RARE Daily

FDA Advisors Narrowly Vote Against Approval of Amylyx’ Drug for the Treatment of ALS

March 31, 2022

Rare Daily Staff

Despite passionate testimony from patients, the U.S. Food and Drug Administration’s Peripheral and Central Nervous System Drugs Advisory Committee by a narrow margin voted against approval of Amylyx Pharmaceuticals’ experimental treatment for the treatment of amyotrophic lateral sclerosis, a rare and fatal condition that affects the motor neurons in the brain and spinal cord.

On the question, “Do the data from the single randomized, controlled trial and the open-label extension study [phase 2 CENTAUR trial] establish a conclusion that sodium phenylbutyrate/taurursodiol [AMX0035] is effective in the treatment of patients with amyotrophic lateral sclerosis (ALS)?,” the committee voted 4 (yes) and 6 (no).

“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,” said Jamie Timmons, head of Scientific Communications of Amylyx. “We are motivated by the hundreds of people impacted by this devastating disease who shared their personal testimonies, both written and spoken, in conjunction with today’s meeting. 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.”

Although the FDA considers the recommendations of its advisory committees, the recommendations by the panel are non-binding. The final decision regarding approval of a pending NDA is made by the FDA. As previously reported, the FDA has granted Priority Review to the NDA for AMX0035 and is expected to make a decision on the approval of AMX0035 by June 29, 2022, under the Prescription Drug User Fee Act.

Amylyx has recently begun enrolling patients in a global phase 3 study in 600 ALS patients that is expected to be completed in 2024.

ALS is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually death.

AMX0035 is a proprietary oral fixed-dose combination of two small molecules: sodium phenylbutyrate (PB), which is a small molecular chaperone designed to reduce the unfolded protein response (UPR), preventing cell death resulting from the UPR, and taurursodiol (TURSO; also known as ursodoxicoltaurine), which is a Bax inhibitor designed to reduce cell death through apoptosis. PB and TURSO were combined in a fixed-dose formulation to reduce neuronal death and dysfunction. AMX0035 is designed to target the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases.

CENTAUR was a multicenter phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized placebo-controlled phase and an open-label long-term follow-up phase. The trial met its primary efficacy endpoint of reducing functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).

Overall, reported rates of adverse events and discontinuations were similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2 percent) in the AMX0035 group. Detailed data from CENTAUR is published in the New England Journal of Medicine (NEJM) and Muscle and Nerve.

The CENTAUR trial was funded, in part, by the ALS ACT grant and the ALS Ice Bucket Challenge, and was supported by The ALS Association, ALS Finding a Cure (a program of The Leandro P. Rizzuto Foundation), the Northeast ALS Consortium, and the Sean M. Healey & AMG Center for ALS at Mass General.


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