Amylyx ALS drug on shaky ground ahead of AdCom meeting

March 29, 2022

The U.S. FDA's Peripheral Central Nervous System Drugs Advisory Committee is holding a meeting and open public hearing tomorrow to discuss Amylyx Pharmaceuticals’ new drug application for amyotrophic lateral sclerosis (ALS) treatment.

But the drug’s fate is shaky at best, especially given the multiple concerns the FDA has expressed in materials released before the meeting.

The drug’s NDA is based on positive results from a small phase 2/3 study of 137 patients called CENTAUR. The agency found the results were “not persuasive” thanks to imbalances within the trial, issues of randomization and implementation, and a subpar method of analysis, according to the reviewers in the Division of Neurology.

As of now, there is no cure for ALS. The disease attacks the nervous system and neurons in the cerebral motor cortex, brainstem and spinal cord. As ALS progresses patients lose their ability for voluntary movement, to speak, swallow and breathe, eventually leading to death.

Amylyx's drug, AMX0035, is a combination of sodium phenylbutyrate/taurusodiol powder that is delivered to patients orally. It works to prevent nerve cell death while promoting regeneration. 

The Massachusetts-based pharma company was founded to try to take a new approach to ALS, focusing on the stress pathways in the endoplasmic reticulum and mitochondria that lead to the degeneration and death of neurons, said Josh Cohen and Justin Klee, founders of Amylyx, in a pre-recorded presentation that will be shown during the upcoming meeting. 

Although results from the CENTAUR trial indicated that AMX0035 slowed ALS progression, the FDA said that Amylyx did not properly account for the deaths that occurred during the trial. There was concern that the study data might not be adequate to serve as evidence for the effectiveness of the drug.

The company launched a phase 3 trial in 600 patients globally that is expected to run until at least 2024. They are also continuing to evaluate results from the CENTAUR study.

The meeting is scheduled for March 30 from 10:00 a.m. to 5:00 p.m. EST. It will be livestreamed on the FDA’s YouTube channel. There will be an open public hearing from 1:30 p.m. to 2:30 p.m. EST on the same day. Participants may submit comments to a public docket by March 29 to be considered by the FDA.