A small remde­sivir study with lots of short­com­ings sug­gests it may be work­ing against Covid-19 — and 1 an­a­lyst fore­casts mid-May roll­out

In a small study in­volv­ing 53 com­pas­sion­ate use cas­es of se­vere­ly af­flict­ed Covid-19 pa­tients, Gilead found en­cour­ag­ing ev­i­dence that sug­gests remde­sivir might be pro­vid­ing a ben­e­fit — but it all has to be borne out in on­go­ing Phase III stud­ies.

Re­port­ing in the New Eng­land Jour­nal of Med­i­cine, re­searchers con­clud­ed that the drug re­sult­ed in the clin­i­cal im­prove­ment of 68% of these pa­tients, Gilead re­ports, but the caveats are ex­treme­ly im­por­tant. The study was small, da­ta may be miss­ing, and there was no ran­dom­ized con­trol group to com­pare against.

Still, Gilead re­ports:

Af­ter 28 days of fol­low-up, the cu­mu­la­tive in­ci­dence of clin­i­cal im­prove­ment, de­fined as dis­charge from the hos­pi­tal and/or at least a two-point im­prove­ment from base­line on a pre­de­fined six-point scale, was 84 per­cent ac­cord­ing to Ka­plan-Meier analy­sis. Clin­i­cal im­prove­ment was less fre­quent among pa­tients on in­va­sive ven­ti­la­tion ver­sus non­in­va­sive ven­ti­la­tion (HR: 0.33 [95 per­cent CI 0.16, 0.68]) and among pa­tients at least 70 years of age (HR vs < 50 years: 0.29 [95 per­cent CI 0.11, 0.74]).

Sum­ma­rized by SVB Leerink an­a­lyst Ge­of­frey Porges:

Of the 30 pa­tients who had been in­tu­bat­ed and ven­ti­lat­ed, 6 (18%) died and 24% had been dis­charged. 47% of all pa­tients in the study had been dis­charged and the cu­mu­la­tive in­ci­dence of clin­i­cal im­prove­ment at 28 days of fol­low-up was 84%….Of the 19 hos­pi­tal­ized pa­tients who were re­ceiv­ing sup­ple­men­tal oxy­gen, 1 (5%) died and the vast ma­jor­i­ty of the rest (17) had been dis­charged. By com­par­i­son, we would have ex­pect­ed a mor­tal­i­ty of ~50-90% among the ven­ti­lat­ed pa­tients and 5-10% among the non-ven­ti­lat­ed, (non ICU) oxy­gen sup­port­ed pa­tients, im­prove­ment in out­comes of 20% that we had been ex­pect­ing, and is like­ly to of­fer con­sid­er­able re­lief to physi­cians, pa­tients and in­vestors.

While some groups will like­ly push for an im­me­di­ate ap­proval to start us­ing remde­sivir, Porges thinks that Gilead will still like­ly wait for bet­ter da­ta — with the first round from Chi­na due any day now. But the an­a­lyst thinks this one is like­ly to be good to go for at least lim­it­ed use by mid-May.

Per­haps of equal im­por­tance, the re­searchers in­volved said that there were no new safe­ty is­sues to be seen from ear­li­er tri­als in an­oth­er in­di­ca­tion. A clean safe­ty pro­file will be cru­cial to a snap ap­proval from the FDA and EMA, at a time new drugs are des­per­ate­ly need­ed.

In nor­mal cir­cum­stances, this would be the kind of da­ta that most re­searchers would shrug off as per­haps in­ter­est­ing and sug­ges­tive of bet­ter things to come, but of no re­al im­por­tance. But these aren’t nor­mal times.

“While the out­comes ob­served in this com­pas­sion­ate use analy­sis are en­cour­ag­ing, the da­ta are lim­it­ed,” said Mer­dad Parsey, the CMO Gilead Sci­ences. “Gilead has mul­ti­ple clin­i­cal tri­als un­der­way for remde­sivir with ini­tial da­ta ex­pect­ed in the com­ing weeks. Our goal is to add to the grow­ing body of ev­i­dence as quick­ly as pos­si­ble to more ful­ly eval­u­ate the po­ten­tial of remde­sivir and, if ap­pro­pri­ate, sup­port broad­er use of this in­ves­ti­ga­tion­al drug.”

Remde­sivir is the most ad­vanced of all the an­tivi­rals now be­ing hus­tled through a rapid set of piv­otal stud­ies, and any proof one way or the oth­er is be­ing stud­ied with un­prece­dent­ed in­ten­si­ty in a world fear­ful of the im­pact of the worst out­break in liv­ing mem­o­ry.

The news quick­ly at­tract­ed a few key thumbs up. Er­ic Topol, founder and di­rec­tor of the Scripps Re­search Trans­la­tion­al In­sti­tute in La Jol­la, in par­tic­u­lar not­ed one key sen­tence in the NE­JM:

It is no­table that 17 of 30 pa­tients (57%) where were re­ceiv­ing in­va­sive me­chan­i­cal ven­ti­la­tion were ex­tu­bat­ed, and 3 of 4 pa­tients (75%) re­ceiv­ing EC­MO stopped re­ceiv­ing it; all were alive at last fol­lowup.

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

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?

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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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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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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Mer­ck scraps their $425M Covid-19 drug in lat­est pan­dem­ic set­back

Seven months after paying $425 million cash to acquire it, Merck is scrapping a Covid-19 drug they hoped could provide one of the only treatments for severe hospitalized patients.

Merck’s decision comes after they faced significant and unexpected regulatory delays in getting the drug, known as MK-7110 or CD24Fc, across the finish line. The Big Pharma licensed the drug under the belief that it had already shown sufficient benefit in severe patients and they could help scale it up far faster than OncoImmune, its former owner, could. But in February, the company reported that the FDA insisted Merck run a new trial before seeking authorization.

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Severin Schwan, Roche CEO (Georgios Kefalas/Keystone via AP Images)

Look­ing to ce­ment its lead in packed MS mar­ket, Roche's Ocre­vus un­corks new da­ta in ear­ly-stage pa­tients

Among a positively jam-packed multiple sclerosis market, Roche’s Ocrevus has managed to stand out for what the Swiss drugmaker is calling the most successful launch in its long history. But in order to press its advantage, Ocrevus is looking to earlier-stage patients, and new interim data should help build its case there.

After 48 weeks on Roche’s Ocrevus, 85% of newly diagnosed primary progressing or relapsing MS patients without a history of disease modifying therapy posted no disease activity, including disease progression or relapse, according to interim data set to be presented this weekend at the virtual American Academy of Neurology meeting.