RARE Daily

FDA Advisory Committee Supports Approval of Amylyx Experimental ALS Therapy

September 8, 2022

An advisory committee for the U.S. Food and Drug Administration that previously voted there was not sufficient data to determine whether Amylyx Pharmaceutical’s experimental ALS drug was effective, voted 7 to 2 to recommend the agency approve the therapy AMX0035.

The Peripheral and Central Nervous System Drugs Advisory Committee recommendations, while not binding, will be considered by the FDA in its review of the pending New Drug Application (NDA) for AMX0035. As previously reported, the Prescription Drug User Fee Act target action date for the NDA is September 29, 2022, which was extended by the FDA to allow more time to review additional analyses of data from the company’s clinical studies.

The decision adds to the ongoing debate over the level of evidence of efficacy the agency should require to approve therapies, particularly in the case of fatal diseases with inadequate therapies and small patient populations. The closely watched advisory committee vote comes in the wake of the agency’s controversial approval of Biogen’s Alzheimer’s drug Aduhelm last year that set policymakers off on efforts to place new restrictions on the agency’s accelerated approval pathway.

The testimony of physicians who treat people with ALS as well as members of the ALS patient community and their family members had an effect on the vote. Nearly 1,300 people shared their perspectives on how AMX0035 could benefit their lives or the lives of their loved ones. 

Advisory committee member Tom Montine, chair of the Department of Pathology at Stanford Medicine said testimony from the FDA’s Director of Neuroscience Billy Dunn and Division Director Teresa Buracchio, as well as the testimony of treating physicians led him to change his vote from the previous advisory committee meeting on AMX0035.

“I voted ‘no’ in March, I found helpful in today’s discussion the reviews by Dr. Dunn and Buracchio on judging what substantial evidence is in context and setting the context of the phase 3 trial and seriousness of the disease and unmet medical need,” he said. “The consistent testimonies of experts in treating people with ALS, in aggregate, my judgement moved forward with yes in support.”  

Amyotrophic lateral sclerosis (ALS) is a 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 an oral fixed-dose medication approved in Canada as Albrioza to treat ALS in Canada. It is a combination of sodium phenylbutyrate and taurursodiol, which the company said may reduce neuronal cell death. AMX0035 is also being explored for the potential treatment of other neurodegenerative diseases. If approved, AMX0035 will be the first treatment in ALS that has demonstrated a significant slowing of disease progression and functional decline, as well as extended survival, in a randomized, placebo-controlled clinical trial, as a standalone therapy or when added to existing approved treatments.

In a briefing document prepared for the Peripheral and Central Nervous System Drugs Advisory Committee, FDA staff wrote that the Amylyx phase 2 CENTAUR study was “adequate and well controlled” with “confirmatory evidence that meets the appropriate standards for approval, especially in the context of a rare and fatal disease such as ALS.”

CENTAUR was a multicenter phase 2 clinical trial in 137 participants with ALS encompassing a six-month randomized placebo-controlled phase and an open-label extension (OLE) long-term follow-up phase. The trial met its primary efficacy endpoint. Administration of AMX0035 (plus standard of care) significantly slowed the rate of functional decline as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS-R) total score compared to placebo (plus standard of care) at the end of the 24-week randomized phase.

CENTAUR results appear to show that AMX0035 was generally well tolerated. Similar rates of adverse events and discontinuations were recorded in the AMX0035 and placebo groups during the 24-week randomized phase. However, gastrointestinal (GI) events occurred with greater frequency (≥2 percent) in the AMX0035 group.

“ALS moves rapidly, is 100 percent fatal and has no meaningful treatments,” said Brian Wallach, co-founder of I AM ALS and person living with ALS. “In this context, a drug that extended life, whether by six, ten or eighteen months, already more than demonstrated sufficient evidence of effectiveness. There is only one right answer here.”  

Editor’s note: This story was updated September 9, 2022 because the original version incorrect characterized the committee’s vote in March.

Author: Rare Daily Staff

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