Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis
Copyright © 2020 Massachusetts Medical Society. BACKGROUND Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known. METHODS In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months. Participants were randomly assigned in a 2:1 ratio to receive sodium phenylbutyrate-taurursodiol (3 g of sodium phenylbutyrate and 1 g of taurursodiol, administered once a day for 3 weeks and then twice a day) or placebo. The primary outcome was the rate of decline in the total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) through 24 weeks. Secondary outcomes were the rates of decline in isometric muscle strength, plasma phosphorylated axonal neurofilament H subunit levels, and the slow vital capacity; the time to death, tracheostomy, or permanent ventilation; and the time to death, tracheostomy, permanent ventilation, or hospitalization. RESULTS A total of 177 persons with ALS were screened for eligibility, and 137 were randomly assigned to receive sodium phenylbutyrate-taurursodiol (89 participants) or placebo (48 participants). In a modified intention-to-treat analysis, the mean rate of change in the ALSFRS-R score was −1.24 points per month with the active drug and −1.66 points per month with placebo (difference, 0.42 points per month; 95% confidence interval, 0.03 to 0.81; P=0.03). Secondary outcomes did not differ significantly between the two groups. Adverse events with the active drug were mainly gastrointestinal. CONCLUSIONS Sodium phenylbutyrate-taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Secondary outcomes were not significantly different between the two groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol in persons with ALS. (Funded by Amylyx Pharmaceuticals and others; CENTAUR ClinicalTrials.gov number, NCT03127514.).
New England Journal of Medicine
Digital Object Identifier (DOI)
Paganoni, Sabrina; Macklin, Eric A.; Hendrix, Suzanne; Berry, James D.; Elliott, Michael A.; Maiser, Samuel; Karam, Chafic; Caress, James B.; Owegi, Margaret A.; Quick, Adam; Wymer, James; Goutman, Stephen A.; Heitzman, Daragh; Heiman-Patterson, Terry; Jackson, Carlayne E.; Quinn, Colin; Rothstein, Jeffrey D.; Kasarskis, Edward J.; Katz, Jonathan; Jenkins, Liberty; Ladha, Shafeeq; Miller, Timothy M.; Scelsa, Stephen N.; Vu, Tuan H.; Fournier, Christina N.; Glass, Jonathan D.; Johnson, Kristin M.; Swenson, Andrea; Goyal, Namita A.; Pattee, Gary L.; and Andres, Patricia L., "Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis" (2020). Neurology. 577.