Amylyx Plans to File for Approval of AMX0035 in US

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by Marta Figueiredo PhD |

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Amylyx Pharmaceuticals plans to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) in the coming months for approval of its investigational oral therapy AMX0035 for amyotrophic lateral sclerosis (ALS).

The decision follows recent discussions with the FDA, including a pre-NDA meeting held July 15, and is a U-turn from the agency’s previous decision, which requested data from a large Phase 3 clinical trial called PHOENIX (NCT05021536) before considering AMX0035 for approval.

A previous petition, signed by more than 50,000 people, and a call-to-action meeting with the FDA asked that the therapy be approved based on positive findings of the completed CENTAUR Phase 2/3 trial (NCT03127514). These initiatives were driven by the ALS Association and I AM ALS.

“We are thrilled to move toward the U.S. submission of an NDA for AMX0035 and look forward to continuing to work with the FDA,” Joshua Cohen, Amylyx’s co-founder, co-CEO, and chairman, said in a press release.

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Merit Cudkowicz, MD, CENTAUR’s co-principal investigator, said that “this is another great step forward for Americans living with ALS.”

“In the CENTAUR trial, led by the Northeast ALS Consortium [NEALS] and the Healey & AMG Center at Mass General, AMX0035 was found to both slow ALS progression and extend life,” added Cudkowicz, who is a co-founder of NEALS and the director of the Healey & AMG Center for ALS.

Similar applications, supported by CENTAUR results alone, are currently being reviewed by Health Canada and set for filing with the European Medicines Agency by the end of the year. Amylyx is also actively discussing with health authorities elsewhere the best path for approval in their respective countries.

“We’re endlessly grateful for all of the support and efforts of ALS Finding a Cure, the ALS Association, I AM ALS, the Healey & AMG Center at Mass General and the Northeast ALS Consortium, and all CENTAUR trial participants for their critical involvement as we approach this milestone,” said Justin Klee, Amylyx’s co-founder, co-CEO, and director.

Amylyx is also exploring the possibility of launching an Expanded Access Program (EAP) in the U.S. that would provide ALS patients early access to AMX0035 before its potential approval. If implemented, the program would run in parallel with FDA’s application review and the PHOENIX trial, also set to start soon. More information on the potential EAP is expected later this year.

AMX0035 is a fixed-dose combination of two orally available small molecules, tauroursodeoxycholic acid and sodium phenylbutyrate, that have been used in the clinic and proven to be safe and well-tolerated.

The therapy is expected to prevent nerve cell death by suppressing stress signals within mitochondria — which provide energy to cells — and the endoplasmic reticulum, a cellular organelle involved in protein production, modification, and transport.

The CENTAUR study evaluated the safety and effectiveness of six months of treatment with AMX0035 against a placebo in 137 adults recently diagnosed with sporadic or familial ALS and with rapidly progressing disease.

Most participants (92%) who completed the trial 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).

CENTAUR’s top-line results showed that the trial met its main goal, with AMX0035 safely and significantly slowing patients’ functional decline relative to a placebo.

In addition, data from CENTAUR and its extension study demonstrated that patients consistently on AMX0035 had a median survival duration that was 6.5 months longer than did those initially assigned to a placebo — representing a 44% lower risk of death.

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The global PHOENIX trial is expected to confirm CENTAUR results in a larger patient population of about 600 adults with ALS whose symptoms began in the past two years — a less-stringent criteria than was required for CENTAUR.

Participants, to be recruited at 55 sites across the U.S. and Europe, will be randomly assigned to receive AMX0035 or a placebo for about 48 weeks (about 11 months).

“For those living with ALS, time is the most important resource, and we remain focused on advancing AMX0035 through the clinical development process as efficiently as possible,” Klee said.

In a separate press release, Amylyx also announced that it is donating CENTAUR data to the PRO-ACT database, the largest ALS clinical trial dataset to date, as well as participants’ samples to the NEALS Biorepository housed at Mass General Hospital and Barrow Neurological Institute.

The PRO-ACT platform, containing nearly 11,000 ALS patient records from 23 completed clinical trials, is currently sponsored by The ALS Association and managed by the Neurological Clinical Research Institute at Mass General Hospital.

The NEALS Biorepository is funded by The ALS Association, Project ALS, ALS Finding a Cure, and donors to the Healey and AMG Center at Mass General.

“It is going to take a consolidated community effort to beat ALS,” Cohen said. “Sharing data and biological samples with integral databases and biorepositories can play an important role in treatment and care breakthroughs if they are continuously updated.”

Klee noted that “keeping data fresh will give the ALS community the information it needs to identify new pathways and approaches to developing new treatments.”