Industry Delighted By ‘Fixed’ USMCA · CUSTOMER SERVICES [email protected] UK &...

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REGULATION

Global Industry Hails Bioequivalence Progress, p.13

LAUNCHES

Amneal Wins Race For US NuvaRing Rival, p.5

BIOSIMILARS

French Body Favors Pharmacy Substitution For Biosimilars, p. 8

Issue 426 • 20 December 2019

Industry Delighted By ‘Fixed’ USMCADAVID WALLACE [email protected]

R evisions to the proposed US-Mex-ico-Canada trade agreement have ‘fixed’ the replacement for the pre-

vious North American Free Trade Agree-ment, according to the US Association for Accessible Medicines. Along with the Canadian Generic Pharmaceutical As-sociation, the AAM welcomed changes that included removing the requirement for a 10-year data exclusivity period for biologics and adding measures favor-able to generics, including incentives for generic competition.

The changes followed recent rumors that US negotiators were preparing to scale back intellectual property provi-sions in the USMCA to help win support for the deal from US Democrats.

While the full text of the revised pro-

posals was not immediately available, the US House of Representatives’ com-mittee on ways and means issued a fact-sheet summarizing the major changes.

These included:• removing the provision requiring

parties to provide at least 10 years of exclusivity for biologics;

• removing the provision requiring parties to confirm that patents would be available for new uses of known products, which would have “locked in the practice of ‘patent evergreen-ing’ in which pharmaceutical com-panies obtain hundreds of patents related to a product to block generic competition and price reductions”;

• removing the provision requiring three additional years of exclusivity

for clinical information submitted in connection with new uses of pre-viously-approved pharmaceuticals – “another way that pharmaceutical companies delay competition and access to affordable medicines”;

• a revised regulatory review provision “to clarify the circumstances in which generic and biosimilar companies may use a patented invention so that they can obtain marketing approval on day-one of patent expiration”;

• a revised data-protection provision “to incorporate limitations in US law that foster generic competition”;

• a revised patent linkage provision “to remove the ‘hard linkage’ of regu-latory approval and patent status.” An annex to the agreement requires Mexico to ensure that “all interested parties receive notice and an oppor-tunity to be heard,” while the revision also “includes language that permits incentives for generic competition and improves transparency”; and

• a revised patent-term adjustment provision “to provide non-exhaustive examples of limitations on the ad-justment of patent terms for regula-tory delays.”

MODEL FOR FUTURE US TRADE DEALS“Taken in whole,” the factsheet states, “these substantial changes House Demo-crats secured are a true transformation of the original USMCA.”

“The USMCA that the Trump adminis-tration proposed was not enforceable and failed to make critical updates to the exist-ing NAFTA,” it insists. “Democrats rejected that weak agreement and negotiated extensive improvements that make this new version of the USMCA a good deal for workers, patients, and our environment.

CONTINUED ON PAGE 4

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IN THIS ISSUE

“The US Association for Accessible Medicines said

that changes to the USMCA had ‘fixed’

the trade deal”

As we prepare for the holiday season, the North American ge-nerics and biosimilars industry has received a surprise present that it might not have expected, in the form of revised proposals for a trade deal between the US, Mexico and Canada that are far more favorable to the off-patent industry than the previously proposed terms.

Praising the revisions, the US Association for Accessible Medi-cines said that changes to the USMCA – such as removing the requirement for 10 years of data exclusivity for biologics, as well as opening the door to incentives for small-molecule generics – had ‘fixed’ the trade deal (see front cover).

This week has also been a big week for Amneal, as the major US player has won the race to secure approval for a generic ver-sion of NuvaRing (p.5) while also striking a deal to take control of federal healthcare provider AvKARE (p.16). First generic ap-provals have also been seen in the US for generic versions of Gilenya (p.10) and Afinitor (p.17).

Meanwhile, the International Generic and Biosimilar Medicines Association has welcomed moves towards harmonizing global bioequivalence requirements (p.13) at the same time as it has renewed its opposition to a brand-backed global database of patent information (p.19).

The next issue of Generics Bulletin will be published on 10 January 2020

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COVER /Industry Delighted By ‘Fixed’ USMCA

5 Amneal Wins Race For US NuvaRing Rival

7 Amgen Gets US Infliximab Nod

8 French Body Favors Pharmacy Substitution For Biosimilars

10 Three US Fingolimod Approvals Raise Legal Stakes

12 Price Watch UK: Concessions Hit And Miss As Some UK Prices Treble

13 Global Industry Hails Bioequivalence Progress

14 Julphar Focuses On Quality As Carle Departs

15 Hikma And Civica Ship Eight Essential Injectables

16 Amneal Takes Control Of AvKARE In US

17 Endo And Teva Are First With US Everolimus

19 IGBA Urges WIPO To Revoke Patent Database Support

20 Polpharma Pursues Tysabri Through Antelope Trial

21 Momenta Pays Out On Enoxaparin Shut-Out

22 Teligent Slammed By FDA Warning Letter

23 Bio-Thera Gets Chinese Nod To Proceed On Ustekinumab

AAM Criticizes Lower Health Care Costs ActReforms to the US 180-day exclusivity incentive included in the Blocking Act that is part of the Lower Health Care Costs Act could cost the US healthcare system approximately $1.7bn, the AAM has warned.

https://bit.ly/2RY2SzW

Gene Techno Collaborates With Kishi Kasei On AfliberceptGene Techno Science and Kishi Kasei have struck a deal to jointly develop a Japanese aflibercept biosimilar rival to Eylea.

https://bit.ly/2MfBJ8j

Lannett Reports Insulin Glargine Trial SuccessLannett’s Phase I trial for biosimilar insulin glargine has met “all primary endpoints,” the company has announced. The rival to Sanofi’s Lantus is being developed by Lannett with partner HEC through a deal for which financial details have just been revealed.

https://bit.ly/2qYtfef

Meitheal Gets US Enoxaparin ApprovalThrough its partnership with majority stakeholder Nanjing King-Friend Biochemical Pharmaceutical, Meitheal Pharmaceuticals has received FDA approval for enoxaparin, a generic rival to Lovenox.

https://bit.ly/2EoDA68

NeuClone’s Trastuzumab Trial SucceedsNeuClone has reported that its NeuCeptin proposed biosimilar trastuzumab has successfully met all primary and secondary endpoints in a Phase I clinical trial.

https://bit.ly/35tn4O6

exclusive online content

The next issue will be on 10 January 2020. For online access please contact [email protected]

SEASON’S GREETINGSSEASON’S GREETINGSWishing our readers a joyful

holiday season and all the best for 2020.

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INTELLECTUAL PROPERTY

This revised agreement is a win for the US economy and American families.”

Moreover, the factsheet states, “it will serve as the new standard for all future US trade deals.”

The changes could therefore have a knock-on effect on other trade deals involving the US. Before the latest revi-sions to the USMCA proposals, the Brit-ish Generic Manufacturers Association had warned that the US’ “usual practice in free trade agreements” suggested that in a possible future trade deal be-tween the US and UK, the US was likely to push for “intellectual property re-quirements which go beyond World Trade Organization standards and would delay competition from generic and biosimilar medicines.”

AAM DECLARES ‘VICTORY’Responding to the revised USMCA provi-sions, the AAM said the changes repre-sented “a victory for America’s patients.”

“Today’s agreement reached by the Congressional Trade Working Group and the Trump administration represents a victory for patients,” said AAM president and CEO Chip Davis. “The revised text creates greater opportunities for patients in Mexico, Canada and the US to access less expensive medicines and promotes a competitive pharmaceutical market across the three countries.”

“The improved pharmaceutical provi-sions create the balance between access to medicines and support for innovation that was included in bipartisan 2015 Trade Promotion Authority legislation,” Davis pointed out. “The AAM is pleased that Congress and the administration have made changes to USMCA that sup-port open markets, greater competition and improved cost savings for patients and the three healthcare systems.”

The AAM has also produced a video to

mark the occasion and explain the changes.In it, the AAM states that the USMCA now:• does not “lock in high drug prices”;• does not “expand pharmaceutical

monopolies”;• removes barriers to generic and bio-

similar market access; and• incentivizes generic market entry.“To the USMCA working group and

USTR – thank you for putting America’s patients first,” the video says. “We appre-ciate all you have done to ensure patients

have access to affordable medicines.”The AAM’s vice-president for trade and

international affairs, Jonathan Kimball, said that the negotiations appeared to have “resulted in significant improve-ments that will increase access and af-fordability of medicines and create a global standard for new trade agree-ments in the future.”

CANADA’S CGPA PRAISES DEALMeanwhile, Jim Keon, president of Can-ada’s CGPA, said that the deal included “several improvements to the pharma-ceutical intellectual property aspects of the agreement,” adding that these were expected to be included in the revised version of the deal being signed by the three countries.

The CGPA said it would undertake “a careful review” of the revised text “to ensure that the anticipated changes are fully reflected in the final text of the revised treaty.”

Nevertheless, the improvements “rep-resent an important win for the Canadian healthcare system and patients’ access to affordable prescription medicines in Canada and throughout North Amer-ica,” Keon declared.

Noting that Canada’s Parliamentary Budget Officer had estimated that con-cessions made by Canada in version of the USMCA signed in 2018 “would have cost Canadians as much CAD169m ($128m) more per year for prescription

medicines in the first year alone after they came into effect,” Keon said the CGPA ex-pected that “this potential impact will be eliminated with the changes.”

In particular, Keon highlighted the removal of the 10-year data exclusiv-ity requirement for biologics as being “of particular importance to Canadian pa-tients, public drug plans and employers that sponsor drug benefit plans for their employees,” as this could have “delayed the future introduction of new biosimilar biologic medicines in Canada.”

“The generic and biosimilar medicines industries are strong supporters of trade and the elimination of barriers to trade,” Keon concluded. “Moving forward, trade negotiations must prioritize measures to provide access to affordable medicines for patients and to foster a competitive business environment for the generic and biosimilar medicines industries.”

Published online 11 December 2019

CONTINUED FROM PAGE 1

“The revised text creates greater opportunities for patients in Mexico, Canada and the US to access less expensive medicines and promotes a competitive pharmaceutical market across the three countries” – Chip Davis

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Unrivalled coverage, news and analysis of the global generics, biosimilars and value-added medicines industries


LAUNCHES

Amneal Wins Race For US NuvaRing Rival AIDAN FRY [email protected]

Amneal Pharmaceuticals has im-mediately launched upon ap-proval the first generic alternative

to Merck & Co’s NuvaRing (etonogestrel/ethinylestradiol) vaginal ring. In securing US Food and Drug Administration ap-proval for its EluRyng branded generic, the US generics specialist has outpaced many of its peers that are also targeting NuvaRing as part of strategies to pursue complex generics.

Approved as an abbreviated new drug application, EluRyng vaginal ring, deliver-ing 0.12mg of etonogestrel and 0.015mg of ethinylestradiol per 24 hours, has an ‘AB’ therapeutic equivalence rating to NuvaR-ing, meaning it can automatically be sub-stituted for the off-patent reference brand at pharmacy level in most US states.

Citing IQVIA data for the 12 months ended 31 October 2019, Amneal said the original NuvaRing brand had annual US sales of $976m. The US generics special-ist’s share price spiked up by more 50% upon news of the approval.

“We are pleased to announce FDA ap-proval of EluRyng, one of 15 new, complex products we expect to launch over the next 18 to 24 months,” commented Am-neal’s co-CEOs, Chirag and Chintu Patel.

MANUFACTURING RING DEVICE IN-HOUSE

“This milestone underscores Amneal’s deep scientific and regulatory capabili-ties and our ability to overcome signifi-cant barriers to entry, including complex formulation development and special-ized manufacturing requirements,” they insisted. Amneal is manufacturing the ring device in-house.

“In addition,” the Patel brothers contin-ued, “EluRyng adds a differentiated, com-plex dosage form to our portfolio, and bringing this product to market reflects our commitment to improving afford-able access to complex drug products. Looking ahead, we remain enthusiastic about the additional high-value oppor-tunities in our pipeline that are designed to improve the lives of patients and drive meaningful growth and value-creation

for our shareholders and other stake-holders in 2020 and beyond.”

Presenting Amneal’s half-year results as he returned with brother Chirag to lead the US company in August this year, Chin-tu Patel told investors that the firm’s ge-neric of NuvaRing was “moving positively through the regulatory process”, so he remained “optimistically cautious” about a launch in the fourth quarter of this year.

Other companies pursuing generics of Merck’s contraceptive have been less optimistic about the timing of prospec-tive approvals.

TEVA SEES NUVARING AS 2020 OPPORTUNITY

Asked by analysts about the likely timing of FDA approval for Teva’s version, the Israeli group’s North America commercial head, Brendan O’Grady, said last month that “Nu-vaRing has been moved out to 2020.”

Similarly, the CEO of Mayne Pharma, Scott Richards, told shareholders at the firm’s annual general meeting held in late November that “the most significant pipe-line product is the company’s filing of ge-neric NuvaRing, the largest contraceptive product sold in the US, which is targeted for approval in calendar year 2020.”

“The company has been working close-ly with Mithra, our development and manufacturing partner on FDA questions which are expected to be submitted by the end of this calendar year,” Richards told Mayne’s AGM last month. Pointing out that, as of November 2019, no ge-

nerics to NuvaRing had been approved in the US, he noted that “through public disclosures, we understand several pos-sible competitors have experienced fur-ther delays in their programs.”

Mayne – which is working with Belgian partner Mithra Pharmaceuticals on an estetrol/drospirenone oral contraceptive that it believes could disrupt the hormonal contraceptives market – put annual US NuvaRing sales at around $970m. That figure represented almost a quarter of the $4.0bn combined hormonal contraceptive market in the US, while NuvaRing’s share of the combination hormonal contraceptives market by units was 4.9%, slightly ahead of Allergan’s Lo Loestrin Fe pill with 4.4%.

At the end of 2018, Mithra had revealed that the FDA had issued a complete re-sponse letter for its vaginal ring, which bears the brand name Myring. “In the letter,” Mithra said, “the FDA stated that additional bioequivalence data would be required to support the ANDA, includ-ing the manufacture of new test batches.” This, the Belgian developer admitted, would likely delay Mayne’s US commercial launch of the contraceptive until 2020. Nevertheless, Mithra believed “Myring could be among the first few generic Nu-vaRing products in the US market”.

REDDY’S RESPONDING TO COMPLETE RESPONSE LETTER

Among Mayne’s potential competitors facing delays is Dr Reddy’s Laboratories.

“EluRyng adds

a differentiated,

complex dosage form

to our portfolio”

– Chirag and

Chintu Patel

CONTINUED ON PAGE 7


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LAUNCHES / BIOSIMILARS

The Indian company revealed earlier this year that it had also received a CRL from the FDA, outlining deficiencies in its filing for generic NuvaRing. Reddy’s – which had gained the NuvaRing ANDA as one of eight drugs acquired from Teva in 2016 as part of antitrust clearance for the Israeli group’s takeover of Actavis Generics – had initially hoped to launch its generic version in the first half of calendar 2019.

In early November, Reddy’s CEO Erez Israeli told investors the company ex-pected to file a response to the CRL “in the next few months.” “We cannot yet commit to a specific date,” he added.

The CRL received in August was, he revealed, “related to some specs of the product that we had to address in certain testing. For that, we had to do some ex-periments and to buy certain equipment. This is work that will take a few months, starting from August.”

Glenmark Pharmaceuticals in March 2017 unveiled a development and licensing deal with US-based developer Evestra for a generic of NuvaRing, codenamed EVE119. However, towards the end of last year, the Indian firm listed the generic of NuvaRing as one of four complex generics for which it had shelved development plans in light of the competitive landscape.


“We understand

several possible

competitors have

experienced further

delays in their

programs”

– Scott Richards

CONTINUED FROM PAGE 5 Amgen Gets US Infliximab NodDAVID WALLACE [email protected]

Amgen has announced the ap-proval of its Avsola (infliximab-axxq) biosimilar by the US Food

and Drug Administration. The approval marks the fourth FDA biosimilar approval for Amgen, and also the fourth infliximab biosimilar approved by the US agency.

While the firm did not comment on launch or pricing plans for the rival to Janssen’s Remicade original – which was approved for all of the same chronic inflammatory conditions in-dicated for the reference product – it noted that the biosimilar was “currently not available commercially.”

Amgen said the approval “marks an important milestone for Amgen’s portfolios of both biosimilar and inflammation medicines, as Avsola becomes the fourth biosimilar from Amgen’s portfolio to receive FDA approval, and Amgen’s second biosimilar to re-ceive FDA approval for chronic inflammatory conditions.”

The approved indications cover:• moderate-to-severe rheumatoid arthritis;• moderate-to-severe adult and pediatric Crohn’s disease;• moderate-to-severe adult and pediatric ulcerative colitis;• chronic severe plaque psoriasis;• psoriatic arthritis; and• ankylosing spondylitis.Other biosimilars to Remicade approved by the FDA include the Inflectra (infliximab-

dyyb) version on which Pfizer collaborated with Celltrion – launched in late 2016 – as well as the Ixifi (infliximab-qbtx) biosimilar for which Pfizer received a solo approval but held off on launching. Samsung Bioepis also markets its Renflexis (infliximab-abda) ver-sion, which CEO Christopher Hansung Ko recently said had been “increasing its share of the US infliximab market.”

AMGEN: FOUR US BIOSIMILARS APPROVED, TWO LAUNCHED“The approval of Avsola represents an important milestone across our biosimilar and inflammation portfolios,” insisted Amgen’s vice-president of global commercial opera-tions, Murdo Gordon.

As well as Avsola, Amgen’s portfolio of approved US biosimilars includes the Kanjinti (trastuzumab-anns) and Mvasi (bevacizumab-awwb) oncology treatments – launched ‘at risk’ earlier this year – as well as the Amjevita (adalimumab-atto) rival to Humira that is due to launch on 31 January 2023 under a settlement with AbbVie, leading off a suc-cession of similarly negotiated US launch dates for various Humira biosimilars through-out that year.

“Following July’s exciting launches of our two biosimilars in oncology,” Gordon add-ed, “Avsola highlights Amgen’s long-term commitment to providing more affordable biological treatment options to patients across critical disease states, including chronic inflammatory conditions.”

Amgen recently reported that a “solid start” by Kanjinti and Mvasi following their at-risk launch in July contributed sales of $81m for Amgen in the third quarter of this year. With Kanjinti and Amgevita (adalimumab) in the rest of the world adding another $92m, global biosimilars turnover in the quarter reached $173m.



BIOSIMILARS


French Body Favors Pharmacy Substitution For BiosimilarsDAVID WALLACE [email protected]

B iosimilars should be considered by doctors to be interchangeable with their original biologic brands and

should be able to be substituted by phar-macists, under certain conditions, French off-patent industry association Gemme has declared in a position statement.

While it qualifies its recommendations by saying that such substitution should be limited to the initiation of treatment for certain types of drugs and should only take place “under yet to be defined eco-nomic and practical conditions,” Gemme’s statement nevertheless represents a bold declaration in a European context that has generally seen more caution over the prospect of pharmacy-level substitution for biologics. It also runs against the views of the broader European off-patent indus-try association Medicines for Europe.

Biologic substitution “represents a ma-jor opportunity to develop the market and safeguard the healthcare system,” Gemme argues, urging all healthcare stakeholders to co-ordinate on the issue “in order to win the trust of patients.”

“Developing biosimilars as part of a co-

ordinated healthcare approach – and in-volving all of the healthcare professionals around the patient – would allow a lasting trust to be developed and avoid reproduc-ing the mistakes made with generics, such as the opposition of certain actors and the mistrust of patients,” Gemme says.

Certain patient groups were them-selves demanding biologic substitution, Gemme claims, as long as this was under the control of “expert” pharmacists.

“Biosimilars are subject to the same traceability and safety rules as all other medicines,” Gemme points out, noting that many tools are used to guarantee traceability and observing that France already has “more than 10 years” of expe-rience on interchangeability and the use

of biosimilars in hospitals. The proposed policy was also supported by the lack of any related serious incidents reported in the European pharmacovigilance sys-tem, Gemme suggested.

FRENCH BIOSIMILARS ‘WELL BEHIND’ 80% PENETRATION TARGET

With biologics that are set to lose pat-ent protection by 2030 in France repre-senting sales of around €3.5bn ($3.8bn) when both hospital and outpatient use was taken into account, Gemme said, bio-similars were therefore “an essential axis” for the evolution of healthcare. This was reinforced by the French government’s decision to set a goal of achieving 80% biosimilar penetration for individual mol-ecules within their respective markets by 2022, as part of a broader five-year health-care strategy, the association added.

“However,” Gemme said, “it is clear that we are well behind this target, since the average penetration rate for biosimilars remains very low in France, finding itself even below 10% at the end of the first year of commercialization of a biosimilar.”

“Therefore, substitution – limited to the first issuance for certain types of drugs – would make it possible to un-block this market and to remove the bar-riers to its development, particularly in outpatient use.”

“Widespread penetration of biosimi-lars could generate substantial savings that would help reduce the growing economic pressure on generics and the manufacturing industry,” Gemme sug-gested. “The biosimilars market would in this way constitute a real growth-driv-

“Widespread penetration of biosimilars could generate substantial savings that would help reduce the growing economic pressure on generics and the manufacturing industry” – Gemme


BIOSIMILARS

er for a sector which has seen its value fall sharply in recent years.”

SPECIFIC CONDITIONS YET TO BE DEFINED

Emphasizing that the economic and practical considerations around such substitution “have yet to be defined” and would require “a different model to that of generics,” Gemme highlights in its position statement the much higher research and investment costs needed for biosimilars. “Gemme therefore wish-es to promote a sustainable economic model, which does not damage the market and from which each of the ac-tors can benefit.”

Defining such a model would re-quire consultation with healthcare authorities, pharmacists and doctors, Gemme acknowledges, but suggests that “its implementation could be pro-gressive in order to obtain the support of all the actors.”

The main pharmacist representatives “have already confirmed their agree-ment to a different economic model from that of generics, based on remu-neration for services provided,” Gemme said, “and which would allow the sav-ings generated to be shared fairly be-tween the pharmacist, prescriber and health insurance.”

Gemme’s attestations contrast with recent moves in Germany that have seen industry pushing back against proposals for a framework for biologi-cal substitution, including suggestions it could lead to tendering for biologics. A local physicians’ body has also warned that switching German patients from one biologic to another without involv-ing their doctor could cause patients to perceive biosimilars as having inferior safety and efficacy.

FRENCH LEGISLATION WILL ‘CLARIFY CONFUSION’

Responding to Gemme’s position state-ment, European off-patent industry as-sociation Medicines for Europe pointed to the fact that France’s social security financing law for 2020 had almost been finalized, noting that this would help to clarify issues around biologic substitution.

While various amendments relating to biologic substitution have been pro-posed as the ‘PLFSS 2020’ legislation has made its way through the country’s Senate and Assemblée Nationale, the latest version of the text adopted by the Assemblée Nationale offers some legal certainty around the fact that biologics cannot be substituted by a pharmacist without the involvement of the doctor.

Medicines for Europe director general Adrian van den Hoven told Generics Bulle-tin that the association “strongly encourag-es the French government to continue its efforts to stimulate competition from bio-similar medicines in the draft PLFSS 2020 which is up for vote in the coming weeks. This vote will clarify the confusion sur-rounding biologic substitution which the Biosimilar Medicines Group, a Medicines for Europe sector group, does not support.”

Commenting on Gemme’s position statement, van den Hoven warned that there was “growing evidence that limited healthcare stakeholder community en-gagement can impede biosimilar uptake and constrain the implementation of otherwise supportive policy measures.”

“As stated by French minister for soli-darity and health Agnès Buzyn,” he said, “we should not reiterate with biosimilar medicines mistakes that led to mistrust in generic medicines.”

“The Biosimilar Medicines Group of Medicines for Europe, representing the leading companies developing, manu-

facturing and marketing biosimilar medi-cines across Europe, has never advocated in favor of biologic substitution at phar-macy level,” van den Hoven highlighted.

“Uptake and price erosion – competi-tion – have been realised by many differ-ent means to date, sometime very suc-cessfully,” van den Hoven observed. “None of the means, however, involved pharma-cy substitution,” he emphasized.

“Physician involvement in switching has a proven track record of positive im-pact on biosimilar use while maintaining patient-centricity and expansion of ac-cess and is recognised by a large number of national medicines agencies, medical societies and patient groups.”

“Since 2006,” van den Hoven main-tained, “biosimilar medicines have prov-en to increase access with tremendous health benefits for patients and a wider array of treatment options for physi-cians.” And “several positive measures have been introduced in France to share the benefits of biosimilar medicines with patients, healthcare professionals and hospitals,” he acknowledged.

“Where competition has taken root, there has been a considerable increase of around 120% in patient access, a clear indicator that there were missing op-portunities to treat patients efficiently in the past. For this reason, there should be continued efforts to provide unbiased in-formation for the engagement of patient and healthcare practitioners.”

“We urge the French government to further widen the scope of benefit-shar-ing measures to encourage more use of biosimilar medicines for greater access,” van den Hoven concluded, “and for the sustainability of the healthcare system on which patients rely.”


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Three US Fingolimod Approvals Raise Legal StakesAIDAN FRY [email protected]

L egal stakes around potential gener-ic competition to Novartis’ second best-selling drug, the oral multiple

sclerosis therapy Gilenya (fingolimod), have been raised after the US Food and Drug Administration on 5 December ap-proved the first three generics. The US agency granted final approvals for fingo-limod hydrochloride 0.5mg capsules to Biocon, HEC Pharm and Sun Pharmaceu-tical Industries, having previously issued tentative approvals to Biocon and HEC due to their involvement in ongoing le-gal proceedings.

At the time of writing, none of the three companies holding final abbreviated new drug application approvals for generic rivals to Gilenya had commented on the approvals or their plans to bring the cap-sules to market. Investment bank Jefferies said it viewed at-risk launches as “unlikely.”

INJUNCTION AGAINST LAUNCHES GRANTED IN JUNE

For the immediate future, Novartis ap-pears to be well-placed to stave off com-petition. The Swiss originator, which has set its full-year 2019 financial guidance on the assumption that no generics to Gilenya enter the US market this year, in late June this year obtained a preliminary injunction barring launches by all parties involved in consolidated patent litigation in a Delaware district court.

More than 20 generics defendants had brought validity challenges to the latest-expiring patent listed against Gilenya in the FDA’s Orange Book, US dosage-regimen patent 9,187,405, which expires on 25 December 2027, including a six-month pediatric extension. Those chal-lenges were based on anticipation by the Kappos 2006 prior-art reference, lack of adequate written description, and lack of enablement of utility.

“At trial, defendants will likely fail to persuade me by clear and convincing evi-dence that the asserted claims of the ‘405 patent are invalid due to anticipation by Kappos 2006, or due to lack of adequate written description, or due to lack of en-ablement and utility,” District Judge Leon-

ard Stark stated upon issuing the injunc-tion, which remains in place.

Noting that pediatric exclusivity linked to the US fingolimod molecule patent 5,604,229 would protect Gilenya from competition until mid-August 2019, Stark noted in his June injunction ruling that the ‘405 patent was not eligible to trigger auto-matic 30-month stays on ANDA approval.

NOVARTIS STOOD TO LOSE CONSIDERABLE SALES

Stark said the generics defendants stood “to lose the opportunity to earn on the order of $50m collectively by not being able to compete over approximately the next year, whereas Novartis will irrepara-bly lose a market in which they sell ap-proximately $1.8bn of drugs each year.” Thus, he believed, the balance of harms favored the Swiss originator.

In the first nine months of this year, No-vartis recorded US Gilenya sales down by 1% to $1.302bn, representing just over half of the brand’s global turnover that slipped by 3% to $2.420bn, ranking it sec-ond among Novartis’ leading brands, just behind Cosentyx (secukinumab).

Asked about potential US generic competition to Gilenya on Novartis’ nine-month results call, group CEO Vas Nara-simhan told investors the injunction cov-ered “all generic manufacturers” involved

in the litigation. He refused to comment on court records showing recent dismiss-als of the case and settlements with firms including Mylan and Dr Reddy’s that add-ed to earlier confidential settlements with parties such as MSN, Nostrum and Par.

“We would expect at some point next year the start of a trial in the district court,” Narasimhan stated, adding that he also an-ticipated an appeal on an inter partes review by the US Patent and Trademark Office that had upheld the ‘405 patent as valid.

NOVARTIS CONFIDENT ON LEGAL POSITION

“Those are the next milestones with respect to Gilenya, but we feel very confident with our position, given the language used in the initial inter partes ruling, and the strength of our recent restraining order that was put in place. Overall, we feel good about where we are in this process,” he commented.

Commenting on the FDA’s approval of the first three generics of the oral treatment for relapsing-remitting multiple sclerosis, Janet Woodcock, director of the agency’s Center for Drug Evaluation and Research stated: “Approving safe and effective ge-nerics so patients have more treatment op-tions continues to be a priority for the FDA.”

“Having access to affordable treatments is important for patients with conditions that require ongoing care. The FDA has a longstanding commitment to increasing patient access to lower-cost, high-quality generic medicines,” Woodcock stressed.

The FDA said addressing the challenges related to developing generics and promot-ing more generic competition was a key part of its Drug Competition Action Plan and the agency’s efforts to help increase pa-tient access to more affordable medicines.

If generic fingolimod capsules enter the US, it would act as a further blow to Novar-tis after Teva and Pharmascience recently launched rivals in neighboring Canada fol-lowing the discontinuation of legal disputes over Canadian dosage regimen patent 2,653,569, which expires in June 2027.


“We would expect at

some point next year

the start of a trial in

the district court”

– Vas Narasimhan


BIOSIMILARS

Do you havemoney to burn?Your old NDAs and ANDAs are VALUABLE ASSETS and withdrawing them from theOrange Bookis like BURNING MONEY.

Don’t make the same mistake other owners have already made!For more information: [email protected]

No matter the condition of your A/NDA, it should never be withdrawn

from the Orange Book.We will make you a cash offer, regardless

of the condition or age of your file.

Remember: Once approval of your A/NDA is withdrawn,

there is no way to bring it back!



PRICE WATCH UK

RECENT LAUNCHES

PRODUCT/STRENGTH/PACK SIZE

OCT 2019

MINIMUM

MINIMUM

CHANGE

(%)

OCT 2019

AVERAGE

AVERAGE

CHANGE

(%)

Aripiprazole Tabs 10mg 28 £0.45 -6% £1.02 -3%

Carbimazole Tabs 5mg 100 £2.96 -15% £9.04 -15%

Celecoxib Caps 200mg 30 £2.70 -18% £6.37 -8%

Duloxetine E/C Caps 30mg 28 £0.59 -9% £1.35 5%

Eplerenone Tabs 25mg 28 £1.99 0% £4.43 14%

Escitalopram Tabs 10mg 28 £1.20 -20% £3.07 -9%

Etoricoxib Tabs 90mg 28 £1.24 -17% £2.44 2%

Ezetimibe Tabs 10mg 28 £0.75 -4% £1.20 3%

Febuxostat Tabs 80mg 28 £3.22 -4% £8.79 -18%

Frovatriptan Tabs 2.5mg 6 £3.13 9% £6.23 16%

Ivabradine Tabs 5mg 56 £3.06 1% £4.25 3%

Nefopam Tabs 30mg 90 £3.55 0% £14.21 62%

Nortriptyline Tabs 10mg 100

£3.35 -21% £6.54 -2%

Comparison between the periods 1-31 October 2019 and 1-30 November 2019 of UK trade prices of the most recently-launched generics listed in category M of the Drug Tariff of pharmacy-reimbursement prices. Averages calculated from at least 17 data points (Source - WaveData)

Up to the minute live retail market pricing is available at wavedata.net and historical prices at https://www.bppi.co.ukAlternatively, contact WaveData at [email protected] or +44 (0)1702 425125

ANALYZE

Further information related to this story is available here: https://bit.ly/2tgoEVl

RECENT LAUNCHES

PRODUCT/STRENGTH/PACK SIZE

OCT 2019

MINIMUM

MINIMUM

CHANGE

(%)

OCT 2019

AVERAGE

AVERAGE

CHANGE

(%)

Olmesartan Medoxomil Tabs 10mg 28

£0.67 -11% £1.20 0%

Prasugrel Tabs 10mg 28 £3.85 -2% £7.32 -15%

Pregabalin Caps 150mg 56 £1.62 -4% £3.19 -2%

Rasagiline Tabs 1mg 28 £1.28 -8% £1.96 4%

Rosuvastatin Tabs 5mg 28 £0.45 0% £1.05 15%

Sevelamer Tabs 800mg 180 £48.90 -22% £86.71 -1%

Solifenacin Tabs 5mg 30 £2.63 32% £5.52 6%

Tacrolimus Ointment 0.1% 30g

£15.60 0% £19.23 -1%

Tadalafil Tabs 10mg 4 £0.44 -23% £0.97 -5%

Travoprost Eye Drops 40mcg/ml 2.5ml

£1.55 -8% £2.54 4%

Vardenafil Tabs 20mg 4 £8.20 12% £14.81 3%

Zonisamide Caps 100mg 56 £2.05 -5% £4.56 8%

Concessions Hit And Miss As Some UK Prices TrebleDAVID WALLACE [email protected]

C oncession prices granted by the UK Department of Health and Social Care were hit and miss in

November, according to the latest figures from market researcher WaveData.

Of the eight presentations highlighted by WaveData in its ‘Biggest Risers’ table – based on UK trade prices to independent pharmacists in November – some of the top presentations failed to receive conces-sions, while others received concessions that were out of line with the market reality.

According to the list of November price concessions published by the UK Phar-maceutical Services Negotiating Commit-tee, no concessions were granted by the DHSC for gamolenic acid 40mg capsules in 240-count packs and 80mg capsules in 120-count packs, which saw their average prices rise by 216% to £15.31 ($20.41) and by 212% to £15.33 respectively.

Neither was a concession granted for aspirin 75mg dispersible tablets in 1,000-count packs that experienced a 130% average rise to £14.31.

However, a concession was granted

for nitrazepam 5mg tablets in 28-count packs that saw an average rise of 202% to £2.96, albeit with the DHSC’s concession price falling slightly short at £2.49.

The opposite was true for 56-count packs of lamotrigine 25mg dispersible tab-lets that were granted a concession price of £18.20, way above the average recorded by WaveData that rose by 167% to £4.36.

Meanwhile, 28-tablet packs of propran-olol 10mg and 40mg that saw average price rises of 125% to £2.54 and 147% to £2.91 were granted £2.00 concessions.

Rounding out the concessions for our Biggest Risers, ranitidine 150mg tablets in 60-count packs were granted a concession of £4.07 that was a close match for the ac-tual average that leapt by 137% to £3.86.

TEVA PRICE CUT LEADS AZITHROMYCIN TO FALL

Meanwhile, the Biggest Fallers table for No-vember showed packs of four azithromycin 250mg capsules experiencing an average price drop of 30% to £1.47. “The double-digit average price drop is due to Teva drop-

ping its prices,” WaveData observed.Packs of six azithromycin 250mg cap-

sules saw their average price fall by just under a quarter to £1.91.

Presentations of tadalafil, montelukast, olanzapine, paracetamol, indomethacin and carbimazole followed with average declines of between 29% and 20%. On tadalafil 5mg tablets, WaveData noted that AAH, Alliance, DE and OTC Direct had all dropped their prices.

Moving on to Recent Launches, nefopam 30mg tablets stood out with a 62% average price rise in November. This presentation was granted ‘no cheaper stock obtainable’ status in November, WaveData comment-ed, “when we saw a number of wholesalers/manufacturers increase their prices.”

On the celecoxib price decline, Wave-Data noted that “Numark, DE and Accord dropped their prices in November,” while “the double-digit minimum price de-crease was due to some low offers being made by Elite Pharma.”



REGULATION

Global Industry Hails Bioequivalence ProgressAIDAN FRY [email protected]

T he formal adoption by the Inter-national Council for Harmoniza-tion’s general assembly of a new

topic on bioequivalence for immediate-release solid oral dosage forms has been welcomed by the International Generic and Biosimilar Medicines Association. During its most recent meeting held in Singapore last month, the ICH assembly agreed a concept paper outline for the M13 bioequivalence topic and decided to establish “without delay” a new work-ing group to work on finalizing the con-cept paper and devise a business plan.

“This is the first topic since the ICH re-organization in 2016 that is specifically fo-cused on the generic medicines industry,” pointed out the ICH assembly and man-agement committee member represent-ing the IGBA, Nicholas Cappuccino. “The support of both the regulators and other industry members of the ICH assembly is appreciated given the many priorities for new ICH harmonization topics and the re-sources necessary from all parties to sup-port guideline development,” he added.

STEP TOWARDS OPTIMIZING PRODUCT DEVELOPMENT

Pointing out how essential bioequivalence studies were in establishing the safety and efficacy of immediate-release, solid-dose generics, the IGBA said scientific harmo-nization of study designs for such studies would “allow the streamlining of some important aspects of the conduct of these trials and optimize product development.”

“IGBA membership therefore awaits with excitement the activation of this topic at ICH which will open the door for subsequent important discussions and ICH guidelines on the global development of affordable generic medicines, which are paramount for increasing patient access,” commented the global industry association, which joined the ICH as an industry member of the general assembly in June 2016, and was elected by the assembly to the ICH’s man-agement committee two years later.

Since joining the management com-mittee in 2018, IGBA representatives have worked to ensure that harmoniza-

tion issues of importance to the global generics and biosimilars industries find a place on the ICH’s work schedule.

Significant progress was made at the start of this year, when the ICH published a reflection paper on harmonizing technical and scientific standards for generics that envisaged initially developing guidelines on bioequivalence standards for non-complex oral dosage forms, followed by guidance on more complex dosage forms or products. An informal generic drug dis-cussion group (IGDG) is also to be estab-lished to identify opportunities to include generics in other ICH guidelines.

IGBA PUSHING TO HARMONIZE STANDARDS

In an exclusive interview with Generics Bulletin conducted shortly after the pub-lication of that reflection paper, IGBA sec-retary-general Suzette Kox and chair Jim Keon described the paper as “a recognition by the ICH assembly of the importance of generic medicines in healthcare and the value of harmonization of technical stan-dards to guarantee access to high-quality generic medicines to patients worldwide.”

“An active participation in ICH is an IGBA priority,” Kox stated. “IGBA-nominated ex-perts will need to take a leadership role in the new IGDG,” she said, particularly when it came to scientific contributions and of-fering the benefits of long-standing indus-try experience. “Harmonizing standards is an essential part of an international regu-latory framework, allowing true global generic drug development,” she stressed.

The M13 topic on bioequivalence for immediate-release solid oral dosage forms had been supported in principle during the ICH’s previous biannual meet-ing held in June this year. During the lat-

est meeting held from 16-20 November, the ICH’s 16 members and 32 observers formally adopted the topic, along with a proposal to revise its Q9 guideline on quality risk management.

However, while the assembly decided to delay the Q9 revision in light of other ongoing quality work, it said a new work-ing group for the M13 bioequivalence topic should be set up immediately to start work on finalizing a concept paper and business plan.

EXTRACTABLES AND LEACHABLES GROUP SET UP

Furthermore, the assembly is also es-tablishing a new working group to start work on its Q3E guideline on assessing and controlling extractables and leach-ables for pharmaceuticals and biologics. This topic had been adopted in June, but with a delayed start time.

In total, 14 working groups convened during the ICH’s Singapore meeting, six of which were recently created to work on new topic proposals. The regulatory body described as “particularly noteworthy” the adoption by assembly members – Step 4 in the ICH process – of a new Q12 guideline on technical and regulatory considerations for pharmaceutical product lifecycle man-agement, which was finalized by its work-ing group during the meeting last month.

The ICH said this guideline comple-mented its Q8 to Q11 quality guides and was intended “to promote innova-tion and continual improvement in the pharmaceutical sector, and strengthen quality assurance and reliable supply of product, including proactive planning of global supply chain adjustments.”

According to the ICH, its Q12 guideline “provides a framework to facilitate the management of post-approval chemis-try, manufacturing and controls (CMC) changes in a more predictable and ef-ficient manner across the product life-cycle.” This, the body said, would allow regulatory assessors and inspectors to better understand companies’ pharma-ceutical quality systems for managing post-approval CMC changes.



REGULATION / STRATEGY

The assembly also welcomed the fi-nalization by two working groups not meeting in Singapore of Step 4 adoption processes for the E9(R1) addendum to de-fining the appropriate estimand for clini-cal trial/sensitivity analyses and for the new M9 guideline on biopharmaceutics classification system-based biowaivers.

BIOWAIVERS GUIDELINE REACHES ADOPTION STEP

The M9 guideline, along with its question-and-answer document, provides recom-mendations to support biopharmaceutics classification of medicines and waiving bioequivalence studies. “This guideline will reduce the costs and time of develop-ment and prevent unnecessary exposure of mostly healthy volunteers to medicinal products, as in vivo studies to prove the biopharmaceutical quality of the medici-nal product would not be needed, and therefore, facilitate the patient’s access to medicines or post-approval changes,” the ICH asserted.

Following a recent public meeting on its draft revised E8(R1) guideline on gen-eral considerations for clinical trials that was held at the headquarters of the US Food and Drug Administration in Silver Spring, MD, the ICH assembly is con-sidering opportunities for other work-ing groups to “gather stakeholder input through similar outreach activities.”

The Singapore meeting also saw the ICH assembly re-elect the European Com-mission’s Lenita Lindström-Gommers as chair and Health Canada’s Celia Lourenco as vice-chair, each to serve a two-year term. The FDA’s Theresa Mullin and No-bumasa Nakashima from Japan’s Ministry of Health, Labor and Welfare/Pharmaceu-ticals and Medical Devices Agency were re-elected by the ICH management com-mittee as chair and vice-chair respectively for one-year terms; while representatives from Brazil’s Anvisa regulatory agency were elected by the assembly to the ICH management committee.

The next ICH meeting will take place on 23-27 May 2020 in Vancouver, Canada. At its following biannual meeting in Novem-ber 2020 to be held in Athens, Greece, the ICH plans to commemorate its 30th anni-versary by organizing a conference.


Julphar Focuses On Quality As Carle DepartsAIDAN FRY [email protected]

T roubled United Arab Emirates drugmaker Julphar says it is focusing on “improv-ing quality procedures” to overcome bans on exports to countries including Saudi Arabia, Bahrain, Kuwait and Oman. A new management team is trying to

revive the flagging firm’s fortunes after CEO Jerome Carle departed on 8 December.Julphar’s dramatic downturn in fortunes over the past year has stemmed from export

bans following inspections of its key facility in Ras Al Khaimah, UAE, that have shut off many of its main markets in the Middle East region.

After an audit of the plant conducted in September 2018, the Saudi Food and Drug Authority imposed a suspension on the company exporting its products to Saudi Ara-bia and Bahrain. Stressing that it had been working with the SFDA to address all of the issues highlighted in the inspection report, Julphar said it expected the Saudi authority to re-inspect its facility during the first quarter of next year.

EXPECTING RE-INSPECTIONS IN NEAR FUTUREBy the end of this year, Julphar believes the Gulf Health Council will revisit the Ras Al Khaimah factory on which the authority had placed an export ban to Kuwait and Oman following an inspection conducted in May 2019. The UAE-based company is also hope-ful that its domestic ministry of health will soon clear for sale batches of several prod-ucts that were recalled due to stability concerns.

Following a successful inspection by the UAE ministry of health, the firm says its Jul-phar VI plant has reopened, enabling it to reintroduce its portfolio in its home market. Around 20 product launches are scheduled during the fourth quarter of 2019 and the first quarter of 2020, “covering a broad range of therapy areas.”

At a gross level before discounts and rebates, the UAE accounted for 28% of Julphar’s group turnover in the first nine months of this year, with Saudi Arabia contributing less than 1%.

TURNOVER SLUMPED BY TWO-THIRDSThe company’s net turnover plummeted by two-thirds in the same period to AED222.6m ($60.6m). This resulted in a loss at gross profit level of AED80.3m, while the group’s oper-ating loss was AED351.9m versus AED14.7m in the prior-year period.

Referring to an accumulated loss attributable to equity holders of AED385.2m, equiva-lent to a third of the firm’s capital, auditor Ernst & Young repeated its mid-year warning that “a material uncertainty exists that may cast significant doubt on the group’s ability to continue as a going concern.”

But Julphar – which also trades as Gulf Pharmaceutical Industries – is keen to strike a note of optimism, not only that the export suspensions “will soon be lifted,” but also in light of operational reforms it has undertaken with the help of outside consultants amid a shake-up of senior management.

With the UAE-based company’s board having accepted former Sanofi executive Carle’s resignation as CEO from 8 December, the company in October announced the appointment of Jürgen Lauterbach as chief finance and strategy officer “as part of com-prehensive changes in the executive management structure.”

EX-HIKMA BOSS LAUTERBACH LEADS STRATEGYThe former Fresenius Kabi executive has assumed responsibility for financial operations, tenders, supply chain, logistics and sales operations, strategy and business development. Julphar said Lauterbach, who most recently led Hikma’s Asia-Pacific operations from an office in Hong Kong, would be “tasked with driving a transformation program across all Julphar operations, as well as with developing and implementing the company roadmap.”

Under its revamped management team that also includes recent recruits Georges Ibra-


STRATEGY

him as chief quality officer, Manoj Panan-chukunnath as chief scientific officer and Rita Karam as head of legal affairs, Julphar says it has begun to roll out a “stringent, overhauled quality-control framework guided by international best practice.”

“Customer health and safety sit at the heart of Julphar’s corporate strategy and operations. We are firmly commit-ted to the roll-out of a new, stringent quality-control framework and will re-main focused on keeping the company on track towards its vision,” the group in-sisted. “Julphar has almost four decades of experience in delivering high-quality, innovative and affordable healthcare solutions to families across the globe, and we strongly believe that we will be able to showcase the resilience of our business model.”

The company is also starting to sell off

loss-making non-core assets, such as its wholly-owned Gulf Inject medical sup-plies business in the UAE, as well as its 50.5% holding in its RAK Pharmaceuti-cals venture in Dhaka, Bangladesh.

Commenting on his departure, former Peugeot and Ford executive Carle ex-pressed pride at what the Julphar team had achieved in “improving access to medicines for millions of families across the world.”

“We have launched innovative medicines, built new alliances and partnerships, imple-mented new systems, new culture and built solid foundations for the future,” he main-tained. “From my side, I will be opening a new chapter of my life that will continue to be focused on serving people, patients and consumers across the world.”


“I will be opening a

new chapter of my life

that will continue to

be focused on serving

people, patients and

consumers across the

world” – Jerome Carle

STRATEGY

Hikma And Civica Ship Eight Essential InjectablesDAVID WALLACE [email protected]

H ikma and Civica Rx have announced “imminent shipments” of heparin as well as seven other essential inject-

able medicines in the US, with additional products to follow “in the near term.”

Earlier this year, Hikma and Civica struck a five-year supply deal that will see Hikma manufacture and supply the US firm with 14 essential sterile injectables, as part of Civica’s mission to supply drugs that are often in short supply in US hospitals. Un-der the agreement, Hikma will produce the injectables for Civica as a private la-bel distributor, using Hikma’s abbreviated new drug applications and Civica’s label-ing and national drug code.

“Today’s announcement comes as indus-try experts work to avoid an extended short-age of heparin, the preferred anticoagulant for many hospitalized patients,” Hikma and Civica pointed out, suggesting that shortag-es of the drug – derived from porcine intes-tinal mucosa – could be due to an outbreak of African swine fever that has killed “an un-precedented number of the world’s pigs.”

“The outbreak has predominantly im-pacted China, home to half of the world’s swine population,” Hikma noted. How-

ever, it pointed out, “Hikma sources its heparin raw materials from the US, and has not been impacted.”

The firm also recently chose heparin as its first injectable in the US to be made avail-able in a pre-filled syringe presentation.

FURTHER INJECTABLES TO FOLLOW HEPARIN

As well as heparin, Civica and Hikma said they would be shipping seven further drugs – covering “essential shortage medications” – before the end of the year. These included opioid antagonist naloxone; steroid dexa-methasone; surgical drug glycopyrrolate; prochlorperazine and ondansetron, used to control nausea and vomiting caused by chemotherapy; morphine; and metoprolol.

“We are thrilled to be delivering on our partnership’s promise to ensure vital medi-cations are consistently available for hos-pitals and patients who need them,” said Martin VanTrieste, Civica’s president and CEO. “These shipments reinforce our con-fidence in Hikma’s expertise and manufac-turing capabilities.”

It was “especially gratifying that the initial deliverable of our partnership will

help ensure an increased supply of hepa-rin at a time when there is an ongoing threat to supply,” VanTrieste observed.

Meanwhile, Hikma’s injectables president, Riad Mishlawi, insisted that “as a leading provider of generic injectable medicines, Hikma is committed to working across the US healthcare system on long-term, sustain-able solutions to help ensure a consistent supply of needed medicines to patients.”

“Our partnership with Civica is an excel-lent example of combining Hikma’s strong manufacturing capabilities and strong quality and supply record with Civica’s ex-tensive network of more than 1,100 US hos-pitals,” Mishlawi added. “We are pleased that patients and healthcare providers across the country will now begin benefiting from Civica’s forward-thinking approach.”

Hikma CEO Siggi Olafsson recently told Generics Bulletin that stepping in to provide injectable drugs that are in short supply in the US was paying off for Hikma in terms of stronger and deeper relation-ships with hospitals and their group pur-chasing organizations.




DEALS

Amneal Takes Control Of AvKARE In USDAVID WALLACE [email protected]

Amneal has struck a deal to ac-quire a majority 65.1% share in AvKARE, a US manufacturer and

wholesaler that is “one of the largest pri-vate-label providers of generic pharma-ceuticals in the US federal agency sector.”

Primarily focused on serving the US De-partment of Defense and Department of Veterans Affairs, AvKARE’s customer base also includes the US Army, Air Force, Navy and Marines, NASA and the Department of Agriculture.

Amneal said that acquiring control of AvKARE would provide “a unique oppor-tunity for Amneal to diversify our busi-ness and open growth opportunities in the large, complex and growing federal healthcare market.” The company “utilizes its relationships with more than 50 generic pharmaceutical vendors to offer a propri-etary line of specially packaged products under its own labels.”

Noting that the deal for a 65.1% majority interest in AvKARE and its related affiliate R&S Northeast implied an enterprise value of $340m, Amneal said that following the close of the transaction – which is expect-ed in early 2020, subject to customary clos-ing conditions and regulatory approvals – AvKARE would operate “on a standalone basis as an independent subsidiary of Am-neal.” AvKARE generated earnings before interest, tax, depreciation and amortiza-tion (EBITDA) of around $63m in the year ended 31 October 2019.

Observing that “compliance with regu-lations governing federal procurement of pharmaceuticals is highly complex and requires specialized capabilities, creating

significant barriers to entry for market en-trants, including generic manufacturers,” Amneal said AvKARE’s management team had “more than 50 years of collective expe-rience and expertise providing affordable generic pharmaceuticals to federal agency healthcare providers.” AvKARE also offers a network of warehouses “strategically lo-cated across the continental US.”

PATELS’ STRATEGY FOR AMNEAL INCLUDES M&A

Shortly after Chirag Patel and Chintu Patel returned to being co-CEOs of Amneal ear-lier in 2019 – just over a year after the firm completed its merger with Impax – they said the firm was open to evaluating po-tential merger and acquisition opportuni-ties, even as it looked to restore organic growth through a greater focus on differ-entiated generic and hybrid products.

And as part of a major turnaround plan for Amneal recently unveiled by the Pa-tels, they acknowledged that the firm was actively evaluating small-scale transac-tions in the US.

“When we re-joined Amneal as co-CEOs in August, we outlined a vision for our long-term strategy,” the Patels said. “While we re-main extremely focused on organic growth, we also recognized that M&A would be a key element of our growth story, and that we would pursue the right opportunities that strategically fit our business.”

“We articulated what we would look for: opportunities to complement our exist-ing distribution network, provide us with defensible, durable revenue streams and, ultimately, earnings that are accretive to

ours. The AvKARE transaction meets all of these criteria, and we are excited about the value we expect it will create for patients, shareholders and other stakeholders.”

“Amneal is among the largest generic drug companies domiciled in the US, and prioritizing our American operations and customers remains a top priority. With AvK-ARE, we believe Amneal will be well-posi-tioned to utilize our extensive US-based manufacturing network to supply products to the federal healthcare market. We look forward to completing the AvKARE trans-action and strengthening our focus on pro-viding affordable medicines to patients.”

FOUNDING SHIRLEY FAMILY WILL STAY ON AS MANAGEMENT

Under the terms of the transaction, Amne-al said it would acquire its majority interest “through an unrestricted subsidiary, which will finance the purchase of AvKARE with a new $180m senior secured term loan facil-ity, approximately $75m of balance sheet cash and an approximately $44m seller note, with the balance of the implied enter-prise value contributed through the selling shareholders’ rollover interest in the newly formed subsidiary. The new debt financ-ing will be secured by the newly-formed unrestricted subsidiary and will not impact Amneal’s existing term loan facility.”

AvKARE’s founders, the Shirley family, will retain the contributed rollover interest and will continue to “independently man-age the operations of the business,” with the firm’s leader reporting to Chirag Patel.

Steve Shirley, CEO of R&S Northeast and vice-president of AvKARE said the firms were “pleased to enter into this transaction with Amneal, a leading provider of afford-able medicines to federal agencies and one of our long-term business partners.”

Noting that the Shirley family would “continue to retain a large ownership in-terest in AvKARE,” Shirley said “we look for-ward to continuing to utilize our expertise in supplying affordable generic pharma-ceuticals to federal agencies through our diverse vendor portfolio.”



LAUNCHES

Endo And Teva Are First With US EverolimusAIDAN FRY [email protected]

E ndo International’s Par Pharmaceu-tical and Teva have become the first two companies to secure final ap-

provals from the US Food and Drug Ad-ministration for generic versions of Novar-tis’ Afinitor (everolimus) tablets for treating breast and other cancers.

A day after receiving approval for its everolimus 2.5mg, 5mg and 7.5mg tablets, Par announced that “product is available for immediate shipping.” Teva, which holds ap-proval for the same three strengths as well as for 10mg tablets, had not commented on its launch plans at the time of writing, and everolimus did not feature in the company’s US online product catalog. A Teva spokes-person contacted for comment on the firm’s launch plans has yet not responded.

“We are pleased to bring the first generic Afinitor to market and provide patients with a lower-cost option,” stated Domenic Ciarico, who earlier this year stepped up to become executive vice-president and chief commer-cial officer, Sterile & Generics at Endo. “This launch is a testament to Par’s expertise in manufacturing technically challenging prod-ucts while maintaining excellence in quality.”

Endo, which cited IQVIA data putting an-nual US sales of Afinitor 2.5mg, 5mg and 7.5mg tablets at $412m, obtained tentative FDA approval for everolimus 2.5mg, 5mg, 7.5mg and 10mg tablets in early August this year. Declining to address any entitle-ment to 180-day generic market exclusiv-ity in its tentative approval letter, the FDA noted that its Orange Book listed seven unexpired patents against Afinitor tablets.

PATENT LITIGATION IN DELAWARE COURT

Due to its filing date, one patent – US pat-ent 7,741,338 that expired on 6 December this year – did not require any certification from Endo, which submitted paragraph IV certifications on patent invalidity or non-infringement against the other six listed patents. Charges of infringement brought by Novartis over US patents 7,297,703, for which a pediatric extension expires on 6 June 2020, and 8,436,010 that runs until 22 August 2022, again with pediatric ex-clusivity, were dismissed by a Delaware

district court. But in May this year, the court ordered that Endo’s ANDA should not be approved until pediatric exclu-sivity attached to US patent 5,665,772 expires on 9 March 2020, unless the two parties reached a settlement agreement.

Afinitor was one of three key brands on which Endo said during its third-quarter in-vestors’ call that it had reached legal settle-ments on confidential terms, allowing for US market launches from “late 2019 and beyond.” The other two were Dexilant (dex-lansoprazole) delayed-release capsules and Gattex (teduglutide) for subcutaneous injection. Also under litigation settlements, Endo expects to introduce generics of Cip-rodex (ciprofloxacin/dexamethasone) otic suspension and Kuvan (sapropterin) tab-lets and powder next year, followed in the first quarter of 2021 by a generic of Amitiza (lubiprostone) soft-gel capsules.

On the third-quarter call, CEO Paul Cam-panelli, who is stepping down from the role for personal reasons, said Endo held exclusivity for three out of four everolimus tablet strengths, representing around half of the $800m annual market for the can-cer drug in the US.

While Novartis has reached settlements with certain ANDA filers over Afinitor, it has successfully enforced its intellectual-prop-erty rights against other filers. In May this year, the US Court of Appeals for the Federal Circuit upheld the validity of the origina-tor’s US method-of-use patent 8,410,131 that claims methods of using everolimus to treat advanced renal cell carcinoma. Hikma unsuccessfully argued that the key claims of the ‘131 patent, which expires in May 2026, were obvious in light of prior-art references.

Reporting US sales of Afinitor ahead by 12% to $759m in the first nine months of this year – including a third-quarter 18% leap to $266m – Novartis pointed out that its US everolimus compound patent had been upheld, as had its ‘131 renal cell car-cinoma use patent both in ANDA litigation and in an inter partes review. Acknowledg-ing that it had reached litigation settle-ments with several generic manufacturers, the Swiss group said these deals “may result in limited generic competition for Afinitor towards the end of 2019, and additional generic competition starting in mid-2020.”

Novartis identified generic competition to Afinitor, as well as to its deferasirox-based Exjade and Jadenu brands, as po-tential drags on its financial performance in the fourth quarter of this year.

REDDY’S ROLLS OUT DEFERASIROX PRODUCTS

Dr Reddy’s Laboratories has just introduced in the US generic rivals to Exjade 125mg, 250mg and 500mg tablets for oral suspen-sion as well as to Jadenu 90mg, 180mg and 360mg film-coated tablets. The Indian firm put US Exjade sales at $113m in the year ended September 2019, according to IQVIA data, while Jadenu sales in the same period were around $470m.

Novartis reported nine-month US sales of the two treatments for chronic iron overload down by 7% to $355m. Compa-nies including Alembic, Alkem, MSN, Sun Pharma, Teva and Zydus Cadila currently hold FDA approvals for generic deferasirox drugs equivalent to Exjade and Jadenu.



BIOSIMILARS


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IGBA Urges WIPO To Revoke Patent Database SupportDAVID WALLACE [email protected]

T he World Intellectual Property Or-ganization should revoke its sup-port for a global database of pat-

ent information backed by brand body the International Federation of Pharma-ceutical Manufacturers & Associations, according to the International Generic and Biosimilar Medicines Association.

The IGBA argues that the Pat-IN-FORMED database contains unverified data and lacks appropriate safeguards, making it inappropriate for a United Na-tions agency such as WIPO to endorse.

Introduced in late 2018, the Pat-IN-FORMED database was launched by the IFPMA, WIPO and 20 big pharma compa-nies as a tool to be used by governments to improve medicines procurement pro-grams. While the brand industry argues that the database clearly links public pat-ent information to registered medicines, the off-patent industry has complained that it amounts to patent linkage and will have anti-competitive effects on generics.

‘UNVERIFIED PATENT INFORMATION’“Since September 2018,” the IGBA points out, “WIPO has hosted the IFPMA patent database Pat-INFORMED on its website. This database is simply a posting of unver-ified patent information provided directly by originator pharmaceutical companies.”

In particular, the IGBA points out, “WIPO specifically exempts itself and IF-PMA member companies from any and

all liability for the provision of false or in-accurate information.”

While the IGBA has welcomed some im-provements in the presentation of the da-tabase – including “changes to the WIPO landing page making it more transparent that the data is provided by the compa-nies and that WIPO simply hosts it” – the international off-patent industry body maintains that “the hosting of an unveri-fied industry database by WIPO and with-

out safeguards remains unacceptable.”In a position statement published by

the IGBA, the association argues that the Pat-INFORMED database’s information is “not reliable for procurement purposes as it is supplied and verified by the very originator companies that stand to profit from perceived patent uncertainties.”

“At the very least, Pat-INFORMED directs procurement authorities to contact IFPMA member companies to verify the patent information posted on the WIPO website and, under a cloud of patent uncertainty, provides originator pharmaceutical com-panies with the potential opportunity to negotiate directly with authorities, limit-ing generic companies from an opportu-nity to compete and provide affordable medicines to countries that need them the most,” the IGBA states.“WIPO’s mandate is to promote the pro-tection of intellectual property through-out the world through the co-operation of its member states,” the IGBA maintains. “It is not to promote unverified patent information provided directly by pharma-ceutical companies.”

While the IGBA has raised conflict of in-terest concerns with WIPO’s International Bureau, it says that “these concerns have not been recognized or acknowledged by WIPO to date.”

“By continuing to host the database of IFPMA member companies, WIPO sacri-fices its credibility and weakens its inde-pendence,” the IGBA argues.

Despite attempts by WIPO and IFPMA to absolve themselves of responsibility for flaws in the accuracy of the database’s information, they must still be held ac-countable for promoting the resource, the IGBA maintains.

“The Pat-INFORMED database includes an exceptionally strong disclaimer in the terms of use and the limitations of liability of Pat-INFORMED, whereby WIPO, IFPMA and originator companies accept no liabil-ity for the accuracy of the information con-tained in the database,” the IGBA points out.

“Despite this, WIPO remains accountable for the decision to partner with IFPMA and its pharmaceutical companies, for the pro-

“WIPO’s mandate is to promote the protection of intellectual property

throughout the world through the co-operation of its

member states. It is not to promote unverified

patent information provided directly

by pharmaceutical companies.” – IGBA



INTELLECTUAL PROPERTY / BIOSIMILARS

motion of their unverified patent informa-tion, and for not providing a mechanism to ensure the accuracy of the information provided, as well as for not including the necessary safeguards to limit misuses or abuses of the Pat-INFORMED system.”

IGNORES GOVERNMENT INVOLVEMENT REQUIREMENT

Moreover, the IGBA says, the Pat-INFORMED database runs against the advice of a UN panel on access to medicines by not directly involving governments in the database.

The UN secretary general’s high-level panel on access to medicines final report stipulated in 2016 that “governments should establish and maintain publicly accessible databases with patent infor-mation status and data on medicines and vaccines,” the IGBA notes.

But the Pat-INFORMED database “does not represent a response to this recom-mendation” as it “completely ignores the requirement for the involvements of governments in the initiative,” the asso-ciation argues.

“Further, the high-level panel on access to medicines in no way recommended that the patent information be contained in a publicly-available database containing information provided by originator phar-maceutical companies. Instead, the recom-mendation stipulates that the information would be provided by governments.”

While the IGBA insists that it “welcomes initiatives helping to navigate the maze of patent information,” it concludes that “given the potential negative impact of Pat-INFORMED on pharmaceutical compe-tition, procurement and public health, we believe WIPO should revoke its support for this initiative and advise IFPMA to limit the hosting of its database to its own industry-sponsored website where it belongs.”

Early this year, the IGBA sent a letter to WIPO director general Francis Gurry set-ting out its complaints about the Pat-IN-FORMED database, including that it serves as a tool for patent linkage, contains no mechanisms to ensure accuracy, and is inappropriate for a UN agency to endorse.

IGBA chair Jim Keon suggested strength-ening the World Health Organization’s prequalification system as an alternative to the “flawed” Pat-INFORMED database.


Polpharma Pursues Tysabri Through Antelope TrialAIDAN FRY [email protected]

P olpharma Biologics has started randomizing patients in its Phase III study com-paring the safety and efficacy of its PB006 natalizumab candidate to Biogen’s Tysabri. In total, the company expects to enrol a relatively modest 260 patients

in the 48-week trial.To support its clinical programs, the biosimilars developer has just recruited

Karsten Roth as director of clinical research and development. Former Mundiphar-ma, Cinfa Biotech and Sandoz clinical expert Roth will at Polpharma Biologics work alongside his former Sandoz colleague Alexandra Moulson, who recently joined the company as director of portfolio and strategy, as well as director of the firm’s project management office.

Roth is now leading the natalizumab program, supported by Hendrik Wessels from Polpharma Biologics’ clinical development team. The company has recently enrolled its first adult patients with relapsing-remitting multiple sclerosis at a clini-cal site in Katowice, Poland, in its ‘Antelope’ Phase III study that is also referred to internally as PB006-03-01.

SEVEN COUNTRIES INCLUDE POLAND AND GEORGIAPolpharma Biologics – which has a global commercial alliance for natalizumab with Sandoz – says the study will span seven countries, both within and outside Europe. At present, an entry for the Antelope multi-center, randomized, parallel arm, double-blind study within the US ClinicalTrials.gov register lists six clinical locations in Poland, including the Katowice site, as well as a further four hospitals and clinics in Georgia.

Intended to assess the equivalence in efficacy and similarity in safety of biosimilar PB006 compared to Tysabri in patients with relapsing-remitting multiple sclerosis, the primary outcome measure is evaluating and comparing the change in the cumu-lative number of new active lesions from baseline to week 24.

The 48-week study will see approximately 260 adult patients randomized to receive 12 intravenous 300mg doses, administered every four weeks, of either PB006 or EU-licensed Tysabri. The end-of-study patient visit will be conducted at week 48, four weeks after the final infusion. The listed start date for the study is 1 October 2019, while the estimated study completion date is August 2021.

European supplementary protection certificates for Tysabri based on European patent EP0,804,237 are set to expire in late-July 2020, including six-month pediat-ric extensions. Biogen also holds European patent EP1,485,127, which claims uses


BIOSIMILARS

for reducing inflammation and expires in February 2023. However, Polpharma Biologics and its affiliates have enjoyed notable successes in invalidating the ‘127 patent for lack of novelty and in-ventive step in countries including Ger-many and the Netherlands.

COMMERCIAL DEAL FOR NATALIZUMAB WITH SANDOZ

The recent decision of the Dutch court in favor of Polpharma’s Swiss Pharma In-ternational subsidiary also benefits San-doz, which struck a global licensing deal giving it commercial rights to the PB006 natalizumab biosimilar.

Polpharma Biologics will maintain re-

sponsibilities for development, manu-facturing and supply of the proposed biosimilar, while Sandoz will commer-cialize and distribute the medicine “in all markets upon approval,” through an ex-clusive global license.

Shortly after striking the natalizumab deal with Sandoz, Polpharma Biologics’ Bioeq joint venture with the Strüngmann Group licensed to Coherus BioSciences US commercial rights to the venture’s proposed biosimilar alternative to Genen-tech’s Lucentis (ranibizumab) ophthalmic blockbuster. Coherus is targeting a US launch in 2021.

With Bioeq also working on a rival to Janssen’s Stelara (ustekinumab) anti-

inflammatory agent, Polpharma Biolog-ics also has early-stage candidates for checkpoint-inhibitor antibodies such as ipilimumab, nivolumab and pembro-lizumab that the firm is looking to out-license to partners.

To support its pipeline, the company is building commercial production facil-ity near Warsaw, Poland, in which it is ini-tially installing four 2,000-liter disposable bioreactors, with the potential to treble capacity. This plant is also intended to help the firm position itself as a one-stop-shop contract development and manu-facturing organization for biologics.


Momenta Pays Out On Enoxaparin Shut-OutAIDAN FRY [email protected]

M omenta Pharmaceuticals has agreed to pay $35.0m to set-tle charges brought by Nash-

ville General Hospital that it conspired with marketing partner Sandoz to lim-it competition on generic enoxaparin in the US.

In October 2015, Nashville General Hos-pital had brought a class-action lawsuit in the US District Court for the Middle Dis-trict of Tennessee on behalf of purchas-ers of Lovenox (enoxaparin sodium) and its generic equivalents. The suit alleged that Momenta and Sandoz had sought to prevent Amphastar from selling generic enoxaparin, and thus had violated federal antitrust laws, by manipulating the US ge-neric approval process to bring it within the scope of enoxaparin testing patents held by Momenta.

The settlement reached by Momenta and the hospital on 10 December is subject to final court approval, and potential class members can opt out. The case had been due to go to trial on 7 January next year.

Momenta and Sandoz earlier this year reached a settlement with Amphastar over allegations that they deceived the US Pharmacopoeia into adopting a drug standard test method which they later claimed was covered by their US patent 7,575,886.

In return for abandoning its claim to tre-ble damages, Amphastar received $59.9m.

Since striking deals with Sandoz for both enoxaparin and generic Copaxone (glatiramer acetate), Momenta has “ter-minated all future development of any new or early-stage biosimilar and com-plex generic products.” However, the Massachusetts-based firm is continuing to work on its M710 biosimilar to Eylea (aflibercept), which is in Phase III clinical trials. If the outcome of those studies is positive, Momenta expects its partner Mylan to file a biologics license applica-tion for the M710 diabetic macular ede-ma treatment in 2021.

MOMENTA LAUNCHES $225M PUBLIC OFFERING

To fund its pipeline that includes sev-eral novel biologics, Momenta – which is listed on the Nasdaq stock exchange – has just launched a public offering of 14,516,130 shares, priced at $15.50 each, which should generate gross proceeds of about $225m.

In the first nine months of this year, Amphastar’s sales of the enoxaparin ge-neric syringes that it eventually brought to the US market in early 2012 dipped slightly to $33.9m. The firm recently ex-panded its US enoxaparin offering with

300mg/3ml multiple-dose vials.The rival to Lovenox remained the Cali-

fornian company’s largest product, just ahead of lidocaine and phytonadione, each of which contributed more than $33m to the injectables specialist’s fin-ished pharmaceuticals sales that increased by 19% to $224.0m. Including active phar-maceutical ingredient sales that slipped to $15.0m, Amphastar’s group turnover ad-vanced by 17% to $239.0m.

Around 95% of that total was achieved in the US, while Amphastar posted sales of $10.6m in France, where the firm oper-ates an insulins API facility in Éragny-sur-Epte, north-west of Paris.


COMPLIANCE



MANUFACTURING

Teligent Slammed By FDA Warning LetterJOANNE S. EGLOVITCH [email protected]

T he US Food and Drug Adminis-tration has rebuked New Jersey drug manufacturer Teligent for

lax handling of product complaints as-sociated with generic topical products and for pulling stability samples with-out immediately testing them. The firm was also cited in a recent warning let-ter for not filing field alert reports in a timely manner.

The warning letter was posted on 10 December and follows up on an inspec-tion of the firm’s site in Buena, NJ, after an April inspection. The firm manufac-tures generic topical prescription and cosmetic products.

Teligent recently announced its plans to file a prior approval supplement for an injectable drug in the US as it starts to build out its injectables pipeline.

One of the good manufacturing prac-tice violations noted by the agency was the firm’s lax handling of product com-plaints for its topical products.

The agency said the company failed to adequately review 397 customer com-plaints related to container/closure issues, product separation, lack of effect and ad-verse events between January 2016 and May 2019. The firm attributed these lapses to “underperforming staff” who have since been dismissed.

Yet the FDA was not satisfied with this explanation. “The response was inade-quate because you failed to appropriate-ly address your quality unit not perform-ing their required duties. Your firm must

provide the quality unit with the appro-priate authority, sufficient resources, and staff to carry out its responsibilities to consistently ensure drug quality.”

Agency inspectors also found that over half, or 75 of 127, complaints received during 2018 and 2019 remained open for more than 30 days while six remained open for more than 150 days.

This observation follows on the heels of a recent warning letter issued to Glenmark, which also manufactures ge-neric topical drugs, for its inattention to handling complaints. That firm failed to adequately investigate more than 70 consumer complaints associated with punctures, cracks and holes in some of the topical creams and ointments manu-factured at its Baddi site in India.

FAILED TO TEST SAMPLESThe agency said that Teligent also failed to test stability samples within its specified timeframes on “multiple occasions.” For example, the firm pulled three-month long-term stability sam-ple of one lot of triamcinolone acetoide cream in February 2018 yet did not generate results until eight months later in October 2018.

The firm also pulled six-month acceler-ated condition samples of three lots of ciclopirox suspension in June 2017 yet did not generate results until six months after the test date.

Teligent was also chastised for releas-ing lots of clobetasol propionate, used

to treat skin conditions such as eczema and psoriasis, in June 2017 even though lots were out of specification. The inves-tigation concluded, without adequate supporting evidence, that the root cause was lot-specific sample interactions yet did not have any supporting evidence to support this conclusion.

The company was also chastised for not filing timely field alert reports for out-of-specification results for three generic drug products, flurandrenolide ointment USP, betamethasone dipro-pionate lotion, and triamcinoclone ace-tonide. The FDA requires that field alert reports be filed withing three working days of OOS results.

The agency told the company that the intent of the FAR regulation is to establish an “early warning system” to alert FDA to potential safety problems for drug prod-ucts already in distribution.

The FDA said that similar findings in the warning letter were observed in a previous inspection in October 2017 and that “repeated failures demonstrate that executive management oversight and control of the manufacture of drugs is inadequate.”

The agency said it may withhold ap-proval of new drug applications and supplements listing the firm as a manu-facturer and may withhold approval of requests for export certificates until these problems are corrected.


“The response was inadequate because you failed to appropriately address your quality unit not performing their required duties. Your firm must provide the quality unit with the appropriate authority, sufficient resources, and staff to carry out its responsibilities to consistently ensure drug quality” – FDA


BIOSIMILARS

Bio-Thera Gets Chinese Nod To Proceed On UstekinumabPENELOPE MACRAE

B io-Thera Solutions has received the regulatory go-ahead from the China National Medical Products Administra-tion to carry out a Phase I clinical study on its proposed

biosimilar of Johnson & Johnson’s top-selling psoriasis drug Stelara (ustekinumab).

The proposed biosimilar of monoclonal antibody ustekinum-ab, designated as BAT2206, is the Guangzhou-based company’s fifth biosimilar to go into clinical development. Bio-Thera calls the approval for the Phase I study “an important milestone” for the company. Stelara had global sales of $5.2bn in 2018, a figure expected to hit $7.8bn by 2024.

The Bio-Thera study will compare the safety and pharmacoki-netics of its proposed biosimilar to Stelara sourced from the US and EU. Bio-Thera said the clinical study will be a randomized, double-blind, parallel group, single-dose study that will involve 270 healthy volunteers.

“This Investigational New Drug application approval repre-sents an important milestone for our biosimilar pipeline,” said Shengfeng Li, chief executive of Bio-Thera Solutions. “BAT2206 will be the fifth biosimilar that Bio-Thera will advance into clinical development,” he noted.

Just last month, Bio-Thera announced that itsBAT-1406 had become the first biosimilar referencing AbbVie’s rheumatoid arthritis blockbuster Humira (adalimumab) to get marketing approval in China. The drug, to be sold under the brand name Qletli, was Bio-Thera’s first biosimilar approval as well as only the second made-in-China biosimilar to be approved by the NMPA for entry into the world’s second-largest drug market.

NEUCLONE AND FORMYCON ALSO WORKING ON STELARA BIOSIMILARS

Australia’s NeuClone and Germany’s Formycon have also em-barked on a quest to come up with biosimilar rivals to Stelara. Formycon announced in October the start of a Phase I trial for its FYB202 proposed Stelara biosimilar candidate in a joint venture with Aristo Pharma. NeuClone also said in October that it had begun dosing clinical participants in a Phase I trial with its pro-posed ustekinumab biosimilar, developed in partnership with the Serum Institute of India.

Formycon has said if its clinical trials are successful, its Stelara biosimilar, FYB202, could be launched after the patent expiry of the drug in the US in September 2023 and in the EU in July 2024. It added that marketing authorization approvals in the US and the EU are expected in 2021 if all goes according to plan. Neu-Clone said in October it was seeking “commercialization oppor-tunities with potential partners.”

Bio-Thera, founded in 2003, researches and develops novel therapeutics for the treatment of cancer, auto-immune, cardiovascular diseas-es, and other serious diseases as well as biosimilars for existing, branded biologics to treat a range of can-cer and autoimmune diseases. The company’s chief executive said Bio-Thera is pressing ahead with “developing and commercializing biosimilar products for patients in China and around the world.”

Bio-Thera’s development pipeline includes BAT1706, a bio-similar to Genentech’s Avastin (bevacizumab), which is being evaluated in a global Phase III clinical trial in patients with previously untreated advanced non-squamous non–small cell lung cancer. Bio-Thera announced in early 2019 it had partnered with Cipla in a licensing agreement for its potential bevacizumab biosimilar. Bio-Thera intends to file BAT1706 for regulatory approval with the China National Medical Products Administration, the European Medicines Agency, and the US Food and Drug Administration in 2020.

‘MULTIPLE PROMISING CANDIDATES IN EARLY CLINICAL TRIALS’

Bio-Thera is also pursuing a biosimilar version of Chugai’s Actemra/RoActemra (tocilizumab), currently in Phase III trials. In addition, the firm is working on a biosimilar version of J&J’s Simponi (golimum-ab). The company said it also has “multiple promising candidates” in early clinical trials and IND-enabling studies, focusing on innovative targets in immuno-oncology and autoimmune diseases.

Previously, biosimilars such as 3SBio’s Yisaipu (etanercept) ver-sion of Enbrel had to be reviewed in China under the pathway for new biologics. But in 2015, the then China FDA issued spe-cific guidelines for biosimilar products, opening the floodgates to development activities in the country.

China was a late-comer to biologics. Its biotech market ac-counts for 12% of China’s total drug market, compared to a 25% total market share for the global biotech sector. The Chinese government sees rapid development of biotechnology as criti-cal to tackle the looming challenges facing China’s healthcare system, including caring for a rapidly ageing population.

Frost & Sullivan forecasts China’s biotech market to grow at a five-year growth rate of 16.4% by 2021, making it the world’s fastest-expanding.


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