FDA can do more to en­sure di­ver­si­ty in clin­i­cal tri­als, ex­perts say — in­clud­ing some con­struc­tive bad­ger­ing

The Covid-19 vac­cine and ther­a­peu­tic de­vel­op­ment races have opened many eyes to the re­al­i­ty that clin­i­cal tri­als in the US rarely in­clude the ap­pro­pri­ate num­bers of eth­nic and racial mi­nori­ties. And even when they some­times get close, as with Mod­er­na’s vac­cine, the tri­al had to be de­lib­er­ate­ly slowed to re­cruit ad­di­tion­al Black and His­pan­ic par­tic­i­pants.

Ex­perts con­vened on Mon­day as part of a work­shop at the Na­tion­al Acad­e­mies of Sci­ences, En­gi­neer­ing, and Med­i­cine, and dis­cussed whether the FDA might take a more promi­nent role in ad­vo­cat­ing for more di­ver­si­ty, among oth­er top­ics to in­form the on­go­ing work of the Na­tion­al Acad­e­mies Com­mit­tee on Im­prov­ing the Rep­re­sen­ta­tion of Women and Un­der­rep­re­sent­ed Mi­nori­ties in Clin­i­cal Tri­als and Re­search.

“The FDA has an un­rec­og­nized abil­i­ty to bad­ger spon­sors along the way,” said for­mer FDA com­mis­sion­er Rob Califf, who now works as an ad­vi­sor to Google’s Ver­i­ly Life Sci­ences. The FDA re­view teams al­so can check in on the da­ta around the rep­re­sen­ta­tive pop­u­la­tions and put ad­di­tion­al pres­sure on the spon­sor, he added.

The agency pub­lished fi­nal guid­ance on clin­i­cal tri­al di­ver­si­ty last No­vem­ber, not­ing the ex­tent of chal­lenges for cer­tain groups who con­tin­ue to be un­der­rep­re­sent­ed in many tri­als. But the guid­ance does not add any new re­quire­ments on en­sur­ing di­verse pop­u­la­tions are en­rolled in stud­ies.

Rob Califf

And it’s not just FDA. Califf said he’s push­ing for a wider glob­al dis­cus­sion on how reg­u­la­tors can ad­dress di­ver­si­ty, not­ing that the pub­lic ag­gre­ga­tion of in­for­ma­tion has to be done in ways that peo­ple can uni­ver­sal­ly un­der­stand. There al­so needs to be a bet­ter sys­tem for track­ing post­mar­ket da­ta and un­der­stand­ing how cer­tain drugs af­fect cer­tain pop­u­la­tions and sub­pop­u­la­tions.

“The gap be­tween when a drug is ap­proved and un­der­stand­ing how it should be used and how it af­fects sub­pop­u­la­tions is just a gap­ing hole,” Califf said. “It can’t just be US on­ly.”

Mar­sha Hen­der­son, the FDA’s for­mer as­so­ciate com­mis­sion­er for women’s health, al­so ex­plained the im­por­tance of ad­vo­ca­cy in push­ing for di­ver­si­ty, not­ing that one of the on­ly rea­sons an in­creas­ing num­ber of women are now en­rolled in clin­i­cal tri­als is be­cause there was a con­sis­tent voice.

“FDA is no­to­ri­ous for not fol­low­ing up on cer­tain is­sues be­cause their re­sources are tilt­ed to­ward user fees,” Hen­der­son said. “I think it’s time for more sur­veil­lance.”

The re­cent ex­am­ple of Mod­er­na slow­ing its Covid-19 vac­cine tri­al for sev­er­al weeks last Sep­tem­ber and Oc­to­ber to al­low for more non-white par­tic­i­pants did lit­tle to shift the over­all tri­al, which end­ed up with more than 60% white par­tic­i­pants.

Melanie Ivars­son

Melanie Ivars­son, chief de­vel­op­ment of­fi­cer at Mod­er­na, ac­knowl­edged to the work­shop, with re­spect to her com­pa­ny’s racial and eth­nic de­mo­graph­ics in the vac­cine tri­al: “Was it good enough? No. Could we have done bet­ter? Yes.”

She said the de­ci­sion to stop en­rolling white peo­ple for those few weeks came as “a big shock for the sites” as they were al­so run­ning an­oth­er vac­cine tri­al for Pfiz­er, and they were prepar­ing for tri­als from As­traZeneca and J&J, and “want­ed to move along,” she said. “It’s not just in­dus­try who will solve this prob­lem.”

Com­pa­nies al­so don’t nec­es­sar­i­ly have to slow their clin­i­cal de­vel­op­ment pro­grams to reach more di­verse pop­u­la­tions.

Melis­sa Gon­za­les

Melis­sa Gon­za­les, in­clu­sion prin­ci­pal at Roche’s Genen­tech, ex­plained to the work­shop how, “If you go to the right sites, it’s not re­al­ly a slow­down. Go to where the pa­tients are ac­tu­al­ly seek­ing care, which takes some time to look in­to the clin­i­cal tri­al in­fra­struc­ture. Do the work up­front and en­gage the com­mu­ni­ty pop­u­la­tions … You can’t just show up in the com­mu­ni­ties when there’s a tri­al they need.”

The com­ments fol­low sim­i­lar sen­ti­ments ex­pressed by FDA act­ing com­mis­sion­er Janet Wood­cock and NIH di­rec­tor Fran­cis Collins. “The way in which bio­med­ical re­search works is con­t­a­m­i­nat­ed by struc­tur­al racism,” Collins said.

Califf added on Mon­day, “If you want to look at struc­tur­al racism, go two coun­ties away from any big aca­d­e­m­ic med­ical cen­ter and ask about ac­cess to clin­i­cal care … tri­als in the US are way ahead of clin­i­cal prac­tice.”

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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Chris Gibson (Photo By Vaughn Ridley/Sportsfile for Web Summit via Getty Images)

Re­cur­sion founders gin for­tunes as IPO back­ers show­er $436M on one of the biggest boasts in AI -- based on some very small deals

In the AI drug development world, boasting often comes with the territory. Yet few can rival Recursion when it comes to claiming the lead role in what company execs like to call the industrialization of drug development, with promises of continued exponential growth in the number of drugs it has in the pipeline.

On Friday, the Salt Lake City-based biotech translated its unicorn-sized boasts into a killer IPO, pricing more than 24 million shares at the high end of its range and bringing in $436 million — with a large chunk of that promised by some deep-pocket backers.

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Covid-19 vac­cine halt drags on, an FDA ap­point­ment at long last, the great CRO con­sol­i­da­tion, 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.

Conference season is upon us, and while we’d much prefer to be wandering down the hallways and presentation rooms in person, the team is ready to cover the most consequential data coming out of these scientific meetings. Get in touch early if you have news to share.

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Joe Biden (Carolyn Kaster, AP Images)

Covid-19 roundup: Biden in­vests $1.7B to ad­dress Covid vari­ants; EU puts faith in Pfiz­er with new vac­cine deals

The Biden administration said Friday that it’ll pump $1.7 billion into various programs to address Covid-19 variants as the original strain of Covid-19 makes up only about half of all US cases today.

Most of those new funds, $1 billion in total, will go to expand genomic sequencing so the CDC, states and other jurisdictions can improve their capacity to identify Covid mutations and monitor the circulation of variants. Back in February, US labs were only sequencing about 8,000 Covid-19 strains per week, although the rate of sequencing has increased substantially since then, the administration said.

Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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