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.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Tony Coles, Cerevel CEO

Cerev­el takes the pub­lic of­fer­ing route, with a twist — rais­ing big mon­ey thanks to ri­val da­ta

As public biotechs seek to climb out of the bear market, a popular strategy to raise cash has been through public offerings on the heels of positive data. But one proposed raise Wednesday appeared to take advantage not of a company’s own data, but those from a competitor.

Cerevel Therapeutics plans to raise $250 million in a public offering and another $250 million in debt, the biotech announced Wednesday afternoon, even though it did not report any news on its pipeline. However, the move comes days after rival Karuna Therapeutics touted positive Phase III data in schizophrenia, a field where Cerevel is pursuing a similar program.

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Who are the women blaz­ing trails in bio­phar­ma R&D? Nom­i­nate them for End­points' 2022 spe­cial re­port

Over the past three years, Endpoints News has spotlighted 60 women who have blazed trails and supercharged R&D across the biopharma world. And judging from the response we’ve received, to both our special reports and live events, telling their stories — including any obstacles they may have had to overcome — has inspired our readers in many different ways.

But change takes time, and the fact remains that women are still underrepresented at the upper ranks of the drug-making world.

Bernat Olle, Vedanta Biosciences CEO

Cit­ing 'chal­leng­ing eco­nom­ic en­vi­ron­ment,' PhI­II-ready mi­cro­bio­me biotech lays off 20% of staffers

The market downturn isn’t just sweeping up public biotechs.

Vedanta Biosciences, a developer of oral drugs derived from the human microbiome, is laying off about 20% of its staff — an unfortunately common occurrence these days. But CEO Bernat Olle took the unusual step of sharing the decision on LinkedIn and offering to connect the employees being let go with any company that’s hiring in their areas.

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Hervé Affagard, MaaT Pharma CEO

One year in­to clin­i­cal hold, FDA has more ques­tions about 'pooled' mi­cro­bio­me ther­a­py

The FDA is still wary about a trial testing a microbiome therapy in patients with steroid-resistant acute graft-versus-host disease (aGVHD).

A year after MaaT Pharma’s IND application in the US was first met with a clinical hold, the French biotech said the agency is maintaining the hold. The crux of the matter, MaaT suggested, has to do with the way it puts together its drug candidate, which is administered as an enema (i.e. an injection of fluid into the bowel).

Up­dat­ed: Amid mas­sive re­struc­tur­ing, Bio­gen looks to re­duce phys­i­cal pres­ence in Boston

Biogen is putting a sizable chunk of office and research space in Kendall Square and Weston, MA up for sublease, marking another big change as the biotech grapples with the aftershock of a disastrous and controversial rollout for its Alzheimer’s drug.

The subbleases are “part of Biogen’s overall implementation of the ‘Future of Work,’ which is allowing us to optimize our footprint and reduce the amount of space we occupy, taking into consideration new elements such as the hybrid work model,” Biogen spokesperson Ashleigh Koss wrote in a statement to Endpoints News, adding that the company has had subleases across several buildings for years.

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Pfiz­er launch­es re­bate pro­gram for rare dis­ease pa­tients who have to stop tak­ing Panzy­ga

Pfizer is launching its second-ever rebate program, this time for Panzyga, its treatment for a rare neurological disease of the peripheral nerves.

The program began last month, according to STAT which first reported the news, and offers a refund of out-of-pocket costs for patients who must discontinue their course before the fifth treatment for “clinical reasons.”

Panzyga was approved back in 2018 to treat primary immunodeficiency (PI) in patients two years and older and chronic immune thrombocytopenia (cITP) in adults. It has since picked up an indication in chronic inflammatory demyelinating polyneuropathy (CIDP), a condition that’s characterized by weakness of the arms or legs, tingling or numbness, and a loss of deep tendon reflexes, according to the NIH.

Horizon's back-to-school campaign for children with cystinosis includes an all about me poster as part of a care package box.

Hori­zon read­ies kids and fam­i­lies for back to school with week­long ac­tiv­i­ties around rare dis­ease cysti­nosis

Going back to school is usually a bumpy readjustment from summer freedom for all kids, but especially for kids with chronic health conditions. Horizon Therapeutics is hoping to help smooth the way for some who have the rare disease cystinosis. Cystinosis is a genetic disease that causes the amino acid cystine to build up in different tissues and organs.

The “Gear Up” for school campaign is running all week with different online and at-home events and activities for families and children with cystinosis. Each family who signed up receives a care package mailed to their home including an activity coloring book “Michael’s Show-and-Tell.” The book tells Michael’s story about living with cystinosis while offering kids matching, coloring and finding object games along with information.

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Alessandro Maselli, Catalent CEO

Catal­ent ac­quires North Car­oli­na CD­MO for $475M, boost­ing oral solids work

As Catalent has been expanding its reach in the US this year, as well as recently completing a C-suite shuffle, the company announced last night that it has acquired the CDMO Metrics Contract Services for $475 million from Mayne Pharma Group.

The acquisition will increase Catalent’s capabilities in oral solid formulation development, manufacturing and packaging as well as expand its capacity to handle more highly potent compounds.

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