Who’s de­lay­ing gener­ic com­pe­ti­tion? FDA pub­lish­es a long list of drug­mak­ers they say gamed the sys­tem

Mak­ing good on the ad­min­is­tra­tion’s promise to name and shame drug­mak­ers  — most re­cent­ly re­it­er­at­ed in HHS Sec­re­tary Alex Azar’s speech Mon­day — the FDA has re­leased a list of them, all ac­cused of un­fair­ly with­hold­ing ref­er­ence sam­ples of their drugs in or­der to block gener­ic en­try.

Scott Got­tlieb

On a list of 52 ref­er­ence list­ed drugs (RLDs) post­ed Thurs­day, the FDA de­tailed the names and de­vel­op­ers of each one, along­side the num­ber of ac­cess in­quiries the agency has re­ceived in re­la­tion to them. The pub­li­ca­tion of this list, which you can see be­low, is part of the FDA’s drug com­pe­ti­tion ac­tion plan as it com­mits to ad­dress and im­prove “trans­paren­cy about this and oth­er gam­ing tac­tics that de­lay the gener­ic com­pe­ti­tion Con­gress in­tend­ed.” With­out sam­ple drugs, gener­ic com­pa­nies can­not con­duct bioe­quiv­a­lence stud­ies — a fun­da­men­tal part of any AN­DA.

Ac­cess in­quiries are sub­mit­ted when a com­pa­ny ex­press­ing an in­tent to de­vel­op a gener­ic drug is un­able to ob­tain nec­es­sary sam­ples of the orig­i­nal. Thus, the list is es­sen­tial­ly a doc­u­ment of al­le­ga­tions — the FDA has not in­de­pen­dent­ly in­ves­ti­gat­ed or con­firmed the ac­cess lim­i­ta­tions de­scribed in the in­quiries.

The FDA made a point to dis­tin­guish be­tween those drugs shield­ed un­der the Risk Eval­u­a­tion and Mit­i­ga­tion Strat­e­gy (REMS) pro­gram and cas­es where drug­mak­ers used con­trac­tu­al claus­es to pre­clude dis­trib­u­tors, whole­salers or spe­cial­ty phar­ma­cies from sell­ing to would-be com­peti­tors.

Rough­ly half of the drugs cit­ed falls un­der the purview of REMS with el­e­ments to as­sure safe use (ETA­SU), which brand­ed drug­mak­ers could em­ploy in a num­ber of ways to block ac­cess. In those cas­es, the FDA points out, it has a process in place where­by the RLD spon­sors could pro­vide their prod­ucts to gener­ic ap­pli­cants with­out vi­o­lat­ing the REMS. Giv­en it finds the com­pa­ny’s safe­ty pro­tec­tions sat­is­fac­to­ry, that au­tho­riza­tion would come in the form of a safe­ty de­ter­mi­na­tion let­ter.

Ac­cord­ing to the list, nine out of the 52 drugs have been in­volved in such a let­ter, with the ear­li­est one is­sued in 2009.

Alex Azar

Acte­lion’s Tr­a­cleer, the pi­o­neer­ing pul­monary artery hy­per­ten­sion drug that now be­longs to J&J, tops the list with 14 ac­cess in­quiries. To­geth­er with No­var­tis, the for­mer Swiss biotech has the high­est num­ber of prod­ucts — four — that gener­ic com­peti­tors have claimed to have trou­ble ac­cess­ing. The list was not short of big names, fea­tur­ing Cel­gene (for Revlim­id, Poly­mast and Talo­mid), Glax­o­SmithK­line (Pro­mac­ta), Roche (Ac­cu­tane) and gener­ic gi­ant Te­va (Clar­avis).

In re­sponse, in­dus­try group PhRMA said it’s con­cerned that the list lacks “prop­er con­text” and “con­flates” sev­er­al is­sues. There is an im­por­tant dif­fer­ence, for in­stance, be­tween prod­ucts men­tioned in com­plaints and those for which the FDA has re­ceived a re­quest for a safe­ty de­ter­mi­na­tion let­ter,

“Ad­di­tion­al con­text is es­sen­tial and we be­lieve the Agency should give in­no­va­tor com­pa­nies the op­por­tu­ni­ty to sub­mit their ap­pro­pri­ate­ly redact­ed re­sponse to the re­cip­i­ent of a safe­ty de­ter­mi­na­tion let­ter,” a spokesper­son said in an email to STAT.

Cel­gene, whose Revlim­id got 13 ac­cess in­quiries, told Reuters that all three of its prod­ucts on the FDA list all re­quire rig­or­ous safe­ty con­trols due to the sever­i­ty of their side ef­fects, and that two of them al­ready have gener­ic ver­sions set to en­ter the mar­ket in com­ing years.

Go­ing af­ter these tac­tics has been a ral­ly­ing point for FDA Com­mis­sion Scott Got­tlieb, who point­ed­ly called on brand­ed name drug com­pa­nies to “end the shenani­gans” at a pan­el a few months ago. Got­tlieb was backed up by Azar dur­ing his Mon­day speech, in which he called for sham­ing drug mak­ers that refuse to make sam­ples avail­able for gener­ic man­u­fac­tur­ers to use for their de­vel­op­ment work.

We might see how ef­fec­tive the strat­e­gy is when the list gets up­dat­ed in half a year.

Im­ple­ment­ing re­silience in the clin­i­cal tri­al sup­ply chain

Since January 2020, the clinical trials ecosystem has quickly evolved to manage roadblocks impeding clinical trial integrity, and patient care and safety amid a global pandemic. Closed borders, reduced air traffic and delayed or canceled flights disrupted global distribution, revealing how flexible logistics and supply chains can secure the timely delivery of clinical drug products and therapies to sites and patients.

In fi­nal days at Mer­ck, Roger Perl­mut­ter bets big on a lit­tle-known Covid-19 treat­ment

Roger Perlmutter is spending his last days at Merck, well, spending.

Two weeks after snapping up the antibody-drug conjugate biotech VelosBio for $2.75 billion, Merck announced today that it had purchased OncoImmune and its experimental Covid-19 drug for $425 million. The drug, known as CD24Fc, appeared to reduce the risk of respiratory failure or death in severe Covid-19 patients by 50% in a 203-person Phase III trial, OncoImmune said in September.

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Pascal Soriot (AP Images)

UP­DAT­ED: As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

Bob Nelsen rais­es $800M and re­cruits a star-stud­ded board to build the 'Fox­con­n' of biotech

Bob Nelsen spent his pandemic spring in his Seattle home, talking on the phone with Luciana Borio, the scientist who used to run pandemic preparedness on the National Security Council, and fuming with her about the dire state of American manufacturing.

Companies were rushing to develop vaccines and antibodies for the new virus, but even if they succeeded, there was no immediate supply chain or infrastructure to mass-produce them in a way that could make a dent in the outbreak.

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Carl Hansen, AbCellera CEO (University of British Columbia)

From a pair of Air Jor­dans to a $200M-plus IPO, Carl Hansen is craft­ing an overnight R&D for­tune fu­eled by Covid-19

Back in the summer of 2019, Carl Hansen left his post as a professor at the University of British Columbia to go full time as the CEO at a low-profile antibody shop he had founded called AbCellera.

As biotech CEOs go, even after a fundraise Hansen wasn’t paid a whole heck of a lot. He ended up earning right at $250,000 for the year. His compensation package included a loan — which he later paid back — and a pair of Air Jordan tennis shoes. His newly-hired CFO, Andrew Booth, got a sweeter pay packet than that — which included his own pair of Air Jordans.

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Leonard Schleifer, Regeneron CEO (Andrew Harnik/AP)

Trail­ing Eli Lil­ly by 12 days, Re­gen­eron gets the FDA OK for their Covid-19 an­ti­body cock­tail

A month and a half after becoming the experimental treatment of choice for a newly diagnosed president, Regeneron’s antibody cocktail has received emergency use authorization from the FDA. It will be used to treat non-hospitalized Covid-19 patients who are at high-risk of progressing.

Although the Rgeneron drug is not the first antibody treatment authorized by the FDA, the news comes as a significant milestone for a company and a treatment scientists have watched closely since the outbreak began.

Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

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Am­gen sev­ers 14-year Cy­to­ki­net­ics part­ner­ship, bail­ing on ome­cam­tiv af­ter mixed PhI­II re­sults

Amgen is shrugging off a 14-year development alliance and the tens of millions of dollars spent to develop a new heart drug at Cytokinetics after a Phase III trial turned up weak data — leaving Cytokinetics to soldier on alone.

Omecamtiv mecarbil technically worked, meeting the primary composite endpoint in the Phase III GALACTIC-HF study. But it missed a key secondary endpoint, which analysts had been following as a key marker for success — reduction of cardiovascular (CV) death. While Cytokinetics celebrated the results, its stock tanked 43% upon the news, and analysts warned of an uncertain path ahead. Now, Amgen wants out.

News brief­ing: Ab­b­Vie part­ner Teneo­bio ex­pands tech li­cense with CAR-T play­er Po­sei­da; Ar­genx buys PRV from Bay­er for $98M

Teneobio may be best known for its pact with AbbVie and Gilead, but before its big break the bispecific player had licensed its antibodies for a different use: as binders in CAR-T therapies being developed by Poseida.

Now, the biotechs are expanding their partnership, with Poseida exercising four options to deploy Teneobio’s heavy chain only domain antibodies commercially.

The commercial licensing fees remained under wraps, but Teneobio is eligible for $250 million in milestones for these CAR-Ts against undisclosed targets.