In his­toric vote, mR­NA vac­cines go 2 and 0 as FDA ex­perts unan­i­mous­ly back Mod­er­na's Covid-19 vac­cine

Come Sat­ur­day, the US will like­ly have two Covid-19 vac­cines.

The FDA’s ad­vi­so­ry com­mit­tee on vac­cines vot­ed unan­i­mous­ly Thurs­day — with one ab­sten­tion — to rec­om­mend an emer­gency use au­tho­riza­tion for Mod­er­na’s mR­NA-based Covid-19 shot, set­ting the agency up to like­ly is­sue the EUA on Fri­day. The agency does not have to lis­ten to the com­mit­tee but usu­al­ly does.

“The ev­i­dence that has been stud­ied in great de­tail on this vac­cine high­ly out­weighs any is­sues that we’ve seen,” Stan­ford in­fec­tious dis­ease pe­di­a­tri­cian Hay­ley Gans said. “And I think re­al­ly sup­ports us be­ing able, with the pan­dem­ic, move for­ward and fi­nal­ly pro­vide a safe and ef­fec­tive way of get­ting to herd im­mu­ni­ty.”

The unan­i­mous vote con­trast­ed with last week’s ad­vi­so­ry hear­ing on Pfiz­er-BioN­Tech’s own mR­NA shot, where four com­mit­tee mem­bers vot­ed against the ques­tion put to them and one ab­stained. But the dis­crep­an­cy may come down to a mi­nor dif­fer­ence be­tween the two ap­pli­ca­tions.

Pfiz­er asked for an EUA to vac­ci­nate any­one 16 years of age or old­er, but some mem­bers of the com­mit­tee were con­cerned that Pfiz­er did not con­duct suf­fi­cient test­ing on 16 and 17 year olds and vot­ed ac­cord­ing­ly, even though they sup­port­ed vac­ci­nat­ing any­one over 18. Mod­er­na on­ly re­quest­ed an EUA for peo­ple 18 and up, as­suag­ing the com­mit­tee’s con­cerns.

Nev­er­the­less, some ad­vi­so­ry mem­bers still sparred with the FDA over the word­ing of the ques­tion put be­fore the com­mit­tee, fear­ing that the word­ing may mis­lead the pub­lic in­to be­liev­ing that the vac­cine has been ful­ly ap­proved. They of­fered adding “ex­per­i­men­tal” or “emer­gency use au­tho­riza­tion” to the ques­tion.

“This can be in­ter­pret­ed as rec­om­mend­ing full ap­proval,” said NCAT’s Michael Kuril­la. “That may… pre­clude not on­ly ad­e­quate eval­u­a­tion of this vac­cine but al­so fu­ture and on­go­ing Covid vac­cines in de­vel­op­ment.

FDA of­fi­cials and oth­er mem­bers, how­ev­er, quick­ly shot down the idea.

“The ques­tion is nev­er when do you know every­thing, it’s when do you know enough,” said Paul Of­fit, an in­fec­tious dis­ease physi­cian at Chil­dren’s Hos­pi­tal of Philadel­phia.

Kuril­la ab­stained over the word­ing, as well as con­cerns that an ex­pand­ed ac­cess pro­to­col may have been more ap­pro­pri­ate than an EUA, al­low­ing tri­als to con­tin­ue to col­lect ran­dom­ized da­ta.

An EUA for Mod­er­na would rough­ly dou­ble the amount of vac­cine im­me­di­ate­ly avail­able in the U.S., from over 20 mil­lion dos­es to over 40 mil­lion dos­es. The vac­cine is al­so eas­i­er to dis­trib­ute as it can be han­dled at the same tem­per­a­ture as most ap­proved vac­cines — un­like Pfiz­er’s shot — and the U.S. has ex­er­cised op­tions to ac­quire 200 mil­lion dos­es through June.

While prof­fer­ing dozens of ques­tions, the com­mit­tee nev­er ex­pressed se­ri­ous con­cerns about the safe­ty or ef­fec­tive­ness of the vac­cine. Mod­er­na an­nounced pre­vi­ous­ly that the vac­cine was 94.1% ef­fec­tive at pre­vent­ing symp­to­matic Covid-19. Al­though the FDA re­view re­vealed that the vac­cine ap­peared less ef­fec­tive in vol­un­teers over 65 — 86.5% pro­tec­tion — com­pa­ny ex­ec­u­tives not­ed that the dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant.

In­stead, dis­cus­sion cen­tered on rare po­ten­tial side ef­fects and Mod­er­na’s plan for what to do with ad­verse events. The FDA’s re­view turned up one sur­pris­ing se­ri­ous event: Two vol­un­teers who had pre­vi­ous­ly re­ceived a der­mal fill­ing ex­pe­ri­enced fa­cial swelling af­ter re­ceiv­ing the vac­cine.

The pan­el asked re­peat­ed­ly the al­ler­gic re­ac­tions that have emerged in the two weeks since Pfiz­er’s vac­cine was in­oc­u­lat­ed. Al­though Mod­er­na said they did not see any cas­es of ana­phy­lax­is in their study — out­side of one al­ler­gic re­ac­tion two months out, from some­one with a soy al­ler­gy — they al­so not­ed it as one po­ten­tial se­ri­ous event to mon­i­tor long term.

Still, Mod­er­na CMO Tal Zaks cau­tioned that each com­po­nent of the com­pa­ny’s lipid nanopar­ti­cle, which may have trig­gered the al­ler­gic re­ac­tion in Pfiz­er re­cip­i­ents, was dif­fer­ent chem­i­cal­ly than the Pfiz­er-BioN­Tech vac­cine.

“While we all might say, oh there’s an LNP here, there’s a lipid and mR­NA, there­fore they must be all be the same,” he said. “I would not nec­es­sar­i­ly as­sume that.”

The on­ly point of con­tin­u­al fric­tion be­tween Mod­er­na and the pan­el arose around the ques­tion of what the com­pa­ny should do with their Phase III tri­al af­ter an EUA is is­sued. The group was skep­ti­cal last week when Pfiz­er pro­posed grad­u­al­ly un­blind­ing par­tic­i­pants as they be­come el­i­gi­ble for vac­cine un­der CDC pri­or­i­ty guide­lines. Mod­er­na want­ed to go fur­ther, im­me­di­ate­ly of­fer­ing the vac­cine to all place­bo par­tic­i­pants, re­gard­less of whether they would be el­i­gi­ble.

Mod­er­na ex­ec­u­tives said that they need­ed to un­blind to pre­vent vol­un­teers from drop­ping out of the study, and be­cause place­bo par­tic­i­pants are and would con­tin­ue to be in­fect­ed. They said they could vac­ci­nate them with clin­i­cal sup­ply of the vac­cine that would not draw from their com­mer­cial sta­ble.

“Ad­di­tion­al se­vere cas­es and death are a ques­tion more of when than a ques­tion of if,” Mod­er­na se­nior vice pres­i­dent Jacque­line Miller said.

Many ad­vi­sors re­ject­ed the ap­proach, propos­ing that Mod­er­na ei­ther fol­low Pfiz­er’s plan or adopt an ap­proach where the tri­al would stay blind­ed but par­tic­i­pants in the vac­cine arm would get place­bo and vol­un­teers in the place­bo arm would re­ceive vac­cine, al­low­ing com­par­isons on dura­bil­i­ty and long-term ad­verse events. A few, how­ev­er, backed the Mod­er­na ap­proach, say­ing the blind­ing pro­pos­al and even the Pfiz­er ap­proach may be in­fea­si­ble.

The de­bate got to the point that at least two dif­fer­ent ad­vi­sors pro­posed the agency al­low the pan­elists to vote on the is­sue, al­though they had not orig­i­nal­ly been asked to do so.

“It seems to me that there’s an as­sump­tion that Mod­er­na is go­ing to do what it’s go­ing to do. It doesn’t have to be that way,” Shel­don Taub­man, the con­sumer ad­vo­cate on the pan­el, said. “We weren’t asked to vote on it, but we could vote on it.”

Mar­i­on Gru­ber, di­rec­tor of the of­fices of vac­cine re­search at the FDA, though, neu­tral­ized that idea, cit­ing the “com­plex­i­ty of the sit­u­a­tion” and the fact that they did not ask the com­mit­tee to vote on the same is­sue at the Pfiz­er tri­al. The hear­ing end­ed with­out a res­o­lu­tion.

“I think we gave FDA a sense of our with that we could do a crossover blind­ed de­sign, but the re­al­iza­tion that that may be im­pos­si­ble,” com­mit­tee chair Arnold Mon­to said. “FDA will be ne­go­ti­at­ing with Mod­er­na about the way they will ad­dress this prob­lem.”

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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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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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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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.

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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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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