A New Drug Application has been submitted to the Food and Drug Administration (FDA) for AMX0035 (sodium phenylbutyrate and taurursodiol) for the treatment of amyotrophic lateral sclerosis (ALS).

AMX0035 is an oral, fixed-dose coformulation of sodium phenylbutyrate and taurursodiol, also known as ursodoxicoltaurine. By targeting the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration pathways in ALS, AMX0035 is expected to reduce neuronal death and dysfunction.

The application is supported by data from the randomized, double-blind, placebo-controlled phase 2 CENTAUR trial (ClinicalTrials.gov Identifier: NCT03127514), along with the open-label extension study (ClinicalTrials.gov Identifier: NCT03488524).

The CENTAUR trial evaluated the efficacy and safety of AMX0035 in 137 adults with ALS. Patients were randomly assigned 2:1 to receive AMX0035 orally or via feeding tube once daily for the first 3 weeks, then twice daily if tolerated for 24 weeks, or placebo. Results showed that AMX0035 met the primary endpoint demonstrating a statistically significant slowing of functional decline at 24 weeks, as measured by the Revised-ALS Functional Rating Scale. 

The CENTAUR-OLE study evaluated the long-term safety of AMX0035 in 95 patients with ALS who completed the CENTAUR study. After a follow-up of 3 years, interim survival analysis showed that patients who received AMX0035 during the placebo-controlled phase of CENTAUR had a 44% lower risk of death compared with those who received placebo during the placebo-controlled phase (hazard ratio 0.56; 95% CI, 0.34-0.92). Median survival duration was reported to be 25 months (95% CI, 19-33.6) among patients who started on AMX0035 and 18.5 months (95% CI, 13.5-23.2) among those who started on placebo.

The rates of adverse events and discontinuations were found to be comparable between the groups. Gastrointestinal events were reported with greater frequency in the AMX0035 arm.

“For people living with ALS and their physicians, this is a significant development offering hope of a potential new treatment option that has been shown to slow ALS disease progression and extend the time families that face this life-threatening disease have together,” said Sabrina Paganoni, MD, PhD, principal investigator of the CENTAUR trial, investigator at the Healey & AMG Center for ALS at Massachusetts General Hospital and Assistant Professor of PM&R at Harvard Medical School and Spaulding Rehabilitation Hospital.


Amylyx Pharmaceuticals submits New Drug Application (NDA) for AMX0035 for the treatment of ALS. News release. Amylyx Pharmaceuticals, Inc. Accessed November 2, 2021. https://www.businesswire.com/news/home/20211102005320/en/Amylyx-Pharmaceuticals-Submits-New-Drug-Application-NDA-for-AMX0035-for-the-Treatment-of-ALS