AMX0035 is an oral, fixed-dose coformulation (sodium phenylbutyrate-taurursodiol) designed to reduce neuronal death by mitigating endoplasmic reticulum and mitochondrial dysfunction in amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and other neurodegenerative diseases. 

In the CENTAUR trial, adults with definite ALS (revised El Escorial criteria) ≤18 months from symptom onset were randomized 2:1 to AMX0035 or placebo for 24 weeks. The primary efficacy endpoint in CENTAUR was the rate of decline in Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) total score. The prespecified population for efficacy analysis was the modified intent-to-treat (mITT) population receiving ≥1 dose of study drug with ≥1 postbaseline ALSFRS-R. 

Participants completing the randomized phase were eligible to enroll in an open-label extension (OLE), receiving AMX0035 for up to 132 weeks. An all-cause survival analysis (interim cutoff, July 2020) spanned the randomized and open-label phases with follow up for ≤35 months. In this analysis, vital status for all participants including those who discontinued, were lost to follow-up, or did not enroll in the OLE was determined by OmniTrace in a search of public records. AMX0035 safety was assessed in the randomized and open-label phases. Survival and safety analyses incorporated all randomized CENTAUR participants (intent-to-treat [ITT] population). 

137 participants were randomized in CENTAUR (AMX0035, n=89 [ITT], 87 [mITT]; placebo, n=48 [ITT/mITT]). In the 24-week randomized phase, the mean ALSFRS-R total score decline was significantly slower with AMX0035 vs placebo (difference, 0.42 points/mo; P=0.03). Risk of death was 44% lower in the group treated with AMX0035 vs the group receiving placebo (P=0.02) over up to 35 months of follow-up; median survival was 25.0 months and 18.5 months, respectively, a 6.5 month longer median survival in the originally randomized to AMX0035 group. Similar rates of adverse events were observed in the AMX0035 and placebo arms. 

Administration of AMX0035 resulted in statistically significant retention of function and longer overall survival in people with ALS.