New re­search ques­tions FDA’s re­liance on and in­abil­i­ty to en­force post­mar­ket­ing re­quire­ments

As the FDA has in­creas­ing­ly re­lied on post­mar­ket­ing re­quire­ments (PMRs) to sup­port its ap­proval de­ci­sions, a new study pub­lished in the Mil­bank Quar­ter­ly dis­cuss­es how the FDA’s lack of abil­i­ty to en­force PMRs re­veals an agency “on guard against a set of larg­er po­lit­i­cal threats to its man­date.”

The study’s pub­li­ca­tion fol­lows a re­cent re­port from the FDA show­ing that most of the re­quired PMRs and vol­un­tary post­mar­ket­ing com­mit­ments (PM­Cs) are pro­gress­ing on sched­ule.

Matthew Herder Dal­housie

But as Matthew Herder, di­rec­tor of the Health Law In­sti­tute at Dal­housie Uni­ver­si­ty, ex­plains in his pa­per, “FDA has dif­fi­cul­ty en­forc­ing the time­ly com­ple­tion of PMRs, but act­ing up­on PMR da­ta once in hand is more vexed.”

An uniden­ti­fied FDA of­fi­cial told Herder dur­ing his in­ter­views with 23 past and present FDA lead­ers: “[E]ven if you get the study, and you of­ten do, some­times they don’t con­firm the ef­fi­ca­cy of the prod­uct. […] What is FDA sup­posed to do with that? There’s now a huge and vo­cal con­stituen­cy for the prod­uct. Whether or not the study showed it worked, there are peo­ple out there who think it worked, and lots of peo­ple with a fi­nan­cial stake in it. It be­comes a po­lit­i­cal night­mare to try to take a prod­uct off the mar­ket that’s al­ready de­vel­oped that con­stituen­cy by be­ing ap­proved for a pe­ri­od of time. […] [I]n some ways [it’s] a big­ger prob­lem than whether you get the da­ta. It’s whether you can do any­thing with it when you have it.”

Over­all, Herder told Fo­cus that in his con­ver­sa­tions with FDA of­fi­cials, “What I found most sur­pris­ing was how acute­ly aware most FDA of­fi­cials were of the en­force­ment chal­lenges in­volved with PMRs, yet — at the same time — fierce­ly de­fen­sive of con­tin­u­ing to re­ly on them.”

He dis­cuss­es in the pa­per how the FDA lacks the le­gal au­thor­i­ty to with­draw an ap­proval that car­ries a PMR due to a spon­sor’s fail­ure to ful­fill the PMR, and how com­pa­nies “like­ly abide by the terms of a PMR not be­cause they fear FDA en­force­ment, but rather be­cause the ap­proved in­di­ca­tion car­ry­ing the PMR is one of sev­er­al in­di­ca­tions in a se­quence that they plan to sub­mit to the agency.”

Defin­ing what a PMR en­tails at the time of a new treat­ment’s ap­proval can al­so be chal­leng­ing.

“They tend to be short de­scrip­tions of the ques­tion(s) that the FDA would like to have an­swered through one or more post­mar­ket stud­ies, but they of­ten fail to spec­i­fy what type of study de­sign should be em­ployed to an­swer the ques­tion(s) of in­ter­est. Of 110 clin­i­cal tri­als that were en­com­passed in a cross‐sec­tion­al analy­sis of all PMRs is­sued by the FDA dur­ing 2009‐2012, many, if not most, ‘did not re­port enough in­for­ma­tion to es­tab­lish use of ran­dom­iza­tion, com­para­tor type, al­lo­ca­tion, out­come, and num­ber of pa­tients to be en­rolled,’” the study finds.

FDA of­fi­cials al­so may be ret­i­cent to hold up an ap­proval be­cause the de­tails of a PMR are not yet set­tled.

And as the FDA con­tin­ues its push to­ward fur­ther us­ing re­al-world ev­i­dence, one cur­rent FDA of­fi­cial told Herder: “You just let pa­tients take them, and some­how all of these mas­sive in­sur­ance data­bas­es will cough up an an­swer at the end of a year or two about how well the prod­ucts work and how safe they are. We’re not re­al­ly any­where near that de­gree of so­phis­ti­ca­tion in our abil­i­ty to an­a­lyze those big datasets, but there’s a huge amount of pres­sure to push off lots of da­ta col­lec­tion there with­out a lot of method­ol­o­gy to do it.”

Herder added in an email to Fo­cus: “I think the in­abil­i­ty to ef­fec­tive­ly en­force PMRs presents tremen­dous risks for pub­lic health, es­pe­cial­ly for the pro­por­tion of drugs with a PMR that were ap­proved on the ba­sis of lim­it­ed ev­i­dence.”


RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.


Zachary Brennan

managing editor, RAPS

Scott Gottlieb, AP Images

Scott Got­tlieb is once again join­ing a team that en­joyed good times at the FDA un­der his high-en­er­gy stint at the helm

Right after jumping on Michael Milken’s FasterCures board on Monday, the newly departed FDA commissioner is back today with news about another life sciences board post that gives him a ringside chair to cheer on a lead player in the real-world evidence movement — one with very close ties to the FDA.

Aetion is reporting this morning that Gottlieb is joining their board, a group that includes Mohamad Makhzoumi, a general partner at New Enterprise Associates, where Gottlieb returned after stepping out of his role at the FDA 2 years after he started.

Gottlieb — one of the best connected execs in biopharma — knows this company well. As head of FDA he championed the use of real-world evidence to help guide drug developers and the agency in gaining greater efficiencies, which helped set up Aetion as a high-profile player in the game.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Deborah Dunsire. Lundbeck

UP­DAT­ED: Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

A year after taking the reins as CEO of Lundbeck, Deborah Dunsire is making a bold bid to beef up the Danish biotech’s portfolio of drugs in what will likely be a direct leap into an intense rivalry with a group of giants now carving up a growing market for new migraine drugs.

Bright and early European time Monday morning the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation of a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month. In a followup call, Dunsire also noted that the company will likely need 200 to 250 reps for this marketing task on both sides of the Atlantic. And analysts were quick to note that the dealmaking at Lundbeck isn’t done, with another $2 billion to $3 billion available for more deals to beef up the pipeline.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

San Diego cou­ple charged with steal­ing trade se­crets, open­ing Chi­nese biotech as DOJ crack­down con­tin­ues

A San Diego couple has been charged with stealing trade secrets from a US hospital and opening a business based off those secrets in China as the controversial industry-wide crackdown on alleged corporate espionage continues. On the same day, the Department of Justice announced they had arrested Beijing representative Zhongsan Liu for allegedly trying to obtain research visas for government recruiters.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Bio­gen pulls the plug on prized IPF drug from $562M+ Stromedix buy­out

One of Biogen’s attempts to branch out has flopped as the biotech scraps a mid-stage program for idiopathic pulmonary fibrosis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Warts for the win: Aclar­is' lead drug clears piv­otal study

Aclaris Therapeutics has found a way to get rid of the warts and all.

The company — which earlier this month decided to focus on its arsenal of kinase inhibitors — on Monday unveiled positive data from a pivotal study testing its lead experimental drug for use in common warts.

The drug, A-101, was tested in a 502-patient study called THWART-2 — patients enrolled had one to six warts before qualifying for the trial. Patients either self-administered A-101 topical solution or a vehicle twice a week over a two-month period. A higher proportion of patients on the drug (a potent hydrogen peroxide topical solution) saw their warts disappear at day 60, versus the vehicle (p<0.0001) — meeting the main goal of the study.  Each secondary endpoint also emerged in favor of A-101, the company said.

Tower Bridge in London [Shutterstock]

#UK­BIO19: Join GSK’s Hal Bar­ron and a group of top biotech ex­ecs for our 2nd an­nu­al biotech sum­mit in Lon­don

Over the past 10 years I’ve made a point of getting to know the Golden Triangle and the special role the UK biopharma industry plays there in drug development. The concentration of world class research institutes, some of the most accomplished scientists I’ve ever seen at work and a rising tide of global investment cash leaves an impression that there’s much, much more to come as biotech hubs are birthed and nurtured.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Charles Nichols, LSU School of Medicine

Could psy­che­delics tack­le the obe­si­ty cri­sis? A long­time re­searcher in the field says his lat­est mouse study sug­gests po­ten­tial

Psychedelics have experienced a renaissance in recent years amid a torrent of preclinical and clinical research suggesting it might provide a path to treat mood disorders conventional remedies have only scraped at. Now a preclinical trial from a young biotech suggests at least one psychedelic compound has effects beyond the mind, and — if you believe the still very, very early hype — could provide the first single remedy for some of the main complications of obesity.

Ac­celeron drops a de­vel­op­ment pro­gram as #2 drug fails to spark func­tion­al ben­e­fits in pa­tients with a rare neu­ro­mus­cu­lar ail­ment

Acceleron is scrapping a muscular dystrophy development program underway for its number 2 drug in the pipeline after pouring over some failed mid-stage secondary data.

Gone is the ACE-083 project in patients with facioscapulohumeral muscular dystrophy. Their drug hit the primary endpoint on building muscle but flopped on key secondaries for functional improvements in patients, which execs felt was vital to the drug’s success.