enerics ulletin nforma · from India’s Strides Pharma Science as it has decided to step away from...

8 February 2019No.385

Pharma IntelligenceInformaBulletin

Genericsgener icsbul let in .pharmaintel l igence . informa.com

WOCKHARDT

Wockhardt Slides To Loss Amid US Oncology Push, p. 13

MERGERS & ACQUISITIONS

Strides Sells Australian Business To Arrow-Apotex Merger, p. 4

EVEROLIMUS

UK Disregards EPO’s Opinion On Everolimus Patent, p. 8

Mylan’s Nod For US Advair Rival Puts It A Year Ahead Of The PackDAVID WALLACE [email protected]

Mylan has received a long-awaited approval for the first US generic rival to GlaxoSmithKline’s (GSK’s)

Advair Diskus (fluticasone/salmeterol) asth-ma treatment, putting the firm around a year ahead of other US generics being pur-sued by competitors Sandoz and Hikma.

Mylan has announced plans to launch its Wixela Inhub version – which has been approved in three strengths, fluticasone/salmeterol 100μg/50μg, 250μg/50μg, and 500μg/50μg – by the end of Febru-ary, with patents protecting Advair hav-ing now expired.

In the first nine months of 2018, GSK saw its US Advair sales fall by 30% at constant

exchange rates to £798 million (US$1.05 billion), at the same time as US sales of its Ellipta respiratory portfolio grew by 27% on the same basis to £832 million.

HIKMA AND SANDOZ LOOKING TO 2020Sandoz chief executive Richard Francis recently indicated that the company was aiming to refile its generic this year, af-ter receiving a complete response letter (CRL) in February 2018, but was forecast-ing a launch of “early 2020”.

Acknowledging that Sandoz had previ-ously been eyeing a 2019 launch, Francis said this was “still a possibility based on the timelines of the US Food and Drug

Administration (FDA) and the broad win-dow they give”.

He admitted, however, that Sandoz was “looking at that a bit more conservatively and that’s the reason why we say 2020 now”.

Almost a year ago, Hikma was told by the FDA that it and development partner Vectura needed to complete an additional clinical endpoint study to support its ap-plication for an Advair rival, having re-ceived a CRL in May 2017 indicating that their abbreviated new drug application (ANDA) was not ready for approval, a de-cision disputed by the company. (Also see “Hikma must add an Advair study” - Gener-ics Bulletin, 16 Mar, 2018.)

Hikma chief executive Siggi Olafsson indi-cated last year that the firm was rerunning a key study and would be submitting its data to the FDA “as soon as we can in 2019”, with potential approval and launch in 2020.

Vectura and Hikma recently expanded their respiratory collaboration with a deal aimed at developing versions of GSK’s El-lipta portfolio. (Also see “Hikma and Vectu-ra ally on Ellipta rivals” - Generics Bulletin, 16 Nov, 2018.)

LONG PATH TO APPROVALThe FDA nod signals the end of a three-year road towards approval for Mylan’s generic, which has resulted in the firm receiving multiple CRLs over its applica-tion since it was first filed in January 2016. (Also see “Mylan awaits further Advair CRL” - Generics Bulletin, 22 Jun, 2018.)

Having in August last year received a priority designation from the FDA and a re-vised goal date in mid-October 2018 (Also see “Mylan gets October date for US Advair” - Generics Bulletin, 31 Aug, 2018.), Mylan

CONTINUED ON PAGE 4

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2 | Generics Bulletin | 8 February 2019 © Informa UK Ltd 2019

I N T H I S I S S U E

from the [email protected]

A major milestone in the US generics market was achieved this week with the US Food and Drug Administration (FDA) granting the very first approval for a generic version of GlaxoSmith-Kline’s Advair Diskus respiratory brand, in the form of Mylan’s Wixela Inhub (see front cover).

Developing bioequivalent versions of res-piratory drugs with accompanying devices has provided hurdles for the generics indus-try, and the road to US approval for an Ad-vair Diskus generic has been a long one with plenty of setbacks.

Nevertheless, the imminent launch of Wixela Inhub can be seen as a real feather in Mylan’s cap: not only does Advair Diskus still represent a substantial financial oppor-tunity for generic competition, but the FDA approval also appears to put Mylan around a year ahead of its closest rivals developing their own version of the respiratory block-

buster, such as Sandoz and Hikma.Elsewhere this week we have seen big moves

from India’s Strides Pharma Science as it has decided to step away from its Australian busi-ness in favour of a series of opportunities in North America (p.4).

Pfizer has set out its biosimilars strategy for the near future after recently axing develop-ment of five pre-clinical biosimilars programs (p.6), while Biogen (p.7) and Biocon (p.11) are seeing their investments in biosimilars reap rewards.

Meanwhile, there have been interesting movements in the US as an appeals court handed down a ruling that will help origina-tors to extend monopolies through patent-term adjustments (p.15), at the same time as industry has received backing from the coun-try’s pharmacy benefit managers (PBMs) for several pro-biosimilars policies (p.12).

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COVER / Mylan’s Nod For US Advair Rival Puts It A Year Ahead Of The Pack

4 Strides Sells Australian Business To Arrow-Apotex Merger

5 Akorn Appoints Young To Executive Team And Adds Two To Board

6 Pfizer Eyes Three Oncology Biosimilar Launches In 2019 As Sterile Injectables Problems Persist

7 Benepali Surge And Imraldi Gains Drive Biogen Biosimilars Past US$500m

8 UK Disregards EPO’s Opinion On Everolimus Patent

9 Dutch Court Departs From German Position On Pemetrexed

11 Biosimilars Begin To ‘Pay Off’ For Biocon

12 PBMs Propose Pro-Industry Policies Amid Pricing Pressure

13 Wockhardt Slides To Loss Amid US Oncology Push

14 Amgen Eyeing ‘Sustainable Opportunities’ In Non-US Biosimilars Markets

15 US Appeals Ruling Extends Life Of Some Patents

Mylan Gears Up To Launch US Advair Rival This MonthMylan has revealed that its Wixela Inhub US rival to GSK’s Advair Diskus will be on the market by the end of February, acting quickly after their recent FDA approval.

https://bit.ly/2MPcg4q

Alvotech To Develop Biosimilar Assets With US$300m Financing DealAlvotech will further develop its biosimilar assets through a US$300 million financing deal that will also enable the firm to “fuel continued growth” and be used for refinancing existing debt.

https://bit.ly/2SvbxdU

Antibiotics, Ibuprofen And Ranitidine Are Needed UrgentlyDonations of commonly used antibiotics, anti-inflammatory agents and ulcer drugs are urgently needed to support a community health program in Myanmar.

https://bit.ly/2DUsab6

Strides Builds North American Presence With Acquisitions In US And CanadaWhile planning to exit its Australian business, Strides Pharma Science has bolstered its presence in North America by gaining full control of its joint venture with Vivimed Labs, along with acquiring Vensun Pharmaceuticals in the US. The Indian firm has also bought a majority stake in Canada’s Pharmapar.

https://bit.ly/2t9XYlQ

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6 11 15



D E A L S

CONTINUED FROM PAGE 1

president Rajiv Malik had indicated that he was “confident that this is the last turn”, al-though the approval ultimately missed the October deadline. (Also see “Mylan’s Wixela is ‘imminent’” - Generics Bulletin, 26 Oct, 2018.)

MORE FDA GUIDANCE ON COMPLEX GENERICS IMMINENT

“Today’s approval of the first generic drug product for one of the most commonly prescribed asthma and chronic obstruc-tive pulmonary disease (COPD) inhalers in the US is part of our longstanding com-mitment to advance access to lower cost, high quality generic alternatives,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research (CDER). This “will bring more competition to the market which will ultimately ben-efit the patients who rely on this drug”.

“The FDA recognizes challenges compa-nies face when seeking to develop hard-to-copy complex generics, such as drug-device combination products, including when the drugs are incorporated into in-halation devices like this,” noted the FDA’s deputy Commissioner for policy, planning, legislation and analysis, Anna Abram.

“We are committed to advancing new guidance for sponsors to make the de-velopment of generic versions of com-plex products more efficient, and we’re prioritizing review of many applications covering proposed generic complex products for which a generic has not yet been approved.”

Published online 31 January 2019

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Strides Sells Australian Business To Arrow-Apotex MergerGRACE MONTGOMERY [email protected]

S trides Pharma Science has agreed to sell its entire Australian business, including its local Arrow unit, to the

Arrow-Apotex entity that resulted from the pair’s previously-announced merger, following a review of the Indian firm’s cor-porate strategy and the Australian market.

The decision comes as the Indian com-pany is bolstering its presence in the US by converting its 50:50 joint venture with Vivimed Labs to 100% Strides ownership and acquiring Vensun Pharmaceuticals, as well as building out its Canadian opera-tions with a majority stake in Pharmapar (Also see “Strides Builds North American Presence With Acquisitions In US And Cana-da” - Generics Bulletin, 1 Feb, 2019.).

Strides will sell its complete stake in Arrow for A$394 million (US$248 million) to entities owned and operated by Dennis Bastas, ex-ecutive chairman and co-founder of Arrow. Bastas was named to lead the combination as executive chairman when Strides and Apotex first agreed to merge their Austra-lian businesses in May 2018 (Also see “Apotex and Strides to merge Australia units” - Generics Bulletin, 11 May, 2018.). Strides has revealed that the new entity will be called ‘Arrotex’.

Stating that it would retain access to the intellectual property (IP) of 140 prod-ucts in the Arrow portfolio, Strides said it would enter into a 10-year preferred sup-ply agreement with Arrotex, to result in potential annual earnings before interest, tax, depreciation and amortization (EBIT-DA) of A$15-A$20 million.

Noting that Arrow would pay-out A$39 million minority interest, Strides said it would receive A$300 million as an upfront payment at the closure of transaction, while the remaining A$94 million would be deferred through a secured instrument.

Of the proceeds, the company said it would use US$150-US$160 million to pare its debt, while US$90-US$100 million would be used to expand in other markets.

The merger transaction would have delivered Strides a minimum ownership of 50% in the combined entity, and while Strides had considered acquiring full

ownership, the Indian firm noted that this “would have resulted in significant increase of debt on the balance sheet”. In addition, it added, the “estimated combined synergies and EBITDA could not support the leverage the company was comfortable with”.

“It was clear to us that the synergies that we originally envisaged were not panning out in the timeframe that we had antici-pated,” stated Arun Kumar, Strides’ found-er and chief executive officer (CEO).

“Strides preferred an exit strategy which is in the best interest of shareholders,” the company explained, following additional due diligence and approval from the Aus-tralian Competition and Consumer Com-mission in September last year (Also see “Apotex-Strides tie-up is cleared by ACCC” - Generics Bulletin, 28 Sep, 2018.).

The transaction is subject to certain con-ditions, including the conclusion of defini-tive agreements, approval of Strides’ share-holders and the successful completion of the Arrow-Apotex merger, which is due to complete by 31 March 2019.

US OVERTAKES AUSTRALIA AS STRIDES’ LARGEST MARKET

The news comes as Strides revealed that the US overtook Australia as the firm’s largest market in the company’s finan-cial third quarter ended 31 December 2018. Contributing over a third of group turnover that rose by 6% to Rs7.98 billion (US$98.1 million), Strides’ US business de-livered a “stellar performance”, with sales advancing by 6% to Rs2.85 billion.

The firm has also just announced plans to bolster its presence in the US, by in-creasing its stake in Vivimed to 100% and acquiring Vensun. “With the number


D E A L S

REGIONTHIRD-QUARTER SALES

(RS MILLIONS) CHANGE (%)PROPORTION OF TOTAL

(%)

US 2,850 +6 36

Australia 2,407 +2 30

Other Regulated Markets 1,254 +55 16

Institutional 871 -17 11

Africa 601 -4 8

Strides Pharma Science 7,984 +6 100

Breakdown by region of Strides Pharma Science’s sales in its financial third quarter ended 31 December 2018 (Source - Strides Pharma Science)

of corporate actions announced,” com-mented Kumar, “we are looking forward to a right-sized growth with improved mar-gins and strengthened balance sheet.”

He added that the firm was “particularly satisfied with the outcomes of our course-corrected strategy in the US market”. Strides last year outlined plans to adopt a “recalibrated strategy” in the US, with a fo-cus on launches through its own commer-cial front-end rather than through part-ners (Also see “Strides plans for US growth” - Generics Bulletin, 31 Aug, 2018.).

In its financial year to date, Strides filed 16 abbreviated new drug application (ANDA) submissions with the US Food and Drug Administration (FDA) and ob-tained 11 approvals.

Looking ahead, Strides maintained that growth in the US will be “driven by linearity in filings and approvals with significant up-side from the new strategic acquisitions”.

While Australian turnover was “flat” –

increasing by 2% to Rs2.41 billion – the firm maintained that this was “in line with seasonality” and “largely due to year-end channel de-stocking”.

‘Other regulated markets’ enjoyed a 55% sales rise to Rs1.25 billion, driven by portfo-lio and market expansion. The firm has just built out its Canadian presence by acquir-

ing 80% of Pharmapar in Canada; and ob-served a ramp-up in filings in South Africa.

This increase managed to offset declines in both Strides’ Institutional and African busi-nesses, which slid by 17% to Rs871 million and by 4% to Rs601 million respectively.

Published online 1 February 2019

Akorn Appoints Young To Executive Team And Adds Two To BoardGRACE MONTGOMERY [email protected]

A korn has named Christopher Young as its executive vice-pres-ident of global operations, re-

porting to president and chief executive officer (CEO) Doug Boothe. The US-based injectables and ophthalmics specialist has also added two new members to its board.

With 25 years of pharmaceutical expe-rience, Young most recently served as the executive vice-president of global opera-tions for Alvogen. Prior to that, he held the role of vice-president of operations in the US and India for Actavis.

Akorn said that Young brings to the firm “a strong history of US and global expertise in operations, supply chain, integration, re-mediation and operational excellence”. “His leadership and skills are well matched for the current challenges that the company is fac-ing with increased competition and a com-plex regulatory landscape,” Akorn stated.

“I am excited to have a leader of Chris’s cal-iber, with a track record of success in our in-dustry, to lead our operations organization as we revitalize Akorn,” commented Boothe.

At the same time, the firm has named Thomas Moore and Boothe as directors of the board. Moore “brings 35 years of stra-tegic and operational pharmaceutical in-dustry experience” as a former executive at Abbott, including as president of Hospira USA from 2009 until his retirement in 2014.

Stating that Moore “brings significant industry expertise to our board of direc-tors”, Boothe maintained that “his first-hand experience navigating complex regulatory environments will be a tre-mendous resource for the company”.

Boothe also revealed that Akorn had decided to engage PJT Partners as its financial advisor, AlixPartners as its op-erational advisor, and Cravath, Swaine & Moore as its legal counsel to “assist with the development of our business plan and engagement with key stakeholders”.

Boothe, former president of Impax’ generics division, was late last year ap-pointed as Akorn’s new chief after head Raj Rai decided to retire Also see “Akorn Selects Doug Boothe As CEO” - Generics

Bulletin, 21 Dec, 2018.). The news of Rai’s retirement came as Fresenius Kabi suc-cessfully pulled out of a planned US$4.75 billion merger with the US firm (Also see “Akorn’s Chief Steps Down After Losing Kabi Deal” - Generics Bulletin, 11 Dec, 2018.)

Soon after Boothe took the reins at the start of 2019, Akorn’s chief operating of-ficer, Bruce Kutinsky, stepped down from the role with immediate effect (Also see “Akorn’s Chief Operating Officer Heads For The Exit Days Into Doug Boothe’s Tenure” - Generics Bulletin, 8 Jan, 2019.)

The firm has also had several manu-facturing setbacks over the past year – in January 2019, Akorn received a warning letter from the US Food and Drug Admin-istration (FDA) for its US sterile manufac-turing plant in Decatur, Illinois (Also see “Akorn Hit With FDA Warning For Deca-tur Site In US” - Generics Bulletin, 10 Jan, 2019.), after being issued a 24-page ‘Form 483’ inspection report last July.




S T R AT E G Y

Pfizer Eyes Three Oncology Biosimilar Launches In 2019 As Sterile Injectables Problems PersistDEAN RUDGE [email protected]

P fizer is “looking forward” to launch-ing up to three oncology biosimi-lars this year and receiving as many

as four US Food and Drug Administration (FDA) biosimilar approvals, management told investors during the debut earnings call of newly-instated group chief execu-tive officer Albert Bourla.

Angela Hwang, group president of the newly-created Pfizer Biopharma-ceuticals Group, also doubled down on previous comments that the company anticipated more favorable dynamics in the oncology biosimilars space; in com-parison to its much-publicized strug-gles to garner US share for its inflamma-tion and immunology (I&I) biosimilar, Inflectra (infliximab-dyyb).

But while a surge in total biosimilar sales was a boon to Pfizer’s top line in 2018, led by Inflectra/Remsima across the globe, continued manufacturing sup-ply constraints affecting the company’s Sterile Injectables Pharmaceuticals busi-ness in the US mitigated sales growth.

These manufacturing and supply issues, in tandem with greater competition across the injectables portfolio, also led Pfizer to a near US$3 billion write down of generic sterile injectable assets, which were picked up through the company’s US$17 billion takeover of Hospira in September 2015.

FOUR APPROVALS AND THREE LAUNCHES IN 2019

By the end of this year, Pfizer believes it could augment its US biosimilars port-folio with the approval of biosimilars to Avastin (bevacizumab), Herceptin (trastuzumab) and Rituxan (rituximab). Of rituximab in the US, Hwang said, “Our plans are on track, and we are planning to launch [biosimilar] Rituxan in 2019. We look forward to receiving the approval and then planning for our launch.”

FDA approval for Pfizer’s biosimilar to Humira (adalimumab) could materialize in the final quarter of 2019; although a patent settlement with Humira sponsor AbbVie will keep Pfizer’s I&I biosimilar off

the market until November 2023.These four biosimilars “taken together

represent a potential blockbuster oppor-tunity for Pfizer,” Bourla said.

Hwang insisted that Pfizer’s experience with infliximab in the US “really is not a great analogy for what might be to come with our new oncology biosimilars, just because there are very different dynamics in the I&I space compared to the oncology space.”

The big difference in the I&I space in the US, Hwang said, was the exclusionary con-tracting practices of Remicade (infliximab) sponsor Johnson & Johnson, “which has really prevented and been a great impedi-ment to our ability to grow the I&I bio-similar. Rebates rather than net price have really driven, I think, formulary access,” Hwang opined. “And that has been a great barrier to our ability to grow.”

Pfizer, she reiterated, saw different dy-namics in the oncology space. “And that is because oncology drugs are shorter in duration of therapy, so that allows new patients to turn over faster. And it will make it easier for the physicians to initiate new patients on oncology biosimilars,” she said, providing customers with faster and greater cost savings.

EX-US BIOSIMILAR SALES SURPASS US$500M

With sales of Inflectra in the US more than doubling in 2018, from US$118 million in 2017 to US$259 million, Pfizer’s total bio-similar sales surged by 45% as reported to US$769 million; and by 41% on an opera-tional basis, excluding the impact of for-eign exchange.

More than US$500 million of biosimilar sales came from outside the US, the bulk being in developed European markets.

Pfizer comes into the new year on the back of two US biosimilar approvals and launches in 2018: Retacrit (epoetin alfa-epbx) and Nivestym (filgrastim-aafi). It also bagged a positive opinion from the European Medicines Agency’s (EMA’s) committee for medicinal products for hu-man use (CHMP) for its Zirabev (bevaci-

zumab) biosimilar to Avastin in December.Further down the road, however, Pfizer

earlier this month confirmed it had axed development of five pre-clinical biosimilar programs, as well as around 150 related staff, asserting that it saw better value in using research and development dollars for its innovative pipeline (Also see “Pfizer Axes Staff And Five Pre-Clinical Biosimilars To Fund Late-Stage Innovative Programs” - Generics Bulletin, 15 Jan, 2019.).

In 2018, the company’s research and development expenses, within its Essen-tial Health operating segment, fell by 11%, “primarily due to decreased spending for biosimilars as several programs have reached completion.”

SUPPLY ISSUES WILL “SIGNIFICANTLY IMPROVE”

Although Pfizer’s US Sterile Injectables busi-ness took a bit of a shellacking in 2018 – sales dropped by a fifth to US$2.43 billion – Bourla maintained that the company expected manufacturing and supply issues “to be sig-nificantly improved by the end of 2019.”

Meanwhile, he said, Pfizer continued “to expect this business to be a solid growth contributor in the future.”

On Pfizer’s corresponding fourth-quar-ter earnings call for 2017 a year ago, the company said in relation to the Hospira acquisition, “We were aware [of] manufac-turing issues that were confirmed during the due diligence process, but we have a robust action plan in place and we believe that we’ll make progress during 2018 to-wards reducing sterile injectable shortag-es, and that will include investing capital into those specific plants.”

At the tail end of last year, Pfizer’s warn-ing letter-stricken manufacturing facility


S T R AT E G Y

Global sales of Inflectra/Remsima leapt by 53% as reported to US$642 million in 2018, Pfizer reports, com-prising US$259 million in the US and US$383 million in other markets. US$319 million of this stemmed from Developed Europe markets, a rise of 22% year-on-year. Pfizer’s global non-infliximab biosimilar sales increased by 13% to US$127 million last year, the firm booking US$7 million in the US after launch-ing Nivestym (filgrastim-aafi) and Retacrit (epoetin alfa-epbx) towards the end of the year. The remaining US$120 million came, also, mostly from Developed Europe.

Benepali Surge And Imraldi Gains Drive Biogen Biosimilars Past US$500mDEAN RUDGE [email protected]

B ecoming the first company to offer the three main anti-TNF biosimilars across Europe, combined with en-

joying its most successful launch of a bio-similar, allowed Biogen to report biosimi-lar sales that crashed through the US$500 million barrier in 2018.

Sales boomed by 44% to US$545 million, driven by the launch of Imraldi (adalim-umab) in mid-October “in several European markets,” as well as strong gains for Bene-

pali (etanercept) and Flixabi (infliximab); the two other biosimilars Biogen sells in Europe on behalf of the Samsung Bioepis joint ven-ture between itself and Samsung BioLogics.

Biogen has increased its equity stake in Samsung Bioepis from around 5% to 49.9%, having last year exercised its option to do so at a cost of approximately US$700 million. (Also see “Samsung deal costs Biogen US$700mn” - Generics Bulletin, 6 Jul, 2018.)

In 2019, Massachusetts-based Biogen

expects double-digit revenue growth from its biosimilars business, “primarily driven by the launch of Imraldi.” More than 100,000 patients across Europe are currently being treated with Biogen biosimilars, according to the firm’s own data.

IMRALDI WON GERMAN SUPPLY CONTRACT

Turning over around US$17 million from Imraldi during the six weeks it was on the

in McPherson, Kansas – a former Hospira asset – was flagged for eight manufactur-ing deficiency observations by the FDA, including seven repeat observations (Also see “FDA Flags Up Repeat Issues At Pfizer’s McPherson Plant in Kansas” - Generics Bul-letin, 13 Dec, 2018.).

US$2.6BN TECHNOLOGY RIGHTS WRITTEN OFF

On the back of weakness in the US, global Sterile Injectables sales fell 8% as report-ed to US$5.21 billion. In non-US markets, Pfizer’s Sterile Injectables sales climbed by 5% as reported, and 3% on an opera-tional basis, to US$2.78 billion, driven by sales in emerging markets rising by 14% to US$1.73 billion.

But Pfizer recorded US$3.12 billion worth of asset impairment charges in 2018, up from US$395 million in the prior year, almost all of which stemmed from Hospira assets.

Write-offs comprised: US$2.6 billion re-lated to finite-lived developed technology rights; US$242 million related to finite-lived licensing agreements; and US$80 million re-lated to finite-lived in-process research and development. The remaining US$117 million related to a multi-antigen vaccine program.

“In 2018, the intangible-asset impairment charges associated with the generic sterile injectable products reflect, among other things, updated commercial forecasts, re-flecting an increased competitive environ-ment as well as higher manufacturing costs, largely stemming from ongoing manufac-turing and supply issues,” Pfizer commented.

NEWLY-ESTABLISHED THREE-TIER BUSINESS STRUCTURE EXPLAINED

Both biosimilars and sterile injectables now fall under the remit of the Pfizer Biopharmaceuticals Group, or PBG. Pfizer describes the business like this: “A sci-ence-based innovative medicines busi-ness, which includes all of the Innovative Health business units (except Consumer Healthcare) as well as a new Hospital business unit that commercializes Pfizer’s global portfolio of sterile injectable and anti-infective medicines. Pfizer also in-corporated its biosimilar portfolio into its Oncology and Inflammation & Immunol-ogy business units.”

Pfizer also now has a global, off-patent branded and generic established medi-cines business, called Upjohn. The name is a throwback to a portion of the for-mer Pharmacia business Pfizer acquired in April 2003: Pharmacia was created in April 2000, when the legacy Pharmacia & Upjohn business merged with Monsanto and Searle.

Upjohn includes the majority of Pfizer’s off-patent solid oral dose legacy brands, including Lyrica (pregabalin), Lipitor (atorv-astatin), Norvasc (amlodipine), Viagra (silde-nafil) and Celebrex (celecoxib), as well as certain generic medicines.

Pfizer announced the new three-busi-ness structure last July (Also see “Pfizer to divide firm into three businesses” - Generics Bulletin, 27 Jul, 2018.).


Breakdown by region of Pfizer’s biosimilar sales that increased by 45% to US$769 million in 2018 (Source - Pfizer)

Sales of Pfizer's Inflectra/Remsima InfliximabBiosimilar By Region In 2018; And Sales Of All Other

Biosimilars, Excluding Inflectra/RemsimaGlobal sales of Inflectra/Remsima leapt by 53% as reported to US$642 million in 2018, Pfizer reports,

comprising US$259 million in the US and US$383 million in other markets. US$319 million of thisstemmed from Developed Europe markets, a rise of 22% year-on-year. Pfizer's global non-infliximabbiosimilar sales increased by 13% to US$127 million last year, the firm booking US$7 million in theUS after launching Nivestym (filgrastim-aafi) and Retacrit (epoetin alfa-epbx) towards the end of the

year. The remaining US$120 million came, also, mostly from Developed Europe.

Inflectra/Remsima

40.34%

49.69%

3.74%6.23% US

Dev Europe

Dev Rest of World

Emerging Markets

Other Biosimilars

5.51%

81.10%

1.57%

11.81%US

Dev Europe

Dev Rest of World

Emerging Markets

Breakdown by region of Pfizer's biosimilar sales that increased by 45% to US$769 million in 2018 (source: Pfizer)

Inflectra/Remsima

Sales of Pfizer's Inflectra/Remsima InfliximabBiosimilar By Region In 2018; And Sales Of All Other

Biosimilars, Excluding Inflectra/RemsimaGlobal sales of Inflectra/Remsima leapt by 53% as reported to US$642 million in 2018, Pfizer reports,

comprising US$259 million in the US and US$383 million in other markets. US$319 million of thisstemmed from Developed Europe markets, a rise of 22% year-on-year. Pfizer's global non-infliximabbiosimilar sales increased by 13% to US$127 million last year, the firm booking US$7 million in theUS after launching Nivestym (filgrastim-aafi) and Retacrit (epoetin alfa-epbx) towards the end of the

year. The remaining US$120 million came, also, mostly from Developed Europe.

Inflectra/Remsima

40.34%

49.69%

3.74%6.23% US

Dev Europe

Dev Rest of World

Emerging Markets

Other Biosimilars

5.51%

81.10%

1.57%

11.81%US

Dev Europe

Dev Rest of World

Emerging Markets

Breakdown by region of Pfizer's biosimilar sales that increased by 45% to US$769 million in 2018 (source: Pfizer)

Biosimilars



I N T E L L E C T UA L P R O P E R T Y

market made it “our most successful first-quarter launch of a biosimilar,” the com-pany underlined.

“While it is too early to comment on specific share data, we can say that we are very pleased with Imraldi sales per-formance in the first quarter in the mar-ket, in many cases surpassing the initial rate of uptake from Benepali.”

In Germany, Imraldi entered the mar-ket with a list price that was just over 40% lower than the cost of the reference brand, AbbVie’s Humira, according to the associa-tion of statutory health insurance doctors for the North Rhine region, the KVNO. (Also see “Imraldi sets pace on German price cuts” - Generics Bulletin, 2 Nov, 2018.)

Biogen later won a nationwide supply contract for the biosimilar with Germany’s GWQ group of health insurance funds.

An agreement signed with AbbVie in April 2018 granted Biogen and Samsung Bioepis patent licenses for the use and sale of Imraldi in Europe, on a country-by-country basis; in return, the firms make royalty payments to AbbVie.

With sales ahead by three-tenths to US$485 million in 2018, the Benepali bio-similar to Amgen’s Enbrel (etanercept) “continues to be the market leader in coun-tries such as the UK, Denmark and Norway,” Biogen revealed, “and became the market leader in Germany in the fourth quarter.”

The remaining US$43 million stemmed

from sales of Flixabi, a near five-fold rise on the US$9 million reported for 2017.

In the crowded European infliximab mar-ket, Biogen competes with Sandoz’ Zessly, Pfizer’s Inflectra and the Remsima biosimi-lar marketed by Celltrion’s network of part-ners. All biosimilars reference Merck Sharp & Dohme’s (MSD’s) Remicade original.

Reporting second-quarter results last year, Biogen had warned that sales growth for its biosimilars was likely to slow in the second half of 2018, with pricing pressure projected to outweigh volume growth. (Also see “Biogen says sales will slow but lauds supply” - Generics Bulletin, 3 Aug, 2018.)


UK Disregards EPO’s Opinion On Everolimus Patent AIDAN FRY [email protected]

U K Patent Court Judge Sir Colin Birss has disregarded a European Patent Office (EPO) decision to

invalidate a method-of-use patent pro-tecting Novartis’ Afinitor (everolimus) in granting the originator an injunction against a generic version of the breast-cancer treatment that Dr Reddy’s is seek-ing to bring to the UK market.

Acknowledging that the EPO’s Opposi-tion Division had in September 2018 held invalid for added matter the key claim 1 of European patent EP2,269,603 – which covers combining rapamycin derivatives such as everolimus with exemestane to treat breast tumors, and expires in Febru-ary 2022 – Birss nevertheless issued an in-junction on the basis of Reddy’s allegedly infringing the ‘603 patent. Novartis has ap-pealed against the EPO’s invalidity finding.

Noting that Reddy’s already held a marketing authorization for everolimus with a full range of indications, including

treating breast tumors in combination with exemestane, Birss said the Indian firm intended to launch in the UK after a six-month pediatric extension to a sup-plementary protection certificate (SPC) linked to European patent EP0,663,916 expired on 17 January this year. (Also see “Everolimus SPC Expiries May Not Be End Of The Story” - Generics Bulletin, 9 Jan, 2019.)

The Indian generics specialist had already conceded infringement if the ‘603 use pat-ent was valid, but brought an invalidity de-fense on the sole ground of added matter.

However, Birss, in taking an opposite view to the EPO, said that on the basis of ev-idence before him “there was no arguable case that the patent was invalid”. The EPO’s Opposition Division had, he contended, taken “an unduly technical approach” that had lost sight both of the disclosure in the patent application as a whole, as well as of the prominence of ‘Compound A’ – everoli-mus – in that document.

EVEROLIMUS ‘SINGLED OUT’Noting that a review of added matter re-quired comparing the explicit and implicit disclosures offered to a skilled person by the patent application and granted pat-ent, Birss acknowledged that the applica-tion disclosed a wide class of rapamycin derviatives and a broad range of indica-tions. However, he said, everolimus in the

form of Compound A was “singled out”.“There is clear and unambiguous dis-

closure that the combination of the com-pounds [disclosed in the application] as a whole with aromatase inhibitors could be used for the breast-cancer indication,” Birss observed, adding that exemestane was specifically identified as such an aromatase inhibitor. Thus, the combination in claim 1 of the ‘603 patent was “expressly taught”.

Having taught that the class of rapamy-cin derivatives could be combined with aromatase inhibitors such as exemestane to treat breast cancer, the application also specifically pointed to everolimus, or Compound A, as “the paradigm rapamy-cin derivative to choose”.

Turning to how commercial evidence supported Novartis’ motion for an injunc-tion, as well as the counterclaim for revo-cation tabled by Reddy’s, Birss concluded

“There is a real risk of unquantifiableharm either way”



that “since there is a real risk of unquanti-fiable harm either way” – to Novartis from “irrecoverable price depression” after ge-neric entry, and to Reddy’s from losing its “first-mover advantage” – “the right thing to do is to grant an interim injunction”.

RESTRAINT COVERS LAWFUL INDICATIONS

Having decided to grant an injunction, Birss then addressed the form his order would take. The suggestion from Reddy’s that the order carve out sales for non-in-fringing indications other than breast can-cer “just stores up trouble for the future”, he decided, especially as “the breast-cancer indication represents 90% of the UK mar-ket for everolimus”. In drawing a “clear line” on what was prohibited, Birss recognized that “I am restraining Dr Reddy’s from sup-plying some product which would be used lawfully for indications outside the claim”.

On a proposal from Reddy’s that the UK’s Department of Health or National Health Service (NHS) be parties to cross-under-takings as bodies that would bear the cost of paying brand rather than generic prices during the injunction, Birss pointed out that neither the Department nor any NHS trust was before the court. But while he re-fused to extend the cross-undertaking to include them, he pledged to write to the Department and other relevant entities to invite them to join the case.

Birss also offered to hear the litigating parties on whether the court “should be writing a letter to the Boards of Appeal of the EPO to invite them to expedite the opposition appeal proceedings having regard to the existence of national in-fringement proceedings”.

Of Novartis’ global Afinitor/Votubia sales that rose by 2% to US$1.56 billion last year, US$929 million came in the US, where the Court of Appeals for the Fed-eral Circuit recently overturned a dis-trict court’s decision that US everolimus compound patent 5,665,772 was invalid for obviousness-type double patenting. The ‘772 patent is scheduled to expire on 9 March 2020, including a six-month pediatric extension. (Also see “Brecken-ridge, Endo and Hikma’s Advantage On Everolimus Is Snatched Away On Appeal” - Generics Bulletin, 10 Dec, 2018.)


Dutch Court Departs From German Position On PemetrexedAIDAN FRY [email protected]

S andoz has failed to convince a re-gional court in the Netherlands that European patent EP1,313,508

protecting Lilly’s Alimta oncology brand is invalid in light of prior art.

In upholding the validity of the ‘508 patent covering combinations of peme-trexed with folic acid and vitamin B12, the regional court in The Hague knowingly departed from a determination by Ger-many’s federal patent court last year to re-voke the patent that ran until 2021. (Also see “Germany invalidates patent on peme-trexed” - Generics Bulletin, 27 Jul, 2018.)

Acknowledging the “different out-come” in the German proceedings, the Hague court pointed out that the federal patent court had based its finding of lack of inventive step in part on different prior art to that cited in the Dutch dispute. The Hague court also noted that it “expected soon” to hand down its verdict in Lilly’s suit versus Fresenius Kabi over infringe-ment of the ‘508 patent.

SANDOZ CITED A RANGE OF PRIOR ART

Sandoz relied on a variety of prior-art references to support its lack-of-novelty argument, including: a Worzalla abstract and study on the effects of folic acid on tumors in mice; a Jackman book on using anti-folate drugs in cancer therapy; and a Calvert article on the toxicity of anti-folate cancer agents.

On Worzalla, the Hague court found that Sandoz had “not explained in any way” what a skilled person would have taken from the researchers knowing that the mice’s feed contained vitamin B12. Thus, the key claims of the ‘508 patent must be considered to be new.

“Sandoz’ primary inventiveness attack takes Jackman as the starting point,” the court observed, summarizing the ge-nerics firm’s argument as being that the book revealed the combination of peme-trexed and folate, while a skilled person would have had “a reasonable expecta-tion of success” of adding vitamin B12 to

alleviate the side effects of pemetrexed.But the Hague court was persuaded

by Lilly’s counterargument that, by the priority date of the ‘508 patent around three years after Jackman was published, a skilled person would have looked be-yond Jackman and considered follow-up studies that showed using folic acid would impede the efficacy of peme-trexed, requiring higher doses to be ad-ministered. The court ordered Sandoz to pay legal costs of €300,000 (US$342,200) plus interest.


“Acknowledging the different outcome

in the German proceedings, the

Hague court pointed out that the federal

patent court had based its finding of

lack of inventive step in part on different

prior art”


West and the diamond logo, Westar and AccelTRA are trademarks or registered trademarks of West Pharmaceutical Services, Inc., in the United States and other jurisdictions.

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West and the diamond logo, Westar and AccelTRA are trademarks or registered trademarks of West Pharmaceutical Services, Inc., in the United States and other jurisdictions.

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Biosimilars Begin To ‘Pay Off’ For BioconANJU GHANGURDE [email protected] DEAN RUDGE [email protected]

B iocon reaped strong gains in its financial third quarter as its biosimilars portfolio gained traction in several markets and the Indian firm underscored that it isn’t

perturbed by ongoing commentary around the commercial viability for biosimilars in the US.

Biocon and partner Mylan’s Fulphila (pegfilgrastim-jmdb), a biosimilar to Amgen’s Neulasta that Mylan launched in the US last July, continued to gain market share, while sustained sales momentum for products like biosimilar trastuzumab in Latin America and Africa, Middle East and Turkey (AFMET) contrib-uted to the strong showing.

“Our biosimilars strategy is beginning to pay off with the launch of our biosimilars in the US and EU and we are greatly encouraged by the recent regulatory approvals of other key biosimilars in in global markets,” Biocon chair, Kiran Mazumdar-Shaw said on the company’s earnings call.

Sales from Biocon’s biologics segment, comprising bio-similars and novel biologics, more than doubled to Rs4.49bn (US$63.3 million), a rise of 136%; and the segment recorded an earnings before interest and tax (EBIT) margin of 30%, driven

by increased penetration of pegfilgrastim in the US. Biocon and Mylan’s Semglee (insulin glargine) biosimilar was

launched in the European Union (EU) during the quarter, as well as in South Korea under the Glarzia name; while their Ogivri (trastu-zumab) biosimilar, which received a marketing approval from the European Commission, is now “ready for launch” in Europe.

Mylan has also commercialized biosimilar adalimumab in-li-censed from Fujifilm Kyowa Kirin Biologics in the EU, with Biocon receivings an undisclosed ‘economic benefit’ in this deal.

Overall sales for Biocon’s financial third-quarter ended 31 De-cember 2018 rose 43% to Rs15.7bn, an increase that enabled the firm’s pre-tax profit to soar by 93% to Rs2.89 billion.

“We have delivered the highest ever revenue and profit growth in absolute terms,” Biocon underlined.

NO US HEADWIND SEEN Mazumdar-Shaw also indicated that Biocon intends to stay the course in developing biosimilars for the US despite signs of a pullback in the space by some players amid challenging market dynamics.

Biocon, she maintained, remains “very committed” and en-couraged by the “kind of noises and voices” it is hearing about the “absolute need” for developing biosimilars to help US payers “balance” their healthcare spend.

“And I think they do see biosimilars as a very integral part of health economics as they did with generics. So, I don’t see any headwind for us in terms of developing biosimilars for the US market.” Mazumdar-Shaw said in response to an analyst’s query.

The company, she added, remained committed to increasing and expanding its pipeline of biosimilar products under devel-opment with partners Mylan and Sandoz – the latter for the so-called ‘next wave’ of immunology and oncology biosimilars – in addition to its own portfolio going forward.

“I don’t think we are seeing any kind of negative signals from the US market,” Mazumdar-Shaw reiterated.

FULPHILA TRACKING AS PER PLAN The Biocon top brass was, however, measured about specifics on the progress made by Fulphila in the US and expectations around how pricing dynamics could play out.

Biocon’s chief executive officer and joint managing director, Arun

Biocon's Sales By Business Segment In Its FinancialThird Quarters Ended 31 December 2016, 2017 And

2018Having suffered a sales decline in its financial third quarter ended 31 December 2017, Biocon's

Biologics business, comprising biosimilars and novel biologics, roared back to growth in the thirdquarter of the Indian firm's 2019 financial year. Key developments included the launch of the Mylan-partnered Fulphila (pegfilgrastim-jmdb) biosimilar in the US; as well as the firms' Semglee (insulinglargine) biosimilar in the European Union. Another highlight for Biocon was its Small Molecules

APIs and generic formulations business delivering 27% sales growth to Rs4.69 billion - thanks in partto the launch of atorvastatin tables in the US and continued gains from rosuvastatin and simvastatin.

"We recorded an increase in API sales in Latin America, Europe and to India-based customersdelivering to the US market," Biocon noted.

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

FY17 Q3 FY18 Q3 FY19 Q3

Rs2.22bnRs1.90bn

Rs4.07bn

Rs1.23bnRs1.56bn

Rs2.12bn

Rs3.32

Rs3.88

Rs4.67

Biologics Small Molecules Branded Formulations Research Services

Breakdown by business region of Biocon's sales in its financial third quarter ended 31 December 2018 (source: Biocon). All figuresare rounded to the nearest ten million rupees.

Having suffered a sales decline in its financial third quar-ter ended 31 December 2017, Biocon’s Biologics busi-ness, comprising biosimilars and novel biologics, roared back to growth in the third quarter of the Indian firm’s 2019 financial year. Key developments included the launch of the Mylan-partnered Fulphila (pegfilgrastim-jmdb) biosimilar in the US; as well as the firms’ Semglee (insulin glargine) biosimilar in the European Union. An-other highlight for Biocon was its Small Molecules APIs and generic formulations business delivering 27% sales growth to Rs4.69 billion - thanks in part to the launch of atorvastatin tables in the US and continued gains from rosuvastatin and simvastatin. “We recorded an increase in API sales in Latin America, Europe and to India-based customers delivering to the US market,” Biocon noted.

Breakdown by business region of Biocon’s sales in its financial third quarter ended 31 December 2018 (Source - Biocon). All figures are rounded to the nearest ten million rupees.



S T R AT E G Y

Chandavarkar, maintained that Fulphila was “tracking to plan,” with “good growth” month-on-month in terms of market share gains.

“It’s going exactly as we had anticipated; the numbers are in the public domain. We had indicated that of the covered market of syringes, we are seeing traction month-on-month and at this stage we are somewhere in the mid-teens,” Chandavarkar said on the earnings call.

To an analyst’s question on the outlook for price erosion as more players enter the fray for biosimilars, Chandavarkar said that, over time, prices would come down; but how rapidly they declined depended on markets, tenders or retail, the number of competitors and the “psychology” of the competitors, “whether people are keen to gain volume at the cost of eroding value or people want to sustain market share.”

“It’s a very dynamic place and too early to hazard a guess in

terms of specific guidance. I don’t think there’s enough experi-ence out there unlike the abbreviated new drug application (ANDA) business to say exactly what the trend would be,” Chan-davarkar added.

The Indian firm also noted how Coherus, which recently launched its pegfilgrastim in the US, also publicly announced that its whole-sale acquisition cost (WAC) would be at the same level as Mylan.

Coherus’ biosimilar pegfilgrastim Udenyca (pegfilgrastim-cbqv) was launched at a list price of $4,175 – 33% lower than the reference product’s undiscounted cost and on par with pricing for Fulphila (Also see “Coherus BioSciences Outlines ‘Very Different Approach’ And Raises Another US$75m To Launch Udenyca” - Ge-nerics Bulletin, 11 Jan, 2019.)


PBMs Propose Pro-Industry Policies Amid Pricing PressureAIDAN FRY [email protected]

L ong-held targets for the US off-patent industry, such as shorter data exclusivity for original biologics, identical non-proprietary naming for biologics and biosimilars and

eliminating abuse of safety programs that restricts access to drug samples, are among a raft of policy ideas that America’s pharmacy benefit managers (PBMs) are putting forward as solu-tions to controlling prescription drug costs.

On biologic drugs, the PBM’s Pharmaceutical Care Manage-ment Association (PCMA) is calling for the data exclusivity pe-riod for reference biologic drugs to be reduced from 12 to seven years. This curtailed protection would, it contends, “still provide a sufficient return” for originators, “while also speeding more af-fordable biosimilars to market”.

Former President Barack Obama’s administration had consis-tently pushed for seven-year exclusivity for biologics, but ulti-mately bowed to originator pressure to allow a 12-year term as part of a raft of compromises reached to push through the ‘Obam-acare’ Affordable Care Act (ACA).

“Use of different names will only create confusion among pa-tients and providers and inhibit prescribing of biosimilars” - PCMA

Abuses of orphan-drug exclusivities, through which originators are gaining protection for “blockbuster drugs with script volume in the tens of millions”, must also be tackled. “Orphan exclusivity peri-ods should apply to only those drugs originally approved by the US Food and Drug Administration (FDA) under an orphan indication and only for the orphan indication itself,” the association insists.

Biosimilar labelling and naming should be improved, the PCMA advises in letters sent to several congressional commit-tees in advance of hearings on prescription drug costs and pric-ing. “Substitutable biosimilars should bear identical names and labels to their innovator analogs,” the PBM’s body argues. “Use of different names will only create confusion among patients and providers and inhibit prescribing of biosimilars.”

While the FDA continues to be an international outlier in as-signing four-letter suffixes to the non-proprietary names of all biosimilars and some novel biologic drugs, the agency’s ap-proach has found some support. Proponents claim that the suf-fixes are an aid to pharmacovigilance.

AMGEN-SPONSORED ARTICLE SUPPORTS DISTINCT NAMESIndeed, an Amgen-sponsored review article recently published in the Generics and Biosimilars Initiative Journal (GaBi) stresses “the need for distinct nomenclature for originator and biosimilar products”. “Distinguishable suffixes for biologicals will allow better product tracking and awareness around product effectiveness/outcomes, which ultimately will strengthen physician and patient comfort with biosimilars,” the authors from companies including Parexel and Syneos Health assert. “Early data belie the notion that the US differential naming approach hinders the possibility of a favorably biosimilar marketplace and the ability for a biosimilar sponsor to compete successfully.”

In the small-molecule generics sector, the PCMA recommends encouraging greater use of generics among people enrolled in the Medicare Part D low-income subsidy. “Allowing plans to lower gener-ic cost-sharing for these beneficiaries would save money for benefi-ciaries, taxpayers and the Medicare program,” the association main-tains, pointing out that the Medicare Payment Advisory Commission (MedPAC) had already recommended lower cost-sharing for generics and raised enrolee costs for brands subject to generic competition.

URGES PASSAGE OF CREATES ACT TO AID SAMPLES ACCESSPicking up on another industry bugbear, the PCMA appeals to legislators to eliminate abuse of risk evaluation and mitigation strategies (REMS). A “small minority” of originators, it says, are us-ing such safety programs as an excuse to withhold product sam-ples needed by generic and biosimilar developers. Such abusive


H E A D L I N E N E W SR E G U L AT I O N

Wockhardt Slides To Loss Amid US Oncology PushAIDAN FRY [email protected]

Wockhardt’s pre-tax loss increased more than sevenfold to Rs1.21 billion (US$17.0 million) in the Indian firm’s

financial third quarter ended 31 December 2018. The profit slide came despite 4% group turnover growth to Rs10.5 billion on a 29% lo-cal-currency rise in the US.

The group maintained its gross margin at 56%, but its staff costs increased by 8% to Rs2.20 billion and research and development spending advanced by just over a quarter to Rs790 million. As a result, research and develop-ment spending as a percentage of sales reached 7.6%, up from 6.2% in the prior-year period.

Higher interest costs and expenses due to exchange-rate fluctuations also contributed to the company’s pre-tax loss surging from Rs160 million in the prior-year period.

“Costs of ongoing remedial measures also continued to impact profitability,” Wockhardt acknowledged. The Indian group is con-tinuing to address deficiencies highlighted by the US Food and Drug Administration (FDA) at several of its production sites, in-cluding at key plants in India that are subject to US import alerts.

The Indian firm obtained just one abbreviated new drug ap-plication (ANDA) approval between April and December last year, leaving 70 ANDAs pending approval. However, using an Indian contract manufacturer, Wockhardt recently secured FDA approv-al for its imatinib mesylate 100mg and 400mg tablets, generic equivalents to Novartis’ Gleevec leukemia brand, and intends to launch “in a short period of time”.

“Wockhardt is building a portfolio of oncology products in the US and has several pending ANDAs for oncology products,” comment-ed the group’s founder, chairman and CEO, Habil Khorakiwala. “On-cology and other specialty products have always been a priority area for our US business and this product will further boost this focus.”

US TURNOVER ADVANCED BY 39% AS REPORTED

New product launches from third-party manufacturing sites and “increased market share” for some of its US portfolio pushed up the Wockhardt US operation’s reported sales by 39% in its third quarter to Rs2.43 billion, equivalent to 23% of group turnover.

The Indian group generated just over a third of its turnover in its domestic market, where sales slipped by 7% to Rs3.63 billion. Emerging markets contributed about 12% of group turnover with sales ahead by 15% to Rs1.25 billion.

Another three-tenths of turnover came from Europe, where sales slid by 4% on weakness in the UK and Ireland. Turnover in the UK declined by 6% as reported, and 13% in local-cur-rency terms, to Rs2.48 billion. Irish sales fell by 16% as report-ed, and by 23% in euros, to Rs350 million. Those reverses were mitigated slightly by French sales strengthening by 15% to Rs150 million.


Wockhardt's Sales SplitGains in the US and Emerging markets more than compensated for declines in Europe and Indiaduring Wockhardt's financial third quarter ended 31 December 2018

Third Quarter

Third Quarter

34.70%

30.11%

23.23%

11.95%

India Europe US Emerging Markets

Nine Months

Nine Months

38.14%

30.41%

19.25%

12.20%


Wockhardt's sales in its financial third quarter and nine months ended 31 December 2018, rounded to the nearest Rs10 million

Wockhardt's Sales SplitGains in the US and Emerging markets more than compensated for declines in Europe and Indiaduring Wockhardt's financial third quarter ended 31 December 2018

Third Quarter

Third Quarter

34.70%

30.11%

23.23%

11.95%


Nine Months

Nine Months

38.14%

30.41%

19.25%

12.20%


Wockhardt's sales in its financial third quarter and nine months ended 31 December 2018, rounded to the nearest Rs10 millionWockhardt’s sales in its financial third quarter and nine months ended 31 December 2018, rounded to the nearest Rs10 million

practices could, it proposes, be prohibited by passing the draft Creating and Restoring Equal Access to Equivalent Samples (CRE-ATES) or similar legislation.

Perhaps less welcome to industry is the PBMs’ plan to curtail companies’ freedom to settle patent litigation by eliminating so-called ‘pay-for-delay’ agreements; whereby there is a transfer of some element of value from the patent holder to the generic challenger as part of a deal that delays generic competition until a future date.

Passing the CREATES Act and combating patent abuse by orig-inators were among six policy proposals recently put forward by US off-patent industry body the Association for Accessible Medi-cines (AAM). The other four were: reducing out-of-pocket costs for low-income seniors; eliminating the penalty on generics in Medicaid; clearing the way for biosimilars in the US; and increas-

ing access to affordable medicines in trade agreements.To highlight both these six policy ideas, as well more generally

the value that generics and biosimilars create for the US health-care system, among lawmakers, the AAM has recently launched a ‘Prescription for Savings’ campaign that includes television spots and videos on media channels such as YouTube.

Setting out statements for the record as the Congress hear-ings took place, the AAM stressed that the US generics market was “fundamentally different” to that for patented brands, given the lack of direct price competition in the latter. Rising brand prices and lower generics prices had led to brands accounting for 77% of all prescription-drug spending, despite only account-ing for one in 10 prescriptions filled in the US, it observed.




S T R AT E G Y

Amgen Eyeing ‘Sustainable Opportunities’ In Non-US Biosimilars MarketsDEAN RUDGE [email protected]

Amgen’s biosimilars strategy in non-US markets is to focus on larger markets with “a more balanced dynamic and sustain-able opportunity,” ahead of markets “experiencing strong

uptake at more discounted pricing levels,” management says.News of the company’s approach came as Amgen broke new

ground by reporting biosimilar sales for the first time: the launch of the firm’s Kanjinti (trastuzumab) and Amgevita (adalimumab) biosimilars in European markets brought in US$34 million in the fourth quarter of the year; for a total of US$55 million in 2018.

The US-based player is also continuing to throw its support be-hind the nascent US biosimilars market, insisting, “While some have speculated as to the strength of the biosimilar market in the US, we see biosimilars representing an important market for the future.”

INCREMENTAL CONTRIBUTION FROM TENDER MARKETS EXPECTED Discussing Amgen’s global biosimilars business during its 2018 fourth-quarter earnings call, head of global commercial operations Murdo Gordon noted, “Our European launches for Kanjinti and Amgevita are underway. While it’s still early in the launch cycle, the market is playing out as we anticipated, and we’re pleased with our performance to date.”

The US$55 million of sales in 2018, from a baseline of zero, rep-resented a sliver of total Amgen revenues that increased by 3% to US$22.5 billion last year.

Outside of the US, Gordon said, Amgen saw “important differences between products and markets in terms of biosimilar uptake and price erosion. Recent launches in markets such as Norway and the Nether-lands are experiencing strong uptake at more discounted pricing lev-els; while in other, larger markets including Germany and France, there is a more balanced dynamic and sustainable opportunity.

“Our strategy is to focus primarily on these more sustainable mar-kets, which we expect will drive our biosimilar revenues in the next several years,” Gordon underlined. “We also expect incremental contri-bution from competing selectively in certain tender driven markets.”

PATIENTS SCREENED FOR SOLIRIS BIOSIMILAR In Europe, Amgen confirmed, it had recently submitted a mar-keting authorization application to the European Medicines Agency (EMA) for its ABP 710 biosimilar to Remicade (infliximab).

This was on the heels of a biologics license application filed with the US Food and Drug Administration (FDA) in December.

Also, in the US, Amgen revealed that it late last year resubmitted its application for Kanjinti, following receipt of an FDA complete re-sponse letter last year. The company anticipates a six-month review.

“ABP 798, our biosimilar Rituxan (rituximab), met all of its primary and secondary end points in a Phase III trial in patients with rheu-matoid arthritis,” noted David Reese, vice-president of research and development. “And we anticipate the completion of the second Phase III trial in non-Hodgkin’s lymphoma later this year.”

Furthermore, Amgen has also begun screening patients in the

Phase III study of ABP 959, its biosimilar to Soliris (eculizumab). “We expect enrolment to begin anytime now,” noted chief finan-cial officer David Meline. “The launch of the trial was really predi-cated on regulatory discussions that we have around the world to agree on the appropriate design, endpoints and approvability.”

Chairman and chief executive officer Bob Bradway said Amgen was “in pretty good shape” over biosimilar eculizumab, not least because the company had recently received a favorable decision in challenging a Soliris patent in the European Union (EU). An Amgen spokesperson explained to Generics Bulletin, “Last week, Amgen par-ticipated in an opposition hearing that resulted in the revocation of a 2027-expiring EU patent directed to the Soliris dosage form.”

EUROPEAN NEULASTA TO ERODE BY MORE THAN 25% Despite the entry of Mylan and Biocon’s Fulphila (pegfilgrastim-jmdb) biosimilar to Amgen’s Neulasta (pegfilgrastim) in the US last July, Gordon revealed that Amgen had exited the fourth quarter of 2018 maintaining a 96% share of the long-acting fil-grastim market, with Amgen’s proprietary Onpro on-body injec-tor holding a “majority share, at over 60%.”

Acknowledging Coherus BioSciences’ Udenyca (pegfilgrastim-cbqv) that launched on 3 January, Gordon said, “Our guidance anticipates the possibility for other competitors to enter the US during 2019.”

Biocon management recently told investors that Fulphila was “track-ing to plan,” with “good growth” month-on-month in terms of market share gains. “It’s going exactly as we had anticipated. We had indicated that of the covered market of syringes, we are seeing traction month-on-month and at this stage we are somewhere in the mid-teens.”

In Europe, Gordon pointed out, Amgen now faced competition from three pegfilgrastim biosimilars, which had all launched “over the last four months:” further competition in 2019 is also anticipated.

Five players – Accord, Cinfa/Mundipharma, Coherus, Mylan/Biocon and Sandoz – currently hold pan-European marketing authorization approvals for biosimilar pegfilgrastim products.

“Consistent with our long-held expectations related to Europe, with numerous competitors launching in a short time window,” Gor-don said, “we expect European sales to decline over 25% year-over-year. More broadly, with the uncertainty over the eventual number of competitors on a global basis and their launch timing there is a range of possible outcomes for Neulasta in 2019.”

Management revealed uncertainty over the end results of ongo-ing patent litigation over Amgen’s Sensipar (cinacalcet). Teva briefly launched a generic and quickly took it off the market after reaching a settlement with Amgen, announced at the beginning of this year.

“With regard to Sensipar, we’re confident in the strength of our intellectual property. However, uncertainty as to the timing and intensity of competition will remain until the outcome of litigation becomes clear,” Meline said.




US Appeals Ruling Extends Life Of Some PatentsAIDAN FRY [email protected]

G enerics developers in the US may have to wait longer to enter the market after the US Court of Appeals for the Fed-eral Circuit handed down a ruling that will help origina-

tors to extend their monopolies through patent-term adjustments (PTAs). In handing to Supernus Pharmaceuticals and partner United Therapeutics an additional 546 days of patent life, appeals judges Timothy Dyk, Jimmie Reyna and Alvin Schall reversed and remanded a Virginia district court’s decision to award summary judgement to the US Patent and Trademark Office (USPTO).

Supernus’ dispute with the USPTO centred on US patent 8,747,897, which is entitled ‘Osmotic drug delivery system’ and to which United is the exclusive licensee. The ‘897 patent derived from simultaneous US and international patent applications that Supernus submitted in April 2006, with the USPTO issuing the patent on 10 June 2014, almost three years after the European Patent Office (EPO) had issued an equivalent patent, EP2,010,189.

Dates of particular relevance in the case included: 22 February 2011, on which Supernus filed a request for continued examina-tion (RCE), permitting the USPTO examiner to consider additional information following an initial rejection; and 29 November 2012, the date on which Supernus informed the USPTO via a supple-mental information disclosure statement (IDS) about opposition proceedings against the European ‘189 patent brought by Sandoz.

PATENT-TERM ADJUSTMENT WAS REDUCED BY 646 DAYSBased on the 646-day gap between these two events, the USPTO reduced Supernus’ PTA for the ‘897 US patent by the 646 days to 1,386 days. This was to reflect the applicant’s delay in prosecut-ing the patent.

Appealing against the Virginia district court’s summary judg-ment that the USPTO had acted accordingly in reducing the PTA due to applicant delay, Supernus argued that it could not have taken any efforts to conclude prosecution of its US patent ap-plication during the 546-day period between filing its RCE on 22 February 2011 and the EPO’s notifying Supernus of Sandoz’ op-position on 21 August 2012. The originator conceded that it failed to engage in ‘reasonable efforts’ to prosecute its US application in the 100 days between getting EPO notification on 21 August 2012 and submitting its IDS to the USPTO on 29 November 2012.

“On the basis of the plain language of the statute, we hold that the USPTO may not count as applicant delay a period of time during which there was no action that the applicant could take to conclude prosecution of the patent.” - Judge Jimmie Reyna

Writing for the appeals panel, Reyna said the district court had erred in applying the Court of Appeals’ Gilead ruling on the PTA statute to the Supernus’ case. “Gilead simply did not address the pre-condition – failure to engage in reasonable efforts – at issue here,” he stated, identifying the “precise question” at issue in the present case as: “Whether the USPTO may reduce PTA by a pe-riod that exceeds the ‘time during which the applicant failed to engage in reasonable efforts to conclude prosecution.’”

“On the basis of the plain language of the statute,” Reyna ad-

judicated, “we hold that the USPTO may not count as applicant delay a period of time during which there was no action that the applicant could take to conclude prosecution of the patent.” “Do-ing so,” he pointed out, “would exceed the time during which the applicant failed to engage in reasonable efforts.”

“The USPTO’s interpretation of the statute would unfairly pe-nalize applicants, fail to incentivize applicants not to delay, and fail to protect applicants’ full patent terms,” Reyna objected.

ADDS AROUND 18 MONTHS TO PATENT TERM FOR ORENITRAMLaw firm Wilson Sonsini Goodrich & Rosati, which represented Supernus in the case, said the Court of Appeals’ decision had giv-en the originator an additional one-and-a-half years of patent life for the Orenitram (treprostinil diolamine) pulmonary hyperten-sion drug marketed by United. The Orange Book maintained by the US Food and Drug Administration (FDA) lists the ‘897 patent as protecting the extended-release tablets until 8 October 2029.

Reacting to the Court of Appeals’ verdict, law firm Finnegan, Hen-derson, Farabow, Garrett & Dunner argued that “this opinion serves as a reminder to all patent owners to review the USPTO’s PTA calcu-lation and, if you disagree, act quickly to preserve your rights”.

“Check PTAs awarded in recently issued cases to determine wheth-er your facts match those of Supernus and whether days that were docked do not in fact stem from a ‘failure to engage in reasonable efforts’,” it advised, pointing out that patent holders had two months from a patent issuing to request a reconsideration by the USPTO.


“On the basis of the plain language of the statute, we hold that the USPTO may not count as applicant delay a period of time during which there was no action that the

applicant could take to conclude prosecution of the patent.” - Judge Jimmie Reyna


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