FDA shoots down a biotech’s last-stand pa­tient pitch af­ter fault­ing da­ta

Stealth Bio­Ther­a­peu­tics ap­peared un­sure its pitch for an ul­tra-rare dis­ease would be ac­cept­ed when sub­mit­ting an NDA in Au­gust, and on Wednes­day its fears came to pass.

The FDA is­sued Stealth a re­fusal to file let­ter for a can­di­date look­ing to treat Barth syn­drome, the biotech an­nounced Wednes­day morn­ing. It’s a move not en­tire­ly un­ex­pect­ed, giv­en Stealth’s own ad­mis­sion ear­li­er this year that the agency didn’t find ex­ist­ing da­ta to sup­port NDA re­view.

Though this may have al­ways been in the cards, Stealth has said nu­mer­ous times it sub­mit­ted the ap­pli­ca­tion not on the ba­sis of new da­ta but be­cause Barth syn­drome pa­tient ad­vo­cates pe­ti­tioned the com­pa­ny. The Barth Syn­drome Foun­da­tion asked Stealth to do so in No­vem­ber 2020 de­spite know­ing the FDA’s hes­i­ta­tion, not­ing sev­en Barth pa­tients — or 3% of the world’s Barth pop­u­la­tion — died in the pre­ced­ing 13-month pe­ri­od.

Re­gard­less, in­vestors turned their thumbs down at the news, send­ing Stealth’s pen­ny stock shares $MI­TO 11% low­er in ear­ly Wednes­day trad­ing.

Ac­cord­ing to Stealth’s re­count­ing, reg­u­la­tors gave the biotech the same rea­son it had pre­vi­ous­ly ex­plained, find­ing the NDA to be lack­ing an ad­e­quate and well-con­trolled tri­al that would sup­port ev­i­dence of ef­fi­ca­cy. Stealth had sub­mit­ted da­ta from an open-la­bel ex­ten­sion and com­pared it with a ret­ro­spec­tive nat­ur­al his­to­ry study.

Reg­u­la­tors had in­sist­ed, how­ev­er, that Stealth con­duct an ad­di­tion­al Phase III tri­al. Da­ta from the open-la­bel ex­ten­sion like­ly would not “add mean­ing­ful­ly to the ev­i­dence to sup­port an NDA,” Stealth re­vealed in April. But to con­duct such a study in an ul­tra-rare dis­ease with so few pa­tients wouldn’t be fea­si­ble, Stealth and the ad­vo­cates ar­gued.

The drug in ques­tion is known as elamipre­tide, Stealth’s for­mer lead drug that flopped a Phase III for mi­to­chon­dr­i­al dis­ease in late 2019. Elamipre­tide failed the two key end­points on the 6-minute walk test and a score on fa­tigue symp­toms for pa­tients with pri­ma­ry mi­to­chon­dr­i­al my­opa­thy, Stealth said at the time.

But the com­pa­ny in­sist­ed it saw a po­ten­tial ef­fi­ca­cy sig­nal for Barth syn­drome and filed with the FDA af­ter be­ing asked by the pa­tient com­mu­ni­ty.

Stealth was try­ing to fol­low the path laid out by Sarep­ta sev­er­al years ago when the com­pa­ny con­vinced the FDA to ap­prove its Duchenne drug with lim­it­ed clin­i­cal da­ta. In that in­stance, the vig­or and per­sua­sive­ness of ad­vo­cates proved a key el­e­ment in win­ning over reg­u­la­tors, some­thing that echoed in this sum­mer’s con­tro­ver­sial ap­proval of Bio­gen’s new Alzheimer’s drug.

The bal­ance be­tween need­ing con­trolled tri­als, tiny pa­tient pop­u­la­tions and Big Phar­ma’s busi­ness in­cen­tives con­tin­ues to sti­fle drug de­vel­op­ment in a wide range of ul­tra-rare dis­eases, of­ten leav­ing it up to biotechs to try to fill the void. Ear­li­er this month, the biotech Retro­tope said its pro­gram for in­fan­tile neu­roax­on­al dy­s­tro­phy didn’t achieve sta­tis­ti­cal sig­nif­i­cance but re­searchers saw enough pos­i­tive sur­vival da­ta to po­ten­tial­ly con­tin­ue stud­ies.

So­cial im­age: Ree­nie Mc­Carthy, Stealth Bio­Ther­a­peu­tics CEO

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Janet Woodcock (AP Images)

Janet Wood­cock plots her fu­ture at FDA, with se­nior ad­vi­sor role to fall back on if Califf wins con­fir­ma­tion

Acting FDA commissioner Janet Woodcock has been the face of just about every drug approval decision at the agency since the turn of the century. Since the pandemic began, she’s moved between the top of the drugs center to the head of therapeutics at Operation Warp Speed, leading the drive for work on Covid-targeted mAbs and antivirals.

Looking forward — and pending a quick Senate confirmation to cement Rob Califf’s return to the top of FDA early next year — Woodcock’s role at the agency will again be in flux.

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Richard Pazdur (via AACR)

Ac­cel­er­at­ed ap­proval re­forms need mean­ing­ful con­fir­ma­to­ry tri­al im­prove­ments, pro­fes­sors write in Sci­ence

Outside of Covid-19, 2021 has been the year of the accelerated approval.

Beginning last spring, FDA openly challenged six “dangling” accelerated approvals (hadn’t confirmed their clinical benefit yet), three of which were later pulled by the companies.

Then in June, FDA pulled out the accelerated approval pathway, seemingly out of nowhere, to sign off on Biogen’s controversial Alzheimer’s drug Aduhelm. It hadn’t even been mentioned at the drug’s adcomm.

Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.