FDA push­es eczema de­ci­sion for Eli Lil­ly's Olu­mi­ant, Pfiz­er's abroc­i­tinib back 3 months — rais­ing more ques­tions for the JAK class

The FDA re­view ex­ten­sions for JAK in­hibitors are stack­ing up.

Af­ter Eli Lil­ly and In­cyte dis­closed late Tues­day that their sup­ple­men­tal NDA for Olu­mi­ant in mod­er­ate to se­vere atopic der­mati­tis was hit with a 3-month de­lay, Pfiz­er re­vealed ear­ly Wednes­day that its ex­per­i­men­tal abroc­i­tinib is meet­ing the same fate. With Olu­mi­ant, the agency need­ed time to “re­view ad­di­tion­al da­ta analy­ses sub­mit­ted by Lil­ly in re­sponse to re­cent in­for­ma­tion re­quests from the FDA,” ac­cord­ing to a state­ment. Pfiz­er didn’t spec­i­fy a rea­son in its re­lease.

In ad­di­tion, the agency is al­so knock­ing back by 3 months a re­view of Pfiz­er’s Xel­janz for the treat­ment ac­tive anky­los­ing spondyli­tis.

The set­back puts Lil­ly and Pfiz­er in the same boat as Ab­b­Vie, which re­vealed days ago that reg­u­la­tors asked for an up­dat­ed ben­e­fit-risk pro­file of its JAK in­hibitor Rin­voq, push­ing their PDU­FA date to Q3 of 2021.

Safe­ty con­cerns with JAK in­hibitors are not new. In fact, fol­low­ing a rocky de­vel­op­ment path that in­volved an ini­tial re­jec­tion and re­stric­tions in dos­ing, Olu­mi­ant’s ini­tial ap­proval in rheuma­toid arthri­tis came with black box warn­ings on height­ened risks for se­ri­ous in­fec­tions, ma­lig­nan­cy and throm­bo­sis. Rin­voq sports a sim­i­lar la­bel.

The is­sues came to the fore again ear­li­er this year, when Pfiz­er an­nounced that its drug, Xel­janz, has failed the six-year safe­ty study man­dat­ed by the FDA.

Across 4,362 pa­tients, those who re­ceived ei­ther a low or high dose of Xel­janz ex­pe­ri­enced more ma­jor car­dio­vas­cu­lar events — such as stroke and heart at­tack — than those on Hu­mi­ra or En­brel. They al­so had high­er rates of can­cer, with Pfiz­er fail­ing to hit non-in­fe­ri­or­i­ty on both pri­ma­ry end­points.

Ilya Yuf­fa

Ilya Yuf­fa, pres­i­dent of Lil­ly Bio-Med­i­cines, says they stand by the ef­fi­ca­cy of Olu­mi­ant. The drug had scored wins in mul­ti­ple late-stage stud­ies in atopic der­mati­tis, beat­ing cor­ti­cos­teroids and place­bo in clear­ing eczema.

More re­cent­ly, it’s al­so gained promi­nence as the FDA grant­ed emer­gency use au­tho­riza­tion to a com­bi­na­tion of Olu­mi­ant and Vek­lury (remde­sivir) for hos­pi­tal­ized Covid-19 pa­tients who need sup­ple­men­tal oxy­gen, ven­ti­la­tors or life sup­port.

But its uti­liza­tion in atopic der­mati­tis has al­ways been ques­tioned. SVB Leerink an­a­lyst An­drew Berens pre­vi­ous­ly pre­dict­ed that it will play a “mi­nor role” in the dis­ease:

Giv­en the dom­i­nance of (Re­gen­eron’s) Dupix­ent in the mod­er­ate and se­vere AD mar­ket and known safe­ty risks of in­fec­tions, ma­lig­nan­cies, and throm­bo­sis with oral JAK in­hibitors, we be­lieve oral, sys­temic JAK in­hibitors may not cap­ture a mean­ing­ful por­tion of the AD mar­ket. While this pro­file rep­re­sents lim­i­ta­tions of the JAK class for sys­temic ther­a­py, we be­lieve this could open the door for a greater role for top­i­cal JAK us­age, which could be pre­scribed in con­junc­tion with non-JAK sys­temic treat­ment.

In­cyte, which had ini­tial­ly come up with the drug and al­lied with Lil­ly in ex­change for $90 mil­lion up­front back in 2009, has pulled out of co-fund­ing the de­vel­op­ment but con­tin­ues to be el­i­gi­ble for roy­al­ties on sales.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 107,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 107,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

As­traZeneca-Alex­ion merg­er slides through FTC re­view af­ter sup­posed M&A crack­down pos­es no bar­ri­ers

The AstraZeneca-Alexion megamerger received a good sign Friday, despite warning signs of the tides turning against large M&A pharma deals.

US regulators at the FTC have cleared the acquisition for approval, AstraZeneca announced, all but signing off on the deal to go through once it officially closes in the third quarter. AstraZeneca originally said it was planning to buy out Alexion back in December for $39 billion.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 107,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 107,000+ biopharma pros reading Endpoints daily — and it's free.

David Stack, Pacira Biosciences CEO

In high­ly un­usu­al move, Paci­ra sues med­ical jour­nal for li­bel over its non-opi­oid painkiller

A New Jersey biotech whose only approved drug is used as a painkiller after surgeries is suing a scientific journal, its editors and a handful of authors for libel after the publication printed numerous papers and editorials that the company says discredited the drug.

Pacira Biosciences filed the complaint against the American Society of Anesthesiologists in the US District Court for New Jersey on Wednesday afternoon. A February issue of the group’s journal Anesthesiology printed three articles and other content full of “bias” that “seriously disparaged” the drug Exparel, Pacira claimed.

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.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 107,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.