Rare dis­ease drug­mak­ers to Con­gress: Don't gut the ac­cel­er­at­ed ap­proval path­way

The con­tro­ver­sy over the FDA’s ac­cel­er­at­ed ap­proval path­way is heat­ing up.

Last week, the FDA’s top on­col­o­gy of­fi­cial Rick Paz­dur said the path­way is “un­der at­tack,” large­ly due to the agency’s re­cent ac­cel­er­at­ed ap­proval of Bio­gen’s con­tro­ver­sial Alzheimer’s drug and the sur­ro­gate end­point used in that de­ci­sion. In the mean­time, three ac­cel­er­at­ed ap­proval in­di­ca­tions have been pulled since Ju­ly 1 (two from Bris­tol My­ers Squibb and one from Mer­ck in re­cent weeks), even as Paz­dur called on crit­ics of the path­way to not miss the more pos­i­tive, big pic­ture, with some can­cer drugs prov­ing to be enor­mous­ly help­ful and ap­proved years be­fore their con­fir­ma­to­ry tri­als were com­plet­ed.

Now, a coali­tion of rare dis­ease drug­mak­ers is seek­ing to de­fend the use of the path­way, rais­ing con­cerns with a re­cent call from the non­par­ti­san MAC­PAC to in­crease re­bates around drugs ap­proved un­der the FDA’s ac­cel­er­at­ed path­way. The rare dis­ease firms claim such a move on re­bates would dis­in­cen­tivize drug de­vel­op­ers from pur­su­ing ther­a­pies in oth­er­wise in­tractable dis­ease ar­eas, the coali­tion said in a re­cent let­ter to top con­gres­sion­al health com­mit­tees.

While MAC­PAC did not rec­om­mend a spe­cif­ic in­crease in re­bates for those treat­ments ap­proved un­der the ac­cel­er­at­ed path­way, the agency, which ad­vis­es Con­gress and HHS, notes that the amount needs to be sig­nif­i­cant enough to “pro­vide a mean­ing­ful re­duc­tion in spend­ing and pro­vide a strong in­cen­tive to en­cour­age com­ple­tion of the con­fir­ma­to­ry tri­al, but not so large as to dis­cour­age de­vel­op­ment of drugs for con­di­tions that dis­pro­por­tion­ate­ly af­fect Med­ic­aid ben­e­fi­cia­ries.”

Pro­vid­ing that en­cour­age­ment to com­plete the con­fir­ma­to­ry tri­al could be help­ful in some ways. For in­stance, with Sarep­ta, its con­fir­ma­to­ry tri­al for the con­tro­ver­sial ac­cel­er­at­ed ap­proval of its DMD drug Ex­ondys 51 may end up tak­ing a decade to com­plete.

But the Rare Dis­ease Com­pa­ny Coali­tion — com­posed of drug­mak­ers in­clud­ing Al­ny­lam, Sarep­ta, Agios, and oth­ers, some of which have won ap­provals via the ac­cel­er­at­ed path­way in re­cent years — dis­agree with the MAC­PAC rec­om­men­da­tions, main­tain­ing that high­er re­bates on ac­cel­er­at­ed ap­proval drugs for rare dis­eases may ac­tu­al­ly do the re­verse and de­lay those post-ap­proval con­fir­ma­to­ry tri­als even fur­ther.

“Tar­get­ing a dis­tinct, and high­er re­bate for ac­cel­er­at­ed ap­proval ther­a­pies, as MAC­PAC’s pro­pos­al does, could de­prive pa­tients who suf­fer from cer­tain con­di­tions the im­por­tant, safe, and ef­fec­tive ther­a­pies they need. In many cas­es, these ther­a­pies are the on­ly ef­fec­tive course of treat­ment for their dis­ease. It is a strik­ing omis­sion that the MAC­PAC pro­pos­al did not in­clude an analy­sis of the im­pact on pa­tient ac­cess to treat­ments nor con­sid­er the voice of im­pact­ed com­mu­ni­ties,” the coali­tion wrote.

While on­ly 7% of rare dis­eases have an FDA-ap­proved treat­ment, the coali­tion ex­plains how mem­bers of Con­gress in­ter­est­ed in fur­ther strength­en­ing the ac­cel­er­at­ed ap­proval path­way should “rec­og­nize the harm­ful con­se­quences of un­der­cut­ting re­im­burse­ment, cov­er­age and pa­tient ac­cess to ac­cel­er­at­ed ap­proved ther­a­pies and in­stead fo­cus on mean­ing­ful op­por­tu­ni­ties to op­ti­mize FDA’s gov­er­nance and im­ple­men­ta­tion of this path­way in a way that ac­counts for evolv­ing sci­ence and da­ta gen­er­a­tion in the post-mar­ket set­ting and con­tin­ues to keep pa­tients front and cen­ter.”

So­cial: Jose Luis Ma­g­a­na, AP Im­ages

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; 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.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty


I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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