Jakob Lindberg, Oncopeptides CEO

ODAC gives a big thumbs-down to On­copep­tides' dan­gling ac­cel­er­at­ed ap­proval in mul­ti­ple myelo­ma

ODAC on Thurs­day vot­ed over­whelm­ing­ly against keep­ing the ac­cel­er­at­ed ap­proval for On­copep­tides’ Pepax­to, 14 vot­ing “no,” and 2 “yes” to the FDA’s ques­tion of: “Is the ben­e­fit-risk pro­file of mel­pha­lan flufe­namide fa­vor­able for the cur­rent­ly in­di­cat­ed pa­tient pop­u­la­tion?”

It’s been more than 15 months since Swe­den-based On­copep­tides first pre­sent­ed to the FDA its failed re­sults from a con­fir­ma­to­ry tri­al, known as OCEAN, fol­low­ing its 2021 ac­cel­er­at­ed ap­proval of Pepax­to (mel­pha­lan flufe­namide) as a fifth-line ther­a­py for mul­ti­ple myelo­ma.

The FDA sound­ed no clos­er on Thurs­day to com­ing around on the com­pa­ny’s re-an­a­lyzed ben­e­fits too, and sev­er­al ODAC mem­bers ex­pressed se­ri­ous reser­va­tions.

Andy Chen

ODAC pan­elist Andy Chen of Ore­gon Health & Sci­ence Uni­ver­si­ty ques­tioned the neg­a­tive over­all sur­vival ben­e­fit in an­nounc­ing his “no” vote, while An­tho­ny Sung of Duke Uni­ver­si­ty said he didn’t think the ben­e­fit out­weighs the risks.

The road has been a rocky and un­ortho­dox one for On­copep­tides, which near­ly a year ago told FDA it would with­draw this in­di­ca­tion be­fore de­cid­ing to re­scind that with­draw­al re­quest, find­ing a new re­analy­sis of da­ta that showed some sta­tis­ti­cal­ly sig­nif­i­cant PFS.

Christo­pher Lieu

“We shouldn’t be us­ing drugs that may ac­tu­al­ly be harm­ing pa­tients,” ODAC pan­elist Christo­pher Lieu, from Uni­ver­si­ty of Col­orado Can­cer Cen­ter, said in an­nounc­ing his “no” vote. “The da­ta do not sup­port the use of this.”

And the FDA’s pre­sen­ta­tions and com­ments made clear at Thurs­day’s meet­ing it would be dif­fi­cult to budge.

“Spon­sors need to pro­vide sub­stan­tial ev­i­dence. Not post-hoc analy­ses,” OCE head Richard Paz­dur said at one point in the ear­ly af­ter­noon dis­cus­sion.

FDA re­view­er Alexan­dria Schwarsin pre­sent­ed find­ings to ODAC from the con­fir­ma­to­ry OCEAN RCT re­sults that said the me­di­an OS re­mained short­er in the mel­pha­lan arm than the stan­dard of care arm from the tri­al. FDA al­so con­duct­ed its own analy­ses on re­vised PFS re­sults that On­copep­tides claimed were pos­i­tive, and found a lack of ro­bust treat­ment ef­fect, with Schwarsin not­ing that giv­en the OS detri­ment, any pos­i­tive PFS would still not sup­port clin­i­cal ben­e­fit.

Klaas Bakker

On­copep­tides CMO Klaas Bakker pre­sent­ed the com­pa­ny’s take on the con­fir­ma­to­ry re­sults, con­clud­ing that Pepax­to does show ben­e­fit in a sub­set of pa­tients — with no au­tol­o­gous stem cell trans­plan­ta­tion (AS­CT) or post AS­CT pro­gres­sion greater than 36 months, seek­ing to keep ap­proval un­der a re­vised la­bel with cer­tain “pro­posed lim­i­ta­tions of use.”

But the FDA made clear that On­copep­tides’ sub­group analy­sis was not pre­spec­i­fied, and FDA’s Schwarsin not­ed how sub­group analy­ses can be mis­lead­ing as the agency iden­ti­fied sur­vival dif­fer­ences in sub­group analy­ses from OCEAN based on the month of ran­dom­iza­tion.

ODAC chair Jorge Gar­cia and pan­elist Scott Wald­man of Thomas Jef­fer­son Uni­ver­si­ty not­ed the wide gaps be­tween the On­copep­tides and FDA per­spec­tives, but com­mit­tee mem­bers made clear the sub-hoc analy­ses were hy­poth­e­sis-gen­er­at­ing and did not change the OS re­sult.

Nicole Gorm­ley

Nicole Gorm­ley, di­rec­tor of the FDA’s di­vi­sion of hema­to­log­ic ma­lig­nan­cies II, told ODAC mul­ti­ple times that from FDA’s per­spec­tive, there were “sev­er­al con­cerns” with the al­tered PFS and the com­pa­ny’s un­prece­dent­ed re­assess­ment, which she al­so called “high­ly un­usu­al” and “da­ta dredg­ing.” Re­gard­less, she added, this change still rep­re­sents a very small dif­fer­ence in PFS, and the change did not im­pact the neg­a­tive over­all sur­vival.

“We don’t agree a PFS that’s sta­tis­ti­cal­ly sig­nif­i­cant was in­di­cat­ed. But even if we did, this tri­al did not pro­vide a demon­stra­tion of safe­ty and ef­fec­tive­ness,” Gorm­ley said. Un­like some oth­er end­points, OS is both a safe­ty and ef­fi­ca­cy end­point, she said, and “we can have dis­cus­sions on PFS meet­ing sta­tis­ti­cal sig­nif­i­cance — that’s not the most ger­mane is­sue. That’s the worse OS.”

The FDA does not have to fol­low ODAC’s ad­vice but of­ten does.

And even if Pepax­to is pulled in the US, that may not spell its end. Out­side the US, the Eu­ro­pean Med­i­cines Agency’s CHMP in June rec­om­mend­ed a full mar­ket­ing au­tho­riza­tion ap­proval for mel­pha­lan flufe­namide in the EU.

Ear­li­er on Thurs­day, ODAC al­so vot­ed against Spec­trum Phar­ma­ceu­ti­cals’ po­ten­tial lung can­cer drug pozi­o­tinib’s ben­e­fit-risk pro­file, by a vote of 9-4.

Justin Klee (L) and Joshua Cohen, Amylyx co-CEOs (Cody O'Loughlin/The New York Times; courtesy Amylyx)

Ad­vo­cates, ex­perts cry foul over Amy­lyx's new ALS drug, cit­ing is­sues with price, PhI­II com­mit­ment

Not 24 hours after earning the first ALS drug approval in five years, Amylyx Pharmaceuticals’ Relyvrio is already drawing scrutiny. And it’s coming from multiple fronts.

In an investor call Friday morning, Amylyx revealed that it would charge about $158,000 per year, a price point that immediately drew backlash from ALS advocates and some outside observers. The cost reveal had been highly anticipated in the immediate hours after Thursday evening’s approval, though Amylyx only teased Relyvrio would cost less than previously approved drugs.

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Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Land­mark Amy­lyx OK spurs de­bate; Some... pos­i­tive? Alzheimer's da­ta; Can­cer tri­al bot­tle­neck; Sanofi's CRISPR bet; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

After brief stops in Paris and Boston, John Carroll and the Endpoints crew are staying on the road in October with their return for a live/streaming EUBIO22 in London. The hybrid event fireside chats and panels on mRNA, oncology and the crazy public market. We hope you can join him there.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Up­dat­ed: Al­ny­lam re­in­forces APOL­LO-B patisir­an da­ta be­fore head­ing to the FDA

Weeks after uncorking some mostly positive data for patisiran in transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, Alnylam is bolstering its package with new exploratory and subgroup data before shipping it off to regulators.

The RNAi drug maintained “generally consistent” benefits in efficacy and quality of life across several prespecified subgroups at month 12, Alnylam announced on Friday afternoon, including age, baseline tafamidis use, ATTR amyloidosis type, baseline six-minute walk test score and others.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

#AAO22: J&J’s first look at com­mon eye dis­ease port­fo­lio pads the case for PhII of gene ther­a­py

CHICAGO — While the later-stage drug developers in the geographic atrophy field are near the finish line, Johnson & Johnson’s Janssen is taking a more deliberate route, with a treatment that it hopes to be a one-time fix.

The Big Pharma will take its Hemera Biosciences-acquired gene therapy into a Phase II study later this year in patients with GA, a common form of age-related macular degeneration that impacts about five million people worldwide. To get there, Janssen touted early-stage safety data at the American Academy of Ophthalmology annual conference Saturday morning, half a day after competitors Apellis and Iveric Bio revealed their own more-detailed Phase III analyses.

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Jerome Durso, Intercept Pharmaceuticals CEO

In­ter­cep­t's OCA fails a PhI­II NASH tri­al, rais­ing fresh doubts about its years­long quest for an OK

Intercept Pharmaceuticals has run into another big setback in its yearslong quest to win an approval for OCA in NASH. The biotech put out word Friday morning that its Phase III REVERSE study failed the primary endpoint for the liver disease, sending its share price into a tailspin.

There was no significant improvement in fibrosis among the patients suffering from cirrhosis who were treated with obeticholic acid, with investigators hunting for a minimum 1-stage histological improvement in the disease after 18 months of therapy.

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Bo Cumbo, new Solid Bio CEO

Sol­id Bio gets a new CEO, $75M cash and drops lead drug as big in­vestors ju­ry-rig a merg­er deal

Three months after Endpoints News broke the story that gene therapy outfit AavantiBio had gutted its CMC group in a reorganization, the biotech’s CEO has helped engineer a merger with struggling penny stock player Solid Bio. And he’s going to remain in charge of the combined operation, as Solid founder Ilan Ganot steps aside.

The merger news this morning features some high-profile investors.

Perceptive Advisors, RA Capital Management and Bain Capital Life Sciences are leading a $75 million raise to add to the pool of cash Solid will have after the tie-up. That will leave Solid $215 million in cash as Bain’s Adam Koppel jumps on the board — enough to pay for ops and get through some key data milestones on their way into 2025.

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