Robert Califf, FDA commissioner (Michael Brochstein/Sipa USA/Sipa via AP Images)

FDA chief Rob Califf: The busi­ness of health is boom­ing but peo­ple's out­comes aren't im­prov­ing

While re­fer­ring to him­self as liv­ing in the prover­bial “over­time” of life at the age of 70, new­ly Sen­ate-con­firmed FDA chief Rob Califf said his hope, at the end of his sec­ond run at the agency, is to leave the sys­tem in a way that en­ables peo­ple to bet­ter find out the truth about the risks and ben­e­fits of prod­ucts the FDA reg­u­lates.

The famed clin­i­cal tri­al­ist from Duke, who al­so re­cent­ly spent time at Google’s par­ent com­pa­ny Al­pha­bet, made clear that his vi­sion is to fair­ly eval­u­ate the re­al val­ue and worth of new prod­ucts, and to quick­ly dis­pose of in­ves­ti­ga­tion­al prod­ucts that aren’t use­ful.

“We do not have that sys­tem now,” Califf said, al­though he said com­pared to “where we were, we have a great sys­tem.”

On the part not done as well in the US vs. the rest of the world, Califf point­ed to the fact that the US is one of the great­est in­ven­tors in the world but in last place for life ex­pectan­cy among oth­er high-in­come coun­tries.

“I’m in love with the term sub-op­ti­miza­tion,” Califf said, defin­ing the term as a sys­tem with many parts that are in­cen­tivized to op­ti­mize their own well-be­ing, but the sys­tem as a whole is less than the sum of the parts.

“I think that is an Amer­i­can prob­lem right now,” he said re­fer­ring to sub-op­ti­miza­tion, not­ing that the busi­ness of health care has nev­er been bet­ter but the out­comes of the peo­ple the sys­tem is try­ing to serve are not do­ing bet­ter.

On his promis­es to Con­gress re­gard­ing ac­cel­er­at­ed ap­proval re­forms, Califf told Matt Her­p­er at a STAT News event Thurs­day that “the amount of heat gen­er­at­ed in the dis­cus­sion is in­verse­ly pro­por­tion­al to qual­i­ty of the stud­ies done.”

He al­so made clear that he doesn’t think it’s with­in the role of the FDA com­mis­sion­er, as a po­lit­i­cal ap­pointee, to make de­ci­sions on spe­cif­ic prod­ucts (al­though this in­ter­pre­ta­tion has been dis­put­ed, as was the case with his de­ci­sion to ap­prove Sarep­ta’s DMD drug eteplirsen). The peo­ple who make the de­ci­sions on prod­ucts are full-time civ­il ser­vants who have no con­flicts of in­ter­ests, he not­ed, and it’s their job to make these ap­proval de­ci­sions.

“My job is to make sure what the rules are of the game, and the in­ter­ac­tion with the out­side world, and look­ing across at sys­tem­at­ic poli­cies that would im­prove things,” he said.

In the cas­es men­tioned, he said, re­fer­ring to the re­cent ALS drug that went be­fore an ad­comm ear­li­er this week and Bio­gen’s con­tro­ver­sial Alzheimer’s drug, “there were re­al im­per­fec­tions in the way the stud­ies were done that make it hard.” Pa­tients who need ther­a­pies des­per­ate­ly need to be sure the stud­ies ac­tu­al­ly an­swer the ques­tion rel­e­vant to their needs, he added.

While not­ing that the de­f­i­n­i­tion of an ac­cel­er­at­ed ap­proval is that an in­ves­ti­ga­tion­al drug is “rea­son­ably like­ly” that an un­val­i­dat­ed sur­ro­gate would lead to clin­i­cal ben­e­fit, he ex­plained that the path­way does lead lots of com­pa­nies to get in­to sur­ro­gate end­points, which might not nec­es­sar­i­ly be a low­er qual­i­ty study, but it’s a dif­fer­ent study.

But he said he thought it’s usu­al­ly naïve com­pa­nies that are go­ing af­ter these un­val­i­dat­ed sur­ro­gates with low­er-qual­i­ty stud­ies, rather than com­pa­nies try­ing to get away with less clin­i­cal work.

So how to im­prove the sys­tem for ac­cel­er­at­ed ap­provals?

“I think you’re aware there’s con­sid­er­a­tion of im­prove­ments cur­rent­ly,” he said, re­fer­ring to FDA’s leg­isla­tive pro­pos­als. “It’s that space in be­tween the ap­proval and the fi­nal de­ter­mi­na­tion of clin­i­cal risks/ben­e­fits. Right now the sys­tem is painful­ly slow to get good an­swers. Reg­u­la­to­ry sci­ence stud­ies have come to dif­fer­ent con­clu­sions, but es­sen­tial­ly we need to get good stud­ies done af­ter the ap­proval in a very ef­fi­cient way, as quick­ly as pos­si­ble.”

On the top­ic of FDA-CMS re­la­tions, which have been a point of in­ter­est in re­cent months as CMS has so far balked at cov­er­ing Aduhelm wide­ly, Califf called for “a smooth hand-off from FDA to CMS,” as the two “need to co­or­di­nate so CMS is equipped to make the right de­ci­sion.”

In the lead up to his Sen­ate con­fir­ma­tion, Califf pre­vi­ous­ly dis­cussed the need for con­fir­ma­to­ry tri­als to speed up af­ter these ac­cel­er­at­ed OKs. Com­par­ing the ac­cel­er­at­ed path­way to a re­lay race, Califf ar­gued the “FDA runs the first lap, gets to the end, drops the ba­ton down on the ground, and some­one else like CMS has to fig­ure out where the ba­ton is, pick it up and start all over.”

A ques­tion from the au­di­ence at the Stat event al­so asked Califf if he might re­lease the agency’s com­plete re­sponse let­ters, or re­jec­tions to phar­ma com­pa­nies, a move Califf’s pre­de­ces­sor Scott Got­tlieb vowed to do but didn’t.

“The com­plete re­sponse let­ters — there aren’t that many of them,” Califf said, while not­ing that he’s not op­posed to re­leas­ing them, it’s “not as big of a deal as many peo­ple make it.” Bad ap­pli­ca­tions get weed­ed out more fre­quent­ly now ear­li­er in the ap­proval process, and the CRLs of­ten have to do with man­u­fac­tur­ing is­sues, which are redact­ed, he said.

“One of the many things I want to work on is mis­in­for­ma­tion,” Califf said. “I want to be very proac­tive.”

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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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.

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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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.

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.”

Sen. Bill Cassidy (R-LA) (J. Scott Applewhite/AP Images)

Sen­ate un­veils its ver­sion of ac­cel­er­at­ed ap­proval re­forms as bi­par­ti­san duo calls on FDA and PTO to work to­geth­er

The Senate is joining its House counterparts and advancing accelerated approval pathway reforms to the FDA user fee legislation that must be signed by President Joe Biden before the end of September or else the FDA will have to start laying off its staff.

While Sen. Richard Burr (R-NC) warned yesterday that the user fee deals could be delayed by the infant formula crisis, the newly introduced bill on Friday shows how the Senate is aligning with its House counterparts on similar accelerated approval reforms.

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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. 

Nassim Usman, Catalyst Biosciences CEO

Af­ter $60M Ver­tex deal, group of Cat­a­lyst share­hold­ers claims biotech could’ve sold as­sets three years ago

Catalyst Biosciences was down to five employees in March, and the biotech needed to do something after two rounds of layoffs, a nixed collaboration and a culling of its hemophilia program.

In came Vertex, with $60 million to buy up the South San Francisco biotech’s preclinical complement drugs, which target the system that bridges the body’s innate and adaptive immune response and a class most known for Ultomiris and Soliris. The deal includes CB 2782-PEG, the dry AMD drug that Biogen no longer wanted in March.

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