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The FDA’s final decision on AMX0035 is expected by June 29, 2022
The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted 6 to 4 against whether the data from the single trial for AMX0035 supports it as an effective treatment of amyotrophic lateral sclerosis (ALS). At issue was whether a single phase 2 trial was enough to demonstrate the drug slowed the progression of the disease.
AMX0035, developed by Amylyx Pharmaceuticals, is designed to target the two pathways in involved in ALS, including the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration. It is 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.
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.
But in materials released ahead of the 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.
“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,” Jamie Timmons, M.D., head of scientific communications of Amylyx, said in a press release.
ALS is progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. The incidence is 1 to 2.6 cases per 100,000 people annually. The average age of onset of ALS is currently 58 to 60 years and the average survival from onset to death is three to four years.
The company’s applications in Europe and Canada for AMX0035 are under review.
In March 2022, Amylyx, launched an expanded access program for the therapy. The program runs in parallel to the phase 3 trial of AMX0035 and patients not eligible for this phase 3 trial may access the therapy through the expanded access program.