Amylyx’s New ALS Drug Review Impeded as FDA Members Disagreed with Clinical Trial Results

AMX0035, an amyotrophic lateral sclerosis (ALS) drug from Amylyx Pharmaceuticals, was granted Orphan Drug Designation by the FDA in 2017. Until the end of last year, Amylyx continued to seek approval from the FDA to skip the Phase III clinical trial and evaluate AMX0035 directly. Still, the FDA has been adamant in its refusal to budge on the issue.

In December 2021, the FDA finally decided to conduct a priority review of Amylyx’s proposed drug discovery registration (NDA).  The hearing is held in March, and the FDA’s Advisory Committee is invited to evaluate the Phase II clinical trial results of AMX0035. The final vote of the members was 6-4, with a majority of votes against the proposal. Results of the committee’s vote will be used as the basis for FDA’s review, and a final decision on approval or disapproval will be announced by June 29, 2022.

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Drug Delaying Neurodegeneration Offers Possible New Treatment Options for ALS Patients

ALS is a disease caused by the death of motor neurons in the brain and spinal cord. Depending on the progress of the disease, it can lead to deterioration of muscle function, inability to move and speak, respiratory paralysis, and eventually death.

Taurursodiol protects the brain’s energy-producing mitochondria, where degenerative diseases can develop if their functions are impaired, while Sodium Phenylbutyrate is associated with the signalling function of the endoplasmic reticulum (ER). Currently there are ALS patients who are already taking both of them. Once the FDA approves AMX0035, insurance companies will be responsible for the cost of these drugs.

AMX0035 has shown positive results in the CENTAUR Phase 2 trial, demonstrating its effectiveness in delaying the progression of the disease. Amylyx is currently recruiting for the Phase 3 PHOENIX Trial of AMX0035, hoping for accelerated approval by the FDA.

FDA Committee Takes a Negative View of AMX0035 Clinical Trial Results

At the FDA Advisory Committee hearing on March 30, experts reviewed and voted on whether AMX3005 could skip the Phase III clinical trial and provide ALS patients with a compelling new treatment option based solely on data from the existing single, randomized Phase II clinical trial. Dozens of ALS patients and lobbyists made presentations at the meeting based on the need for the treatment. Then, the FDA Advisory Committee experts deliberated the issue and made their votes.

With 6 negative votes and 4 affirmative votes, the FDA expressed concerns about the Phase II clinical trial of AMX0035. The majority of the members considered that the efficacy of AMX0035 was not convincing enough in the results and that it only modestly slowed the progression of the disease. In addition, the way Amylyx conducted the clinical trial was also questioned by the committee members, who remarked that there were too many problems with the collection and analysis of clinical data.

Though Disappointed by FDA’s Stance, Amylyx is Still Pushing Hard for Approval

Jamie Timmons, Head of Scientific Communications at Amylyx, commented that the FDA’s attitude would not dishearten the company. He said, “We remain confident in the data from the Phase 2 CENTAUR trial and the potential benefits of AMX0035 as a treatment option for people living with ALS. We are also encouraged by the expert ALS physicians who shared their clinical perspectives. Our application is under review by the FDA, and we remain committed to pursuing its approval given the pressing need for new treatments for ALS.” 

Calaneet Balas, CEO of Amylyx, responded to the results saying that the company “cannot allow perfection to stand in the way of real progress toward turning ALS from a fatal disease into a livable one. ” She further added that “The FDA’s own ALS Guidance acknowledges that people with ALS are willing to accept greater risk for the possibility of some benefit. People with ALS and their loved ones deserve better and the FDA has the tools to accomplish this with urgency.”

Although the FDA will consider the recommendations of the Advisory Committee, they are non-binding, and the final decision rests with the FDA. Given that the FDA has previously granted a priority review to AMX0035, the final approval or disapproval must be announced no later than June 29, 2022.

Written by Aurora Mau/ Translated by Richard Chau

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GeneOnline Team