Results of a pivotal phase 2/3 clinical trial (NCT03127514) evaluating tauroursodeoxycholic acid (TUDCA) /sodium phenylbutyrate (PB) combination (AMX0035; Amylyx Pharmaceuticals, Cambridge, MA) for treatment of amyotrophic lateral sclerosis (ALS) has been published in the New England Journal of Medicine (NEJM). Data from the trial show that TUDCA/PB treatment decreased the rate of decline on the ALS functional rating scale (ALSFRS-R) and was well tolerated by participants who took the drug. TUDCA/PB is an investigational neuroprotective therapy designed to reduce the death and dysfunction of motor neurons that occur in ALS .
After 24 weeks of treatment with TUDCA/PB, participants had an average ALSFRS-R score that was 2.32 points higher than those treated with placebo(P=.03). A change from baseline analysis indicated people treated with TUDCA/PB scored 2.92 points higher at the end of 24 week follow up (P=.01).
Most CENTAUR participants (77%) were receiving an approved ALS therapy (riluzole, edaravone, or both) during and/or before trial entry. Sensitivity analyses accounting for the duration of treatment under riluzole, edaravone, or both confirmed that the treatment effect of TUDCA/PB was independent of background approved ALS therapies.
“I am so proud of the ALS community efforts that made this milestone possible ” said Dr. Merit Cudkowicz, MD, chief medical officer from ALS Finding a Cure, director of the Sean M. Healey & AMG Center for ALS, chief of Neurology at Mass General, and the Julianne Dorn professor of Neurology at Harvard Medical School. “The CENTAUR study was designed and run through NEALS, was supported by a partnership between The ALS Association and ALS Finding a Cure and is a phenomenal example of what can happen when a community works closely together to accelerate ALS progress.”
Michelle L. Dougherty, MD, FAES, FAAN
James Geyer, MD, and Paul Cox
Nidhiben Anadani, MD