enerics ulletin nforma...a comprehensive search, Doug quickly rose to the top of the list due to his...

11 January 2019No.381

Pharma IntelligenceInformaBulletin

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

PRECEDEX

Fresenius Kabi eyes Precedex Premix (dexmedetomidine) market as US court axes two patents, p. 14

AKORN

Akorn has named Doug Boothe as president and chief executive officer, effective 1 January 2019, p. 4

CANADA

Canada’s Competition Bureau closes probe into access to samples, which began in November 2016, p. 10

Hetero’s Amarox Expands In Europe By Acquiring Tarbis From Spain’s FerrerDEAN RUDGE [email protected]

H etero’s European Amarox sub-sidiary has secured a “seamless entry” into the retail, hospital and

tender businesses in Spain by acquiring Tarbis Farma from the Barcelona-based Ferrer group for an undisclosed sum.

With a “robust product portfolio and an extensive marketing network with well-experienced personnel in the retail busi-ness across Spain,” Tarbis provides Amarox a “strong front-end marketing presence” in the region, according to the Indian firm.

“The company has currently over 225 marketing authorizations,” a Hetero spokes-

person told Generics Bulletin, turning over around €11 million (US$12.6 million) per year. Ferrer says that it “entered the generic drug market with its Tarbis brand in 2000.”

HETERO TO FORAY INTO EU GENERICS AND BRANDED GENERICS

“We are predominantly recognized as a leading active pharmaceutical ingredient (API) player around the world and known for introducing first-time generics in markets. Europe has been one of the key markets for Hetero,” the spokesperson

noted. “This acquisition will enable us to foray into the generics/branded generics market in Europe through our subsidiary.”

IMPROVING COGS AMONG HETERO PRIORITIES

Hetero revealed that it had a three-prong strategy to “turn around” Tarbis, includ-ing lowering the firm’s cost of goods sold (COGS). “All products of Tarbis are [current-ly] manufactured in the European Union (EU), hence COGS are high,” Hetero noted.

Meanwhile the firm says that it will grow Tarbis’ portfolio by launching new prod-ucts, with two ‘day one’ launches set for 2019; and also plans to “aggressively in-crease” Tarbis’ market share.

A V Narasa Reddy, executive director of Hetero Labs, said that the acquisition “fits very well with Hetero’s growth strategy in EU,” as well as serving as a platform in Eu-rope for the company’s existing portfolio and pipeline of products.

AMAROX ALREADY HAS OFFICES IN THE UK AND GERMANY

Hetero notes that Amarox is continuing to set up locations across the EU, with offices already established in the UK and Germany.

In Europe, the Indian firm’s Hetero Eu-rope subsidiary, which is also based in Barcelona, currently submits applications for registration, as well as assisting part-ners with European submissions. “Our aim is to develop, compile and submit more than 20 dossiers annually, lever-aging Hetero’s vast portfolio from other markets across the globe,” the firm has previously stated.

Published online 2 January 2019

2 | Generics Bulletin | 11 January 2019 © Informa UK Ltd 2018

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I N T H I S I S S U E

from the [email protected]

Happy New Year! We hope that our readers have enjoyed the closing days of 2018 and have already begun making a positive start to 2019.

As you will see from the contents of this issue, the generics, biosimilars and value-added medi-cines industries never stop moving – meaning that despite many of us enjoying a short break and a chance to catch our breath in recent weeks, there are still plenty of recent developments to catch up on as we kick off the new year.

The first days of January brought a key deal for Hetero in Spain, with the Indian firm’s Am-arox subsidiary securing entry into the Spanish market through acquiring local player Tarbis Farma from the Ferrer group (see front cover). Shortly after, Kashiv Pharma announced a deal for Adello Biologics in the US (p.11)

These followed hot on the heels of biologics alliances in late December for both Sandoz and Fuji Pharma (p.5), reminding us that the deal-making environment in the world of generics and biosimilars never stays still for long.

Meanwhile, Akorn is heading into 2019 under new leadership after appointing Doug Boothe to take over as chief executive officer from Raj Rai (p.4). And Teva has set out plans to move its global headquarters in Israel from Petah Tikva to Tel Aviv, as part of an ongoing transformation of the company that has been spearheaded by chief executive officer Kåre Schultz (p.6).

In the world of biosimilars, the latest data pub-lished by Italian off-patent industry association Assogenerici has revealed the positive impact of competition on rituximab over the past 18 months (p.7), while Belgium is seeing construc-tive messaging from local medicines authorities and health insurers promoting the benefits of biosimilar competition (p.12).

And in the US, patent litigation continues to throw out both wins and losses for the generics industry, with Fresenius Kabi enjoying a triumph on dexmedetomidine (p.14) at the same time as Aurobindo failed on an inter partes review chal-lenge to extended-release metformin (p.15).

genericsbulletin.pharmaintelligence.informa.com 11 January 2019 | Generics Bulletin | 3

inside:

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COVER / Hetero’s Amarox Expands In Europe By Acquiring Tarbis From Spain’s Ferrer

4 Akorn Selects Doug Boothe As CEO

5 Sandoz Forms Insulin Biosimilars Deal With Gan & Lee

5 Fuji Pharma Invests US$50 Million In Alvotech

6 Teva To Relocate Global HQ To Tel Aviv

7 Italian Biosimilar Usage Leaps By Over Half

8 Leaks And Prejudice Must End In US Multi-State Pricing Case

10 Canada Closes Probe Into Access To Samples

11 Kashiv Pharma Swallows Up Adello Biologics, Becoming Kashiv BioSciences

12 Belgian Body Bolsters Awareness Of Biosimilars

13 Senator Wants US Government To Make Generics

14 Fresenius Kabi Eyes Precedex Premix Market As US Court Axes Two Patents

15 Aurobindo Fails To Invalidate Andrx Metformin Patent

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6 11 14


P E O P L E

Akorn Selects Doug Boothe As CEOGRACE MONTGOMERY [email protected]

A korn has named Doug Boothe as president and chief executive officer (CEO), effective 1 January

2019, shortly after announcing that head Raj Rai had “decided to retire”.

On December 7, Akorn said it had “en-gaged in a formal search for a new CEO to lead the company into its next phase” fol-lowing Rai’s decision to step down. (Also see “Akorn’s Chief Steps Down After Losing Kabi Deal” – Generics Bulletin, 11 Dec, 2018.)

The announcement came as the Dela-ware Supreme Court ruled against Akorn, enabling Fresenius Kabi to walk away from the firms’ US$4.75 billion merger that was first agreed in April 2017.

The US company said that Boothe brings “deep pharmaceuticals expertise and a proven track record as Akorn looks forward to its next phase as an indepen-dent company committed to rebuilding shareholder value”.

“Boothe is an industry veteran with extensive accomplishments in the spe-cialty, generic and OTC pharmaceuticals business,” the firm continued. “He brings

to Akorn a long history of senior level ex-pertise in general management, strategy, sales and marketing, product selection, supply chain and business development in the US and global arenas.”

Akorn cited Boothe’s abilities to “pro-duce strong revenue growth for specialty and generic products and lead compa-nies through challenging environments

with key stakeholders”, noting that he had “overseen many successful new product development projects, regulatory reviews and approvals, paragraph IV litigations and commercial launches”. “He has also reinvigorated research and development, regulatory, compliance and supply-chain platforms in his past roles.”

Most recently, Boothe served as the president of the US$600 million generics division of Impax. He held the role for al-most two years, until Impax merged with Amneal in May 2018.

He also served as Perrigo’s executive vice-president and general manager from January 2013 to July 2016, where he was responsible for the firm’s US pharmaceuti-cals business, including generics and spe-cialty pharmaceutical products.

Boothe was also previously CEO of Ac-tavis’ US manufacturing and marketing division, and held senior positions at Al-pharma and Pharmacia Corp.

“My fellow board members and I are truly excited to welcome Doug to Akorn at this pivotal time for the company,” com-mented chairman Alan Weinstein. “After a comprehensive search, Doug quickly rose to the top of the list due to his proven track record in helping build businesses, navigate regulatory complexities and guide companies through competitive market environments.”

“I am excited and humbled with the op-portunity to lead Akorn and our dedicated employees,” stated Boothe, “as we focus our energies toward expanding our offer-ings to customers, improving our financial performance and enhancing long-term shareholder value.”

Published online 21 December 2018

“After a comprehensive search, Doug

quickly rose to the top of the list due to his proven

track record”

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D E A L S

Sandoz Forms Insulin Biosimilars Deal With Gan & LeeGRACE MONTGOMERY [email protected]

S andoz has partnered with Chinese biopharmaceutical firm Gan & Lee to market insulin biosimilars that are currently in early and clinical stages of development in the Europe-

an Union (EU), the US and other key territories.The commercialization and sales agreement aims to bring to mar-

ket biosimilar versions of glargine, lispro and aspart forms of insu-lin, which Sandoz observed are the “three top insulin medicines by sales”. Under the terms of the deal, Sandoz will be fully responsible for commercializing these medicines in the EU and US, as well as in Switzerland, Japan, South Korea, Canada, Australia and New Zealand.

With support from Sandoz, Gan & Lee will be responsible for manufacturing and developing the medicines used to treat pa-tients with type 1 and type 2 diabetes, and “shall adhere to the stringent manufacturing requirements established for Sandoz bi-osimilars”. Other specific terms of the agreement are confidential.

DEAL ENABLES SANDOZ TO EXPAND BIOSIMILARS BUSINESS

Sandoz stated that the partnership enables the firm to “expand [its] existing endocrinology portfolio over the long-term, in-line with its strategy to expand its biosimilars business, and enter the insulins business at attractive investment terms”.

“It also builds on the scientific and commercial expertise of Sandoz, including the approval and launch of eight biosimilar medicines,” the firm continued, “while leveraging the collaborator’s experience in de-veloping quality insulin medicines and high-volume manufacturing.”

Gan & Lee is a biopharmaceutical company with “20 years’ ex-perience specializing in research, development, production and commercialization of insulin and its analogues in China”. Not-ing that it currently has marketing and distribution contracts in “about 20 countries”, the firm stated that last year it launched a Phase III clinical trial in the US for insulin glargine.

“We are delighted to achieve this comprehensive agreement with Sandoz,” commented Kai Du, Gan & Lee’s corporate vice-president of international business development. “Through the collaboration, we are expecting to provide patients in regulated markets outside of China with more treatment choices.”

Noting that the agreement covers markets where it “does not have existing commitments”, the company said that the “strategic co-operation will be a milestone for Gan & Lee’s global business”.

GROWING DEMAND ANTICIPATED

Noting that “over 400 million people worldwide have diabetes”, Sandoz pointed out that “the amount of insulin required to treat type 2 diabetes alone is expected to increase by more than 20% from 2018 to 2030”.

Stefan Hendriks, the firm’s global head of biopharmaceuticals, added that “tackling the personal and healthcare burden of diabe-tes has become a global priority”. “With a majority of insulin ther-apy offered by just a few companies, healthcare systems and the insulin supply are under increasing pressure to meet the growing demands,” he said. “Sandoz is proud to expand our endocrinology portfolio into insulins to help people living with diabetes access the medicines they need for the long-term.”

SANDOZ PARTNERS WITH ARES GENETICS FOR ANTI-INFECTIVES PLATFORM

Separately, Sandoz has teamed up with Ares Genetics to jointly develop a digital anti-infectives platform for the development and lifecycle management of antibiotics. The firms intend to cre-ate a platform that combines established microbiology labora-tory methods with advanced bioinformatics and other methods.

“In the short to mid-term, the collaboration aims to rapidly and cost-effectively repurpose existing antibiotics and design value-added medicines, with the objective of expanding indication areas and overcoming antibiotic resistance,” Sandoz explained.

The platform aims in the longer term to “inform development of novel anti-infectives that are less prone to resistance, thus helping to preserve antibiotics as an effective treatment option”.

The agreement covers the first phases of the collaboration, dur-ing which Sandoz will provide agreed research and development funding to Ares. No further financial details were disclosed.


Fuji Pharma Invests US$50 Million In AlvotechGRACE MONTGOMERY [email protected]

F uji Pharma has acquired a 4.2% stake in Alvotech for approx-imately US$50 million, in a move that “further strengthens the partnership between the companies and reflects long-

term commitment” from both firms. In November, biosimilars developer Alvotech and Fuji Pharma

formed an exclusive development and commercialization agree-ment for Alvotech’s biosimilar portfolio in Japan. Under the part-nership, it was agreed that Alvotech would be responsible for

developing and supplying “multiple high-value biosimilar assets from its current product pipeline”.

Alvotech’s current pipeline consists of six monoclonal anti-bodies (mAbs) aimed at treating cancer, autoimmune, inflam-matory and other diseases, including rivals to AbbVie’s Humira (adalimumab) and Janssen’s Stelara (ustekinumab), the latter us-ing perfusion fermentation technology. The “first products [are] expected to be brought to market in 2020”, the firms noted.


B U S I N E S S S T R AT E G Y

When the deal was first announced, the companies stated that the partnership had been made “with a view to establishing a long-term relationship that also gives Fuji Pharma the opportunity to invest in Alvo-tech’s capital structure”. “In partnering with Fuji Pharma, Alvotech will gain access to Japan’s fast-growing biosimilars market, forecasted to grow by as much as 35% on a compound annual growth rate (CAGR) basis over the coming years,” they added.

Founder Robert Wessman pointed out that Alvotech had “established itself as a fully-integrated biopharmaceutical company, ranging from cell-line devel-opment of biosimilars to manufacturing, clinical development and registrations”.

“I am delighted to welcome such a pres-tigious investor on board, who brings sig-

nificant industry experience in the Asia-Pa-cific (APAC) region,” he commented, noting that Fuji Pharma’s chairman Hirofumi Imai had joined Alvotech’s board of directors.

Japan’s Fuji Pharma is “mainly engaged in the manufacture and sale of prescrip-tion-based pharmaceutical products”, with a focus on hormone medicines for obstetrics and gynaecology therapies, as well as injectable drugs including radio-pharmaceutical products.

Fuji Pharma observed that it was among

the first in Japan to develop and obtain biosimilar approval in the country for its filgrastim BS injection syringe, a recom-binant human granulocyte colony-stimu-lating factor (GCSF) drug in 2012. The firm went on to launch its second biosimilar, darbepoetin alfa, a year later.

“At Fuji, we strongly believe in Alvotech’s one-of-a-kind biologics development and scalable manufacturing capabilities,” stated Imai. “Our investment reflects the long-term business collaboration that we are committed to.”

Key shareholders in Alvotech following the transaction are Wessman’s Aztiq Pharma investment vehicle, generics firm Alvogen – led by Wessman – and Fuji Pharma.


“Alvotech will gain access to Japan’s fast-growing biosimilars market”

Teva To Relocate Global HQ To Tel AvivGRACE MONTGOMERY [email protected]

Teva has revealed that its global headquarters in Israel will relocate from Petah Tikva to Tel Aviv, with

an expected move-in date of “mid 2020”.“Teva has been working in the past few

years to find a new location to serve as Teva’s consolidated global headquarters, replacing the many sites currently scat-tered in the Petah Tikva area,” a company spokesperson told Generics Bulletin.

Noting that the building will be leased, he stated: “We have chosen a site located in Ramat Hayal, Tel Aviv, at a new build-ing which will be housed in full by Teva’s headquarters’ employees.”

“Combining into one site will fulfil our goal of working as One Teva, and will be an efficient and cost-effective solution, gen-erating significant savings from a business and operations point of view,” the spokes-person maintained.

“The building will provide our workers with a convenient and technologically ad-vanced work environment, in accordance with the standards befitting the company, its culture, heritage and values, and will enable us all to work together in an effi-cient and collaborative manner, helping us move Teva forward.”

PLANS TO MOVE HQ IN US FORMALIZED

Earlier this year, the Israeli firm outlined plans to relocate its Teva USA headquar-ters from North Wales, Pennsylvania, to Parsippany-Troy Hills, New Jersey. In Octo-ber, Teva’s top executives, including chief executive officer Kåre Schultz and North American head Brendan O’Grady, formal-ized during a ceremony the company’s commitment to consolidate its commer-cial operations in North America in the Parsippany-Troy Hills region.

Supported by a 10-year US$40 million tax incentive offered by New Jersey’s Economic Development Authority, the US move will, Teva detailed at the time, involve “more than 1,000 high-wage jobs and the transfer and creation of more than 800 positions”.

The relocations form part of Teva’s glob-al restructuring plan that includes reduc-

ing the number of sites from which it op-erates. Schultz set out the plans around a year ago, stating that the company would reduce its cost base by around US$3 bil-lion annually by the end of 2019 to help improve the firm’s overall profitability.

As well as cutting the number of loca-tions operated by Teva – including ulti-mately halving from 80 the number of manufacturing facilities worldwide, with up to 25 sites facing closure by the end of 2019 – the Israeli firm is also aiming to re-duce its global workforce by around 14,000, or more than 25% of the total. A reduction of more than 9,000 full-time equivalents (FTEs) has already been achieved.


“Combining into one site will fulfil our

goal of working as One Teva, and will be an efficient and cost-

effective solution”


M A R K E T I N T E L L I G E N C E

Italian Biosimilar Usage Leaps By Over HalfDAVID WALLACE [email protected]

I talian biosimilars volumes as measured by unit-dose increased by 51.1% to 10.7 million units in the first nine months of

2018, according to figures published by the Italian Biosimilars Group within local off-patent industry association Assoge-nerici. Over the same January-September 2018 period, originator biologics subject to biosimilar competition saw a decline of 8.8% to 28.4 million units.

Citing the launch of biosimilar rituximab in July 2017 as being a key “disruptive” influence on the Italian biosimilars mar-ket, Assogenerici observed that biosimi-lar rituximab had within a year captured 48.2% of the molecule’s market by volume, and almost a third by value.

FILGRASTIM LEADS BIOSIMILAR PENETRATION

Of the 21 biosimilars available in Italy as of September 2018 – across 11 different molecules – filgrastim biosimilars boast-ed the highest penetration rate, account-ing for 95.0% of filgrastim volumes by unit-dose and 90.3% by value.

Epoetin biosimilars enjoyed a 76.8% vol-ume and 63.8% value share, while rivals to Remicade (infliximab) captured 72.1%

of the molecule’s market by volume and 56.7% by value.

Etanercept biosimilars captured a third of the market from Pfizer’s Enbrel by vol-ume, and accounted for around a quarter of etanercept sales by value. And soma-tropin followed with a volume share of 21.7% and value share of 17.8%.

Biosimilar versions of insulin glargine made up 17.2% of volumes and 12.6%

of the molecule’s market by value, while follitropin alfa biosimilars took 13.5% by volume and 13.2% by value.

Rounding out the list were enoxaparin ri-vals – which managed to capture just 3.2% of volumes and 1.8% of the market value – and insulin lispro which accounted for just 2.3% of units sold and 1.43% of sales by value.

SMALL-MOLECULE GENERICS SEE A BOOST

Turning to small-molecule generics, As-sogenerici said that a volume penetration rate of 22.1% had been achieved over the 12 months to September 2018, with gener-ics sales accounting for around 413 million packs of a total market of 1.87 billion. The 22.1% figure continued the rising trend over previous years that had seen a 21.5% figure achieved in 2017 and 20.7% in 2016.

By value, generics captured 13.5% of sales – or €1.41 billion (US$1.60 billion) of a €10.4 billion overall market at ex-factory prices – which again represented a steady increase over 12.4% in 2017 and 11.4% in 2016. Assogenerici praised the market’s “positive performance”.

The 22.1% volume penetration rate compared to off-patent brands that cap-tured 52.2% of the total market, with pro-tected brands making up the remaining 25.8%. This meant that generics captured three-tenths of the market available.

By value, the split was somewhat differ-ent, with the 13.5% share enjoyed by ge-nerics comparing to 48.2% for off-patent brands and 38.3% for protected brands. This meant that generics captured just 22% of the available off-patent market by value.

When it came to the hospital channel, Assogenerici noted, generics accounted for 26.8% of volumes but just 6.1% of value at ex-factory prices. The volume figure repre-sented a steady increase over the years – since 2009, when the figure was just 10.0% – but the value figure, while an improve-ment over the past few years, fell short of the 6.8% high-water mark achieved in 2014.

With off-patent brands commanding 39.1% of hospital volumes – and protect-ed brands the remaining 34.2% – generics

By value, generics captured 13.5% of sales – or

€1.41 billion of a €10.4 billion overall market.


M A R K E T I N T E L L I G E N C E

were occupying just over two-fifths of the available off-patent hospital market, Asso-generici observed.

INFORMATION CAMPAIGN LAUNCHED

Meanwhile, Italy has just launched the third iteration of its ‘Io Equivalgo’ informa-tion campaign to promote awareness and “spread the culture” of generic medicines. Assogenerici said the campaign – which is supported by local medicines agency AIFA – would help to “build strategies of intervention, communication and sensiti-zation” to support the uptake of generics.

Insisting that the campaign was “part of a broader strategy of empowerment and health literacy”, Assogenerici said the

campaign aimed to make patients aware of generics; to provide patients with an “informed choice” that would provide an economic benefit; promote transparency on pricing policies; and reduce waste due to lack of therapeutic adherence, which was sometimes caused by interruption of treatment for economic reasons.

The ‘Io Equivalgo’ campaign is sup-ported by a dedicated website at www.io-equivalgo.it, as well as an app, a Facebook page and leaflets in Italian and seven other languages: Arabic, Bengali, Chinese, English, French, Spanish and Tigrinya.

PAYBACK REVISION WELCOMED

As the Italian generics and biosimilars in-dustry heads into 2019, Assogenerici has

welcomed a planned reform of the coun-try’s ‘payback’ system that the associa-tion says favours small-to-medium-sized enterprises (SMEs) in the sector.

“The government has heard the request for greater equity coming from our sec-tor,” said Assogenerici president Enrique Häusermann, referring to the exclusion of companies in the generics and biosimilars sector from the same requirements as in-novators, as well as the introduction of extra protection for SMEs with turnover under €3 million.

This, Häusermann said, “demonstrates the willingness to listen and dialogue on the part of the government”.


Leaks And Prejudice Must End In US Multi-State Pricing CaseDAVID WALLACE [email protected]

I n a filing that reads like a Who’s Who of top generics firms, more than a dozen companies have asked a Pennsylvania

district court to intervene with an order to stop parties to a multi-state lawsuit over generics pricing from leaking infor-mation and releasing prejudicial informa-tion to the press.

Apotex, Aurobindo, Citron, Dr Reddy’s and Glenmark are among the companies filing the request, along with Lannett, Lupin, Mayne Pharma, Mylan and Endo’s Par. Perrigo and Sandoz round out the list, alongside Sun with its Taro unit and Teva, including its Actavis business.

Referring to an article published by the Washington Post in early December titled ‘In-vestigation of generic ‘cartel’ expands to 300 drugs’, the generics firms complain that “cer-tain plaintiffs continue to appear far more interested in litigating their claims in the media rather than before this court in this multidistrict litigation (MDL) proceeding”.

In particular, the filing points to Con-necticut’s assistant attorney general as being “featured prominently in the article, which contains extensive quotes and in-formation disclosing non-public informa-tion concerning the states’ investigation,

including allegations not even made in the litigation to date”.

This included revealing the number of companies and drugs at issue in the inves-tigation, publicizing the states’ purported conclusions about the pricing patterns of the generics firms, and providing details about alleged harm.

‘MEDIA BLITZ’

“Notably, the Washington Post article con-firmed that the Connecticut assistant at-torney general’s statements represented the first public disclosure of details con-cerning the expanded nature of his in-vestigation into the generic drug pricing industry, including the number of drugs at issue and number of companies under investigation,” the filing stated.

Claiming that more recent public state-ments by attorneys general from Con-necticut and Louisiana constituted a “me-dia blitz”, the filing complains that they “provided specific quotes from confiden-tial documents produced under Connecti-cut law – which prevents such public dis-closure – speculated about damages that may have been suffered, and disclosed additional details about a supposed forth-

coming complaint; details that the attor-neys general have declined to share with defense counsel or the court”.

“The court is about to make case-shap-ing decisions on the viability of complaints that have already been filed, as well as on the appropriate scope of discovery based on those complaints,” the generics firms point out.

They suggest that “inflammatory com-ments like those made by the Connecticut assistant attorney general, Connecticut attorney general and Louisiana attorney general are likely to foster the impression that a conspiracy encompassing hun-dreds of additional drugs must exist, even

“Some of the allegations reported in

the press have not even been made

in this litigation.”

CONTINUED ON PAGE 10


L I T I G AT I O N

though the states have not yet converted their expanded investigation into specific allegations in a filed complaint”.

This has left the generics firms with “no means to dispel the corrosive effects of these comments by public officials charac-terizing their own investigation as encom-passing hundreds more drugs than are mentioned in the complaints filed to date”.

Meanwhile, comments on the likelihood of settlements and a reference to there be-ing “a lot of nervous people out there” con-stituted a “thinly veiled threat to current and future defendants”, the filing claims.

“These statements not only further ag-gravate the prejudice caused by earlier statements, but they demonstrate that without an order from this court limiting such statements, it will be impossible to seat a neutral jury pool, should this litiga-tion proceed to trial.”

‘RANK SPECULATION AND INNUENDO PREVAIL’

Setting out the generics firms’ belief that they have “meritorious defences and look forward to defending themselves vigor-

ously in the courtroom”, the filing com-plains that it is “entirely inappropriate for the litigation to take place in the media, where rank speculation and innuendo prevail and due consideration of all the facts is impossible”.

“This is particularly true where, as here, some of the allegations reported in the press have not even been made in this litigation.”

Prejudice – in the form of a “tainted jury pool”, as well as “harmful disclosure of sen-sitive commercial information, impinging on the orderly structure of the MDL pro-ceedings” and having a “broad negative impact on shareholders, investors and em-

ployees” – has already occurred, the gener-ics firms point out, “and will worsen if this practice persists”.

“The apparent leak of redacted, sealed material reflects the need for an order ad-monishing all parties to strictly comply with this court’s orders, applicable state laws, and ethical duties to protect confi-dential information, or face sanctions in the event of non-compliance,” the filing argues.

It calls for “an order admonishing coun-sel for the plaintiff states and all plaintiffs to refrain from making extra-judicial state-ments that violate ethical rules and state laws, admonishing all parties to abide by this court’s pre-trial and protective orders or face sanctions, and any other relief this court finds appropriate”.

“It is unfair to force defendants to litigate under the looming shadow of unspeci-fied and unproven allegations, especially those that have not yet been asserted in any filed complaint,” the generics firms de-clare. “The states’ untested, unproven alle-gations should be made and adjudicated in court, not in the media.”


CONTINUED FROM PAGE 8

“The states’ untested, unproven allegations should be made and adjudicated in court,

not in the media.”

Canada Closes Probe Into Access To SamplesAIDAN FRY [email protected]

Canada’s Competition Bureau has closed an investigation into whether three originators – Cel-

gene, Pfizer and Sanofi – abused a domi-nant position to restrict access to drug samples that generics companies need to prove bioequivalence. The watchdog said it had found “insufficient evidence to demonstrate that competition has been

substantially lessened or prevented”.However, the Bureau said that evidence

it had gathered during its investigation supported the suggestion that generics firms sometimes faced barriers that im-peded their access to reference brands. “In some cases,” it stated, “these barriers may be due to the actions of brand manufac-turers.” Any such conduct, it warned, “may warrant further enforcement or advocacy action in the future”.

INVESTIGATION BEGAN IN NOVEMBER 2016

Pursuant to a court order, the watchdog had obtained information directly from the three originators, as well as from “nu-merous third parties, including key private and public stakeholders in the pharma-ceutical industry”. The probe had been triggered in 2016 by allegations made by generics firms that they were being “in-

creasingly impeded in access to Canadian Reference Products (CRPs) through phar-maceutical wholesalers”. The Bureau start-ed its investigation in November 2016, looking both at whether Celgene, Pfizer and Sanofi were imposing restrictions on wholesalers and other distributors that prevented them supplying CRPs to gener-ics firms, as well as how the originators dealt with direct requests for CRP samples.

In particular, the Bureau considered whether Celgene’s ‘RevAid’ program of distributing its Revlimid (lenalidomide) cancer brand through limited channels was anti-competitive, but found insuffi-cient evidence. And while “in at least one case, Celgene has imposed conditions on the supply to a generic, which the generic has characterized as unnecessary and burdensome”, the watchdog said its deci-sion to drop its enquiry had been shaped by “the fact that certain generics were


D E A L S

ultimately able to obtain sufficient CRPs through other means”.

“The Bureau will remain vigilant and pursue any allegations of conduct that may harm competition in this industry.”

For Pfizer and Sanofi, the Bureau “did not find sufficient evidence” that either had policies or practices that restricted the supply of CRPs by wholesalers. In-deed, it commended Pfizer for co-oper-ating and for sending in June this year a notice letter to its own staff and to dis-tributors stating that it “does not have a policy restricting generics’ access to its pharmaceutical products, and that there

should be no discrimination between ge-nerics and other customers”.

“When businesses set up roadblocks to prevent competitors from getting their products to market, the Bureau takes no-tice,” insisted its interim Commissioner of Competition, Matthew Boswell. “In the pharmaceutical industry, this is critical because competition ultimately leads to more affordable drugs for Canadians. The Bureau will remain vigilant and pursue any allegations of conduct that may harm competition in this industry.”

ACKNOWLEDGING SIMILAR ISSUES IN THE US ON REMS

Noting the legislative action that was un-derway across the border in the US, as well as the US Food and Drug Administration’s (FDA’s) public statement made at the end of May about the potential exploitation of risk evaluation and mitigation strategies (REMS), Canada’s Competition Bureau ob-served that domestically “similar legislative or policy approaches have not yet been undertaken to address the broader issue of access to CRPs for pharmaceuticals that are subject to risk-management programs”.


“The Bureau will remain vigilant and pursue any allegations of conduct that may harm competition in this industry”

Kashiv Pharma Swallows Up Adello Biologics, Becoming Kashiv BioSciencesDEAN RUDGE [email protected]

C ontract research and drug deliv-ery specialist Kashiv Pharma has acquired biosimilars developer

Adello Biologics for an undisclosed sum, adopting the new identity Kashiv BioSci-ences and lining up Adello’s chief execu-tive officer as its own.

The combination of Kashiv and Adello creates a “fully integrated pharmaceutical and biotechnology company,” according to the former, offering advanced drug-delivery technology, biosimilars and spe-cialty pharmaceutical products.

Chintu Patel, Adello’s chief executive of-ficer and co-founder of Amneal, which has history with both companies, will become Kashiv BioSciences’ chief executive officer. Kashiv has its base in Bridgewater, New Jersey; Adello is based in nearby Piscat-away, as well as Chicago, Illinois.

“Kashiv will now be known as Kashiv Bio-Sciences with its headquarters in Bridge-water, New Jersey, plus research and de-velopment and manufacturing facilities in Bridgewater and Piscataway, New Jersey, Chicago, Illinois and Ahmedabad, India,” the firm explained.

COMBINATION CREATES A ‘BROAD BUSINESS OFFERING’

As a result of the acquisition, Kashiv Bio-Sciences’ broad business offering spans• Drug delivery platforms incorporating delayed-release technology and gastric retention systems that improve the effi-cacy and safety of known drugs;• A 505(b)(2) pipeline of seven development products targeting unmet clinical needs;• Biosimilars;• Prodrugs;• And, as part of a development collabo-ration with Amneal, 10 approved generic products and an additional 13 generic prod-ucts in advanced stages of development, including several complex generic products.

“The combined breadth of expertise in small and large molecules, peptides, pro-

teins and monoclonal antibodies will en-able us to develop products with meaning-ful clinical differentiation and a compelling value proposition for patients, physicians and payers,” Chintu Patel commented.

KASHIV HAS PROPRIETARY TECHNOLOGY PLATFORMS

Established in October 2010, Kashiv fo-cuses on innovative drug delivery systems and specialty drug products for the treat-ment of debilitating diseases. Under the leadership of outgoing chief executive officer Navnit Shah, Kashiv has created proprietary technology platforms for ex-tended and time-specific oral delivery of small molecules, including a novel gastric retention system, GRANDE, and a chrono-biological delivery system, KRONOTEC.

ADELLO FILGRASTIM BIOSIMILAR PENDING FDA APPROVAL

Adello’s current biosimilars pipeline com-prises filgrastim, which has been accepted for review by the US Food and Drug Ad-ministration (FDA); pegfilgrastim, in clinical development; adalimumab in pre-clinical development; as well as other undisclosed assets, also in pre-clinical development.

In October 2017, Amneal signed a license and commercialization agreement with Adello, picking up exclusive rights in the US to the filgrastim and pegfilgrastim assets.

Chintu Patel, Kashiv BioSciences’ new head, became chief executive officer of Adello in May 2018, replacing Peter Moesta. Following the merger of Amneal and Impax, Chintu and his brother Chirag became co-chairmen of the combination,


D E A L S

moving from the positions of co-chairmen and co-chief executive officer of the his-toric Amneal company.

ADELLO AND KASHIV MEMBERS OF THE ‘AMNEAL ALLIANCE’

Adello and Kashiv have both historically operated within the so-called Amneal Al-liance of Companies.

Amneal previously described the al-liance like this: “Each company is inde-pendent of the others but is strategically aligned to bring significant value and growth potential to the alliance members

through collaboration and leveraging the strength of the group for the benefit of each member.”

The latest list of the so-called AE Com-panies – “formed in collaboration with the founders of Amneal Pharmaceuticals, Chi-rag and Chintu Patel, and key leadership from member organizations” – names Am-neal, Prolong Pharmaceuticals and Asana BioSciences, along with Adello, which was known as Therapeutic Proteins Interna-tional until 2016.

Amneal has various business agreements with both Adello and Kashiv. At the same

time as it signed the biosimilars agreement for filgrastim and pegfilgrastim, Amneal bought a building from Adello in Ireland “to further support its inhalation dosage form.”

With Kashiv, Amneal’s partnership spans the 10 approved generic products and ad-ditional 13 generic products in advanced stages of development. In June 2017, Am-neal picked up product rights to an estradiol product from Kashiv for US$25 million plus US$10 million in contingency payments.


Belgian Body Bolsters Awareness Of BiosimilarsDAVID WALLACE [email protected]

A public information campaign “to en-lighten patients about biologic med-icines and to encourage the pre-

scription of biosimilars” has been launched by Belgian medicines agency AFMPS, in conjunction with local health insurer INAMI.

Explaining that the campaign was aimed at “informing patients about biologic medi-cines, which widen the field of possibilities for treating certain serious and chronic ill-nesses like diabetes, autoimmune diseases and cancer”, AFMPS highlighted that using biosimilar versions “had a positive effect on the accessibility of our healthcare system”.

As well as informing patients, AFMPS said it wanted to raise awareness among doctors, who had a “decisive role” as pre-scribers of biosimilars.

“When biosimilars are introduced onto the market, they lead to a reduction in the price and reimbursement base of the bio-similar and the reference biologic,” AFMPS explained, adding that this decline of up to 30% could produce “significant savings” for Belgium’s healthcare system. “The budget margin created by prescribing biosimilar drugs makes it possible to reinforce more innovative treatments for more patients.”

As part of the campaign, AFMPS has announced further measures to support biosimilar prescribing:• “Regular monitoring” of biosimilar pre-scribing will take place;• A study will be launched on doctors’ rea-sons for prescribing certain drugs, focusing

on both doctors’ and patients’ concerns;• An ‘ambassador’ for biosimilars will be appointed, with responsibility for “co-or-dinating, supporting and monitoring the various actions planned”;• And a pilot scheme will be initiated en-couraging doctors to prescribe anti-tu-mor necrosis factor (anti-TNF) biosimilars outside of hospitals.

On this final point, AFMPS said doctors would “benefit from additional fees for the additional efforts made in terms of commu-nication, information and patient follow-up”.

To raise awareness among the general public, the AFMPS campaign is taking a

multi-media approach, including posters, radio spots, online banners and internet promotions – including a dedicated web-site for biosimilars, www.medicamentsbi-osimilaires.be and social media activities – as well as a brochure for patients.

A series of images used as part of the campaign show faces with a line drawn down the centre. One side represents pa-tients, with captions indicating that they use biologic medicines to treat their con-ditions. Meanwhile, the other side repre-

sents doctors, with the common caption “to treat my patients, I prescribe biosimilar medicines … just as effective and with a positive effect on our healthcare system”.

Supporting information on the AFMPS website includes a question-and-answer section covering the nature of biological medicines and their production process, as well as an extensive section on biosimi-lars that describes their nature, production process and authorization pathway, while explaining that they are “highly similar” to their reference brands.

Further questions cover the specific bio-logical medicines that are authorized and marketed in Belgium, along with switch-ing between brand biologics and biosimi-lars, and pharmacovigilance activities.


AFMPS said usingbiosimilars “had a positive effect on accessibility”


R E G U L AT I O N

Senator Wants US Government To Make GenericsAIDAN FRY [email protected]

T he US Federal Government would manufacture certain generic drugs, under legislation tabled by US Democratic Senator Elizabeth Warren. The Massachusetts Senator is

also calling for a Congressional investigation into alleged price-fixing in the US generics market that she feels is “plagued by nu-merous market failures”.

“Pharmaceutical companies shouldn’t get to jack up prices on generic drugs whenever they feel like it,” Warren argued. “That’s why I’m calling for Congressional hearings on generics price-fix-ing. I’ve got a plan to fix this broken market and make prescrip-tions more affordable.”

Warren’s Affordable Drug Manufacturing Act that received its first reading in Senate on 18 December – along with a companion bill sponsored by Representative Jan Schakowsky in the House of Representatives – would amend the Public Health Service Act to establish an Office of Drug Manufacturing within the federal De-partment of Health and Human Services (HHS). That office would be authorized to make generics under three key conditions:• No company is currently manufacturing a given drug• Only one or two companies are producing the drug, and the price has spiked or the drug is in shortage• Only one or two companies produce the drug, the price is a barrier to patient access, and the drug is listed as an essential medicine by the World Health Organization (WHO)

By also authorizing public manufacturing of active pharma-ceutical ingredients (APIs) via her bill, Warren believes she will encourage new entrants into the US generics arena.

The Office would also have the authority to make any drug that the federal government had licensed, including under existing compulsory-licensing authorities. Publicly-produced drugs would be sold at “a fair price that covers manufacturing costs while ensuring patients have access to these drugs”, while manufacturers will be able to obtain rights to such products if they agree to keep them on the market at a fair price.

The draft act states that, in determining a fair price for an ap-plicable drug, the Office should consider:• The impact of price on patient access to the drug• The cost of the drug to federal or state healthcare programs• The cost to the federal government of manufacturing the drug• The administrative cost of operating the Office• The cost to acquire and manufacture drugs• The impact of price on market competition for the drug in question

In particular, the draft legislation would require the Office to begin public production of insulin within one year. It also sets a one-year limit for the Office to have started making, or entered into contracts for the production of, at least 15 drugs. Within three

years, that number is to have risen to at least 25 products.Warren’s letter to the chairmen of Senate committees on finance,

judiciary and health, education, labor and pensions cites Washington Post reports of the US generic market being “most likely the largest cartel in the history of the US”. She also highlights an ongoing probe into alleged anti-competitive behavior by authorities in 47 states, as-serting that the industry is “riddled with price-fixing schemes”.

The Senator asks her colleagues to, in January 2019, “open a bipartisan committee investigation” into the price-fixing allega-tions and to hold hearings on the findings of the investigation.

Warren is not alone in having the US generics industry in her crosshairs. Senator Orrin Hatch – co-author of the Hatch-Waxman generics framework – has just re-introduced legislation that would force generics and biosimilars firms to choose only one path to challenge patents.

HATCH SEEKS TO LIMIT PATENT- CHALLENGE OPTIONS

The Hatch-Waxman Integrity Act of 2018 would require gener-ics challengers to choose between the Hatch-Waxman patent-linkage scheme that offers accelerated approvals and potential 180-day exclusivity or an inter partes review at the US Patent and Trademark Office (USPTO) that is “cheaper and faster than Hatch-Waxman litigation but does not provide the advantages of a streamlined generic approval process”. The bill would apply simi-larly to patents on biologic drugs.

Applauding Hatch’s proposal tabled with his Republican col-leagues Senator Thom Tillis and Congressman Bill Flores, brand industry body the Biotechnology Innovation Organization (BIO) argued that the “carefully-crafted balance” of the Hatch-Waxman framework had in recent years “been undermined by unforeseen gamesmanship which forces innovators of new therapies to defend their intellectual property against needlessly repetitive attacks, in multiple court systems under differing rules”.

Having already tabled the legislation earlier this year, Hatch de-cided not to offer his bill as an amendment to the Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act that was passed by the US Senate Judiciary Committee in June 2018, rec-ognizing that his proposal “goes beyond the scope of CREATES”.

Independent Senator Bernie Sanders, along with Democratic Representative Ro Khanna, has introduced the draft Prescription Drug Price Relief Act that would create an international reference-pricing system.

The bill aims to ensure that Americans do not pay more for prescription drugs than the median of prices in five countries – Canada, France, Germany, Japan and the UK. “If pharmaceuti-cal manufacturers refuse to lower drug prices below that level,” Sanders and Khanna warned, “the federal government would approve cheaper generic versions of those drugs, regardless of any patents or market exclusivities in place”.


“I’ve got a plan to fix this broken market and make prescriptions more affordable”


L I T I G AT I O N

Fresenius Kabi Eyes Precedex Premix Market As US Court Axes Two PatentsDEAN RUDGE [email protected]

Fresenius Kabi has taken a mighty step towards introducing a generic of Hospira’s Precedex Premix (dexmedetomidine) 4μg/ml ready-to-use, diluted formulation more than a de-

cade ahead of patent expiry following a favourable US district court ruling.

Illinois District Court Judge Rebecca Pallmeyer ruled that the only asserted claims of two US patents expiring in 2032 are inval-id, siding with Kabi’s assertions of obviousness and concluding that it had proven so by “clear and convincing evidence.”

Responding to the decision, a Pfizer spokesperson told Generics Bulletin, “Pfizer is disappointed by the ruling and plans to appeal.” Kabi explained to Generics Bulletin that the company “typically doesn’t comment on matters of intellectual property (IP) litigation and that’s the approach we’re taking with this case.”

Kabi received final ANDA approval on 29 November for its dex-medetomidine hydrochloride in 0.9% sodium chloride injection, in 80μg/20ml, 200μg/50ml, and 400μg/100ml single-dose containers.

LITIGATION HAD INVOLVED FIVE PATENTS; NARROWED TO TWO

Litigation between the firms over the German firm’s abbreviated new drug application (ANDA) had previously involved five Pre-cedex Premix patents, all expiring on the same day: 4 July 2032, including a six-month period of pediatric exclusivity.

However, following an earlier claim construction order, Ho-spira dropped all but one claim each of US patent 8,648,106 and US patent 9,616,049.

Kabi had stipulated that its proposed dexmedetomidine prod-uct would infringe those claims but maintained its challenges to their validity.

Per the US Food and Drug Administration’s (FDA’s) Orange Book, two further patents shield Hospira’s brand: US patent 9,320,712 that also expires on 4 July 2032 with the pediatric exclusivity; and US method-of-use patent 6,716,867 that runs until 1 October 2019 with similar exclusivity.

The German firm had previously counterclaimed for a declaration that the ‘712 patent is invalid, or, alternatively, that Kabi’s actions will not infringe.

Pfizer, Hospira’s parent, reported US Precedex sales of US$82 million in the first nine months of this year, a decline of a fifth.

PRECEDEX PREMIX REPLACED PRECEDEX CONCENTRATE

An earlier dexmedetomidine product that must be diluted with sa-line solution, Precedex Concentrate, has been on the market since 1999. Hospira received FDA approval to market the ready-to-use Precedex Premix in 2013, obtaining between 2012 and 2017 the five patents previously asserted in the case.

With Hospira agreeing to narrow patents asserted against Kabi, at-issue in the case was the validity of claim 6 of the ‘106

patent and claim 8 of the ‘049 patent. The ‘106 and ‘049 patents cover the same basic subject matter – “the medication itself” – and share a title: “Dexmedetomidine Premix Formulation.” The patents also share a common specification.

Both sides agreed that relevant prior art in the matter includ-ed US patent 4,910,214, which issued in 1990 and disclosed and claimed the use of dexmedetomidine as a sedative; Hospira’s original Precedex Concentrate formulation; Dexdomitor, a ready-to-use, 500 µg/ml dexmedetomidine hydrochloride (HCl) formu-lation used in animals; and an assortment of references relating to ready-to-use drug formulations and glass storage containers.

In arguing that claim 6 of the ‘106 patent was invalid as obvi-ous, Kabi asserted that the prior art expressly disclosed the fol-lowing claim limitations: a ready-to-use, sealed glass container with 4µg/ml dexmedetomidine HCl.

The court agreed, finding that:• Precedex Concentrate combined with the knowledge of a per-son of ordinary skill in the art (POSA), including knowledge that would be informed by other prior art documents, taught a ready-to-use, sealed glass container with 4µg/ml dexmedetomidine HCl.• A POSA would have been motivated to combine the disclo-sures in Precedex Concentrate, and other prior art to create a ready-to-use 4µg/ml dexmedetomidine HCl formulation, stored in a Type I glass vial, sealed with a coated rubber stopper.• Precedex Concentrate combined with Dexdomitor expressly disclosed a ready-to-use, sealed glass container with 4 µg/mL dexmedetomidine HCl.• A POSA would have been motivated to combine the disclo-sures in Precedex Concentrate and Dexdomitor to create a ready-to-use 4µg/ml dexmedetomidine HCl formulation, stored in a Type I glass vial, sealed with a coated rubber stopper.

“More central to the parties’ dispute,” the court noted, was the so-called ‘about 2%’ limitation of the ‘106 patent. This refers to lan-guage in claim 1 of the ‘106 patent, on which claim 6 is dependent, requiring that the formulation exhibit no more than a 2% decrease in dexmedetomidine concentration after storage for five months.

Kabi acknowledged that the prior art did not expressly dis-close this limitation, but argued it was inherent and therefore “supplied” by the claim limitation.


L I T I G AT I O N

Siding with Kabi, the court found that all stability data in the record for 4µg/ml dexmedetomidine HCl formulations stored in a glass vial, sealed with coated rubber stoppers, and stored at room temperature showed that there was “no more than about 2%” loss in concentration at five months.

Therefore, the “about 2%” limitation of the ‘106 patent was inherent in a 4µg/ml dexmedetomidine HCl formulation under those storage conditions, the court found.

The court acknowledged that in a recent decision in which claim 6 of the ‘106 patent had been asserted against Amneal, a Delaware District Court had determined that Amneal failed to establish inherency of the ‘about 2%’ limitation. This was be-cause Amneal, in that court’s view, offered no expert testimony regarding the scientific principles underlying its inherency argu-ment, and relied on “just two” examples of stability data covering the claimed 4µg/ml dexmedetomidine concentration.

“The record before this court is different,” Pallmeyer under-lined. “Kabi has offered far more than two examples of stability data for the 4µg/ml preferred embodiment, all of which show that the drug lost no more than 2% of its concentration at five months. Additionally, unlike Amneal, Kabi has offered expert tes-timony regarding the chemical properties of dexmedetomidine.”

EVIDENCE SUPPORTING SECONDARY CONSIDERATIONS WAS ‘WEAK’

The court also rejected Hospira’s secondary considerations of non-obviousness. Although Hospira had offered some evidence that Fresenius Kabi expected challenges in developing a ready-to-use product, it had presented no evidence of any “failed at-tempts,” the court found.

The ‘214 patent had “barred Hospira’s competitors from enter-ing the market from its issuance in March 1990 until its expira-tion in July 2013,” the court noted. “Based on the limited record of secondary considerations before the court, the failure of others to outpace Hospira in creating a ready-to-use product is more likely attributable to a legal inability to do so than an ac-tual inability to do so.”

The court only considered briefly the asserted claim 8 of the ‘049 patent, as in its post-trial briefing, Hospira did not challenge Kabi’s contention that the claim was invalid as obvious. Neverthe-less, it found that Precedex Concentrate disclosed that the formu-lation had a pH range of 4.5 to 7.0, which is within the range of 2 to 10 claimed in claim 8 of the ‘049 patent; and that a POSA would have been motivated to ensure that the pH range of a ready-to-use dexmedetomidine product fell within two and ten.

Therefore, the claim was ruled obvious.

MULTIPLE PRECEDEX PREMIX ANDA FILERS FIGHTING PFIZER IN COURT

In its third-quarter financial filing with US Securities and Ex-change Commission (SEC), Pfizer reveals that it has been notified of multiple ANDAs for Precedex Premix. Amneal’s ruling in Janu-ary brought a decision of invalidity against three of the patents expiring in 2032, on top of that finding of validity against the ‘106 patent. Both sides have appealed the ruling.

Baxter, Endo’s Par, Gland Pharma and Jiangsu Hengrui Medi-cine have also been sued for filing ANDAs. Ben Venue settled its case in June 2016.


Aurobindo Fails To Invalidate Andrx Metformin PatentDAVID WALLACE [email protected]

A urobindo has failed in its attempt to invalidate via the inter partes review (IPR) process a US patent protecting an extended-release once-daily version of metformin.

The firm had challenged as unpatentable US patent 6,866,866, which is listed in the US Food and Drug Adminis-tration’s (FDA’s) Orange Book against Andrx brands Fortamet (metformin) and Actoplus Met XR (metformin/pioglitazone) and expires on 17 March 2021. The patent discloses a con-trolled-release dosage form of metformin suitable for once-a-day dosing in the ‘fed’ stage. It states that this improves bio-availability compared to the ‘fasted’ state – the opposite of the alternative Glucophage brand.

However, the Patent Trial and Appeal Board (PTAB) within the US Patent and Trademark Office (USPTO) said Aurobindo had “not demonstrated by a preponderance of the evidence that the challenged claims are unpatentable”.

Aurobindo’s challenge revolved primarily around Claim 1 of the ‘866 patent, which discloses a mean ‘Tmax’ – or time after administration of the dosage form at which the highest plasma concentration of the drug is achieved – of 5.5-7.5 hours.

The Indian company argued that a skilled artisan would have combined prior art known as Timmins and Cheng to arrive at a mean range of about 4.67-6.33 hours, which it said was “well within the range claimed” by Claim 1.

But the PTAB concluded that “the petition and evidence of re-cord provide no independent factual basis for the argument that the combination of Timmins and Cheng renders this [Tmax] limi-tation obvious”. Aurobindo “has not shown sufficiently that com-bining the teachings of Timmins and Cheng … would have re-sulted in a dosage form that provides a mean Tmax of metformin from 5.5 to 7.5 hours after administration”, the PTAB emphasized.

“We note that 4.67-6.33 hours does not include 6.34-7.5 hours, which is over half of the range recited in Claim 1,” the PTAB added.

Aurobindo’s arguments over dependent claims 2-25 of the ‘866 patent – which set out other Tmax ranges, percentages of metfor-min or metformin salt released within specific time periods after administration, and details of the dosage form, including specific features of the core – were similarly rejected by the PTAB.


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