Ac­cel­er­at­ed ap­provals un­der fire again as piv­otal tri­als typ­i­cal­ly take about as long as con­fir­ma­to­ry tri­als, re­search shows

One of the ma­jor rea­sons the FDA’s ac­cel­er­at­ed ap­proval path­way re­ceives so many ac­co­lades and so much sup­port is that it speeds new and hope­ful­ly im­proved drugs to pa­tients, usu­al­ly in on­col­o­gy, while con­fir­ma­to­ry ev­i­dence on the clin­i­cal ben­e­fit can be gath­ered.

But a new re­search let­ter pub­lished Tues­day in JA­MA Net­work Open rais­es fresh ques­tions about the path­way, mak­ing the case that be­cause the dif­fer­ence in the amount of time it takes to run the con­fir­ma­to­ry tri­al vs. the piv­otal tri­al is typ­i­cal­ly sim­i­lar, the com­pa­nies might as well run the equiv­a­lent of the con­fir­ma­to­ry tri­al first.

The re­search comes as HHS is look­ing in­to the ac­cel­er­at­ed path­way, and as FDA has been sharply crit­i­cized for us­ing the path­way to ap­prove Bio­gen’s Alzheimer’s drug, de­spite scant ev­i­dence that it ac­tu­al­ly pro­vides a clin­i­cal ben­e­fit. The FDA al­so grant­ed Bio­gen a long run­way (9 years) to com­plete its con­fir­ma­to­ry tri­al.

Look­ing at 32/45 in­di­ca­tions ap­proved via the ac­cel­er­at­ed path­way, the Yale re­searchers, led by first au­thor Joshua Wal­lach, found that over­all the me­di­an piv­otal tri­al du­ra­tion was 10 months, while the post-ap­proval tri­al du­ra­tion was 17 months.

“These find­ings raise ques­tions about the use of ac­cel­er­at­ed ap­proval pro­gram for cer­tain ther­a­peu­tic agents, es­pe­cial­ly if postap­proval con­fir­ma­to­ry tri­als nei­ther con­sis­tent­ly eval­u­ate clin­i­cal out­comes nor are much longer than piv­otal tri­als us­ing sur­ro­gate end­points,” the au­thors not­ed.

They al­so cit­ed the in­cred­i­bly long de­lay be­tween the time of the ac­cel­er­at­ed nod and when the con­fir­ma­to­ry tri­al re­sults are ac­tu­al­ly re­port­ed.

“The me­di­an time from ap­proval to FDA-es­tab­lished postap­proval tri­al re­sults re­port­ing dead­lines for spon­sors was 50 months (3-116 months), a me­di­an of 30 months (range, -19 to 106 months) more than the postap­proval tri­al du­ra­tions,” the au­thors wrote.

But they al­so note some of the lim­i­ta­tions to the study, like their re­liance on on­ly pub­licly avail­able da­ta, the fact that dif­fer­ent is­sues crop up with dif­fer­ent ther­a­peu­tic ar­eas (i.e., rare dis­ease ac­cel­er­at­ed ap­provals vs. on­col­o­gy), and the fact that once a drug is mar­ket­ed un­der an ac­cel­er­at­ed ap­proval, it can take much longer to en­roll a postap­proval tri­al.

Mean­while, in an­oth­er re­search let­ter pub­lished by Wal­lach in JA­MA Open Net­work on Tues­day, the au­thors poured cold wa­ter on the idea, of­ten float­ed by in­dus­try and in­clud­ed in the 21st Cen­tu­ry Cures Act, that the FDA should con­sid­er re­ly­ing on re­al-world da­ta to try to ver­i­fy the clin­i­cal ben­e­fits of drugs grant­ed ac­cel­er­at­ed ap­provals based on sur­ro­gate out­comes:

“The find­ings of this cross-sec­tion­al study sug­gest that none of the 50 FDA-re­quired postap­proval con­fir­ma­to­ry tri­als for ther­a­peu­tic agents grant­ed ac­cel­er­at­ed ap­proval be­tween 2009 and 2018 could have been fea­si­bly em­u­lat­ed us­ing cur­rent­ly avail­able claims and/or struc­tured EHR da­ta. In par­tic­u­lar, the nar­row­ly de­fined in­di­ca­tions and strict in­clu­sion and ex­clu­sion cri­te­ria of the FDA-re­quired postap­proval con­fir­ma­to­ry tri­als pre­clud­ed em­u­la­tion us­ing RWD.”

The re­searchers said their find­ings sug­gest that cur­rent ob­ser­va­tion­al meth­ods and RWD “can com­ple­ment, but are un­like­ly to re­place, postap­proval con­fir­ma­to­ry tri­al re­quire­ments.”

On that same front, the FDA re­cent­ly pub­lished a draft guid­ance at­tempt­ing to spell out just how to use RWD, and how messy it can be.

Bio­mark­er 'roadmap­s' and the fu­ture of can­cer R&D; Cur­tain rais­es on #AS­CO22; Pfiz­er, No­var­tis tack­le drug ac­cess; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

While this was not a week for earth-shattering news, there were certainly a lot of interesting tidbits. If you found this recap helpful, please recommend it to your friends and colleagues. We’ll see you on the other side of the long weekend.

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Keep­ing pres­sure on Am­gen, Mi­rati draws mixed re­views on lat­est cut of KRAS da­ta

As the close runner-up to Amgen’s Lumakras in the KRAS race, any data cut from Mirati’s adagrasib continues to draw scrutiny from analysts. And the latest batch of numbers from ASCO is a decidedly mixed bag.

While a quick comparison suggests that adagrasib spurred slightly more responses and led to a longer overall survival than Lumakras among a group of non-small cell lung cancer patients, its duration of response appears shorter and the safety profile continues to spark concern.

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Ann is one of ViiV Healthcare's newest spokespeople as the retired school administrator speaks up about her HIV status.

GSK's Vi­iV de­buts next evo­lu­tion in HIV med Dova­to cam­paign with new spokes­peo­ple and new mes­sage

When Ann saw the first TV commercials for HIV medicine Dovato, she didn’t see herself represented. So the 74-year-old retired school administrator who’s been living with HIV since 1998, reached out to GSK’s ViiV Healthcare and asked why not?

Now Ann is one of three people starring in ViiV’s latest Dovato campaign called “Detect This.” The next-step evolution in the branded campaign plays on the word “detect” — often used in describing HIV status under control as undetectable — but in this case, uses the word as a directive for people to understand they can use fewer medicines.

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Switzer­land to de­stroy over 600,000 ex­pired dos­es of Mod­er­na Covid vac­cine

As concerns related to uptake and distribution continue to linger, Switzerland is among the first countries that plans to destroy hundreds of thousands of expired and unused Covid-19 vaccine doses.

The European country said it plans to destroy more than 600,000 doses of Moderna’s Spikevax Covid-19 vaccine as the doses have reached their expiration date.

However, Moderna CEO Stéphane Bancel told the World Economic Forum in Davos, Switzerland that he’s in the process of throwing 30 million doses in the garbage, exclaiming, “We have a big demand problem.”

HHS Secretary Xavier Becerra (Jacquelyn Martin/AP Images)

HHS fin­ish­es off Trump-era rule that would've erased ba­sic FDA regs with­out fre­quent re­views

HHS on Thursday finalized its decision to withdraw a rule, proposed just before former President Donald Trump left office, that would’ve caused thousands of HHS and FDA regulations to automatically expire if they weren’t reviewed within two years, and every 10 years thereafter.

The decision follows the filing of a lawsuit last March, in which several nonprofits alleged that the outgoing administration planted “a ticking timebomb” for HHS, essentially forcing it to devote an enormous amount of resources to the unprecedented and infeasible task of reviewing thousands of regulations regularly.

Co-CEOs Chintu and Chirag Patel (Amneal)

Look out, Neu­las­ta: A 5th biosim­i­lar is com­ing

As Neulasta sales slip, Amgen has yet another biosimilar to look out for: Amneal Pharmaceuticals and Kashiv Biosciences’ Flynetra.

Flynetra became the fifth approved biosimilar to Neulasta on Friday, snagging a win in neutropenia, a condition common among chemotherapy patients where neutrophils, a type of white blood cell that fights infection, are too low.

As of last summer, the list price of Neulasta was more than $6,400 per dose. It’s designed to be taken in a single dose per chemotherapy cycle. Amneal declined to reveal how much it intends to charge for Flynetra in an email to Endpoints News. 

Lina Khan, FTC chair (Graeme Jennings/Pool via AP Images)

Pile-on over PBMs con­tin­ues with FTC com­ments and a new bi­par­ti­san Sen­ate bill

More than 500 stakeholders sent comments to the FTC on whether the commission should look further into pharma middlemen, known as PBMs, with many of the commenters calling for more federal oversight.

Similar to the critical open comment period in a deadlocked FTC session last February, pharmacies and pharmacy groups are continuing to call out the lack of transparency among the top 3 PBMs, which control about 80% of the market.

Pharma brands are losing their shine with US consumers who are now thinking about the economy and inflation instead of Covid. (Credit: Shutterstock)

Phar­ma brands fade in an­nu­al Har­ris con­sumer vis­i­bil­i­ty poll: Mod­er­na drops off and Pfiz­er dips

As Covid-19 concerns are fading in the US, so is biopharma visibility. The annual Axios Harris Poll survey to determine and rank the 100 most top-of-mind brands in the US finds Moderna, which was No. 3 last year, not on the list at all for 2022, and Pfizer sinking 37 spots.

However, it’s not that Moderna or Pfizer did anything wrong, it’s just that Americans have moved on to other worries beyond Covid.

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Tran­si­tion to new Eu­ro­pean clin­i­cal tri­als in­fo sys­tem starts slow­ly

At the end of January, the European Medicines Agency officially launched its new clinical trials info system (CTIS), although the migration to the new platform has only really just begun, and sponsors have until the end of January 2023 before all initial trial applications must be submitted through CTIS.

Overall, 56 clinical trial applications have been submitted in CTIS during the first 3 months since the launch of the system on Jan. 31, according to new data posted by the EMA. By comparison, about 4,000 new trials are authorized each year across Europe.