EMA and FDA his­tor­i­cal­ly agree on just about every new drug ap­proval, but is that slow­ly chang­ing?

The EMA and FDA con­cur more than 90% of the time in their de­ci­sions to ap­prove new drugs, ac­cord­ing to a new study from EMA and FDA of­fi­cials that looked at 107 ap­pli­ca­tions from 2014 to 2016.

In just eight of the 107 ap­pli­ca­tions, the FDA ini­tial­ly de­clined to ap­prove a new drug or bi­o­log­ic while the EMA ap­proved it, al­though in all eight of those cas­es, the FDA end­ed up ap­prov­ing that drug or bi­o­log­ic. And in one case (Take­da’s Nin­laro (ix­a­zomib) for mul­ti­ple myelo­ma), the FDA ap­proved the treat­ment and the EMA ini­tial­ly did not, but lat­er did.

“Over­all, tak­ing ac­count of the re­sub­mit­ted and re­ex­am­ined ap­pli­ca­tions, the EMA and the FDA had fi­nal dis­cor­dant mar­ket­ing au­tho­riza­tion de­ci­sions for two drugs: cori­fol­litropin al­fa and ataluren,” the study notes, as both were ap­proved by the EMA and not the FDA.

More re­cent­ly, how­ev­er, the EMA’s Com­mit­tee for Med­i­c­i­nal Prod­ucts for Hu­man Use (CHMP) adopt­ed neg­a­tive opin­ions for two drugs in 2018 that were ap­proved by FDA in 2017, and one sick­le cell drug in 2019 that was al­so pre­vi­ous­ly ap­proved by FDA. In ad­di­tion, CHMP raised ques­tions about Mit­subishi Tan­abe Phar­ma’s treat­ment for amy­otroph­ic lat­er­al scle­ro­sis, which with­drew its ap­pli­ca­tion this year, and which was ap­proved by FDA in 2017.

“Di­ver­gence in ap­proval de­ci­sions, type of ap­proval, and ap­proved in­di­ca­tion were pri­mar­i­ly due to dif­fer­ences in agen­cies’ con­clu­sions about ef­fi­ca­cy based on re­view of the same da­ta or dif­fer­ing clin­i­cal da­ta sub­mit­ted to sup­port the ap­pli­ca­tion,” the study pub­lished in Clin­i­cal Phar­ma­col­o­gy & Ther­a­peu­tics found.

In the more re­cent case of the sick­le cell drug, the FDA said its ap­proval was based on a tri­al show­ing that pa­tients treat­ed with En­dari (glu­t­a­mine) ex­pe­ri­enced few­er hos­pi­tal vis­its for sick­le cell crises, on av­er­age, when com­pared to place­bo. But the EMA’s CHMP said it “con­sid­ered that the main study did not show that [glu­t­a­mine] was ef­fec­tive at re­duc­ing the num­ber of sick­le cell crises or hos­pi­tal vis­its.”

The study al­so notes how the FDA more com­mon­ly grant­ed ac­cel­er­at­ed ap­provals (12/25 in on­col­o­gy and 5/8 in hema­tol­ogy) than the EMA grant­ed con­di­tion­al mar­ket­ing au­tho­riza­tion or au­tho­riza­tion un­der ex­cep­tion­al cir­cum­stances (7/25 in on­col­o­gy and 2/8 in hema­tol­ogy).

But sub­mis­sions in these ar­eas of­ten oc­curred lat­er to the EMA than the FDA, and of­ten in­clud­ed ad­di­tion­al clin­i­cal tri­als or more ma­ture da­ta from the same clin­i­cal tri­al than were sub­mit­ted to the FDA. “In those in­stances, the EMA was more like­ly than the FDA to grant stan­dard ap­proval (where­as the FDA is­sued ac­cel­er­at­ed ap­proval) or a broad­er in­di­ca­tion,” the study said.

The study al­so found the EMA had a high­er rate of first-cy­cle ap­provals than the FDA, and the re­searchers “ob­served re­mark­able sim­i­lar­i­ty in the ba­sic sci­en­tif­ic and da­ta in­ter­pre­ta­tion is­sues raised by the FDA and the EMA dur­ing re­views of the same ap­pli­ca­tions. Specif­i­cal­ly, most of the FDA’s sec­ond cy­cle ap­provals (i.e., ap­provals af­ter re­sub­mis­sion of the ap­pli­ca­tions) were based on sub­mis­sion by the spon­sor of the same ad­di­tion­al da­ta that EMA had re­ceived dur­ing its ini­tial re­view ei­ther from the start or fol­low­ing re­quest af­ter clock‐stops.”

In their dis­cus­sion of the re­sults, the study au­thors al­so note the study’s lim­i­ta­tions, such as on­ly us­ing two years’ worth of da­ta. But over­all, the two agen­cies are com­mu­ni­cat­ing and work­ing to­geth­er more close­ly than in years past.

“The high rate of con­ver­gence in the au­tho­ri­sa­tion of new med­i­cines at EMA and the FDA is the re­sult of ex­pand­ed in­vest­ment in di­a­logue and co­op­er­a­tion since 2003 and has fos­tered align­ment be­tween the EU and the US with re­spect to de­ci­sions on mar­ket­ing au­tho­ri­sa­tions, while both agen­cies eval­u­ate ap­pli­ca­tions in­de­pen­dent­ly of each oth­er,” said Zaide Frias, head of the EMA’s hu­man med­i­cines eval­u­a­tion di­vi­sion.

So­cial im­age: Shut­ter­stock, AP


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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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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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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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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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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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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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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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