Why does the FDA se­lect cer­tain drugs for ad­comm meet­ings? Re­searchers want to know

Al­though their num­bers have dwin­dled in re­cent years, FDA ad­vi­so­ry com­mit­tees have been in the spot­light, and some ex­perts are now seek­ing re­forms to make them more use­ful, in­clud­ing a trio of lead­ers from Har­vard’s Pro­gram on Reg­u­la­tion, Ther­a­peu­tics, and Law writ­ing in the New Eng­land Jour­nal of Med­i­cine.

The per­spec­tive ex­plains the way in which the FDA typ­i­cal­ly fol­lows the guid­ance from its ad­comm, al­though about once an­nu­al­ly, it doesn’t, and those missed con­nec­tions can lead to ma­jor blun­ders, as in the case of Bio­gen’s new Alzheimer’s drug ad­u­canum­ab, which won ap­proval via the ac­cel­er­at­ed path­way af­ter no ad­comm mem­bers vot­ed in fa­vor of its full ap­proval, but then failed to ob­tain cov­er­age from CMS, which re­quest­ed ad­di­tion­al ran­dom­ized tri­als.

One of the POR­TAL co-au­thors, Aaron Kessel­heim, re­signed from the ad­comm that re­viewed ad­u­canum­ab, and this lat­est ar­ti­cle hones in on an im­por­tant and of­ten non-trans­par­ent as­pect of the ad­comm process: that the FDA “has full dis­cre­tion over not on­ly whether to fol­low ad­vi­so­ry com­mit­tee rec­om­men­da­tions but al­so whether to con­vene an ad­vi­so­ry com­mit­tee in the first place.”

Co-au­thor Ameet Sarpat­wari told End­points that two of the cri­te­ria that FDA might con­sid­er when de­cid­ed when to sched­ule an ad­comm “are the qual­i­ty of the avail­able ev­i­dence and the de­gree of harm from type I and II er­rors. Ad­di­tion­al­ly, an emerg­ing body of re­search has raised ques­tions about can­cer and or­phan drug ap­proval stan­dards — these cat­e­gories of ap­provals may al­so ben­e­fit from a de­fault pre­sump­tion that ad­vi­so­ry com­mit­tees will be held.”

Back in 2016, Lin­da Ann Sher­man, for­mer di­rec­tor of the FDA’s ad­vi­so­ry com­mit­tee over­sight and man­age­ment staff, ex­plained how the de­ci­sion to grant an ad­comm is usu­al­ly at the dis­cre­tion of a di­vi­sion di­rec­tor, and those med­ical prod­ucts that are se­lect­ed are usu­al­ly cho­sen be­cause there’s a “new tech­nol­o­gy or some el­e­ment of con­tro­ver­sy.”

But Sarpat­wari calls on FDA to is­sue guid­ance, “pro­vid­ing more clar­i­ty and con­sis­ten­cy on when it will con­vene ad­vi­so­ry com­mit­tees for new drug ap­provals. As part of this process, it would be a good idea to so­lic­it in­put from var­i­ous stake­hold­ers.”

Sev­er­al of the re­cent meet­ings, par­tic­u­lar­ly around Covid-19, have been high­ly con­tro­ver­sial, in­clud­ing one re­cent one high­light­ed by the Har­vard au­thors.

In this case, vac­cine ex­perts over­whelm­ing­ly vot­ed against au­tho­riz­ing a boost­er shot for every­one 16 or old­er (16 to 2), so the FDA then sought a new vote on a ques­tion not in­clud­ed in the meet­ing’s agency on whether the FDA should just au­tho­rize a third dose for se­niors and those at high­er risk for se­vere Covid-19, which they vot­ed unan­i­mous­ly in fa­vor of, and the FDA au­tho­rized.

But sev­er­al top FDA vac­cine lead­ers re­signed in the wake of a push for “boost­ers for all,” and the FDA lat­er ex­pand­ed el­i­gi­bil­i­ty to all adults and teens with­out turn­ing to an ad­comm.

The NE­JM per­spec­tive al­so notes a ma­jor de­cline in the num­ber of ad­comms in re­cent years, as in 2010, more than 50% of new­ly ap­proved drugs had re­ceived an ad­comm meet­ing pri­or to their ap­proval, but in 2021, the pro­por­tion had dropped to 6%.

A McK­in­sey re­port found that 37% of FDA-ap­proved new chem­i­cal en­ti­ties or new bi­o­log­i­cal en­ti­ties from 2001 to 2010 were sub­ject to an ad­comm meet­ing, so it’s un­clear if those two years were out­liers, as the pan­dem­ic has not on­ly caused all ad­comm meet­ings to move vir­tu­al­ly, but has re­sult­ed in few­er meet­ings over­all.

But Sarpat­wari told End­points that these two years are not out­liers and “but rather part of a steady de­cline,” not­ing two Health Af­fairs pa­pers he co-au­thored in 2010 and 2021.

Ac­cord­ing to FDA’s ad­comm cal­en­dar, CDER or CBER has held 21 ad­comm meet­ings so far in 2022 (16 nov­el drug ap­provals, al­though not every ad­comm was for a nov­el drug ap­proval), com­pared with 26 meet­ings in 2021 (50 nov­el drug ap­provals), and 28 in 2020 (53 nov­el drug ap­provals).

Mean­while, the Har­vard au­thors in NE­JM call on FDA to make three changes:

  1. Is­sue guid­ance ex­plain­ing “how it de­cides whether to con­vene ad­vi­so­ry com­mit­tees, and it could com­mit to con­ven­ing them for cer­tain types of de­ci­sions (e.g., ac­cel­er­at­ed ap­provals).
  2. Pub­lish in ad­vance the ques­tions it plans to ask (which the agency of­ten does, al­though as in the case of the Covid-19 boost­ers, the ques­tions can change on the fly), and it could “de­vel­op a stan­dard­ized ques­tion struc­ture for con­sid­er­ing the ap­proval or au­tho­riza­tion of a med­ical prod­uct.”
  3. Pub­licly ex­plain (via an es­tab­lished pro­ce­dure) reg­u­la­to­ry de­ci­sions that run con­trary to ad­comm rec­om­men­da­tions.

“Even when the FDA has le­git­i­mate rea­sons for dis­agree­ing with an ad­vi­so­ry com­mit­tee, it owes the pub­lic a thor­ough ex­pla­na­tion of its rea­son­ing. If the agency does not im­ple­ment these prac­tices it­self, Con­gress can con­sid­er leg­is­la­tion re­quir­ing these changes,” Joseph Ross, Kessel­heim, and Sarpat­wari write.

Ed­i­tor’s note: Ar­ti­cle up­dat­ed to in­clude com­ment from co-au­thor Ameet Sarpat­wari of POR­TAL.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Who’s spend­ing and who’s cut­ting from Big Phar­ma’s $127B R&D bud­get? Here are the top 15 play­ers

A couple of the Big 15 biopharma companies in R&D hit the gas on research spending last year. Merck and Sanofi still have lots to prove in the pipeline, and they’re willing to gamble large sums to make a better future for themselves.

Doing nothing would be infinitely worse.

But collectively, the top players rang up a modest 2.4% increase in spending in 2022, which didn’t cover inflationary pressures. And that set the tone for an extraordinarily cautious year for the industry — even as it laid out about $127 billion to advance new drugs or up the ante on approved therapies.

Endpoints Premium

Premium subscription required

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

Jeff Bluestone (R), Sonoma Biotherapeutics CEO

Jef­frey Blue­stone brings his start­up haul to $400M+, join­ing forces with Re­gen­eron on cell ther­a­pies

These days, when Jeffrey Bluestone gets together with his contemporaries in science, the conversation often turns to retirement plans.

But a little more than three years ago, Bluestone reached a momentous turning point in his career, exiting a prestigious post at UCSF, where he had spent decades in the scientific pursuit of new therapies. And it had nothing to do with retirement anytime in the near future.

Endpoints Premium

Premium subscription required

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

Sally Susman, Pfizer EVP and chief corporate affairs officer

Q&A: Pfiz­er cor­po­rate com­mu­ni­ca­tions chief Sal­ly Sus­man dis­cuss­es book craft­ed in pan­dem­ic and per­son­al lessons

From the political arena to the finance and beauty industries to pharmaceuticals, Pfizer’s Sally Susman has broken barriers, stereotypes and conventions. And now the chief communicator is “Breaking Through,” the title of her first book about effective and innovative communications launching today. The full official title is “Breaking Through: Communicating to Open Minds, Move Hearts, and Change the World.”

Endpoints Premium

Premium subscription required

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

Gun­ning for 2023 ap­proval, GSK de­tails PhI­II da­ta for Jem­per­li in front­line en­dome­tri­al can­cer

GSK has a new slate of data to offer on its PD-1 inhibitor, Jemperli — data that the pharma giant hopes will cement one of the four drug approvals it’s expecting this year.

While Jemperli (dostarlimab) is already approved for a subset of patients with second-line endometrial cancer, GSK set out in the Phase III RUBY trial to test it as an earlier line of treatment while also enrolling a broader group of patients. In an interim analysis, Jemperli was shown to extend progression-free survival for both the subset and the overall trial population when added to chemotherapy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,800+ biopharma pros reading Endpoints daily — and it's free.

Es­pe­ri­on sues Dai­ichi Sankyo, de­mand­ing pay­ment of $300M mile­stone for car­dio drug

Esperion is suing its business partner Daiichi Sankyo, saying the Japanese drugmaker is improperly refusing to pay a $300 million milestone that the biotech company will be owed after reporting positive data from a large trial of its cardiovascular drug Nexletol.

The 2019 deal between the companies had Daiichi Sankyo pay $150 million upfront plus another $150 million after the first sales of the drug. But another major payout was tied to an outcomes study reported this month, known as CLEAR. Esperion, in its suit against Daiichi, argues that the drug’s more than 20% reduction of heart attack risk is enough to trigger a $300 million payout from Daiichi once it’s added to the drug’s label.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,800+ biopharma pros reading Endpoints daily — and it's free.

Robert Califf, FDA commissioner (Photo by Drew Angerer/Getty Images)

House com­mit­tee to in­ves­ti­gate FDA's re­sponse to on­go­ing drug short­ages

Republican leaders of the House Committee on Energy & Commerce sent a five-page letter yesterday announcing an investigation into the ongoing drug shortages that have rankled the US during the pandemic and the FDA’s response to it.

The letter, signed by Chair Cathy McMorris Rodgers (R-WA), explains how shortages have become more common over the past decade, while pointing to a report from the National Academies of Science, Engineering and Medicine finding that drug shortages have been “on the rise” over the past several decades and are lasting longer, with new drug shortages in the US seeing a 30% increase from 2021 to 2022.

Eli Lil­ly to in­crease in­vest­ment to $1B in­to new Irish man­u­fac­tur­ing fa­cil­i­ty — re­port

The US pharma giant Eli Lilly will be increasing its financial commitment to a manufacturing site in Ireland.

According to a release from Ireland’s Industrial Development Agency (IDA) on Monday, Lilly will be investing another $500 million in its manufacturing facility in Limerick, Ireland — bringing the total investment into the facility to approximately $1 billion.

In January of last year, Lilly announced it was placing a $446 million investment into the site to expand active pharmaceutical ingredient and monoclonal antibody production.

Uğur Şahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

BioN­Tech read­ies for plunge in Covid sales, will boost mR­NA and on­col­o­gy pipelines

BioNTech is estimating €5 billion (nearly $5.4 billion) in Covid-19 vaccine sales this year, a marked drop from €17.1 billion ($18.5 billion) in 2022 — and way off analysts’ expectations of around €8 billion ($8.6 billion).

In BioNTech’s year-end earnings call on Monday, it reported a total of €17.3 billion ($18.7 billion) in 2022 revenue, almost all from vaccine sales, which include those via its Pfizer deal and direct sales.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,800+ biopharma pros reading Endpoints daily — and it's free.