Gene ther­a­py deaths push back Astel­las-Au­den­tes' ap­proval by at least two years

The three deaths in an Astel­las gene ther­a­py tri­al last year will push back the ex­per­i­men­tal ther­a­py’s ap­proval by “more than two years” as Astel­las plans a sec­ond study, the com­pa­ny told End­points News in an email Tues­day. That means a reg­u­la­to­ry ap­pli­ca­tion would not come un­til at least mid-2022.

When Astel­las bought out the gene ther­a­py biotech Au­dentes for $3 bil­lion in De­cem­ber 2019, the Japan­ese phar­ma be­lieved they could file for ap­proval for their lead can­di­date in the US in mid-2020 and in Eu­rope in the lat­ter half of 2020. The ther­a­py was a one-time treat­ment for a rare and dead­ly mus­cle-wast­ing dis­or­der X-linked my­otubu­lar my­opa­thy, or XLMTM, and ex­ec­u­tives be­lieved the 26-per­son study would be enough to se­cure ap­proval.

But in May, the first of what would ul­ti­mate­ly be three pa­tient deaths oc­curred af­ter suf­fer­ing a se­vere re­ac­tion to a high dose of the vec­tor. The study was halt­ed while in­ves­ti­ga­tors tried to de­ter­mine what hap­pened.

Al­though the FDA agreed to al­low Astel­las to re­sume the study at a low­er dose last De­cem­ber, they have yet to en­roll new pa­tients. The com­pa­ny said in the Tues­day email that they planned to do so by June. The path to ap­proval, how­ev­er, re­mains un­cer­tain.

“We can’t pro­vide an ac­cu­rate time­line at this stage,” a spokesper­son said. “But fil­ing with the FDA and EMA is ex­pect­ed to be de­layed more than two years.”

The plan for sub­mis­sion, they said, had changed. Orig­i­nal­ly, Astel­las planned on sub­mit­ting the ther­a­py for ap­proval for pa­tients of all ages af­ter com­plet­ing the first tri­al, known as AS­PIRO, even though AS­PIRO on­ly en­rolled pa­tients up to the age of five.

Now, how­ev­er, they be­lieve they need to fin­ish the AS­PIRO tri­al and then run a sec­ond study for pa­tients over the age of 5. The three boys who died — al­most all XLMTM pa­tients are male — were among the old­est and largest pa­tients in the ini­tial tri­al, mean­ing they re­ceived among the high­est dos­es and raised con­cerns about how to bring the ther­a­py to old­er pa­tients.

Astel­las is wait­ing to com­plete dos­ing in AS­PIRO be­fore plan­ning the sec­ond tri­al, the spokesper­son said, “so that ad­di­tion­al clin­i­cal da­ta can best in­form the ap­proach.” The com­pa­ny plans to meet with the FDA this spring and the EMA this sum­mer to pre­pare for a fil­ing.

Ear­li­er this week, Astel­las an­nounced that it had writ­ten off $540 mil­lion of the $3 bil­lion buy­out, cit­ing their be­lief that the drug would be ap­proved lat­er and for a small­er pa­tient pop­u­la­tion than orig­i­nal­ly thought.

De­spite the trag­ic set­backs, in­ves­ti­ga­tors say the ther­a­py re­mains a promis­ing treat­ment for a ge­net­ic dis­ease that kills most pa­tients be­fore they reach adult­hood. Kids who re­ceived a low dose of the ther­a­py hit key mo­tor mile­stones for the first time: Six out of six were able to breathe with­out a ven­ti­la­tor and five out of six were able to walk for the first time.

Still, Astel­las has drawn crit­i­cism from out­side ex­perts and ex­ec­u­tives for fail­ing to dis­close or pub­lish de­tailed in­for­ma­tion around the pa­tients’ deaths, leav­ing open the ques­tion of pre­cise­ly what went wrong and how to pre­vent it in the fu­ture.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; 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.

I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

Endpoints Premium

Premium subscription required

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

BAR­DA slows its $9B en­gine for new Covid-19 ther­a­peu­tics

The Biomedical Advanced Research and Development Authority is cooling its jets in looking for new, potential Covid-19 treatments, at least in the near term.

An HHS spokesperson told Endpoints News via email, “to date, BARDA has obligated more than $9 billion for the development and/or purchase of 13 therapeutics, beginning in February 2020 with support to develop Regeneron’s monoclonal antibody therapeutic. Therapeutics are an important element of the COVID-19 response, and we are focused on the programs currently underway and/or in negotiation using the funds available to us.”

Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

UP­DAT­ED: Apel­lis bags FDA nod for Soliris chal­lenger with a dif­fer­ent path­way to PNH — but can it slay the gi­ant?

With a blockbuster rare disease giant in its sights in Alexion’s Soliris, small biotech Apellis has reason to think its competitor is worthy of the spotlight. Now, with the FDA on its side, Apellis will get its chance to be the David to Alexion’s Goliath.

The FDA on Friday approved Empaveli (pegcetacoplan), a C3 complement inhibitor the biotech thinks can prove a worthy challenger to Alexion’s C5 inhibitors Soliris and follow-up drug Ultomiris in rare disease paroxysmal nocturnal hemoglobinuria (PNH).

Jason Kelly (Photographer: Kyle Grillot/Bloomberg via Getty Images)

Gink­go nabs $DNA, biotech's most sought af­ter tick­er, for free in sweet­en­er from NYSE

When Ginkgo went comparison shopping for a financial market to list their now $15 billion company, the New York Stock Exchange had a back-pocket sweetener the Nasdaq couldn’t offer: The most sought-after ticker in biotech, $DNA.

DNA — the most famous three letters in biology and the ticker for the world’s first biotech, Genentech, from 1999 until it was bought out by Roche for $48 billion in 2009 — will now be the ticker for Ginkgo, a 12-year-old synthetic biology startup with grand ambitions to change not only how drugs, but also everyday products like meat and perfumes, are made.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.