Richard Pazdur (via AACR)

Ac­cel­er­at­ed ap­proval re­forms need mean­ing­ful con­fir­ma­to­ry tri­al im­prove­ments, pro­fes­sors write in Sci­ence

Out­side of Covid-19, 2021 has been the year of the ac­cel­er­at­ed ap­proval.

Be­gin­ning last spring, FDA open­ly chal­lenged six “dan­gling” ac­cel­er­at­ed ap­provals (hadn’t con­firmed their clin­i­cal ben­e­fit yet), three of which were lat­er pulled by the com­pa­nies.

Then in June, FDA pulled out the ac­cel­er­at­ed ap­proval path­way, seem­ing­ly out of nowhere, to sign off on Bio­gen’s con­tro­ver­sial Alzheimer’s drug Aduhelm. It hadn’t even been men­tioned at the drug’s ad­comm.

And just this week, the FDA can­celled an­oth­er ad­comm to re­view two more dan­gling AAs, one of which was pulled by Se­cu­ra Bio.

The rain of crit­i­cism con­tin­ues to pour on­to FDA, as two pro­fes­sors from the Uni­ver­si­ty of Penn­syl­va­nia and Boston Uni­ver­si­ty on Thurs­day af­ter­noon pub­lished a new per­spec­tive in Sci­ence ar­gu­ing that the ear­ly ac­cess to these new med­i­cines un­der the AA path­way is not be­ing fol­lowed up with the ap­pro­pri­ate proof in the con­fir­ma­to­ry tri­als.  They said that the Aduhelm ap­proval al­so risks FDA’s rep­u­ta­tion and un­der­mines “its core role in keep­ing the mar­ket free of worth­less or dan­ger­ous med­ical prod­ucts.”

As the alarm bells sound, Rick Paz­dur’s On­col­o­gy Cen­ter for Ex­cel­lence at FDA ini­ti­at­ed a re­view of the ac­cel­er­at­ed ap­proval path­way about a year ago, while more re­cent­ly, HHS’ In­spec­tor Gen­er­al said it al­so will re­view the path­way, fol­low­ing that ac­cel­er­at­ed OK for Aduhelm.

“One ap­proach OIG should con­sid­er is ex­am­in­ing the de­tails of tri­als that have fur­ther eval­u­at­ed a drug’s ap­proved in­di­ca­tion af­ter mar­ket­ing ap­proval, look­ing to dis­tin­guish the fea­tures of tri­als that were more ver­sus less suc­cess­ful,” pro­fes­sors Hol­ly Fer­nan­dez Lynch and Christo­pher Robert­son wrote, adding:

Ac­cel­er­at­ed ap­proval is an im­por­tant reg­u­la­to­ry path­way worth try­ing to save, if the ev­i­dence sug­gests that mean­ing­ful im­prove­ments in con­fir­ma­to­ry tri­als are pos­si­ble. While this ev­i­dence is gath­ered, com­pa­nies, pa­tients, and pol­i­cy-mak­ers should pri­or­i­tize ef­forts to mean­ing­ful­ly im­prove ac­cess to in­ves­ti­ga­tion­al prod­ucts in the preap­proval pe­ri­od, with­out fur­ther push­ing the bound­aries of ac­cel­er­at­ed ap­proval.

Lynch and Robert­son al­so ex­plained how once a drug is mar­ket­ed via the AA path­way, the com­pa­ny’s in­cen­tives to per­form a speedy con­fir­ma­tion tri­al “drop off pre­cip­i­tous­ly,” and pa­tients may al­so be un­will­ing to par­tic­i­pate in a con­fir­ma­to­ry tri­al in which they may be ran­dom­ized to some­thing oth­er than the drug that won ap­proval.

Lynch added via email to End­points that “mean­ing­ful im­prove­ments in con­fir­ma­to­ry clin­i­cal tri­als could be sev­er­al-fold: faster time­lines and stricter dead­lines for com­ple­tion, in­sis­tence on more rig­or­ous de­signs (blind­ing, ran­dom­iza­tion, con­cur­rent con­trols, re­jec­tion of fur­ther use of sur­ro­gate end­points), re­quir­ing con­fir­ma­to­ry tri­al de­sign to be agreed up­on (and per­haps even re­quir­ing the tri­als to be un­der­way) at the time of grant­i­ng ac­cel­er­at­ed ap­proval, and stronger abil­i­ty and will­ing­ness on the part of FDA to rapid­ly pull prod­ucts if post-ap­proval tri­als fail to con­firm ben­e­fit.”

But she said, the “main point of the piece, though, is that pol­i­cy changes need to be in­formed by ad­di­tion­al ev­i­dence about why con­fir­ma­to­ry tri­als are fail­ing to live up to ex­pec­ta­tions. For ex­am­ple, if the is­sue is that not enough pa­tients are will­ing to en­roll in rig­or­ous con­fir­ma­to­ry tri­als, it won’t mat­ter for FDA to in­sist on them and we’ll need to fig­ure out al­ter­na­tive ways to en­cour­age par­tic­i­pa­tion or bet­ter ways to pro­cure ac­cess pri­or to mar­ket­ing ap­proval while still gath­er­ing rig­or­ous da­ta.”

An­na Kaltenboeck, health econ­o­mist and pol­i­cy re­searcher at Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter, and ICER’s Aman­da Mehlman and Steven Pear­son al­so pub­lished an ar­ti­cle in the Jour­nal of Com­par­a­tive Ef­fec­tive­ness Re­search in Au­gust out­lin­ing 10 pos­si­ble ways to re­form the ac­cel­er­at­ed ap­proval path­way.

The re­searchers point­ed to sim­i­lar re­forms in the pre­mar­ket and post­mar­ket tri­als, such as by strength­en­ing the se­lec­tion and use of sur­ro­gate end­points, de­vel­op­ing stan­dard­ized re­view tem­plates and re­quir­ing greater use of ran­dom­ized con­trolled tri­als, as well as cre­at­ing a new la­bel alert for ac­cel­er­at­ed drugs and bet­ter en­forc­ing the com­ple­tion of con­fir­ma­to­ry tri­als.

An­oth­er re­view of ac­cel­er­at­ed ap­provals, pub­lished in JA­MA Open Net­work last month, al­so raised ques­tions about the use of AA path­way for cer­tain drugs, “es­pe­cial­ly if postap­proval con­fir­ma­to­ry tri­als nei­ther con­sis­tent­ly eval­u­ate clin­i­cal out­comes nor are much longer than piv­otal tri­als us­ing sur­ro­gate end­points,” the au­thors wrote.

Graphic: Alexander Lefterov for Endpoints News

Small biotechs with big drug am­bi­tions threat­en to up­end the tra­di­tion­al drug launch play­book

Of the countless decisions Vlad Coric had to make as Biohaven’s CEO over the past seven years, there was one that felt particularly nerve-wracking: Instead of selling to a Big Pharma, the company decided it would commercialize its migraine drug itself.

“I remember some investors yelling and pounding on the table like, you can’t do this. What are you thinking? You’re going to get crushed by AbbVie,” he recalled.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,600+ biopharma pros reading Endpoints daily — and it's free.

Mar­ket­ingRx roundup: Pfiz­er de­buts Pre­vnar 20 TV ads; Lil­ly gets first FDA 2022 pro­mo slap down let­ter

Pfizer debuted its first TV ad for its Prevnar 20 next-generation pneumococcal pneumonia vaccine. In the 60-second spot, several people (actor portrayals) with their ages listed as 65 or older are shown walking into a clinic as they turn to say they’re getting vaccinated with Prevnar 20 because they’re at risk.

The update to Pfizer’s blockbuster Prevnar 13 vaccine was approved in June, and as its name suggests is a vaccine for 20 serotypes — the original 13 plus seven more that cause pneumococcal disease. Pfizer used to spend heavily on TV ads to promote Prevnar 13 in 2018 and 2019 but cut back its TV budgets in the past two fall and winter seasonal spending cycles. Prevnar had been Pfizer’s top-selling drug, notching sales of just under $6 billion in 2020, and was the world’s top-selling vaccine before the Covid-19 vaccines came to market last year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,600+ biopharma pros reading Endpoints daily — and it's free.

Albert Bourla (Photo by Steven Ferdman/Getty Images)

UP­DAT­ED: Pfiz­er fields a CRL for a $295M rare dis­ease play, giv­ing ri­val a big head start

Pfizer won’t be adding a new rare disease drug to the franchise club — for now, anyway.

The pharma giant put out word that their FDA application for the growth hormone therapy somatrogon got the regulatory heave-ho, though they didn’t even hint at a reason for the CRL. Following standard operating procedure, Pfizer said in a terse missive that they would be working with regulators on a followup.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,600+ biopharma pros reading Endpoints daily — and it's free.

Florida Gov. Ron DeSantis (AP Photo/Wilfredo Lee, File)

Opin­ion: Flori­da is so mAb crazy, Ron De­San­tis wants to use mAbs that don't work

Florida Gov. Ron DeSantis is trying so hard to politicize the FDA and demonize the federal government that he entered into an alternate universe on Monday evening in describing a recent FDA action to restrict the use of two monoclonal antibody, or mAb, treatments for Covid-19 that don’t work against Omicron.

Without further ado, let’s break down his statement from last night, line by line, adjective by adjective.

Alexander Lefterov/Endpoints News

A new can­cer im­munother­a­py brings cau­tious hope for a field long await­ing the next big break­through

Bob Seibert sat silent across from his daughter at their favorite Spanish restaurant near his home in Charleston County, SC, their paella growing cold as he read through all the places in his body doctors found tumors.

He had texted his wife, a pediatric intensive care nurse, when he got the alert that his online chart was ready. Although he saw immediately it was bad, many of the terms — peritoneal, right iliac — were inscrutable. But she was five hours downstate, at a loud group dinner the night before another daughter’s cheer competition.

Endpoints Premium

Premium subscription required

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

Not cheap­er by the dozen: Bris­tol My­ers be­comes the 12th phar­ma com­pa­ny to re­strict 340B sales

Bristol Myers Squibb recently joined 11 of its peer pharma companies in limiting how many contract pharmacies can access certain drugs discounted by a federal program known as 340B.

Bristol Myers is just the latest in a series of high-profile pharma companies moving in their own direction as the Biden administration’s Health Resources and Services Administration struggles to rein in the drug discount program for the neediest Americans.

Joaquin Duato, J&J CEO (Photo by Charles Sykes/Invision/AP)

New J&J CEO Joaquin Du­a­to promis­es an ag­gres­sive M&A hunt in quest to grow phar­ma sales

Joaquin Duato stepped away from the sideline and directly into the spotlight on Tuesday, delivering his first quarterly review for J&J as its newly-tapped CEO after an 11-year run in senior posts. And he had some mixed financial news to deliver today while laying claim to a string of blockbuster drugs in the making and outlining an appetite for small and medium-sized M&A deals.

Duato also didn’t exactly shun large buyouts when asked about the future of the company’s medtech business — where they look to be in either the top or number 2 position in every segment they’re in — even though the bar for getting those deals done is so much higher.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,600+ biopharma pros reading Endpoints daily — and it's free.

Amgen's Twitter campaign #DearAsthma inspired thousands of people to express struggles and frustrations with the disease

Am­gen’s #Dear­Asth­ma spon­sored tweet lands big on game day, spark­ing thou­sands to re­spond

Amgen wanted to know how people with asthma really felt about daily life with the disease. So it bought a promoted tweet on Twitter noting the not-so-simple realities of life with asthma and ended the post with a #DearAsthma hashtag, a megaphone emoji and a re-tweet button.

That was just over one week ago and the responses haven’t stopped. More than 7,000 posts so far on Twitter replied to #DearAsthma to detail struggles of daily life, expressing humor, frustration and sometimes anger. More than a few f-bombs have been typed or gif-ed in reply to communicate just how much many people “hate” the disease.

FDA slams Eli Lil­ly's 'mis­lead­ing' In­sta­gram ad for its type 2 di­a­betes in­jec­tion

In a first for 2022, the FDA’s Office of Prescription Drug Promotion has issued an untitled letter, which was recently sent to Eli Lilly over what the agency calls a “misleading” and “particularly concerning” Instagram ad the company posted for its type 2 diabetes drug Trulicity.

The questionable Instagram post, which has since been deleted by Lilly, failed to adequately communicate the indication and limitations of use associated with Trulicity, FDA says.