Robert Califf, FDA commissioner (Sipa via AP Images)

The ac­cel­er­at­ed ap­proval path­way is evolv­ing in plain sight, with or with­out con­gres­sion­al help

FDA lead­ers have made clear that re­form­ing the ac­cel­er­at­ed ap­proval path­way is a pri­or­i­ty, and with sev­er­al re­cent ac­tions, the agency has sig­naled that it’s will­ing to take ac­tion on those re­forms even with­out im­me­di­ate move­ment from Con­gress.

The lat­est sign of this evo­lu­tion oc­curred to­day, as GSK an­nounced it was pulling its fifth-line mul­ti­ple myelo­ma drug Blenrep at the FDA’s re­quest — just 15 days post-con­fir­ma­to­ry tri­al fail an­nounce­ment.

The ur­gency in the FDA’s re­quest shows the ex­tent to which the agency is be­com­ing more nim­ble. In oth­er AA cas­es, such as with the failed con­fir­ma­to­ry tri­al for Co­vis’ preterm birth drug Mak­e­na in 2018, the agency’s abil­i­ty to pull the drug has been de­layed by four years, with a re­cent hear­ing that should lead to a fi­nal de­ci­sion in the com­ing months.

Resh­ma Ra­machan­dran, as­sis­tant pro­fes­sor in the De­part­ment of Med­i­cine at Yale Uni­ver­si­ty, told End­points News that the Blenrep move is “def­i­nite­ly a sign that FDA is tak­ing steps to trans­form the AA [ac­cel­er­at­ed ap­proval] with­out Con­gress ex­plic­it­ly giv­ing them au­thor­i­ty. Tech­ni­cal­ly, Con­gress does not need to, giv­en how broad the statute is cur­rent­ly, but it does pre­vent FDA from ei­ther mak­ing such changes as ex­cep­tions or be­ing called out by com­pa­nies for veer­ing away from reg­u­la­to­ry prece­dent.”

But with­out con­gres­sion­al ac­tion, there may be gaps be­tween how quick­ly some of the larg­er phar­ma com­pa­nies pull their AAs and aren’t as fi­nan­cial­ly im­pact­ed by those pulls, com­pared with small­er com­pa­nies that may on­ly have one or a few ac­cel­er­at­ed ap­provals in their pipelines.

Rachel Sachs, law pro­fes­sor at Wash­ing­ton Uni­ver­si­ty School of Law in St. Louis, not­ed to End­points that the statute spec­i­fies that ex­pe­dit­ed with­draw­al pro­ceed­ings must in­clude an op­por­tu­ni­ty for an in­for­mal hear­ing, so if a com­pa­ny in­sists on a hear­ing, “it’s not clear to me FDA can de­cline. (The com­pa­ny does not have to in­sist on one, of course.)”

Oth­er AA re­forms left out of the user fee pack­age sought to en­sure a more time­ly with­draw­al process for ac­cel­er­at­ed ap­provals, as well as to pro­vide the agency with the au­thor­i­ty to re­quire con­fir­ma­to­ry tri­als to be up and run­ning pri­or to grant­i­ng an ac­cel­er­at­ed ap­proval.

Of­fi­cials from the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence made clear in a re­cent pa­per the need to en­sure these con­fir­ma­to­ry tri­als are un­der­way when an AA is grant­ed, as they showed the me­di­an time to with­draw­al is 3.8 years if the con­fir­ma­to­ry tri­al was on­go­ing at the time of ap­proval, com­pared with 7.3 years if such a tri­al had not been ini­ti­at­ed.

And the FDA has tak­en heed of the da­ta and re­form re­quests. ADC Ther­a­peu­tics ear­li­er this month an­nounced that it had to de­lay a sub­mis­sion be­cause the FDA re­quest­ed that a con­fir­ma­to­ry tri­al be ful­ly en­rolled pri­or to the fil­ing, with the com­pa­ny not­ing that FDA

pro­vid­ed strong guid­ance that, for it to con­sid­er an ac­cel­er­at­ed ap­proval path, a ran­dom­ized con­fir­ma­to­ry Phase 3 study must be well un­der­way and ide­al­ly ful­ly en­rolled at the time of any BLA fil­ing.

The agency last month even turned over a new leaf when it comes to trans­paren­cy in ex­plain­ing why it wouldn’t pull an AA for Jazz Phar­ma­ceu­ti­cals’ sec­ond-line treat­ment for adults with metasta­t­ic small cell lung can­cer de­spite a failed con­fir­ma­to­ry tri­al.

So what was the cat­a­lyst for all of this re­cent ac­tion and re­form talk? Most like­ly the FDA’s much-cri­tiqued de­ci­sion to un­ex­pect­ed­ly grant an ac­cel­er­at­ed ap­proval for Bio­gen’s con­tro­ver­sial Alzheimer’s drug Aduhelm, which end­ed up flop­ping com­mer­cial­ly when CMS re­quest­ed more tri­als.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Thomas Gad, Y-mAbs Therapeutics founder and interim CEO

FDA re­jects Y-mAbs’ neu­rob­las­toma drug af­ter tak­ing is­sue with clin­i­cal tri­al de­sign

Uncertainty about clinical trial evidence has led the FDA to hand down a complete response letter for Y-mAbs’ neuroblastoma drug, casting a cloud on the future of a candidate that had gone through a long development journey in a rare pediatric cancer.

Y-mAbs said it’s disappointed “but not surprised” given that the agency’s oncology drug advisory committee had voted 16-0 against its drug’s approval a few weeks ago.

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Raul Rodriguez, Rigel Pharma CEO

Rigel Phar­ma scores FDA ap­proval for leukemia, kick­ing off show­down with Servi­er in IDH1

When Rigel Pharma bought olutasidenib from Forma Therapeutics, it acquired a drug that already secured a PDUFA date at the FDA — for February 2023. But regulators are ready to give their OK sooner than that.

The FDA has approved the IDH1 inhibitor as a treatment for adult patients with relapsed or refractory acute myeloid leukemia who have a susceptible IDH-1 (isocitrate dehydrogenase-1) mutation as detected by an FDA-greenlit test. Rigel will market it as Rezlidhia.

Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and Am­gen are bring­ing cash to cov­er the ta­ble stakes for the Hori­zon M&A game

With the market cap on Horizon Therapeutics $HZNP pushed up to the $23 billion mark today, one of the Big Pharmas in the hunt for a major league buyout deal signaled it’s playing the M&A game with cash.

Paris-based Sanofi, where CEO Paul Hudson has been largely focused on some risky biotech acquisitions to win some respect for its future pipeline prospects, issued a statement early Friday — complying with Rule 2.12 of the Irish takeover rules — making clear that while the certainty or size of an offer can’t be determined, any offer “will be solely in cash.” And Amgen CEO Robert Bradway came right in behind him, filing a statement on the London Stock Exchange overnight that any offer they may make will “likely” be in cash as well.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls

Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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Philip Tagari switch­es Am­gen's dis­cov­ery lab for in­sitro's ma­chine learn­ing tools; CEO Joaquin Du­a­to to chair J&J's board

In February, Philip Tagari will take a few days of retirement and then immediately return to industry. He won’t be leading the therapeutics discovery unit for a large biopharma, though.

He’ll trade in his Amgen hat for chief scientist at a machine learning startup that has reeled in hundreds of millions in capital to lay the groundwork for a much-hyped new model of drug discovery that aims to speed up the time to new clinical assets.

Tim Pearson, Carrick Therapeutics CEO

Pfiz­er backs $60M in­fu­sion in­to Car­rick, teams up on breast can­cer treat­ment

In a big week for Carrick Therapeutics, the company announced $60 million in funding for its lead breast cancer drug and development of a second program, as well as a collaboration with Pfizer for combo development.

The $35 million from Pfizer comes with an agreement under which Pfizer will support Carrick’s Phase II study of samuraciclib in combination with Pfizer’s Faslodex for advanced breast cancer. Along with the investment, Adam Schayowitz, vice president and development head of breast cancer, colorectal cancer and melanoma at Pfizer global product development, will join Carrick’s scientific advisory board.

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Tim Van Hauwermeiren, argenx CEO

Ar­genx pur­chas­es $100M+ FDA pri­or­i­ty re­view vouch­er from blue­bird bio

Argenx’s Vyvgart is due for a speedy review at the FDA, thanks to a $102 million priority review voucher (PRV).

The Netherland-based biotech picked up the PRV from bluebird bio, the companies announced on Wednesday. PRVs shorten a drug’s FDA review period from 10 months to 6 months, though they often sell on the open market for around $100 million each.

Argenx plans on using the express ticket on efgartigimod, its neonatal Fc receptor (FcRn) blocker marketed as Vyvgart for adults with generalized myasthenia gravis (gMG). While Vyvgart won its first approval last December for the chronic neuromuscular disease — which is characterized by difficulties with facial expression, speech, swallowing and breathing — CEO Tim Van Hauwermeiren said in a news release that he plans to “be active in fifteen disease targets by 2025.”