Sodium phenylbutyrate/taurursodiol

Sodium phenylbutyrate/taurursodiol (development code AMX0035) is a combination drug being studied for the treatment of amyotrophic lateral sclerosis (ALS),[1] Alzheimer's disease,[2][3] and Wolfram syndrome.[4] It is a fixed-dose combination of two drugs, sodium phenylbutyrate and taurursodiol (tauroursodeoxycholic acid, TUDCA).

AMX0035 acts by blocking cell death pathways in mitochondria and in the endoplasmic reticulum.[1] Sodium phenylbutyrate is a chemical chaperone that helps proteins maintain their normal conformation, preventing aggregation that may lead to cell death.[1] Taurursodiol improves mitochondrial energy production.[1]

In a phase 2/3 clinical trial, CENTAUR, for ALS AMX0035 showed increased survival times.[5][6][7][8][9] Based on the results, the FDA requested additional studies be performed before approval would be considered.[10] A phase 3 trial for ALS, PHOENIX, is currently recruiting an expected 600 participants across the United States and Europe.[11]

On March 30, 2022, the Food and Drug Administration (FDA) Peripheral and Central Nervous System Drugs Advisory Committee voted 6-4 that data from the single trial, CENTAUR, and its open-label extension, was not sufficiently persuasive to establish that AMX0035 was effective in the treatment of patients with ALS.[12] The FDA is expected to make a final decision on the approval of AMX0035 by June 29, 2022.[13]

A phase 2 trial for Alzheimer's disease, PEGASUS, confirmed the safety and tolerability of AMX0035.[14]