The FDA: Faster, but not nec­es­sar­i­ly bet­ter. And that could threat­en the agen­cy's brand

Faster FDA drug ap­provals may re­flect less rig­or­ous ev­i­den­tiary stan­dards, a new analy­sis sug­gests.

Jonathan Dar­row BWH

In 1962, the reg­u­la­to­ry scruti­ny of med­i­cines by the FDA in­ten­si­fied in re­ac­tion to thalido­mide, an an­ti-nau­sea drug that gained no­to­ri­ety af­ter its link to se­vere skele­tal birth de­fects. Since then, a flood of in­cen­tives has made the US sys­tem of get­ting drugs ap­proved eas­i­er and the agency seem­ing­ly more flex­i­ble. Reg­u­la­to­ry in­cen­tives — such as fast-track and break­through ther­a­py sta­tus, or­phan drug des­ig­na­tions as well as ac­cel­er­at­ed and con­di­tion­al ap­provals — have di­min­ished re­view times and en­cour­aged the use of sur­ro­gate end­points. And while the in­dus­try has en­cour­aged it, some re­searchers see a down­side.

The analy­sis, con­duct­ed by Jonathan Dar­row and oth­ers and pub­lished in JA­MA on Tues­day, found that that this evo­lu­tion has led to the FDA gen­er­al­ly ac­cept­ing less ro­bust ev­i­dence, all the while short­en­ing its re­view times.

The da­ta show that the clas­sic FDA “gold stan­dard” of ac­cept­ing new drug ap­pli­ca­tions based on at least two piv­otal tri­als has fall­en from 80.6% in 1995-1997 to 52.8% in 2015-2017. Mean­while, med­i­cines bran­dish­ing the “or­phan drug” tag — of­ten sig­nal­ing less rig­or­ous stan­dards — have risen from 18% over the pe­ri­od of 1984 to 1995 to 41% be­tween 2008 and 2018.

FDA drug re­view times have de­clined from more than 3 years in 1983 to less than 1 year in 2017 (al­though the to­tal time to get a drug ready for re­view has re­mained steady), the au­thors high­light­ed.

If drugs ap­proved with less ev­i­dence turn out to be prob­lem­at­ic it may lead to “an ero­sion of the ‘FDA ap­proved’ brand,” Dar­row told Reuters.

Joshua Sharf­stein John Hop­kins

“If the stan­dards are dif­fer­ent than they were in the past, it’s im­por­tant for pa­tients and physi­cians to be aware of that,” Dar­row said in an in­ter­view with the wire ser­vice. “Pa­tients and physi­cians need to fo­cus on the ev­i­dence and not the fact of FDA ap­proval. How big are the ben­e­fits, and how cer­tain are we of the ben­e­fits?”

While some of these new drugs have been re­mark­able ad­vances for de­bil­i­tat­ing and of­ten dead­ly dis­eases, “high prices at the high end or in ex­cess of in­de­pen­dent­ly as­sessed mea­sures of val­ue have cre­at­ed bar­ri­ers to ac­cess,” Joshua Sharf­stein from Johns Hop­kins Bloomberg School of Pub­lic Health point­ed out in a JA­MA ed­i­to­r­i­al in re­sponse to the analy­sis by Dar­row et al.

Over­all, the av­er­age an­nu­al num­ber of new drug ap­provals, in­clud­ing bi­o­log­ics, has see­sawed — from 34 be­tween 1990 and 1999 to 25 from 2000 to 2009 and 41 from 2010 to 2018, au­thors of the analy­sis found. One heart­en­ing da­ta point is the me­di­an an­nu­al num­ber of gener­ics — copy­cat ap­provals ac­cel­er­at­ed from 284 — pri­or to the Gener­ic Drug User Fee Act of 2012 — to 488 be­tween 2013 and 2018.

To ac­com­mo­date the high­er vol­ume of drug man­u­fac­tur­ers, the FDA in 1992 was grant­ed the pow­er to col­lect fees for their re­views. Now, the an­nu­al fees col­lect­ed un­der Pre­scrip­tion Drug User Fee Act (PDU­FA) have jumped from $29 mil­lion in 1993 to $908 mil­lion in 2018, the da­ta showed.

Crit­ics have ad­mon­ished the slid­ing door be­tween ex­ec­u­tives in the bio­phar­ma­ceu­ti­cal in­dus­try and the FDA, and un­der­score that the trans­ac­tion­al in­ter­ac­tion be­tween the agency and the in­dus­try does not bode well for an in­de­pen­dent, un­bi­ased re­view of prod­ucts.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

The End­points 11: They've got mad mon­ey and huge am­bi­tions. It's time to go big or go home

These days, selecting a group of private biotechs for the Endpoints 11 spotlight begins with a sprint to get ahead of IPOs and the M&A teams at Big Pharma. I’ve had a couple of faceplants earlier this year, watching some of the biotechs on my short list choose a quick leap onto Nasdaq or into the arms of a buyer.

Vividion, you would have been a great pick for the Endpoints 11. I’m sorry I missed you.

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Dave Lennon, former president of Novartis Gene Therapies

So what hap­pened with No­var­tis Gene Ther­a­pies? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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FDA+ roundup: Bs­U­FA III ready for show­time, court tells FDA to re-work com­pound­ing plan, new guid­ance up­dates and more

The FDA has now spelled out what exactly will be included in the third iteration of Biosimilar User Fee Act (BsUFA) from 2023 through 2027, which similarly to the prescription drug deal, sets fees that industry has to pay for submitting applications, in exchange for firm timelines that the agency must meet.

This latest deal includes several sweeteners for the biosimilar industry, which has yet to make great strides in the US market, with shorter review timelines for safety labeling updates and updates to add or remove an indication that does not contain efficacy data.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

Bob Duggan, Summit CEO (via Summit Investments)

The FDA ob­jects to biotech bil­lion­aire Bob Dug­gan’s PhI­II plans — and he’s not budg­ing

Summit Therapeutics, the Cambridge, MA-based biotech run by billionaire investor Bob Duggan, has found itself in the FDA’s crosshairs.

Last month, Summit announced its intent to combine two Phase III studies for its experimental C. difficile treatment, ridinilazole, into one trial in a process that involved changing the primary endpoint. But regulators do not agree with the new endpoint, the biotech revealed in an SEC filing Tuesday, raising questions about ridinilazole’s ongoing development.

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Joshua Liang, Clover Biopharmaceuticals CEO

With world still in sore need of dos­es, Clover says its Covid-19 vac­cine is 67% ef­fec­tive in Phase III

With concerns about the Delta variant rising and much of the world still in desperate need of vaccine doses, a Chinese biotech announced Wednesday that a new shot has shown positive results in a large trial against Covid-19, including new variants.

Clover Biopharmaceuticals announced Wednesday that its vaccine candidate showed 79% efficacy against the Delta variant in a Phase II/III trial dubbed Spectra, and 67% effective against Covid-19 overall.

Jean Bennett (Brent N. Clarke/Invision/AP Images)

Lux­tur­na in­ven­tor Jean Ben­nett starts a new gene ther­a­py com­pa­ny to tack­le rare dis­eases left be­hind by phar­ma, VCs

A few years ago Jean Bennett found herself in a surprising place for a woman who invented the first gene therapy ever approved in the United States: No one, it seemed, wanted her work.

Bennett, who designed and co-developed Luxturna, approved in 2018 for a rare form of blindness, had kept building new gene therapies for eye diseases at her University of Pennsylvania lab. But although the results in animals looked promising, pharma companies and investors kept turning down the pedigreed ophthalmology professor.

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