Amylyx Seeks U.S. Approval of AMX0035 With FDA Filing

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by Steve Bryson PhD |

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Amylyx Pharmaceuticals is seeking approval in the U.S. for AMX0035, its investigational therapy for slowing functional decline in people with amyotrophic lateral sclerosis (ALS).

The company submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for regulatory review.

The decision had been announced last month following recent discussions with the FDA. The agency had previously requested data from a large Phase 3 clinical trial before considering AMX0035 for approval.

“We are excited to share with the ALS community the exciting milestone that we have submitted our NDA to the FDA for review,” Justin Klee, co-CEO, director, and co-founder of Amylyx, said in a press release.

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Health Canada is currently reviewing a similar application, and the company intends to ask the European Medicines Agency for approval by the end of the year.

“Our team has worked and continues to work around the clock as we know time is of the essence for people living with ALS and their families,” said Joshua Cohen, Amylyx’s co-CEO.

“We will continue to keep the community closely updated on our progress,” Cohen added.

AMX0035 is a combination of two orally available agents — tauroursodeoxycholic acid and sodium phenylbutyrate — that have been used in the clinic and are proven to be safe and well-tolerated.

The therapy is designed to prevent nerve cell death by blocking stress pathways that originate in energy-producing mitochondria and the endoplasmic reticulum, a component within cells involved in protein production, modification, and transport.

The application is based on positive findings from the now completed CENTAUR Phase 2/3 trial (NCT03127514). The study evaluated the efficacy and safety of AMX0035 treatment over six months against a placebo in 137 adults recently diagnosed with ALS and whose disease was progressing rapidly.

Most participants (92%) who completed the trial then chose to enter its open-label extension study (NCT03488524), in which all are receiving the therapy for up to 30 months (about two and a half years).

Top-line results demonstrated that AMX0035 safely and significantly slowed patients’ functional decline, as assessed by the Revised ALS Functional Rating Scale (ALSFRS-R), relative to the placebo.

Overall, the rate of adverse events and the number of discontinuations were similar between AMX0035 and the placebo during the CENTAUR trial. Events of the digestive tract were more frequent — 2% or more — in the AMX0035 group.

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Data from CENTAUR and its extension study also demonstrated that patients who received AMX0035 in CENTAUR had a 44% lower risk of death compared with participants who started with the placebo. The median survival was 25.0 months for those treated with AMX0035 versus 18.5 months in the group that initially received the placebo — a 6.5-month difference.

“For people living with ALS and their physicians, this is a significant development offering hope of a potential new treatment option that has been shown to slow ALS disease progression and extend the time families that face this life-threatening disease have together,” said Sabrina Paganoni, MD, PhD, principal investigator of the CENTAUR trial. Paganoni is an investigator at the Healey & AMG Center for ALS at Massachusetts General Hospital and an assistant professor at Harvard Medical School and Spaulding Rehabilitation Hospital.

“We are so inspired by the people who participated in CENTAUR, the trial investigators, the ALS community, and our partners and team, and we will continue to work tirelessly on behalf of you all,” said Tammy Sarnelli, global head of regulatory affairs of Amylyx. “We will continue to work closely with the FDA throughout the review process to move AMX0035 toward a potential regulatory approval as quickly and efficiently as possible.”

The CENTAUR trial was partly funded by an ALS ACT grant and the ALS Ice Bucket Challenge, and supported by ALS Finding a Cure, The ALS Association, the Northeast ALS Consortium, known as NEALS, and the Sean M. Healey & AMG Center.

Amylyx now plans to launch a global Phase 3 trial — dubbed PHOENIX (NCT05021536) — to confirm CENTAUR’s findings in a larger group of about 600 adults with ALS symptom onset of two years or less. That trial is expected to start later this year.

The company also is considering an expanded access program (EAP) in the U.S. to provide AMX0035 to ALS patients before its potential approval. If started, the program would run alongside the application review and the PHOENIX trial. Further information on the EAP is expected by the end of the year.