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.”

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; 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.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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CBER Director Peter Marks (Susan Walsh/AP Images)

FDA ad­vi­so­ry com­mit­tee votes unan­i­mous­ly in fa­vor of bi­va­lent Covid shots re­plac­ing pri­ma­ry se­ries

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all current vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

The vote marks an effort to clear up confusion around varying formulations and dosing schedules for current primary series and booster vaccines, as well as “get closer to the strains that are circulating,” according to committee member Paul Offit, professor of pediatrics at the Children’s Hospital of Philadelphia.

Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Post-hoc analy­sis: EMA's CHMP re­jects Ipsen's po­ten­tial drug for rare ge­net­ic dis­ease

The European Medicines Agency’s Committee for Medicinal Products for Human Use on Friday rejected Ipsen Pharma’s potential treatment for a rare genetic disease known as fibrodysplasia ossificans progressiva (FOP), which causes extra bone to form outside the skeleton.

The EMA said on its website that it could not draw any firm conclusions on the benefits of the French biopharma’s Sohonos (palovarotene), which selectively targets the retinoic-acid receptor gamma (RARγ), “as the applicant’s conclusion was based on a post-hoc analysis which was neither scientifically nor clinically justified and pre-specified study objectives were not met.”

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FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

Steve Harr, Sana Biotechnology CEO

Four years in, Sana gets first FDA go-ahead to bring can­cer treat­ment in­to the clin­ic

Sana Biotechnology is finally headed to the clinic.

Thursday afternoon, the biotech announced the FDA had cleared its application to start a clinical trial for its allogeneic, or “off-the-shelf,” CAR-T cell therapy targeting the antigen CD19 for patients with B-cell lymphomas and leukemias. Sana said its therapy, dubbed SC291, was designed to evade the immune system, which could help cell therapy produce a more durable response in patients, a concern that has followed such off-the-shelf therapies that use donor cells as opposed to a patient’s own cells.

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Eliot Forster, F-star CEO (Rachel Kiki for Endpoints News)

F-star gets down to the wire with $161M sale to Chi­nese buy­er as na­tion­al se­cu­ri­ty con­cerns linger

With the clock ticking on F-star Therapeutics’ takeover by a Chinese buyer, the companies are still scrambling to remove a hold on the deal from the US government’s Committee on Foreign Investment in the United States.

F-star and invoX Pharma said they are “actively negotiating” with CFIUS “about the terms of a mitigation agreement to address CFIUS’s concerns regarding potential national security risks posed by the transaction.”

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