 2and 3 of the litigation, Rufe said antitrust enforcement actions filedby US states against six firms over drugs such as doxycycline andglyburide were proceeding separately “on a single consolidated,amended complaint”.

“Ultimately,” Rufe concluded, “whether Group 1 defendants’alleged pricing decisions were ‘simple, benign business decisions …or whether they represent concerted effort in violation of the ShermanAct are issues of fact which this court cannot decide on the pleadingsand which require discovery prior to resolution’.” Gn aidan.fry@generics-bulletin.com

Gen 26-10-18 Pgs.1-24.indd 3 24/10/2018 16:00

4 bulletin 26 October 2018

COMPANY NEWS

aidan.fry@generics-bulletin.com

Issue 373 l 26 October 2018

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ISSN 1742-0784

SECOND-QUARTER RESULTS

Better API conditionsboost Jubilant’s salesJubilant Life Sciences credited “better market conditions” for

its active pharmaceutical ingredients (APIs), as with for its USsolid-dosage formulations, for a 29% rise to Rs4.18 billion (US$56.9million) in Generics & API turnover in its financial second quarterended 30 September 2018. The Generics & API unit more thantrebled its earnings before interest, tax, depreciation and amortisation(EBITDA) to Rs1.26 billion, improving its EBITDAmargin by morethan 18 percentage points to 30.2% (see Figure 1).

Having filed three abbreviated new drug applications (ANDAs)for oral solids between April and September 2018, Jubilant ended itsfinancial second quarter with 35 of 96 filed ANDAs for solid-dosageforms pending approval. Another two of a total of four injectableANDA submissions are pending.

Radiotherapy acquisitions helped to lift by 71% to Rs9.08 billionsales by Jubilant’s Specialty Pharmaceuticals unit that also includesallergy therapies and contract-manufacturing revenues. The group iscurrently bolstering its offering by installing a lyophilisation line thatit expects to become operational in its next financial year.

The company’s management team highlighted “continued growthin Specialty Pharmaceuticals and smart recovery in our Generics &API businesses”, as well as strong demand for its Life ScienceIngredients business segment. G

BUSINESS STRATEGY/ANNUAL RESULTS

WBA sees sourcingsavings start slidingGenerics procurement savings achieved through the centralised

Walgreens Boots Alliance Development (WBAD) sourcingorganisation are starting to wane, according to the pharmacy retailingand wholesaling group’s chief financial officer James Kehoe.

Outlining generics purchasing as one of “three valves” that WBApossessed for relieving reimbursement pressure – the other two beingadding prescription scale and achieving greater operating efficiency– Kehoe told investors the impact of “how we purchase generics, andthe significant benefits we have gotten over multiple years” were now“tailing off a little bit”. To compensate for this decline in savings, he

said the group would be “significantly scaling up” its efforts to reduceselling, general and administrative (SG&A) costs.

Kehoe revealed that, last year, WBA had “offset about 70% ofthe pressure” that it experienced from reimbursement reductionsthrough procurement savings for generics and other products. Theremaining 30% came through “overheads management”. ReportingWBA’s annual results, he told investors that the group “could be alittle bit more aggressive on SG&A and procurement in general”.

In its financial year ended 31 August 2018, WBA improved itsoperating profit by 15.4% to US$6.41 billion on a turnover that roseby 11.3% as reported – and by 3.2% on an organic, constant-currencybasis – to US$132 billion as the group integrated US retail stores thatit acquired from Rite Aid. The deal lifted its share of the US retailprescription market to 21.7% as annual sales by its Retail PharmacyUSA division climbed by 12.7% to US$98.4 billion (see Figure 1).G

Figure 1: Breakdown by business division of Walgreens Boots Alliance’s (WBA’s) salesand operating margin in its financial year ended 31 August 2018 (Source – WBA)

Business division Annual sales(US$ millions)

Change(%)

Operatingmargin1(%)

Retail Pharmacy USA 98,392 +12.7 5.0

Retail International 12,281 +4.0 6.9

Pharma Wholesale 23,006 +8.6 2.1

Corporate eliminations -2,142 +2.5 -

WBA 131,537 +11.3 4.7

1 excludes equity earnings in AmerisourceBergen

Figure 1: Breakdown by business segment of Jubilant Life Sciences’ sales andearnings before interest, tax, depreciation and amortisation (EBITDA) margin in itsfinancial second quarter ended 30 September 2018 (Source – Jubilant)

Business segmentSecond-quarter

sales(Rs millions1)

Change(%)

EBITDAmargin(%)

Specialty Pharma 9,080 +71 26.2

Generics & API 4,180 +29 30.2

Pharmaceuticals 13,260 +55 27.5

Life Science Ingredients 8,870 +20 12.3

Others 570 +15 7.4

Jubilant Life Sciences 22,690 +38 20.02

1 rounded to nearest Rs10 million2 includes Rs240 million of unallocated corporate expenses

Gen 26-10-18 Pgs.1-24.indd 4 24/10/2018 16:00

5bulletin26 October 2018

COMPANY NEWS

BUSINESS STRATEGY/THIRD-QUARTER RESULTS

US sale puts Sandoz on the ‘right track’Selling Sandoz’ US solid-dose and dermatology generics portfolio to

Aurobindo for up to US$1.0 billion forms part of setting Novartis’generics division on “the right track” in a challenging environment,according to the Swiss group’s chief executive officer, Vas Narasimhan.

“When you think about howwe are going to drive Sandozmovingforward, a lot of it is about executing a strategy of transformation andshifting the focus to complex generics and biosimilars,” Narasimhantold investors. “We are well on our way to doing that in the US,” headded. “We announced our planned sales of the core generics businessto Aurobindo.”

“Sandoz continues to perform well in a difficult environment,both in the US but also around the world,” he insisted. In Europe, heobserved,Sandozhad just introducedbiosimilarHumira (adalimumab)in four countries, while the firm held approval for infliximab and wasworking towards a fourth-quarter launch of pegfilgrastim.

“Overall, I think Sandoz is on the right track,” Narasimhansummarised.While the division continued to operate in a “challengingenvironment”, he believed “we are taking the steps necessary to putthe division in a place where it can succeed”.

In early September this year, Novartis announced an agreementto sell Sandoz’ US oral-solids and dermatology portfolios toAurobindo for around US$900 million in cash and US$100 millionin potential earn-outs (Generics bulletin, 14 September 2018, page1). “This transaction supports the Sandoz strategy of focusing oncomplex generics, value-added medicines and biosimilars to achievesustainable, profitable growth in the US over the long term,” the Swissgroup stated, adding that it expected to complete the transaction “inthe course of 2019”.

US sales slide by 17%Along with around 300 products that generated six-month sales

of about US$600 million and additional development projects, thesales will include Sandoz’ dermatology development centre andUS manufacturing plants in Wilson, North Carolina, as well as inHicksville and Melville, New York.

Even before reducing the scale of its US operations, Sandozsuffered a 17% slide in total US sales to US$661 million in the thirdquarter of this year, “mainly due to continued industry-wide pricingpressure”. That included a 23% decrease in turnover from US RetailGenerics, which led to global Retail Generics sales falling by 10% asreported, and by 6% at constant exchange rates, to US$1.95 billion(see Figure 1). The Retail total included sales of finished-dose Anti-Infectives under the Sandoz label that fell by 9% to US$201 million.

While the US dragged down Sandoz’global third-quarter turnoverby 6% as reported, and by 4% in constant currencies, to US$2.42billion, Novartis pointed out that the division had grown by 2% ona constant-currency basis outside of the US. Pressure in the US waslargely responsible for eight percentage points of price erosion acrossSandoz’ global operations that more than outweighed four points ofvolume growth.

European sales up by 1% at constant exchange rates, but down by2% as reported, to US$1.20 billion – accounting for half of Sandoz’global turnover – were boosted by launches of the Erelzi (etanercept)and Rixathon (rituximab) biosimilars in the third quarter of last year(Generics bulletin, 7 July 2017, page 13).

“There was a softening of the performance in the Europeanbusiness,” acknowledged Sandoz’ head, Richard Francis, followingfirst-half constant-currency growth of 7% in the region (Genericsbulletin, 27 July 2018, page 7). This was due in part, he explained,to a strong prior-year third quarter with the launches of Erelzi and

Rixathon, while the retail side of the business had been adverselyaffected this year by withdrawing valsartan and “some seasonalbuying patterns”.

“Gooduptake” for bothErelzi andRixathon contributed to double-digit growth in Europe and globally in Biopharmaceuticals sales thatincluded Glatopa (glatiramer acetate) and contract-manufacturingrevenues. “We see these as growth brands as we move into nextyear,” Francis said, noting that while originators were fighting backon pricing, biosimilar penetration had not yet “maxed out”.

“I remain confident about the European business,” Francisproclaimed, highlighting the recent Hyrimoz (adalimumab) roll-outand the impending European launches of both of its GP1111 orZessly (infliximab) and LA-EP2006 or Ziextenzo (pegfilgrastim)biosimilars, with the latter currently awaiting European Commissionapproval after a recent European Medicines Agency (EMA) positiveopinion (Generics bulletin, 28 September 2018, page 15).

Optimistic on adalimumabQuestioned on potential for biosimilar adalimumab to take

market share, Francis commented: “If you look at it historically, everybiosimilar that comes to market in Europe changes the adoption andmoves it outwards.” Citing the strong uptake of rituximab last yearand the fact that Sandoz was one of several players that had enteredwith adalimumab, Francis said “that drives me to be optimistic aboutthe biosimilar penetration [for adalimumab] over the first year”.

Francis said Sandozwasworking towards re-filing its LA-EP2006pegfilgrastim candidate in the US next year. Asked about thedivision’s strategy for re-filing its GP2013 rituximab biosimilar forindications including follicular lymphoma after the US Food andDrugAdministration (FDA) issued a complete response letter (CRL),Francis said Sandoz had been “working closely with the FDA”and had held discussions with the agency on “a path forward forrituximab”. “We are currently awaiting their written feedback just toclarify the next steps,” he revealed.

While Sandoz improved its third-quarter gross margin by 3.4percentage points to 47.2%, sales and marketing investments outsidethe US pushed up selling, general and administration costs by 4% toUS$534 million.

Including a US$110 million intangible-asset charge linked tothe US Aurobindo transaction, Sandoz’ operating profit fell by 8% toUS$358 million, cutting its operating margin by 0.3 points to 14.8%.Gn aidan.fry@generics-bulletin.com

Region/SegmentThird-quartersales (US$millions)

Reportedchange(%)

Constant-currency

change (%)

Europe 1,204 -2 +1

US 661 -17 -17

Asia, Africa, Australasia 366 +3 +6

Canada, Latin America 189 -5 +5

Sandoz 2,420 -6 -4

Retail Generics 1,949 -10 -6

Biopharmaceuticals 349 +20 +21

Anti-Infectives 122 -11 -11

Figure 1: Breakdown by region and business segment of Sandoz’ sales in the thirdquarter of 2018 (Source – Novartis)

Gen 26-10-18 Pgs.1-24.indd 5 24/10/2018 16:00

6 bulletin 26 October 2018

COMPANY NEWSTHIRD-QUARTER RESULTS

Abbott’s EPD unit isoutpacing the marketAbbott’s chairman and chief executive officer, MilesWhite, says that

the firm’s Established Pharmaceuticals Division (EPD) brandedgenerics business focused specifically on key emerging markets“continues to execute its strategy and grow faster than the market inseveral of our priority countries, including India and China”.

In the third quarter of 2018, EPD sales declined by 0.9% toUS$1.16 billion as reported, but rose by 5.9% organically (see Figure1). This included turnover in the firm’s ‘Key Emerging Markets’ thatslid by 2.1% – and rose by 6.8% organically – to US$866 million.Double-digit growth was achieved in “several geographies”, includingRussia and China.

Noting that EPD “is in high growth or at least moderate to highgrowth markets with great tailwinds”, White acknowledged that thesegment “of course has a currency headwind like everything else”.

“In the third quarter, we have seen a tick-up in currency impact,”he observed. “We are clearly moving into a headwind here. We willsee that in the fourth quarter. And I think that is going to continueinto next year.” Excluding the increasing currency headwinds, Abbottis forecasting fourth-quarter “mid single-digit sales growth” forEPD, contributing to a full-year organic rise in group turnover ofapproximately 7%, which is “at the top end of the guidance range weprovided at the beginning of the year”.

Multiple factors driving growthStating that thegroup’spipeline“continues tobehighlyproductive”,

White said: “It is not like we are reliant on a single product or a singlecountry. There is just great diversity of growth across the board.” “Ihave never in my career here seen such breadth across the companyin new products, new product launches and market conditions,” hecontinued. “Even Nutrition right now is doing considerably better thanit has the last couple of years.”

While the firm would “continue to pay down debt”, White saidthat Abbott was “at the point where we have got strategic flexibility”.Reiterating the company’s focus on its organic growth opportunitiesand pipeline, he maintained: “We have not seen a lot on the merger andacquisition front that interests us. We are always doing our homeworkon what possibilities may or may not be out there and what mightinterest us, what might fit our portfolio. But right now, we have notseen anything that draws our attention.” Gn grace.montgomery@generics-bulletin.com

Third-quartersales

(US$ millions)

Reportedchange(%)

Organicchange(%)

Nutrition 1,838 +4.0 +6.1

Diagnostics 1,824 +42.6 +7.5

Key Emerging Markets 866 -2.1 +6.8

Other Markets 293 +2.8 +3.1

Established Pharma 1,159 -0.9 +5.9

Medical Devices 2,815 +8.4 +9.8

Abbott* 7,656 +12.1 +7.8

*total sales from continuing operations include other sales of US$20 million

Figure 1: Breakdown by business segment of Abbott’s sales in the third quarter of2018 (Source – Abbott)

MANUFACTURING/SECOND-QUARTER RESULTS

Alembic’s derma pactpasses FDA inspectionAleor Dermaceuticals, Alembic Pharmaceuticals’ majority-owned

skincare joint venture with fellow Indian company Orbicular(Generics bulletin, 29 April 2016, page 4), has cleared its firstinspection by theUS Food andDrugAdministration (FDA).An agencyaudit at Aleor’s formulations manufacturing facility in Karakhadi,India, was conducted from 15-19 October, and zero observations wereidentified. Stating that the firm was “very pleased to see Aleor maketremendous progress since inception”, Alembic noted that to date, sixANDAs had been filed by the 60/40 joint venture that was formed inApril 2016 “to develop, manufacture and commercialise dermatologyproducts for worldwide markets”.

Alembic – which has just obtained tentative ANDA approval forits alternative to Takeda’s Nesina (alogliptin) 6.25mg, 12.5mg and25mg tablets – in its financial second quarter ended 30 September2018 obtained four tentative approvals from the FDA and submitted

eight ANDAs. This took the firm’s cumulative ANDA filings to 143,of which 13 are tentative and 64 final approvals. That total includesseven approved ANDAs from last year’s acquisition of US playerOrit Laboratories, which also has four US filings pending review.

Alembic Pharmaceuticals’ managing director Pranav Aminsaid that “a one-time supply opportunity arising due to a productshortage in the US market has resulted in higher profits”, as the firmannounced results for its financial second quarter ended 30 September2018. Group turnover increased by over two-fifths to Rs11.3 billion(US$154 million), leading the Indian company to report a 71% pre-tax profit rise to Rs2.70 billion, even with research and developmentexpenditure advancing by 48% to Rs1.45 billion.

Accounting for over half of total sales, International formulationsmore than doubled to Rs5.87 billion (see Figure 1), including a UScontribution that climbed by 128% to Rs4.19 billion. Alembic said itsfocus on the US front-end was “in place” – having already launched41 products in the region, including one introduced in the secondquarter – while non-US countries were “driven by partnerships”.

The Indian firmnoted that turnover from its domestic formulations– that remained stable at Rs3.85 billion – was “not comparable” dueto the introduction of the goods and services tax (GST) last year.Making up 86% of group turnover, global Formulations turnoverlifted by 50% to Rs9.72 billion, while global active pharmaceuticalingredient (API) sales rose by almost a tenth to Rs1.55 billion.

Outlining “growth drivers” for the firm, Alembic said it aimedto “rapidly expand its breadth and quality of pipeline”, includinginjectables, dermatology, ophthalmology and oncology drugs. Gn grace.montgomery@generics-bulletin.com

Figure 1: Breakdown by region and business of Alembic Pharmaceuticals’ sales inits financial second quarter ended 30 September 2018 (Source – Alembic)

Second-quartersales

(Rs millions*)

Change(%)

Proportionof total(%)

International 5,870 +124 52

India 3,850 +-0 34

Formulations 9,720 +50 86

APIs 1,550 +9 14

Alembic 11,270 +43 100

* rounded to the nearest Rs10 million

Gen 26-10-18 Pgs.1-24.indd 6 24/10/2018 16:00

7bulletin26 October 2018

COMPANY NEWS

MANUFACTURING

Lupin’s inhalers plantgets five observationsAfacility in Pithampur, India, that Lupin intends to use to supply

dry-powder inhalers (DPIs) to the US has been served with fiveobservations by the US Food and Drug Administration (FDA).Revealing that the observations were “procedural in nature”, the Indiancompany said the FDA’s audit from 8-18 October of its Unit-3 plantin Pithampur, near Indore, was both a general good manufacturingpractice (GMP) inspection and a pre-approval inspection (PAI) for thefirm’s abbreviated new drug application (ANDA) for a tiotropiumDPI.

Lupin believes it has first-to-file status for its US rival toBoehringer Ingelheim’s Spiriva (tiotropium bromide) DPI asthma andchronic obstructive pulmonary disease treatment (Generics bulletin,25 May 2018, page 5). The company – which is also working ongenerics of Teva’s ProAir (albuterol) and GlaxoSmithKline’s Advair(fluticasone/salmeterol) inhalers – has its generic Spiriva scheduled forUS launch in its 2021-2022 financial year, but is eyeing earlier entrythrough litigation (Generics bulletin, 28 September 2018, page 17).

Forming part of Lupin’s largest formulations campus located ina special economic zone (SEZ), the Pithampur Unit-3 plant containsdedicated modules for manufacturing annually 178 million DPIs and 3millionmetered-dose inhalers (MDIs), aswell as 6milliondermatologicalproducts. The 50,000 sq m Unit-3 plot was opened in 2010, joiningUnit-1 oral solids and active pharmaceutical ingredients (API) facilitiesand Unit-2 solid orals and sterile ophthalmics plants on the campus. G

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BUSINESS STRATEGY

Teva formalises planfor US headquartersTeva’s top executives, including chief executive officer Kåre Schultz

and North American head Brendan O’Grady, have formalisedduring a ceremony the Israeli group’s commitment to consolidateits commercial operations in North America in the Parsippany-TroyHills region of New Jersey, US.

As part of a global restructuring plan that includes reducing thenumber of sites from which it operates, Teva – which already haspremises in Parsippany – will relocate its NorthAmerican headquartersfrom North Wales, Pennsylvania, to the Parsippany-Troy Hills area,where it intends to negotiate a lease on office space. Supported bya 10-year US$40 million tax incentive offered by New Jersey’sEconomic Development Authority, the move will, Teva says, involve“more than 1,000 high-wage jobs and the transfer and creation of morethan 800 positions”.

“New Jersey offers Teva North America a value proposition of aunique biopharma cluster of universities and life sciences organisationsin which Teva can build its future in North America,” O’Grady said.

When the firm announced the relocation earlier this year (Genericsbulletin, 13 July 2018, page 4), New Jersey Governor Phil Murphysaid Teva would expand its existing Parsippany-Troy Hills location toaround 32,500 sq m and would also “transfer and create 843 jobs andretain 232 existing positions”. “The median annual wage associatedwith the more than 1,000 positions is US$128,073,” he pointed out.G

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8 bulletin 26 October 2018

COMPANY NEWSBUSINESS STRATEGY/MANUFACTURING

Idifarma attracts withspray-drying capacityContract development and manufacturing organisation (CDMO)

Idifarma is seeing strong demand for projects, especially forhighly-potent drugs, using the spray-drying technology that is justcoming on stream. Earlier this year, the Spanish company announcedplans to install ‘GEA Niro Mobile Minor’ equipment in a dedicatedarea at its good manufacturing practice (GMP) site in Pamplona, Spain(Generics bulletin, 13 April 2018, page 4).

During an exclusive interview, business development directorManuel Leal told Generics bulletin the spray-drying equipment – themost significant investment the company had made since it moved toits new facilities in 2009 – was capable of producing both clinical andsmall-scale commercial batches of oral-solid drugs, up to Category 4occupational exposure limit/operator exposure band (OEL/OEB). Inaddition, he pointed out, Idifarma was able to use the technology tocreate intermediates with improved solubility that could be formulatedinto oral or injectable drugs.

While other firms offered commercial spray-drying services, Lealacknowledged, he believed only three or four firms worldwide coulddo so for highly-potent drugs such as hormone and oncology drugs –Portugal’s Hovione, Japan’s Fuji and Catalent’s Pharmatek in SanDiego,US. As a niche player, Idifarma would, he contended, appeal to small tomedium-sized clients that required flexibility from their partners.

“Spray drying for highly-potent drugs is exclusive, and we arefinding there is a lot of pent-up demand for this service, because thereare not many companies that can do it,” Leal explained. Expressions ofinterest were already flooding in, not just from European companies,but also from firms in the US and beyond, he revealed, adding that theinvestment had been triggered, in part, by an existing contract to makean intermediate for an injectable medical device.

Typically, Leal said, prospective projects involved improvingthe bioavailability of well-known highly-potent molecules, includingmoves to reformulate injectable drugs into oral delivery forms thatcould reduce the cost, inconvenience and adverse effects of deliveringchemotherapy in large doses over short infusion times. However, heacknowledged, securing reimbursement in Europe was challenging.

Using the capsule-filling capacity that it installed in Pamplonalast year (Generics bulletin, 1 December 2017, page 4), or its existingtablets lines, Idifarma could, Leal pointed out, offer clients an end-to-end solution from solid dispersion to improve the solubility ofintermediates and active pharmaceutical ingredients (APIs) through tocommercial production up to batches of 60-70kg. Printing equipmentfor Falsified Medicines Directive (FMD) serialisation was validatedand ready to use, he added.

Having just had its GMPcertificate renewed by Spanish authorities,Idifarmahas also received clearance fromAustralia’sTherapeuticGoodsAdministration (TGA) that was triggered by contract manufacturing acytotoxic drug. Leal anticipated a visit from Russian inspectors withinthe next couple of years as the firm worked on specialty generics thatwere out-licensed for Russia, and added that clearance from the USFood and Drug Administration (FDA) for commercial batches was“clearly a goal” once Idifarma was cited in a US customer’s dossier.

Noting that Idifarma now employed around 130 people and hadan annual turnover of around €7 million (US$8 million), Leal said thePamplona plant offered ample space for expansion. “Our number ofprojects has almost doubled compared to last year, so we are addingcapacity and recruiting,” he revealed. Gn aidan.fry@generics-bulletin.com

JULPHAR says it is exploring opportunities in Uzbekistan, asthe Commonwealth of Independent States (CIS) member has “greatunrealised potential”. Having just attended a business forum inTashkent, Uzbekistan, the United Arab Emirates (UAE) companynoted that the country was looking to become “a pharmaceuticalmanufacturing hub within the Central Asia region, improvingaccess to socially significant medicines and bringing the country’spharmaceutical regulations in line with international standards”.“Uzbekistan is a country with great, as yet unrealised, potential,”insisted Julphar’s Intercontinental region director, Irfan Nabi Sheikh.

HOVIONE plans to increase its capacity to make oral dosageforms at its site in Loures, Portugal, in response to growing customerdemand. “New commercial-scale equipment for blending, tabletingand coating will complement existing small-scale equipment,” thePortuguese producer outlined, adding that this would support its‘One Site Shop’ concept of offering end-to-end solutions from drugsubstance to drug product. Promising “a unique value propositionwhen it comes to processing amorphous solid dispersions”,Hovione’s vice-president of marketing and sales, Frédéric Kahn,said “our customers now see drug-product manufacturing at thesite where they produce their drug-product intermediate as a naturalextension of the range of value-added services they expect fromus”. In parallel, the firm expects by the end of this year to qualify acontinuous tableting line at its plant in New Jersey, US.

EBOS GROUP – the Australian healthcare wholesaler anddistributor – has agreed to take full control of the country’s TerryWhite virtual pharmacy chain for around A$50 million (US$35million) in cash. Two years ago, EBOS gained a 50.1% stakein Terry White through a merger with its own Chemmart retailpharmacy business. EBOS expects to complete the transaction bythe end of 2018.

CMA – the UK’s Competition and Markets Authority – is invitingfeedback on whether it should investigate Hospira’s planned saleof its compounding business and related assets to Baxter.

RECIPHARM has reversed its decision to halt production at itspowders and granules facility in Höganäs, Sweden, and exploreoptions, including divestment, for the site. The Swedish contractdevelopment and manufacturing organisation (CDMO) said it hadbeen approached by new customers, “adding demand for severalnew products in Höganäs”. The site specialises in sachet and stick-pack filling, and employs around 45 people.

HANLIM PHARMA failed to “follow appropriate writtenprocedures” designed to prevent microbiological contamination ofsterile solutions at its facility in Gyeonggi-do, South Korea, accordingto a warning letter issued by the US Food and Drug Administration(FDA). The agency pointed out in the letter that it had “cited a similarcurrent good manufacturing practice (cGMP) violation regardinginadequate design of your aseptic line in an April 2014 inspection”.Other repeat violations highlighted include a lack of computer controlsthat raised data-integrity concerns. A separate warning letter sent bythe FDA to US-based contract-testing laboratory PharmaceuticalLaboratories and Consultants points out several cGMP deficienciesthat were highlighted in previous inspections and warnings. It alsoobserves that the OTC testing laboratory shared space with a brewery.

UNICHEM has received establishment inspection reports closingout US Food and Drug Administration audits of its Indian activepharmaceutical ingredient (API) plants in Pithampur and Roha.G

IN BRIEF

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9bulletin26 October 2018

MARKET NEWS

REGULATORY AFFAIRS

Canadian competitionhit by sample blockingCanadian originators are ramping up attempts to frustrate generic

development by blocking access to samples, according to theCanadian Generic Pharmaceutical Association (CGPA).

Responding to a recent report in the country’s National Postciting court submissions from the Competition Bureau of Canadathat detailed a rise in originators’ attempts to deny or delay sales togenerics manufacturers, CGPA president Jim Keon pointed out thatthe brand industry had previously supplied generics firms with suchsamples “for decades”. However, he said, this had begun to changein recent years. “All of a sudden, these products are being much moretightly controlled,” Keon said. “I don’t think there’s any doubt thatthis is an attempt to block competition, delay competition.”

Similar practices in the US – including the use of Risk Evaluationand Mitigation Strategies (REMS) to block generic manufacturers’access to samples – have attracted repeated criticism from theAssociation for Accessible Medicines (AAM) as well as the US Foodand Drug Administration (FDA).

The National Post cited the Competition Bureau’s complaint thatbrand companies have “increasingly” been denying or delaying salesto generics manufacturers, in a filing with Canada’s Federal Courtthat forms part of an investigation begun in 2016 into restrictive tradepractices. According to the Bureau’s filing, the National Post notes,the originators’ behaviour could postpone generic launches “andprevent competition for some time”. “Such practices can depriveconsumers and the economy of the benefits of competition includinglower drug costs.” G

REGULATORY AFFAIRS

UK will keep £800m marginCommunity pharmacy funding levels in the UK will be maintained

at £2.592 billion (US$3.36 billion) for the 2018/19 financialyear, the country’s Pharmaceutical Services Negotiating Committee(PSNC) has announced, marking an “improvement on a previouslyplanned funding cut of £33 million for 2018/19”. “This will be split,as previously, to deliver £1.792 billion in fees and allowances and£800 million in medicine margin,” the PSNC outlined.

As part of the deal, Category M prices at which pharmacies arereimbursed for the commonly used off-patent drugs they dispense“will reduce by £10 million per month from November for the nextfive months, until March 2019”, the PSNC observed. This was “torepay excess margin earned by pharmacies in previous years, inparticular 2015/16 for which the results of the margin survey showthat there was a significant over-delivery of margin”. However, thePSNC noted, the recovery of excess margin was £5 million per monthlower than it had been before a summer pause.

Noting that its unanimous agreement to the Department of Healthand Social Care’s (DHSC’s) funding offer had come “after a lengthyand difficult debate” and “rigorous analysis of funding and margindelivery rates”, the PSNC said it recognised “the great difficultiesfaced by [pharmacy] contractors”, but also was mindful of “the needto begin rebuilding constructive working relationships” with the UKgovernment “after a two-year hiatus”. The PSNC said it was keento “move away from the adversarial relationship” that had “haltedprogress” for the past two years. G

INTELLECTUAL PROPERTY/STOCKPILING

EU insurers seekingstockpiling on SPCsAproposed manufacturing waiver under the European Union’s

(EU’s) supplementary protection certificate (SPC) Regulation mustbe amended to allow EU-based manufacturers to stockpile genericsand biosimilars for launch on ‘day one’ after SPC expiry, a bodyrepresenting 50 national statutory social insurance organisations in theEU and Switzerland is demanding.

Furthermore, the European Social Insurance Platform (ESIP) –which covers approximately 250 million citizens in 16 EU memberstates and Switzerland – argues that the manufacturing waiver mustbe applied to existing SPCs, and not only prospectively, as it wouldunder the current proposal from the European Commission.

With the European Council currently considering suggestions toallow EU-based generics and biosimilars companies to make productsduring the SPC term in a bid to strengthen the EU’s manufacturingbase, both supporters and opponents of the proposal are stepping uptheir efforts. Off-patent industry association Medicines for Europerecently warned that “vested interests” such as the originators’ sectorwere seeking to persuade the Council to “neuter” the proposed waiver(Generics bulletin, 19 October 2018, page 10).

In ESIP, Medicines for Europe has a strong supporter ofindustry’s criticisms of the Commission’s waiver proposal, whichwould not let EU-based producers stockpile commercial stocks forlaunch immediately upon SPC expiry and would apply only to SPCsgranted after it comes into effect. Commission officials have publiclyadmitted that such limitations were implemented in the face oflobbying from originators (Generics bulletin, 22 June 2018, page 1).

On stockpiling, ESIP warned that failing to allow EU-basedcompanies to build up pre-launch supplies would, in particular, “delayaccess to biosimilars in the EU” given the more complex productionprocesses required.

The statutory insurers’ body also called on the Council andParliament to apply the waiver to existing SPCs “as it is not acceptablefor patients and healthcare systems to wait 10 years to benefit fromthe revised Regulation when the [Commission’s] impact assessmentreport has identified the problem as urgent”.

Pointing out that the Commission’s current proposal would notcover original drugs that were already on the market, ESIP stressedthat the proposed waiver was intended to “resolve unintendedconsequences” of the SPC regulation on public interest and health. “Itcannot therefore be reasonably argued that immediate application ofthe new rules to existing SPCswould deprive the originator companiesof their due rights,” the insurers’ body maintained. Furthermore, itnoted, when the EU introduced SPCs in the 1990s, originators weregiven the opportunity to apply for additional protection for productsthat were already patented, “with retroactive effect”.

Observing that “EU-based manufacturers’ competitiveness on theinternational market is severely restricted by SPCs”, ESIP said as aconsequence “manufacturers may decide to manufacture outside theEU, potentially resulting in migration of jobs and research to thirdcountries”. The Commission’s own impact assessment report had,it pointed out, recognised the export potential for EU generics andbiosimilars producers under a manufacturing waiver. Such a measure,if implemented effectively, would “have a positive effect on investors’behaviour and on the industry of the sector in general, resulting in greatercompetition between products on the market” that would help ESIPmembers to cope with “sharply increased prices for new drugs”. Gn aidan.fry@generics-bulletin.com

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10 bulletin 26 October 2018

MARKET NEWS

INFORMATION CAMPAIGNS

ESMO is pledging to educateDesire forgreater educationonbiosimilars amongEuropeanoncologists

will be acted upon urgently, their professional body, the EuropeanSociety for Medical Oncology (ESMO), has stated. Preliminary resultsof a biosimilars survey that ESMOplans to publish later this year suggestthat oncologists have only “moderate confidence” in understanding “keyconcepts that underpin biosimilar drug development and use”, whilealmost 87% of respondents wanted more education.

“If more education is what oncologists need,” ESMO presidentJosep Tabernero stated, “being the society of reference that looks aftertheir professional development, we must urgently act on that.” Pledgingto address topics at ESMO’s 2018 congress in Munich, Germany, thismonth, Tabernero said the survey showed extrapolation of indications was“the most common source of misunderstanding among physicians”.G

INTELLECTUAL PROPERTY

Maintain on-sale barargues US industryAltering the current ‘on-sale bar’ that prevents inventors from

commercialising inventions indefinitely before filing a patentapplication would “invite manipulation and foster confusion”, the USAssociation for Accessible Medicines (AAM) has told the country’sSupreme Court ahead of a hearing scheduled for 4 December.

The Supreme Court is due to hear Helsinn Healthcare’s appealagainst the US Court of Appeals’ decision to reverse a district court’sfindings, thereby invalidating four patents protecting the originator’sAloxi (palonosetron) treatment for chemotherapy-induced nausea(Generics bulletin, 5 May 2017, page 11). That decision favouredTeva, which earlier this year launched a generic rival to Aloxi,competing against other generics from Dr Reddy’s and Sandoz,as well as an authorised generic that Cipla licensed from Helsinn(Generics bulletin, 30 March 2018, page 12).

Having granted Helsinn’s writ of certiorari to review the Courtof Appeals’ verdict (Generics bulletin, 29 June 2018, page 13), theSupremeCourtwill inDecember considerwhether, under theUSLeahy-Smith America Invents Act (AIA), an inventor’s sale of an invention toa third party that is obliged to keep the invention confidential qualifiesas prior art for determining the patentability of an invention.

Observing that Teva has already explained why Helsinn’sargument – that, through the AIA, Congress lifted the on-sale bar forany sales in which at least one ‘term’ of sale is not disclosed to thepublic – is foreclosed by the plain text and history of the on-sale barprovision, the AAM warns in an amicus letter to the Supreme Courtthat weakening the bar would have “deleterious consequences forpatients, taxpayers and others who seek more affordable medicines”.

Helsinn’s interpretation would, the industry body cautions, enablean originator to market its drug through a partially confidentialtransaction “and thereby obtain the benefits of commercialisationwithout starting the clock on its patent rights”. “The government’sproposed variant in which only sales to ultimate customers trigger thebar is equally manipulable,” the AAM warns, pointing out that “drugmanufacturers almost never sell directly to consumers”.

“The on-sale bar’s application to sales that are not fully publicpreserves the public’s interest in a market where robust competitionensures better patient outcomes and greater access to life-savingmedicines,” the AAM summarises. G

PRICING AND REIMBURSEMENT

UK market working,Accord report claimsThe UK market is “working and still getting very good value for its

generic medicines”, it “seems”, despite “significant challenges forall in the supply chain” throughout last year, a white paper pennedby Accord Healthcare’s UK managing director, Peter Kelly, argues.

Entitled ‘UK generic medicine price flux? The real data behindthe headlines’, the white paper explains: “In order to fully understandthe market dynamic during this period of volatility it is worth lookingbeyond the headlines and considering the factors involved.”

According to the white paper, three “key elements” causedvolatility in prices and reimbursement in 2017: market factors;concessionary pricing; and average reimbursement. For the first point,Kelly points to the fall in the British pound following the UK’s ‘Brexit’decision to withdraw from the European Union (EU); the withdrawalof various good manufacturing practice (GMP) certifications; and an“overall squeeze” on reimbursement pricing.

From 2015 to 2017, average reimbursement prices per item fell,meaning it took “less movement of price to create a challenge fordispensers to acquire the product below the existing reimbursementprice”, the report states. As Figure 1 shows, the volume of genericmedicines covered by Category M of the Drug Tariff of pharmacy-reimbursement prices has “consistently grown”, while “the averagereimbursement price per pack has reduced by 22%”.

For concessionary pricing, the report states that in 2017 therewas a “clear increase” in both number and value of generic medicinesgranted a concessionary price versus the previous year. “Data revealsthe total value of generic medicines reimbursed through being grantedprice concession status was approximately £75 million (US$97.9million) in 2016 rising to approximately £340 million in 2017.”

Bridging these key elements together within a wider context, thereport says it is important to look at the value of the “vast majority” ofgenerics – those reimbursed in both CategoryM and CategoryA. Takingthe monthly tariff price in both categories – or the concession pricewhere granted – and using market data to volume-weight the pricing,the report states that last year, the average price for a pack of genericmedicine was £2.46, “a decline in real terms” versus £2.80 in 2016.

“An overall reimbursement price of £2.46 per item across morethan 1,000 generic medicines that supply a volume of more than1.1 billion packs of medicine a year seems like the UK market isworking and still getting very good value for its generic medicines,”the paper concludes. The current figure for 2018 is £2.44. Gn dean.rudge@generics-bulletin.com

2.5

0

0.5

1.0

1.5

2.0

Price

2013 2014 2015 2016 20171,000

1,110

1,120

1,130

1,140

1,150

1,160

1,170

1,180

1,190Volume

Price

(£)

Volum

e(m

illions)

Figure 1: Average reimbursement prices and volumes for Category M medicinesbetween 2013 and 2017 (Source - Accord)

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11bulletin26 October 2018

MARKET NEWS

REGULATORY AFFAIRS

Israel consults overbio data exclusivityAconsultation on modifying Israel’s data-exclusivity framework to

cover biological as well as small-molecule drugs has been openedby the country’s Ministry of Health.

Local law firm Ehrlich & Fenster pointed to a ‘call to action’by the Ministry on section 47D of the Pharmacists Ordinance 5741-1981 that asked healthcare professionals and industry stakeholdersfor feedback on an amendment “to amend section 47D with regardsto biological preparations, and the appropriate scope of the proposedamendment”. Currently, section 47D applies only for new chemicalentities, not biologics.

“According to section 47D, subject to certain exceptions,”Ehrlich & Fenster explains, “the Ministry of Health will not permitthe marketing of a ‘new pharmaceutical preparation’ – a drug that isregistered based on the safety and efficiency data of a previously-registered drug – for either six years from the registration date of theoriginal drug in Israel, or six-and-a-half years from the registrationdate of the original drug in another jurisdiction, whichever is earliest.”In practice, the law firm notes, this has “little effect on drugs that areprotected by a patent”.

Nevertheless, “the proposed amendment to section 47D mayhave significant implications on the biosimilar drug market”, thefirm comments, observing that “granting a data-exclusivity period forbiological drugs might pose an additional barrier to enter the market”.G

REGULATORY AFFAIRS

Budget backlash onFrench substitutionAbacklashover proposed changes to generic substitutionmechanisms

in France has gained the support of local doctors’ associations MGFrance, CSMF and SML, as well as pharmacist unions USPO andFSPF. The changes proposed in the country’s 2019 budget involveestablishing a list of “objective medical criteria” to be used by doctorsmarking prescriptions as non-substitutable, as well as reimbursingpatients that refuse generic substitution only for the value of the equivalentgeneric, not the brand (Generics bulletin, 5 October 2018, page 1).

In a joint letter, the five bodies claim that the reimbursementprovisionwill “create conflict and time-consuming situations” betweenpatients, doctors and pharmacists, “without improving quality of care”.Meanwhile, the list of medical criteria for marking prescriptions asnon-substitutable “will never be able to replace the analysis conductedby healthcare professionals” that is able to “take into account theindividual situations and particular characteristics of each patient”.Also, the bodies claim, the measure contradicts France’s requirementthat doctors prescribe by international non-proprietary name (INN).

Insisting that they support policy goals to encourage the use ofgenerics and cut healthcare costs, the five bodies instead propose “toolsto increase prescription within the répertoire of generic equivalents”, aswell as neutralising strategies to circumvent generics, enhancing patientloyalty to generics, limiting the use of marking prescriptions as non-substitutable, and increasing generic and biosimilar penetration. G

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12 bulletin 26 October 2018

MARKET NEWS

REGULATORY AFFAIRS

No appeal for ACCC on LipitorAustralia’s Competition & Consumer Commission (ACCC) has

been denied special leave to appeal the Federal Court ofAustralia’sdecision concerning Pfizer’s Lipitor (atorvastatin). The ACCC hadsought leave to appeal against the decision in late May to dismiss theantitrust watchdog’s complaint against Pfizer over the cholesterol-lowering drug (Generics bulletin, 1 June 2018, page 13).

Although the full court of the Federal Court of Australia hadfound that Pfizer “took advantage of its substantial market power”,the commission noted, it “did not accept the ACCC’s argument thatPfizer had acted for the purpose of substantially lessening competitionor deterring or preventing competitors from competing”. In 2015, theACCC had appealed against an Australian Federal Court finding thatPfizer was not guilty of offering anti-competitive inducements toAustralian pharmacists to stock up on the firm’s own generic versionof Lipitor ahead of patent expiry in May 2012. G

MARKET RESEARCH

Portuguese patientshandle device switchAlmost all Portuguese patients switched from theEnbrel (etanercept)

reference product to a biosimilar rival showed “good adaptation”to the change in delivery device, according to data presented byPortuguese doctors during the recent annual meeting of theAmericanCollege of Rheumatology (ACR) held in Chicago, US.

Detailing a “block switch” of 89 from 98 adults with rheumaticdiseaseswhowerebeing treatedwithEnbrel inaCoimbrarheumatologydepartment, the researchers said 12 patients were ultimately excludeddue to factors including poor adherence and interruption of treatment.In the remaining 77 patients who switched, disease activity forrheumatoid arthritis, psoriatic arthritis and spondyloarthritis remainedstable over the three-month follow-up period, with “no statisticallysignificant differences observed in acute phase reactants, or in patient orphysician global assessment between the two time points”.

Two patient reports of disease exacerbation were “were notconfirmed by clinical and analytical evaluation”, while 93% ofpatients reported adapting well to the biosimilar’s delivery device.

In conclusion, the researchers found the “non-medical switch” tobiosimilar etanercept “did not affect the overall efficacy and safety oftreatment” in the three-month study. However, they believed “a longerobservational period is necessary to assess the long-term response”.

A separate ACR abstract entitled ‘Non-Medical Switch toBiosimilars: What Have We Learned?’ detailed a survey of 51Portuguese physicians in both public and private practice as well as 22patients who experienced a switch to a biosimilar.All of the physiciansconsidered themselves to be “at least reasonably informed” about theconcept of biosimilars, and over three-fifths – 61% – were “reasonablyfamiliar with their prescription”. Among the factors influencingbiosimilar prescribing, efficacy was considered the most relevant,followed by safety and cost. Almost half the physicians had “only amild to moderate degree of confidence in the switching process”.

Of the 22 patients that were surveyed, 15 claimed to have been “atleast reasonably informed” about biosimilars. Half of them expressedconcerns about safety, but barely a quarter raised doubts about efficacy.And while 10 patients accepted the switch “without apprehension”, 11“believed they had no other choice”. G

21 Novembern 2nd Value Added Medicines Conference

Brussels, BelgiumOrganised by Medicines for Europe, this one-day event will look atopportunities presented by value added medicines across the industry.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: events@medicinesforeurope.com. Register online atwww.medicinesforeurope.com/events.

26-27 Novembern EuroPLX 68

Athens, GreeceThis two-day meeting provides an opportunity to discuss andnegotiate agreements, development, in-licensing, marketing,promotion and distribution.Contact: RauCon. Tel: +49 6221 426296 0.E-mail: meetyou@europlx.com. Website: www.europlx.com.

30 January 2019n 12th Pharmacovigilance Conference

London, UKThis is a one-day Medicines for Europe conference which will lookat latest trends and the future direction of pharmacovigilance.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: events@medicinesforeurope.com. Register online atwww.medicinesforeurope.com/events.

30 January-1 February 2019n 18th Regulatory & Scientific

Affairs ConferenceLondon, UKThis conference will follow the Pharmcovigilance event at the samevenue and will provide updates on regulatory developments.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: events@medicinesforeurope.com. Register online atwww.medicinesforeurope.com/events.

4-6 February 2019n Access 2019! AAM Annual Meeting

New Orleans, USAThe Association for Accessible Medicines annual meeting will lookat the future of the generics and biosimilars industry.Contact: Association for Accessible Medicines. Tel: +1 202 249 7100.E-mail: jennifer.soup@accessiblemeds.org. Website: www.accessiblemeds.org/events.

26-27 March 2019n 15th Legal Affairs Conference

Amsterdam, The NetherlandsThis Medicines for Europe event will cover the latest developments inIP, legal affairs, biosimilars and the SPC Regulation.Contact: Lucia Romagnoli. Tel: +44 7562 876 873.E-mail: events@medicinesforeurope.com. Register online atwww.medicinesforeurope.com/events.

EVENTS – November – March 2019

SAVE THE DATE.....The Global Generics & Biosimilars Awards 2019

will be held on 5 November 2019 in Frankfurt, Germany

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13bulletin26 October 2018

PRODUCT NEWS

BREAST CANCER TREATMENTS

Mylan’s trastuzumabis greenlit by CHMPFurther biosimilar competition to Roche’s Herceptin (trastuzumab)

could be on the way in European markets, after Mylan and Biocon’sOgivri (trastuzumab) was backed for a European-wide marketingauthorisation. The committee for human medicinal products (CHMP)within the European MedicinesAgency (EMA) has adopted a positiveopinion, recommending the granting of a marketing authorisationfor Ogivri 150mg powder for concentrate for solution for infusion,indicated for treating breast and gastric cancer. The EuropeanCommission typically acts on the CHMP’s opinion within 67 days,meaning Mylan anticipates a decision by the end of this year.

“The positive CHMP opinion is based on data submitted as partof the marketing authorisation application which included similarityassessment in analytical testing, preclinical and clinical studies,” Mylanexplained. “Results demonstrated no clinically meaningful differencesin quality, potency and safety; therefore, establishing biosimilarity.”

Mylan noted that the firms’ ‘Heritage’ Phase III clinical studydemonstrated “no clinically meaningful differences in terms of safety,efficacy and immunogenicity” in metastatic breast cancer patients,“further reinforcing the highly similar nature of Ogivri”.

Biosimilar competition toHerceptin first came toEuropeearlier thisyear with the roll out of Merck Sharp & Dohme and Samsung Bioepis’Ontruzant, as well as Celltrion’s Herzuma, through commercialisationpartners including Mundipharma, and Amgen and Allergan’s Kanjinti.Pfizer has also received an approval for its Trazimera.

Ogivri was approved by the US Food and Drug Administration(FDA) last year and is the first FDA-approved biosimilar to Herceptinin the US. Additional regulatory approvals have been secured in 35countries around the world, Mylan pointed out.

Also, during its meeting that took place from 15-18 October, theCHMP recommended authorising Actavis’ Perlinring (etonogestrel/ethinylestradiol) vaginal ring generic of Merck Sharp & Dohme’sNuvaring. However, the EMA refused to recommend the granting ofmarketing authorisations for Hetero’s generic Taxol (paclitaxel) product.

Bothapplicationsweresubmitted through theEMA’sdecentralisedprocedure. The agency had stepped in to review the firms’ respectiveproducts following a disagreement among European Union (EU)member states regarding their authorisation.

Actavis submittedPerlinring to theUK’sMedicine andHealthcareProducts Regulatory Agency (MHRA) and sought approval in 22other EU member states plus Iceland and Norway, while the Indianfirm submitted its Paclitaxel Hetero to Portugal’s Infarmed agency,also seeking approval in Germany, the Netherlands and the UK.

ForActavis’generic, the EMAconcluded that, based on evaluationof the currently available data, bioequivalence to Nuvaring has beenshown for the three-week authorised duration of treatment. “Inaddition, there is enough evidence to expect that Perlinring continuesto be effective for an additional fourth week, as is the case forNuvaring,” the EMA commented.

However, the EMArefused to recommend Hetero’s Taxol generic,stating that based on the evaluation of the currently available data, theywere not sufficient to show that Paclitaxel Hetero is ‘bioequivalent’ toTaxol and that their active substances behave in the same way in thebody. Concerns had been raised by the Dutch medicines agency.

The CHMP has also just recommended granting an orphanauthorisation for Lupin’s Namuscla (mexiletine) 167mg capsules, fortreating myotonia in adults with certain hereditary muscle disorders.Gn dean.rudge@generics-bulletin.com

CARDIOVASCULAR DRUGS

Apotex minutes lateon potassium CGTApotex missed by a matter of minutes its opportunity to block

competition to the Canadian company’s potassium chloride 10%oral solution in the US, the US Food and Drug Administration (FDA)has determined.Therefore, the agencydeniedApotex’request to rescindapproval for Novel Laboratories’ abbreviated new drug application(ANDA) for an alternative to Genus Lifesciences’ reference drug.

WhenApotex submitted itsANDAfor potassiumchloride 10%and20% to the FDA for review in October 2017, the company requestedthat the drugs be designated as competitive generic therapies (CGTs),a new sub-class of generics created by the 2017 FDAReauthorizationAct (FDARA) that are potentially eligible for 180-day exclusivity asa reward for creating competition on molecules for which there werepreviously only one or no generics. The FDA granted CGT status toApotex’ ANDA in December 2017, and approved the ANDA on 8August 2018 (Generics bulletin, 31 August 2018, page 17).

In its approval letter sent to Apotex, the FDA acknowledgedthat the company was eligible for 180-day CGT exclusivity as the“first approved applicant” and instructed Apotex that this exclusivitywould begin from the date of first commercial marketing.

However, around three weeks later, at 15.44 on 29 August,the FDA approved Novel’s ANDA for potassium chloride. In itsletter denying Apotex’ request to rescind Novel’s approval, theagency states: “Prior to approving Novel’s ANDA, FDA searched itsrecords and determined that Apotex had not submitted correspondenceindicating that it had begun commercial marketing of potassiumchloride 10% or 20%.”

E-mail sent 42 minutes laterAnd while Apotex also on 29 August notified the agency that it

had commenced commercial marketing of potassium chloride 10%, theFDA said it did not receive notice through its Electronic SubmissionGateway until 21.03, more than five hours after it had granted approvalto Novel. In response to a request by the FDA, Apotex provided aninternal e-mail showing that it ordered shipment of the drug for treatinglow potassium levels in the blood at 16.26 on 29 August, still 42minutes after Novel’s ANDA had been approved.

In refusing to rescind Novel’s ANDA approval, the FDA insistedit was following “the plain language of the statute”, particularly sub-paragraph (B)(v) of Section 505(j)(5) of the Food Drug & Cosmetic(FD&C) Act that was added in 2017 by FDARA. This states that “ifthe application is for a drug that is the same as a CGT for which anyfirst approved applicant has commenced commercial marketing, theapplication shall be made effective on the date that is 180 days afterthe date of the first commercial marketing of the CGT by any firstapproved applicant”.

“In the present case,” the agency explained, “when FDAapprovedNovel’s ANDA 209786, Apotex had not begun marketing eitherstrength of potassium chloride under [its] ANDA 211067. DespiteApotex’ commencement of commercial marketing for potassiumchloride 10% later that same day, the threshold condition in the statute– that ‘any first approved applicant has commenced commercialmarketing’ – had not been met when FDA approved Novel’s ANDA.”

Other than Apotex, Novel and reference-drug holder Genus,Amneal also holds approval for potassium chloride 20mEq/15ml and40mEq/15ml oral solutions, having secured ANDA clearance aboutthree weeks before Apotex, on 19 July this year. Gn aidan.fry@generics-bulletin.com

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PRODUCT NEWSAUTOIMMUNE DISEASES TREATMENTS

English contracts tosave up to £150mnEngland’s National Health Service (NHS) believes it can save up to

£150 million (US$195 million) per year by launching a competitivetender after a six-month paediatric extension to a supplementaryprotection certificate (SPC) protectingAbbVie’s Humira (adalimumab)ended on 16 October.

With more than 46,000 patients currently using Humira forconditions such as rheumatoid arthritis, inflammatory bowel diseaseand psoriasis, NHS England currently spends over £400 million peryear on the blockbuster. The body’s chief pharmaceutical officer, KeithRidge, had previously forecasted a saving of more than £100 million(Generics bulletin, 4 May 2018, page 11). However, that anticipatedonly three, not four, biosimilar entrants (see front page).

With biosimilar adalimumabs from Amgen, Biogen, Mylan andSandoz all either launched or poised to enter the UK market, NHSEngland claims its “managed market share” approach to tenderingrepresents “a first step towards development of a sustainable market”.“This means that no one supplier of adalimumab will be awardedthe whole market, but it provides a strong incentive for suppliers tooffer their best price at the point of tender, with competitive suppliersgaining a greater share of the market than those who price lesscompetitively,” NHS England explained. “If only some tendered pricesare low, awarded shares will be higher for the most competitivelypriced suppliers, but all suppliers will get access to at least some of themarket upon receipt of a compliant bid to avoid dominance.”

Bids for adalimumab supply contracts valued at £560million closedon 22 October, with 12-month deals set to start on 1 December, althoughthese can be extended for another year. The market will be divided into11 hospital groups that will have access to Humira, and both a first-lineand second-line biosimilar, at least one of which will be citrate-freeto limit pain on injection. And from April 2019, NHS England plansto set a “national reference price”, based on the cost of the best-valueadalimumab and the expense to hospitals of switching patients.

With an aim to ensure uptake of biosimilar adalimumab, NHSEngland has enlisted the support of national societies representingpatients with rheumatoid arthritis, ankylosing spondylitis, psoriasisand Crohn’s and colitis. Stressing that “biosimilars are as safe andeffective as the reference products”, the societies commented that“at a time when services are thinking about new contracts, we wouldalso hope that patients’ views are proactively sought and that thingsthat matter to patients, including excipients, device and homecarepackages, are given due consideration”.

According to NHS’ 2016/2017 financial year data, hospitalsaccounted for more than £436 million of NHS England’s total £462million bill for adalimumab, far more than for any other drug.

Under a commissioning framework for biologics publishedby NHS England in September last year (Generics bulletin, 22September 2017, page 5), at least 90% of new patients should beprescribed the best-value biologic within three months of biosimilarentry, and at least 80% of existing patients should be on the best-value biologic within 12 months. NHS England has already madeannual savings of around £210 million through biosimilars (Genericsbulletin, 8 June 2018, page 14).

The British Biosimilars Association (BBA) praised NHS Englandfor having “worked hard to give appropriate advice throughout theservice and to create a procurement plan aimed at ensuring the creationof a competitive multi-source market”. Gn aidan.fry@generics-bulletin.com

LITIGATION

Teva sues FDA overRestasis exclusivityTeva has filed suit against the US Food and Drug Administration

(FDA) in a bid to obtain 180-day market exclusivity for itsgeneric of Allergan’s Restasis (cyclosporine), as well as to challengerecently-implemented agency ground rules on what constitutes a ‘firstapplicant’ for generic drugs. To date, the FDA has not approved anygeneric rivals to Restasis.

The Israeli firm’s complaint in a Columbia district court is inresponse to a ‘letter decision’ the FDAissued in July to abbreviated newdrug application (ANDA) filers for generics of Indivior’s Suboxone(buprenorphine/naloxone) sublingual film. In the letter, the agency setforth a new definition of ‘first applicant’, whereby anANDA applicantdoes not lose this status by failing to provide timely notice of paragraphIV certification to the originator.

Teva now contends that, under that letter decision, it is being“deprived” of its “statutory right to 180 days of marketing exclusivity”for its generic version of the eye-disease drug.As well as a declarationthat its Restasis ANDA product is entitled to 180-day exclusivity,Teva is seeking a declaration that the FDA’s letter decision “wasissued without observance of procedure required by law”.

Meanwhile, Teva asks that the court enjoin the FDA fromapproving any ANDA that references Restasis that was not“substantially complete” as of 14 January 2014 and/or for which theANDA’s sponsor did not submit a “lawfully-maintained paragraph IVcertification” on 14 January 2014 – the date that Teva submitted itsparagraph IV challenge.

In a separate motion for preliminary injunction, Teva says thatunless the FDA is enjoined, the firm will be divested of its right to180-day exclusivity and suffer at least US$50 million in losses it cannever recover.

“Teva earned that reward [the exclusivity period for Restasis]because it was the first generic applicant that complied with the Hatch-WaxmanAct’s requirements for challenging at least one of the patentscovering Restasis,” Teva insists. “Yet FDA now has ruled that anapplicant which concededly did not comply with those requirementsnonetheless qualified for 180-day exclusivity – and thereby blocksevery company which did comply with the statute from qualifying forthe exclusivity period.”

“That perverse result is remarkable in its own right. But it isparticularly startling because FDA took precisely the opposite positionfor nearly two decades,” Teva contends.

The other ANDA filer is not named in the suit by Teva, whichsays it was “blindsided” by the agency in July this year when it issuedthe Suboxone decision.

“Immediate judicial review of FDA’s decision and promptinjunctive relief are essential,” Teva insists. “The FDA already hasapplied its decision to strip Teva of its statutory right to 180-dayexclusivity for at least one generic drug product, and there is noquestion that FDA’s decision will have exactly the same effect here.”

In 2017, a district court ruled that four patents covering Restasisare invalid for being obvious, a decision that is currently subject toappeal. Meanwhile, in July this year, a US Court of Appeals allowed toproceed inter partes review (IPR) challenges to certain Restasis patents,including one fromTeva. The same court has just denied a petition filedbyAllergan and patent licensee the Saint Regis Mohawk Tribe to rehearen banc the court’s finding that tribal sovereign immunity “cannot beasserted” in IPR patent-challenge proceedings. Gn dean.rudge@generics-bulletin.com

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15bulletin26 October 2018

PRODUCT NEWS

AUTOIMMUNE DISEASES TREATMENTS

Biosimilar infliximabUS share only at 7%Biosimilar infliximab players in the US garnered only a 7% share

of the market by volume by the third quarter of this year, theoriginator of the Remicade (infliximab) original, Johnson & Johnson(J&J), has revealed, as it declared that it is not anticipating “any kindof step change” for the market position of the brand in 2019, despitecompetition from two biosimilars.

US Remicade sales fell by 18.2% to US$987 million in the thirdquarter, and by 18.3% to US$2.82 billion in the first nine months of2018. J&J’s market share by volume was around 93%, chief financialofficer JoeWolk told investors during J&J’s third-quarter earnings call.

“Most of that erosion is related to price,” Wolk revealed. “Wecontinue to compete. Based on the safety and efficacy that we’vedemonstrated for a number of years and across all indications, we feelpretty strong that [Remicade] still has a very strong place in the market.”

Pfizer’s Inflectra (infliximab-dyyb) and Merck Sharp & Dohme’sRenflexis (infliximab-abda) biosimilars both compete with J&J’soriginal, but have struggled to claim meaningful share on UScommercial health plans. Pfizer last year sued J&J, claiming thatInflectra’s low sales are due to anti-competitive rebate schemes. J&Jin August failed to have the suit dismissed.

Meanwhile, Wolk noted, J&J continues to expect competitionto its Tracleer (bosentan) antihypertensive and Procrit (epoetin alfa)biologic original before the turn of this year. G

CHOLESTEROL-LOWERING DRUGS

Impurity issue stopsAurobindo irbesartanAcertificate of suitability (CEP) issued for bulk irbesartan made

by Aurobindo Pharma in Hyderabad, India, has been suspendedby the European Directorate for the Quality of Medicines (EDQM).Several other CEPs for irbesartan from other active pharmaceuticalingredient (API) suppliers remain in force.

Announcing the recall in Germany of irbesartan 150mg tablets,as well as of irbesartan/hydrochlorothiazide tablets in 150mg/12.5mg,300mg/12.5mg and 300mg/25mg strengths, Aurobindo explained thatthe EDQM had found the impurity N-nitrosodiethylamine (NDEA)in its bulk drug. Impurity levels per batch varied between ‘notdetectable’ and 0.27 parts per million, the Indian firm revealed.

After the impurity N-nitrosodimethylamine (NDMA) wasdetected in Chinese batches of valsartan in June this year, the EDQMconducted “a complete review of the manufacturing informationsubmitted in all CEP applications for valsartan and other structurallyrelated active substances”. Having already in July suspended avalsartan CEP held by China’s Zhejiang Huahai due to the presenceof NDMAand NDEA, the European body subsequently detected “lowlevels of NDEA” in losartan made by Hetero Labs, but “levels remainbelow the currently acceptable amounts established for this impurity”as investigations continue.

The EDQM is working with the European network of OfficialMedicines Control Laboratories (OMCLs) on sampling and testing. G

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16 bulletin 26 October 2018

PRODUCT NEWS

RESPIRATORY DRUGS

Mylan’s Wixela is ‘imminent’Mylan believes that US Food and Drug Administration

(FDA) approval of its Wixela Inhub generic alternative toGlaxoSmithKline’sAdvairDiskus (fluticasone/salmeterol) respiratoryblockbuster is “imminent”. “Mylan confirms it has not received anynew information request or complete response letter (CRL) from theFDA,” the company said in a statement issued on 22 October.

In August, Mylan had indicated that it had an FDA action datefor Wixela Inhub in “mid-October”, having responded to the agency’sreservations on labelling and chemistry, manufacturing and controls(CMC) voiced in a CRL (Generics bulletin, 31August 2018, page 19).

Mylan has just expanded its US contraceptives portfolio byintroducing a generic of Pfizer’sDepo-Provera (medroxyprogesteroneacetate) 150mg/ml single-dose vials. G

ONCOLOGY DRUGS

Three blockbusters toface 2019 competitionNext year will see biosimilar entry in the US for Roche’s three

highest-selling blockbuster biologic originals, the originatoranticipates, opening up a market that is tracking towards CHF10 billion(US$10.0 billion). “We expect the first entrants of biosimilars to theUS in the first half of next year with MabThera/Rituxan (rituximab),the second half of next year with Herceptin (trastuzumab) and withAvastin (bevacizumab),” Roche’s group chief executive officer, SeverinSchwan, told investors during the company’s third-quarter earnings call.

Mylan last year brokered a settlement deal on Herceptin thatmeant it anticipated “potentially being the first company to launch abiosimilar to Herceptin in the US”, having since received approvalfor the firm’s Ogivri (trastuzumab-dkst) biosimilar developed withpartner Biocon. Amgen holds an approval for an Avastin biosimilar,Mvasi (bevacizumab-awwb), while Celltrion and Teva earlier thismonth saw a US Food and Drug Administration (FDA) committeerecommend the firms’ Rituxan biosimilar, CT-P10, for approval.

At-risk launches expectedAmgen and Celltrion and Teva together are currently embroiled

in patent litigation over their respective bevacizumab and rituximabbiosimilars in US district courts, while Pfizer, Celltrion and Teva,Amgen and Samsung Bioepis have all been sued for challengingpatents protecting Herceptin. Schwan refused to comment on whetherRoche anticipated biosimilar players launching at-risk in 2019.

In the first nine months of this year, the three brands brought insales of CHF7.57 billion in the US: MabThera up by 4% to CHF3.19billion; Avastin flat at CHF2.17 billion; and Herceptin ahead by 12%to CHF2.21 billion, all measured at constant-exchange rates.

Following the entry of rituximab biosimilars across Europeanmarkets early last year, MabThera sales halved to CHF731 millionin Europe in the nine months to 30 September. Herceptin, which hasfaced biosimilar competition in Europe since the second quarter ofthis year, saw sales down by a tenth to CHF1.50 billion.

“We see a difference between the erosion rates between US andEurope,” Schwan said, commenting on Roche’s view of biosimilarpenetration in the two markets. “We don’t expect the erosion rate tobe similar to Europe at this stage, even with some potential additionalactivities by the administration in the US government.” G

CASI PHARMACEUTICALS has acquired from Laurus LabsChinese rights to a dossier for tenofovir disoproxil fumarate thathas been approved by the US Food and Drug Administration (FDA).Although no financial details of the transaction were disclosed, Casinoted that it “will make certain upfront and milestone payments indifferent phases”. Casi’s executive chairman Wei-Wu He statedthat acquiring the filing “enhances our robust and emergent pipelineand is consistent with our broader mission to commercialise FDA-approved drugs in China”. Laurus’ founder and chief executive officerSatyanarayanaChava said the transfer of the hepatitisBdrug “enhancesour strategic focus to leverage our development and manufacturingcapabilities in the markets where we have little presence”.

SANDOZ continues to expect to bring its generic alternative toGlaxoSmithKline’s Advair (fluticasone/salmeterol) asthma andCOPD brand to the US market “at the back end of next year”(Generics bulletin, 27 April 2018, page 1). The firm previouslyreceived a complete response letter (CRL) from the US Food andDrug Administration (FDA) highlighting deficiencies. “We have hadgood discussions and communications with the FDA, and we believewe understand what is necessary to get our generic Advair to themarket,” Sandoz’ global head, Richard Francis, told investors.

ACCORDHEALTHCAREhasintroduceditsPelgraz(pegfilgrastim)biosimilar toAmgen’sNeulasta inGermany at a list price of €1,571.06(US$1,802.43) per 6mg/0.6ml pre-filled syringe. That price representsa discount of around 10% to Neulasta’s list price of €1,740.26.

FRESENIUS KABI has introduced in the US palonosetronhydrochloride, available in a 0.25mg/5ml single-dose pre-filledsyringe. Noting that this was the latest offering from the company’s‘Simplist’ portfolio of ready-to-administer syringes, the Germanfirm observed that the oncology drug was the “first and only USFood and Drug Administration- (FDA-) approved pre-filled deliverysystem for this medication”.

LANNETT will be the exclusive US distributor of eight strengthsof generic Focalin XR (dexmethylphenidate hydrochloride)extended-release capsules for which Adare Pharmaceuticals hasjust obtained US approval. Lannett intends to start marketing theattention deficit hyperactivity disorder (ADHD) drug “within a fewmonths”. Tim Crew, Lannett’s chief executive officer, said thatwhile the agreement currently covered a single product, “we willlook to expand the relationship over time”.

LUPIN has received US Food and Drug Administration (FDA)approval for its triamcinolone acetonide 0.1%ointment. The Indianfirm has also expanded its US dermatology offering by launchinga generic version of Fougera’s Temovate (clobetasol propionate)0.05% ointment, while it has also introduced potassium chloride10% and 20% oral solution (see page 13).

NOVARTIS anticipates generic competition to its Afinitor(everolimus) oncology brand in Europe at the start of next yearwhen six-month paediatric extensions to supplementary protectioncertificates (SPCs) expire. In the US, the Swiss group expects thebrand to face “limited generic competition” at the end of 2019.

ZYDUS CADILA has secured final approval from the US Foodand Drug Administration (FDA) for clobazam 10mg and 20mgtablets, exemestane 25mg tablets and clobetasol propionate 0.05%cream. The company will make all three drugs at its formulationsfacility in Ahmedabad, India. G

IN BRIEF

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PRODUCT NEWS

MULTIPLE SCLEROSIS DRUGS

Mapi advances on GA DepotNo immediate post-injection reactions, “as are frequently seen with

Copaxone and generic glatiramer acetate”, were detected in a PhaseII study for the long-acting glatiramer acetate product that Mylan isdeveloping withMapi Pharma (Generics bulletin, 13April 2018, page12). Presenting two-year clinical data from the Phase II study of its‘GADepot’ candidate at the 34th Congress of the European Committeefor Treatment and Research in Multiple Sclerosis (ECTRIMS), Mapisaid that with all participants receiving a 40mg dose of GA Depotonce every four weeks, “the number of adverse events (AEs) wasconsiderably reduced during the second year of treatment comparedwith the first year”.

“Efficacy results showed there was no significant change in meanexpanded disability status scale (EDSS) score at two years comparedwith baseline in the per protocol population,” Mapi revealed. Theseresults “suggest that GADepot is safe, well tolerated and efficacious”,noted the coordinating primary investigator of the study extension,Shlomo Flechter. “If these results will be confirmed in the placebo-controlled Phase III study, GA Depot has the potential to establish anew standard of care for multiple sclerosis drugs.” The trial is intendedto support a a US filing through the 505(b)(2) hybrid pathway. G

OPHTHALMOLOGY DRUGS

Polpharma and SIFIally on eye diseasesPolpharma has an eye on expanding its current ophthalmic portfolio

with “new specialty products which are unique on the Polishmarket”, under a commercial strategic partnership, “mainly acrossEurope”, it has just formed with Italian ophthalmic specialist SIFI.

Noting that the firms had mutually identified glaucoma anddry eye as the two key therapeutic areas, Polpharma revealed that,under the first stage of the firms’ co-operation, it had out-licensedtwo glaucoma products to SIFI and in-licensed three dry-eye medicaldevices from the Italian firm.

“The agreement will enhance product portfolios,” the Polish firmexplained, “and provide a more comprehensive therapeutic range ofophthalmic therapies to the international market.”

Markus Sieger, chief executive officer of the Polpharma group,said the effectiveness of the products had been proven in clinical trials.The agreement was “very positive news for patients suffering fromdry-eye disease and a great beginning of our co-operation with SIFIwhich, we hope, will cover also other areas in the future”, he said.

Polpharma’s PolfaWarszawa plant in Poland specialises inmakingsterile drugs, including ophthalmic products. Meanwhile, Bioeq – aSwiss-based biopharmaceutical joint venture involving Polpharma– is with Germany’s Formycon developing FYB201, a biosimilarof Genentech’s Lucentis (ranibizumab) treatment for multiple eyediseases (Generics bulletin, 28 September 2018, page 12).

Fabrizio Chines, SIFI’s chairman and chief executive officer,described the “cross-licensing partnership” as a “clear step forward inour business-development strategy”. “By swapping commercial rightsto late-stage assets in different geographies, SIFI will be in a positionto accelerate its international growth, bringing a more comprehensiveproduct range faster to ophthalmologists and patients in key markets.”

Headquartered in Catania, Sicily, SIFI operates directly in Italy,France, Spain, Romania and Mexico with a global staff of over 370.G

OPHTHALMIC DRUGS

Ciclosporin SPC casesent to EU by FranceTwo questions over how to interpret the Court of Justice of the

European Union’s (CJEU’s) landmark Neurim ruling have beenreferred to the CJEU by a French appeals court in a dispute over asupplementary protection certificate (SPC) application for Santen’sIkervis (ciclosporin) ophthalmic drug.

The Neurim ruling from 2012 set out the principle that SPCsmay be granted for an active ingredient on the basis of a givenmarketing authorisation even if the ingredient has previously receiveda marketing authorisation in the EU, provided that the earlierauthorisation covered a different use (Generics bulletin, 3 August2012, page 17). It allowed an SPC for Neurim’s Circadin (melatonin)brand as a treatment for insomnia in humans, even though melatoninhad already been authorised as a veterinary medicine. The SPC wouldcover the new patented use of the product, according to Neurim.

In the French case, Santen had asked French intellectual-propertybody INPI for an SPC to protect its Ikervis brand, based on Europeanpatent EP 057,959,306 which covers ‘oil-in-water type emulsionwith low concentration of cationic agent and positive zeta potential’.The requested SPC was for ‘ciclosporin eye-drops in emulsion’, latermodified to ‘ciclosporin for use in the treatment of keratitis’.

However, the INPI rejected the request – which had been basedon a European Community marketing authorisation for Ikervisgranted on 19 March 2015 – due to the existence of a previousmarketing authorisation granted in 1983 for Sandimmun (ciclosporin).Sandimmun took the formof oral solution and hadmultiple indications,including as an immunosuppressant for transplant patients, as well asfor treating uveitis. Santen appealed against the INPI’s decision.

‘Strict’ or ‘extensive’ interpretationIn arguing that the CJEU’s Neurim decision should be interpreted

“strictly” so as to preclude the grant of the requested SPC for Ikervis, theINPI told the Paris appeals court that the scope of the ‘306 patent shouldalign with that of the new medical use, as was the case in Neurim. The‘306 patent covered an ophthalmic emulsion with ciclosporin as theactive substance and its use to treat keratitis and also uveitis.

Also, the INPI said, to allow for a new SPC, the secondmarketing authorisation should relate to an indication in a newtherapeutic area compared to the first authorisation. Given thatIkervis’ and Sandimmun’s authorisations both related to treatinginflammations of the eye in human patients, the INPI said a newmedical use had not been sufficiently demonstrated.

But Santen argued thatNeurim should apply in amore “extensive”manner. While both Ikervis and Sandimmun involved the use ofciclosporin for anti-inflammatory purposes, Santen acknowledged,the two drugs were used to treat different parts of the eye and fordifferent conditions.

The brand company insisted that Neurim should apply in thecase of a basic patent that protected a new formulation, and alsowas not limited to instances in which the first authorisation was forveterinary purposes and the second human.

In formulating its questions for the CJEU, the Paris appeals courtsaid it was not possible to reach a ‘certain’ interpretation of Neurim’srequirement of a new use. The appeals court therefore asked theCJEU to determine whether Neurim should be applied strictly orextensively, as well as to clarify the extent to which the newmarketingauthorisation must align with the scope of the basic patent. Gn david.wallace@generics-bulletin.com

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18 bulletin 26 October 2018

PRICE WATCH.....UK

Figure 1 (above): Comparison between the periods 1-31 August 2018 and 1-30 September2018 of UK trade prices of the most recently-launched generics listed in categoryM of the Drug Tariff of pharmacy-reimbursement prices. Averages calculated from atleast 23 data points. Figure 2 (top right) and Figure 3 (centre right): Biggest averagetrade-price changes between 1-31 August 2018 and 1-30 September 2018. Averagescalculated from at least 16 data points. Figure 4 (bottom right): Ranking of fastest-moving products subject to the most price offers made to independent UK pharmacists(one strength per ingredient; offers recorded by 30 September). Data for Figures 2, 3and 4 from a basket of about 750 commonly-dispensed generics. Recently- launchedproducts in Figure 1 excluded from Figures 2 and 3 (Source – WaveData).

Aripiprazole tabs 10mg 28 £0.88 -30 £2.06 -10Carbimazole tabs 5mg 100 £21.35 -10 £29.20 -2Celecoxib caps 200mg 30 £0.82 +1 £1.23 +10Cilostazol tabs 100mg 56 £3.33 ±0 £4.96 -5Duloxetine caps 30mg 28 £0.94 -6 £2.19 +10Eplerenone tabs 25mg 28 £3.21 ±0 £5.77 +8Escitalopram tabs 10mg 28 £0.44 ±0 £0.75 -6Etoricoxib tabs 90mg 28 £2.24 +5 £3.97 +17Frovatriptan tabs 2.5mg 6 £2.75 ±0 £5.28 -4Memantine tabs 10mg 28 £0.55 +2 £0.84 +4Montelukast tabs 10mg 28 £0.58 -3 £0.86 -1Nefopam tabs 30mg 90 £4.99 -9 £10.84 +4Nortriptyline tabs 10mg 100 £1.25 -5 £2.88 -47Olmesartan tabs 10mg 28 £0.69 -8 £1.25 -10Pregabalin caps 150mg 56 £2.35 +2 £3.97 -2Raloxifene tabs 60mg 28 £2.25 ±0 £2.99 +6Rasagiline tabs 1mg 28 £1.09 -1 £2.43 +11Rizatriptan tabs 10mg 3 £4.17 -8 £6.80 +6Rosuvastatin tabs 5mg 28 £0.74 -4 £1.14 -7Sevelamer tabs 800mg 180 £23.15 +4 £27.84 +2Sildenafil tabs 100mg 4 £0.23 ±0 £0.41 +5Tadalafil tabs 10mg 4 £0.90 -9 £1.73 +12Telmisartan tabs 80mg 28 £0.88 ±0 £1.27 +7Travoprost drops 40µg/ml 2.5ml £2.23 -11 £4.31 -1Zonisamide caps 100mg 56 £3.59 ±0 £6.25 -10

Omeprazole caps 20mg 28 129 137 137

Simvastatin tabs 40mg 28 119 127 131

Atorvastatin tabs 20mg 28 127 138 119

Citalopram tabs 20mg 28 86 105 113

Lansoprazole caps 30mg 28 119 128 108

Ramipril caps 10mg 28 101 102 108

Fluoxetine caps 20mg 30 109 112 104

Amitriptyline tabs 10mg 28 104 111 104

Bisoprolol fumarate tabs 2.5mg 28 105 98 103

Gabapentin caps 300mg 100 88 97 102

Risperidone tabs 4mg 60 £1.10 ±0 £38.70 +916

Risperidone tabs 1mg 20 £0.95 +352 £4.14 +696

Risperidone tabs 3mg 60 £0.99 ±0 £30.07 +657

Risperidone tabs 6mg 28 £1.57 +43 £17.21 +562

Risperidone tabs 2mg 60 £1.02 ±0 £22.19 +431

Risperidone tabs 1mg 60 £0.49 ±0 £11.68 +295

Nortriptyline tabs 25mg 100 £1.25 -16 £2.80 -62

Celiprolol tabs 200mg 28 £5.99 -1 £7.45 -22

Metformin tabs 850mg 56 £0.42 ±0 £0.70 -22

Celiprolol tabs 400mg 28 £7.70 -7 £12.07 -21

Dexamethasone tabs 500µg 30 £3.25 ±0 £7.72 -14

Repaglinide tabs 1mg 90 £1.05 ±0 £5.13 -11

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

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

RECENT LAUNCHESProduct/Strength/Pack size Lowest Change Average Change

price (%) price (%)

BIGGEST RISERSProduct/Strength/Pack size Lowest Change Average Change

price (%) price (%)

BIGGEST FALLERSProduct/Strength/Pack size Lowest Change Average Change

price (%) price (%)

FAST MOVERSPrice offers as at 30 September 2018

Product/Strength/Pack size July August September

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Risperidone continued to dominate UK price rises in September,according to the latest figures from market researcher WaveData,

with the average price of the antipsychotic rising in the most severecase by a factor of 10. Last month, WaveData pointed to a shortageissue affecting the molecule that it predicted could persist wellbeyond August (Generics bulletin, 28 September 2018, page 19).

As Figure 2 shows, average price rises for 1mg, 2mg, 3mg, 4mgand 6mg tablets in September ranged between 295% and 916%, withthe price to independent UK pharmacists of 4mg tablets in 60-countpacks multiplying on average by more than 10 times to £38.70(US$50.85), even though packs could be bought for as little as £1.10 ifpharmacists shopped around.

Concessions for risperidone offered by the UK’s Departmentof Health and Social Care in September fell short of the averages

reported by WaveData, according to the Pharmaceutical ServicesNegotiating Committee. For 60-count packs of 2mg, 3mg and 4mgtablets, concessions of £21.25, £26.00 and £27.39 compared to actualaverages of £22.19, £30.07 and £38.70 respectively.

Meanwhile, 100-count packs of nortriptyline 25mg tablets led thebiggest fallers in Figure 3 with an average price drop of almost two-thirds, as the 10mg strength reflected an average decline of almost halfin our basket of recent launches (see Figure 1). The steepest averagerise seen among the recent launches came from etoricoxib 90mgtablets, 28-count packs of which saw an average rise of 17% to £3.97.

And our fast movers in Figure 4 showed omeprazole leadingthe pack in terms of the number of offers in the marketplace, closelyfollowed by simvastatin. Atorvastatin followed, with a decline to 119in September, compared to 127 in July and 138 in August. G

Rocketing risperidone dominates UK rises

Gen 26-10-18 Pgs.1-24.indd 18 24/10/2018 16:00

Gen 26-10-18 Pgs.1-24.indd 19 24/10/2018 16:00

20 bulletin 26 October 2018

MARKET RESEARCH

Canada’s generics and biosimilars industry hasfaced unprecedented upheaval over the pastyear. From seeing the introduction of two-

year patent extensions in the wake of the country’strade agreement with the European Union (EU),through ushering in a new five-year local pricinginitiative for generics, to most recently witnessinga Canadian deal with the US and Mexico that willextend data-exclusivity for biologics to 10 years, thepast 12 months have not been short on significantdevelopments for the industry to grapple with.

As president of the Canadian Generic Pharma-ceutical Association (CGPA), Jim Keon is leadinglobbying efforts on all of these fronts, attemptingto secure a sustainable environment for the small-molecule generics industry – that has recently seensales and market share suffer a slight slip in valueterms (see Figure 1) despite maintaining volumegrowth (see Figure 2) at the same time as seeking waysto drive growth in the nascent biosimilars market.

Continued price compression in Canada wasone of the main obstacles facing industry, Keon toldGenerics bulletin in an exclusive interview. “Despitethe massive savings provided to Canadian public andprivate payers in the Canadian market due to furtherprice reductions resulting from agreements reached in2017-18 with Canadian governments,” he explained,“there continues to be public discussion regardingdeeper price cuts and, worse, the introduction oftendering and sole-source contracting.”

Citing Iqvia data, Keon pointed out that whilethe average price of a brand-name prescription inCanada was C$101.00 (US$78.50), the average priceof a generic prescription was just C$20.53, down fromC$26.45 in 2008. Nevertheless, he noted, “pricingpressures in Canada and around the globe arechallenging manufacturers’ ability to continue to offerthe breadth of products that they have in the past”.

As part of efforts to secure a sustainable pricingenvironment, the CGPA at the start of this year agreeda new five-year initiative with the pan-CanadianPharmaceutical Alliance (pCPA) that set reducedpricing levels for 67 commonly-prescribed moleculesrepresentingmore than half of all generic prescriptionsdispensed in Canada in 2017 (Generics bulletin, 2February 2018, page 9). From the start of April, pricesof these molecules were reduced by between 25%and 40%, resulting in overall discounts of up to 90%compared to equivalent brands.

“Previous joint efforts between the pCPA andCGPA have resulted in savings of over C$1 billionto participating drug plans over the past five years,”Keon observed, “and will continue to save $250 mil-lion per year.” Meanwhile, the new initiative wasexpected to save a further C$385 million in its firstyear, and up to C$3 billion over the next five yearsthrough a combination of price reductions and newgeneric launches.

“Akey component of this initiative is that tenderingwill not be pursued by the participating jurisdictionsover the five-year term,” Keon emphasised. “Thegeneric medicines covered in this initiative aremanufactured by multiple generic companies, helpingto ensure a stable supply for Canadian patients.”The stability and predictability offered by the deal“will also help to ensure that generic pharmaceuticalmanufacturers can continue to invest in bringing newcost-saving generic drugs to the Canadian market in thecoming years”, he stated.

Pointing also to another similar pricing dealagreed in Quebec last year (Generics bulletin, 28 July2017, page 9), Keon again said there would be “notendering over the term of the five-year agreement”.Tenders “limit competition and further threaten thecurrent and future supply of cost-saving genericmedicines”, he cautioned, insisting that “tendering isalso incompatible with Canada’s current intellectual-property (IP) regime for pharmaceuticals”.

Tendering “removes the incentive for genericpharmaceutical manufacturers to challenge invalidand/or non-infringed patents and bring new cost-saving generic prescription medicines to market”,Keon noted, observing that “manufacturers rarely,if ever, challenge invalid or non-infringed patents inmarkets with tendering schemes as there is little or noreward in attempting to enter the market early if saleswill be lost to a lower-priced bidder”. Conversely,he said, the scheme agreed with the pCPA “helpsmaintain the incentive for generic pharmaceuticalmanufacturers to challenge invalid and/or non-infringed patents”.

Pricing deal provides certainty“Both the current and previous initiatives between

the pCPA and CGPAhave been important to Canada’sgeneric drug makers,” Keon highlighted, helping toprovide “business certainty” against a backdrop ofprice compression.

Acknowledging that the process of rolling outthe latest framework had not been entirely smooth, hepointed out that “these initiatives were unprecedentedin the Canadian market, so some growing pains wereinevitable”. However, both the pCPA and CGPA hadput in place structures for “regular dialogue to jointlyaddress issues as they arise”, helping ensure that thescheme was implemented successfully.

“To date, both sides appear to be committed to thesuccess of the initiative,” Keon observed.Asked aboutthe possibility of similar initiatives with the pCPA infuture, he stated that the current five-year arrangementwould be “monitored by both parties over the courseof the initiative”, adding that “it seems likely that bothparties recognise the ongoing and future value to anational, co-operative approach to pricing and issuesrelated to market access”.

Turning to regulatory issues, Keon cited as

Canadian industry is seekinglower costs and improvementsMaintaining a

sustainable pricing

environment, achieving

greater international

regulatory convergence,

and bolstering the

biosimilars sector

are among the key

priorities for Canada’s

off-patent industry,

CGPA president Jim

Keon told Generics

bulletin deputy editor

Dave Wallace.

Jim Keon

Gen 26-10-18 Pgs.1-24.indd 20 24/10/2018 16:00

21bulletin26 October 2018

MARKET RESEARCHa major objective for the CGPA “the need forgreater regulatory convergence with our internationalpartners and within the Canadian federation”.

“Canada is a relatively small market with highcosts and barriers to market entry,” he acknowledged.“In order to bring new products to market and ensurethe sustainability of currently marketed products,manufacturers need tobe able to leverageglobal productdevelopment as well as common bulk manufacturing.”“Greater reliance by Health Canada on regulatoryreviews and decisions of trusted peer authorities wouldhelp to minimise market access costs and delayed entryto the Canadian market,” he suggested.

Costs must come down“In order for the generic pharmaceutical industry

to succeed in Canada and benefit Canadians, it needsa stable, predictable pricing environment and it needsco-operation from provincial, territorial governmentand the federal government to reduce the high costsand barriers to market entry,” Keon explained.

“This includes the federal regulatory systemin relation to international standards, it includesthe varied, duplicative and redundant individualprovincial and territorial formulary listing andinterchangeability rules, and it includes Canada’scurrent pharmaceutical patent regime.”

Access toCanadian reference products for researchand development purposes “continues to be a challengeas innovator companies put in roadblocks to blockaccess”, Keon complained (see page 9). “Expandingthe current scope for the use of a foreign-sourcedreference product would aid in increasing genericaccess and reducing regulatory hurdles.”

These challenges came as the IP landscapefor generics and biosimilars in Canada was beingtransformed, not least by the Comprehensive Economicand Trade Agreement (CETA) struck with the EUthat began being implemented just over a year ago(Generics bulletin, 15 September 2017, page 6).

CETA included provisions allowing for two-yearpatent-term extensions in the form of a certificateof supplementary protection (CSP), a Canadiancounterpart to the supplementary protection certificate(SPC) that is used in Europe.

Keon was clear in his assessment of the impactof the trade deal. “Concessions were made in CETAthat required changes to Canada’s pharmaceutical IPlaws,” he stated. “They will increase the costs of drugsfor Canadians in the future.” He said the country’s

parliamentary budget office “has estimated the cost ofthe new CSP at half a billion dollars per year, whenbiologic drugs and drugs dispensed in institutions suchas hospitals, clinics and care facilities are considered”.

Nevertheless, he conceded, “while the CSPsrepresent an unnecessary and harmful concession inour view, we are generally satisfied with the way thegovernment of Canada implemented the system”.Importantly, Keon pointed out, as well as extensionsbeing capped at two years, there was no retroactivity,meaning the system only applies to products approvedafter it was introduced.

“Generic firms will also be able to manufacture forexport during the CSP period,” he added.A counterpartwaiver to allow manufacturing during SPC terms isstill under consideration in Europe, following years oflobbying by local industry body Medicines for Europe.

CETA also altered the patent-litigation pathwayfor generics companies, with changes that Keon said“address some generic industry concerns”. Firstly, hesaid, the new framework “creates a single, unifiedlitigation system”, removingweaknesses of the previoussystem under which generics firms were routinelysued again for patent infringement after patent-linkagelitigation due to the summary nature of the proceedings.

The new system also allowed new evidenceand arguments to be introduced during the courseof litigation, Keon pointed out, whereas “previouslycompanieswere constrained to the arguments containedin the [initial] notice of allegation”. Damages availableto injured generics firms have also been improved,according toKeon, although “some limitations remain”.

Litigation uncertainty remainsHowever, Keon said, “the new system continues to

present risk and uncertainty for genericmanufacturers”.Rules around stays are problematic, while costs forlitigants “are expected to rise considerably under thenew system”. “With continued downward pricingpressure,” he warned, “this may cause companies to bemore selective in litigation.”

Patent litigation for generics firms in Canada hasalso been affected by last year’s Supreme Court rulingon the ‘promise doctrine’ – which directed courtsto read both the patent claims and the disclosure toidentify potential promises, rather than the claimsalone – in which the Supreme Court ruled that thedoctrine was not the correct approach to determinepatent utility (Generics bulletin, 7 July 2017, page 1).

“The Supreme Court decision was disappointing

7

6

5

4

3

2

1

0

35

30

25

20

15

10

5

02013 2014 2015 2016 2017 MAT 06/18

Sales Market share

5.105 5.311 5.4855.767

6.012 5.896

22.6 22.4 21.7 22.0 21.8 21.0

Sales

(C$billion

s)

Market

share(%

)Presc

riptions(m

illions)

500

400

300

200

100

0

Market

share

(%)

75

70

65

60

55

50

Sales Market share

376402

430457

476 486

65.867.3

68.970.5 70.6 70.8

2013 2014 2015 2016 2017 MAT 06/18

Figure 1: Value sales and prescription market share achieved by Canadian generics in2013-2017 and for the 12 months ended June 2018 (Source – CGPA/Iqvia)

Figure 2: Value of prescriptions and market share achieved by Canadian generics in2013-2017 and for the 12 months ended June 2018 (Source – CGPA/Iqvia)

Gen 26-10-18 Pgs.1-24.indd 21 24/10/2018 16:00

22 bulletin 26 October 2018

MARKET RESEARCHto our industry,” Keon said, “particularly in light ofthe North America Free Trade Agreement (NAFTA)arbitration panel decision which had defended theCanadian approach” (Generics bulletin, 24 March2017, page 1). “Further skewing the patent system tothe benefit of originator companies never serves toimprove patient access to medicines.”

“That said, the litigation system and courtinterpretations are always evolving – as are the legalarguments advanced by litigants,” he commented.“As such, the overall decision has not represented asignificant setback for the industry.”

Canadian originators had criticised the ‘promisedoctrine’, as had their US counterparts in lobbyingefforts directed at the US Trade Representative(USTR), which each year publishes a ‘Special 301’report lambasting the IP regimes of non-US countries(Generics bulletin, 4 May 2018, page 1). Despite therecent introduction of CSPs and the Supreme Courtdecision on the promise doctrine, this year saw theUSTR further intensify its criticism of Canada, placingthe country on its Priority Watch List (Genericsbulletin, 18 May 2018, page 14).

Keon’s response was bullish. “The government ofCanada does not accept the legitimacy of the Special301 Report, nor does the CGPA,” he maintained. “Itis a one-sided report that represents the wish list ofrights holders, and does not reflect sound policy orthe reality of the strong Canadian framework forpharmaceutical IP.”

“Both the International Generic and BiosimilarMedicinesAssociation (IGBA) and the USAssociationfor Accessible Medicines (AAM) have madesubmissions as part of this process over the years,”he pointed out, “but the issues raised on behalf of thegeneric and biosimilar medicines industries are notreflected in the USTR reports.”

More recently, Canada has run up against furtherchallenges in its dealings with the US, after thecountries’renegotiation ofNAFTA– alongwithMexico– led to a new agreement that includes a 10-year data-exclusivity period for biologics, adding two years tothe period set out under Canada’s current framework(Generics bulletin, 5 October 2018, page 8).

USMCA is ‘disappointing’Calling the agreement “disappointing”, Keon

emphasised that “Canada was not at the tablewhen harmful intellectual-property provisions werenegotiated between the US andMexico” in initial talks.The pharmaceutical provisions of the new US-Mexico-Canada Agreement (USMCA) would “delay accessto competition from biosimilar biologic drugs inCanada”, he warned.

Similar criticisms have been voiced by industryassociations in the US and Mexico.

More generally, Canada’s biosimilars marketshowed room for improvement, Keon acknowledged,although he did indicate a certain optimism in termsof future development and growth.

Market access was one of the key challengesfor biosimilars in Canada, he observed, stating that“the time from market authorisation to listing hasbeen slow”. Also, “biosimilars sponsors have novisibility to the confidential product-listing agreementssigned between originators and payers”, Keon said,

meaning that “pricing levels available for biosimilarsmay be much lower than anticipated, and may be atunsustainable levels”.

Patient-support programmes operated by brandcompanies also represented a barrier to biosimilars,he said. “All Canadian biologic medicines have someform of patient-support programme,” he explained.“Products administered in hospital settings in othercountries are administrated through private clinicsin Canada that are funded by originator companies.This creates a high barrier to entry for biosimilarssponsors, and such programmes are costly to operatefor products that have lower reimbursement prices thanthe originator product.”

“While many Canadian payers have mandatedthe use of biosimilars for naïve patients,” he noted,“they have been slower to take more interventionistmeasures such as transitioning patients from originatorbiologics to biosimilars.” Nevertheless, he said, “wedo have some optimism and believe some payers arepoised to adopt more interventionist policies to supportbiosimilar uptake”.

Canada should reject bio suffixOn biosimilar naming, Keon pointed out that

Health Canada had been consulting on the additionof a suffix to biosimilar non-proprietary names, buthe maintained that this was “unnecessary for productidentification and pharmacovigilance purposes”.“The addition of a suffix in the US has been usedby originator companies to disparage biosimilars andcreate unnecessary patient concern,” he observed.“We remain concerned that Health Canada may adoptsuch a controversial system, which would be a majorsetback for biosimilars in Canada.”

Meanwhile, there was still uncertainty overwhether the new litigation framework introduced lastyear would allow biosimilar sponsors to “successfullynavigate to bring new products to the market”.

In general, Keon acknowledged, the uptake forbiosimilars had been “very slow for chronic therapies”,despite good uptake for acute therapies. In the 12months ended June 2018, Canadian biosimilars saleswere C$105 million, representing just 1.3% of a totalCanadian biologics market worth C$8 billion.

However, he said, “the landscape is changingrapidly”. “There were six biosimilars approved andmarketed during this 12-month period: Sandoz’Omnitrope (somatropin) and Erelzi (etanercept);Hospira’s Inflectra (infliximab); Eli Lilly’s Basaglar(insulin glargine);Apobiologix’Grastofil (filgrastim);and Merck’s Brenzys (etanercept).”

Moreover, he said, approved biosimilars thatwould likely record their first sales in the thirdquarter of 2018 included Apobiologix’ Lapelga(pegfilgrastim), Merck’s Renflexis (infliximab), “andpossibly Sanofi’s Admelog (insulin lispro)”. Andthere were several further biosimilars under HealthCanada review.

“The process from market authorisation tomarket access has been very inefficient in Canada,”Keon said. “But there have been some encouragingdevelopments this year.” Health Canada and healthtechnology assessment bodies were working moreclosely together so that recommendations would beissued closer to the date of marketing authorisations,

“We must work with

governments and

payers to put in place

the regulatory and

market environment

that will ensure the

continued and future

supply of cost-saving

generic medicines”

Gen 26-10-18 Pgs.1-24.indd 22 24/10/2018 16:00

23bulletin26 October 2018

MARKET RESEARCHhe noted, explaining that “such decisions werepreviously made three months or longer after marketauthorisation”. Furthermore, the pCPAwas “reviewingits price-negotiation process, which could createfurther efficiencies”.

But more could be done, Keon proposed. “Benefitdesigns and coverage policies need to evolve to optimisethe use of biosimilars,” he suggested. “Some public drugplans were quick to adopt preferential listing policiesfor biosimilars. These were generally focused on naïvepatients. Some public plans are now seeking to takemore proactive measures to support the transitioningof patients from originator biologic to biosimilars.Biosimilars Canada supports this direction.”

Specifically, he pointed out, “we have had someearly leaders such as Green Shield Canada. They werequick to communicate and adopt preferential listings forbiosimilars”. However, “overall, private-sector adoptionof biosimilars lags behind public-sector adoption”.

Action needed from payers“Payers need to be interventionist to support

and grow the biosimilars market and generate short-,medium- and long-term value,” Keon urged. “Suchmeasures include providing preferred listing statusfor biosimilars; proactively requiring the transitioningof patients from originator biologics to biosimilars;ending or severely limiting coverage for the originalbiologic upon availability of biosimilar to influenceprescriber behaviour; ensuring sustainable biosimilarpricing levels to encourage companies to invest inbringing future biosimilars in Canada; and considering

what options are available to incentivise physicians toprescribe biosimilars to patients, or to assist with theirefforts to educate patients on transition.”

Looking ahead, Keon said that at a time whenthe generics industry was “facing challenges to itssustainability inCanada”, theCGPA’s “key focus”wouldremain ensuring a “stable, predictable market for ourcompanies and the continued supply and introductionof cost-saving generic prescription medicines”. “Amajor component of this work will be the successfulimplementation of the five-year initiative with thepCPA and the similar agreement with the governmentof Quebec,” he outlined.

“These agreements will provide billions ofdollars in additional savings to Canada’s health-caresystem,” Keon observed. “Now that these significantfurther price discounts have come into effect, wemust work with governments and payers to put inplace the regulatory and market environment that willensure the continued and future supply of cost-savinggeneric medicines.”

“And now that prices of generic prescriptionmedicines have been dramatically reduced,” he argued,“the focus must switch to implementing changes thatincrease their use in Canada.”

“Many of the most widely prescribed genericdrugs offer a massive 90% discount from the prices ofthe equivalent brand-name versions,” he highlighted.“Wewill workwith Canadians to implement strategiesto increase the use of generic prescription medicinesso that the savings provided by these lower prices canbe fully realised.” G

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Gen 26-10-18 Pgs.1-24.indd 23 24/10/2018 16:00

24 bulletin 26 October 2018

PEOPLE

APPOINTMENTS

Crawford to lead Cardinal unitCardinal Health has appointed Victor Crawford as chief executive

officer (CEO) of the firm’s Pharmaceutical segment, effectivefrom 12 November. Jon Giacomin, head of Cardinal’s Medicaldivision, had held the Pharmaceutical CEO role since November2014, taking on the Medical lead role in February this year. Crawford– who most recently served as chief operating officer of healthcare,education and business dining for food, facilities and uniformscustomer service businessAramark – will report toMike Kaufmann.

Kaufmann said thatCrawford “brings awealth of direct experiencewith many of our customers and clearly understands the complexitiesof global supply-chain management in the healthcare arena”. “Hisstrategic focus on customer relationships and in-depth knowledge ofinstitutional management systems will help us build on the successof the various components of our pharmaceutical business includingSpecialty Solutions, Nuclear and Pharmaceutical Distribution.” G

APPOINTMENTS

Ford’s Abbott namedin chief operating roleAbbott has appointed the firm’s executive vice-president of Medical

Devices Robert Ford as its president and chief operating officer,with immediate effect. The 22-year veteran of the companywill assumeresponsibility for all ofAbbott’s operating businesses, in addition to hiscurrent responsibilities for Medical Devices. He will continue to reportto chairman and chief executive officerMiles White.

Having held “various management positions” across several ofAbbott’s businesses, including Diagnostics, Nutrition and MedicalDevices, Ford has been head of the latter division since 2015. As wellas overseeing the group’s acquisition of medical devices firm St JudeMedical that closed in January 2017 – “the largest acquisition inAbbott’shistory” – he previously led the company’s Diabetes Care business andthe launch of its glucose monitoring system FreeStyle Libre.

“Robert is a strong leader who consistently demonstratesAbbott’ssuccessful management philosophy and strategy, and has a successfultrack record of delivering business results,” White commented. G

AAM – the Association for Accessible Medicines – has appointedDana Mariani as director of policy, within the generics industrybody’s policy and strategic alliances team. Before joining theAAM, Mariani was part of a cross-functional project managementorganisation teamatGuidehouse, supporting theCenters forMedicareandMedicaid Services (CMS) quality payment program (QPP). Priorto that, she served as account manager at CareMetx, and for threeyears she held the role of associate business analyst at Lupin.

PFIZER has revealed that chief operating officer (COO) AlbertBourlawill become the firm’s chief executive officer (CEO) from 1January 2019, after the company’s board of directors “unanimouslyapproved” the decision. He succeeds in the role Ian Read, who hasled Pfizer since December 2010 and became chairman a year later.Read will transition from his current roles to executive chairman.

RECIPHARM has welcomed Tobias Hägglöv as chief financialofficer with immediate effect. He will report to the Swedish contract-development and manufacturing firm’s chief executive officer,Thomas Eldered. With “comprehensive experience in finance andmanagement positions”, Hägglöv joins Recipharm from contractmanufacturer LEAX, where he held the same role.

BD – Becton, Dickinson and Company – has promoted companypresident Tom Polen to chief operating officer, a role the firm hasnot had since 2016. Noting that Polen would remain in his currentpresident role – which he has held since April 2017 – BD said hewould continue to report to chairman and chief executive officerVincent Forlenza. “Polenwill have oversight of BD’s three operatingsegments, its innovation and new product development pipeline, andglobal operations for the company, including all manufacturingfacilities and supply-chain operations,” the firm stated.

EUIPO – the European Union Intellectual Property Office – hasappointed Christian Archambeau as executive director, effectiveimmediately. Previously, he was deputy executive director ofEUIPO, and prior to that he held senior management positions inthe European Patent Office (EPO) and the European SpaceAgency.

CASI PHARMACEUTICALS has named Larry Zhang aspresident of CASI Pharmaceuticals Beijing, the firm’s Chineseoperating subsidiary, “to lead commercialisation”. Wei-Wu He,CASI’s executive chairman, said Zhang’s “cross-functional executiveexpertise, particularly in navigating China’s Food and DrugAdministration (CFDA) reforms and governmental affairs withinthe generic pharmaceuticals sector, will be invaluable to CASI’sadvancement and growth as we continue to expand and advance ourpipeline”. Zhang joins from Novartis, where he was vice-presidentand head of public affairs and corporate responsibility in China.

OWEN MUMFORD has selected Shirley Loh as regional managingdirector for theAsia-Pacific region. Noting that she would be based atthe company’sMalaysian hub in Nusajaya, the medical-device designand manufacturing specialist said Loh “will focus on establishing aneffective and efficient market access strategy”. She has for the past sixyears served as marketing director for Medtronic’s restorative therapygroup in the Association of Southeast Nations (ASEAN) region.

PHARMABLOCK has appointed Shijie Zhang as its chieftechnology officer. Bringing to the role “over 20 years of experiencein medicinal chemistry, process chemistry and active pharmaceuticalingredient (API) manufacturing”, Zhang joins fromAgios, where hewas director of process chemistry and API manufacturing. G

IN BRIEF

APPOINTMENTS

Roos set to join Siegfried teamSiegfried has announced that Jürgen Roos has been appointed chief

scientific officer, and will also join the firm’s executive committeeand take on responsibility for research and development (R&D) from1 April 2019. Roos succeeds Siegfried’s chief scientific and strategyofficer Wolfgang Wienand, who was recently appointed to becomechief executive officer from 1 January 2019 (Generics bulletin, 15 June2018, page 16). Wienand will continue to manage Siegfried’s strategyand mergers and acquisitions department, the Swiss firm noted.

Roos joins Siegfried from specialty chemicals firm EvonikIndustries, where he held several management positions in research,development and innovation. Citing Roos’ “profound scientificknowledge”, Wienand said that Roos “enjoys wide experience in themanagement of large R&D organisations and has intimate knowledgeof the pharmaceutical business”. G

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