FDA Convenes Advisory Committee for the Second Time for ALS Therapy

The FDA plans reconvene the Peripheral and Central Nervous System Drugs Advisory Committee to discuss Amylyx Pharmaceuticals’ new drug application for AMX0035 for the treatment of patients with amyotrophic lateral sclerosis (ALS). The committee meeting, scheduled for Wednesday, Sept. 7, 2022, will discuss additional analyses of data from clinical studies.

This is the second meeting of the advisory committee, which will discuss new analysis that the company announced in May 2022 of long-term survival analysis of the phase 2 CENTAUR trial. This new analysis used a different model, the rank-preserving structural failure time model, a method frequently used in oncology to account for placebo crossover. Using this model, AMX0035 is estimated to provide a 10.6-month longer median survival duration for participants.

The FDA had extended the review timeline to Sept. 29, 2022 (formerly June 29, 2022), to allow additional time review this additional analysis.

Related: FDA Extends Review of ALS Therapy

The advisory committee in March 2022 had voted 6 to 4 against the question about whether the data from the single trial for AMX0035 supports it as an effective treatment of amyotrophic lateral sclerosis. At issue was whether a single phase 2 trial was enough to demonstrate the drug slowed the progression of the disease.

In materials released ahead of that first meeting, agency officials indicated several concerns with the single trial, including that the primary analysis was not persuasive, there were issues with randomization, issues with the handling of deaths and missing data, and secondary endpoints were not compelling.

Amylyx submitted with its NDA the results of a single phase 2 trial. CENTAUR was a multicenter trial with 137 patients ALS. It included a 6-month randomized placebo-controlled phase and an open-label long-term follow-up phase. Investigators found the therapy met its primary efficacy endpoint of reducing functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Results were published in the New England Journal of Medicine in September 2020.

AMX0035 is designed to target the two pathways in involved in ALS. It is an oral fixed-dose combination of two small molecules: sodium phenylbutyrate (PB), which is a small molecular chaperone designed to reduce the unfolded protein response, preventing cell death, and taurursodiol (TURSO; also known as ursodoxicoltaurine), which is a Bax inhibitor designed to reduce cell death through apoptosis.

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. The therapy is approved with conditions as Albrioza to treat amyotrophic lateral sclerosis in Canada.