RARE Daily

Amylyx Shares Dive After FDA Experts Voice Concern About ALS Drug Ahead of Advisory Meeting

March 29, 2022

Rare Daily Staff

Shares of Amylyx Pharmaceuticals fell 50 percent after the U.S. Food and Drug Administration posted briefing documents ahead of the March 30 Peripheral and Central Nervous System Drugs Advisory Committee meeting to review the company’s New Drug Application for its treatment for amyotrophic lateral sclerosis, a rare and fatal condition that affects motor neurons in the brain and spinal cord.

Raising the possibility of a potential vote against approving the drug AMX0035, FDA scientists expressed concern about the company’s analyses of efficacy and survival, noting that the data “were not exceptionally persuasive.”

The agency scientists also conceded that the heterogeneity of ALS may have contributed to the results, and whether the unmet need in ALS may outweigh these concerns. In fact, the FDA asked the committee to decide whether data from a single phase 2 trial is sufficient to approve AMX0035 as an effective treatment for ALS.

Amylyx conducted a single phase 2 study to support the NDA, which FDA said, “did not appropriately account for deaths that occurred during the study.” The agency urged Amylyx to begin a phase 3 study to confirm the phase 2 findings. Amylyx continued to evaluate data from an open-label extension study but FDA scientists noted that Amylyx’s main evidence for approval was survival benefit in patients who had received its treatment compared to placebo, but was concerned about the interpretability of its findings given that there were many dropouts in the open-label extension period.

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

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 in an effort 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.

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