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.

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

'Chang­ing the whole game of drug dis­cov­ery': Leg­endary R&D vet Roger Perl­mut­ter leaps back in­to work as a biotech CEO

Roger Perlmutter needs no introduction to anyone remotely involved in biopharma. As the R&D chief first at Amgen and then Merck, he’s built a stellar reputation and a prolific career steering new drugs toward the market for everything from cancer to infectious diseases.

But for years, he’s also held a less known title: science partner at The Column Group, where he’s regularly consulted about the various ideas the VCs had for new startups.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,600+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Pfiz­er hits the brakes on their piv­otal tri­al for a BC­MA/CD3 bis­pe­cif­ic on safe­ty con­cerns while FDA road­block is hold­ing up Duchenne MD PhI­II

Pfizer’s ambitious plan to take a Phase II study of its BCMA CD3-targeted bispecific antibody elranatamab (PF-06863135) and run it through to an accelerated approval has derailed.

The pharma giant said in a release this morning that they have halted enrollment for their MagnetisMM-3 study after researchers tracked three cases of peripheral neuropathy in the ongoing Phase I. They are now sharing info with the FDA as they explore the red safety flag.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,600+ biopharma pros reading Endpoints daily — and it's free.

FDA ex­tends re­search agree­ment with MIT-li­censed or­gan-on-chip sys­tems

The FDA on Wednesday extended its four-year agreement with CN Bio, a developer of single- and multi-organ-on-chip systems used for drug discovery, for another three years.

CN Bio said the scope of the research performed by the FDA’s Center for Drug Evaluation and Research has expanded to include the exploration of the company’s lung-on-a-chip system to help with the agency’s evaluation of inhaled drugs, in addition to the agency’s work on its liver model.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

In quest to meet user fee goals, FDA’s per­for­mance con­tin­ues down­ward trend

A recent update to the FDA’s running tally of how it’s meeting its user fee-related performance goals during the pandemic shows an agency that is not out of the woods yet.

The latest numbers reveal that for a second straight quarter in 2021, the FDA has met its user fee goal dates for 93% of original new drug applications, which compares with 94% and 98% for the previous two quarters in 2020, respectively.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Ngozi Okonjo-Iweala, Director general of WTO (AP Photo/Keystone/Alessandro Della Bella)

Opin­ion: Waiv­ing Covid-19 vac­cine IP could save lives, but where is the man­u­fac­tur­ing ca­pac­i­ty?

Droves of House Democrats in Washington and members of the European Parliament have now glommed onto a major push by India and South Africa at the WTO to abolish all IP around Covid-19 vaccines.

At first blush, waiving this IP sounds like an easy win: More Covid-19 vaccines made locally for more people means more lives saved. Simple enough, especially as low-income countries have received just a tiny fraction of the world’s vaccine allotment so far.

Thomas Schall, ChemoCentryx CEO (file photo)

Chemo­Cen­tryx plunges as FDA rais­es ques­tions about rare dis­ease drug ahead of ad­comm

ChemoCentryx’s stock price on Wednesday was cut in half by the release of FDA briefing documents ahead of a Thursday adcomm, raising questions on the company’s clinical data to support avacopan as a treatment for adults with a rare and serious disease known as anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis.

ANCA-associated vasculitides (AAV) affect small to medium-size blood vessels that can be fatal in less than a year if left untreated, according to FDA. Only Roche’s Rituxan is currently FDA-approved for the treatment of AAV, while glucocorticoids are approved for the broader indication of vasculitis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,600+ biopharma pros reading Endpoints daily — and it's free.

Stéphane Bancel at the Endpoints #JPM20 breakfast panel in San Francisco, January 2020 (Photo: Jeff Rumans, Endpoints News)

Mod­er­na says Covid-19 vac­cine boost­er in­creased im­mune re­sponse against vari­ants of con­cern

About a month after announcing their variant-specific Covid-19 vaccine boosters showed promising results in mice, Moderna says it now has some human data to back it up.

Volunteers given a booster shot about six to eight months after receiving their second dose saw increased antibody levels against SARS-CoV-2 and two variants of concern: B.1.351, which was first identified in South Africa, and P.1, first identified in Brazil, the company said on Wednesday.

Cynthia Butitta (L) and Joe Jimenez

Is that an­oth­er IPO in the mak­ing? Ex-No­var­tis CEO Joe Jimenez and a lead Kite play­er take up new posts at an off-the-shelf ri­val to 2 pi­o­neer­ing drugs

Right on the heels of taking on a $160 million crossover round in a likely leap to Nasdaq, Century Therapeutics CEO Lalo Flores is now pushing ahead with the high-profile ex-Novartis chief Joe Jimenez as chairman.

Jimenez’s greatest fame at Novartis was earned for one of its weakest products, as their pioneering personalized CAR-T Kymriah won the honors for the first such drug to make it to the market. Now a host of players, including Century, are barreling in behind the frontrunners with allogeneic rivals that can be created for off-the-shelf use.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,600+ biopharma pros reading Endpoints daily — and it's free.