Long- term survival of participants in the CENTAUR trial of sodium phenylbutyrate- taurursodiol in amyotrophic lateral sclerosis

Abstract

An orally administered, fixed- dose coformulation of sodium phenylbutyrate- taurursodiol (PB- TURSO) significantly slowed functional decline in a randomized, placebo- controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long- term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB- TURSO or placebo. Participants completing the 6- month (24- week) randomized phase were eligible to receive PB- TURSO in the open- label extension. An all- cause mortality analysis (35- month maximum follow- up post- randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow- up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB- TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34- 0.92; P = .023). Initiation of PB- TURSO treatment at baseline resulted in a 6.5- month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB- TURSO has both functional and survival benefits in ALS.