Long-Term Survival of Participants in the CENTAUR Trial of AMX0035 for ALS
Sabrina Paganoni1,2, Suzanne Hendrix3, Samuel Dickson3, Newman Knowlton3, Eric Macklin4, Josh Cohen5, Justin Klee5, Kent Leslie5, Patrick Yeramian5, Merit Cudkowicz1
1Sean M. Healey and AMG Center for ALS, Massachusetts General Hospital, 2Spaulding Rehabilitation Hospital, 3Pentara Corporation, 4MGH Biostatistics Center, 5Amylyx Pharmaceuticals, Inc
Objective:

To report results of a long-term overall survival analysis of participants in the CENTAUR trial of AMX0035 for ALS.

Background:

AMX0035 is an orally administered, fixed-dose coformulation (sodium phenylbutyrate-taurursodiol) designed to reduce neuronal death by mitigating endoplasmic reticulum and mitochondrial dysfunction. AMX0035 demonstrated a statistically significant functional benefit as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) in participants in the randomized, double-blind, placebo-controlled CENTAUR trial. Similar rates of adverse events were recorded in the AMX0035 and placebo groups during the randomized trial. In a July 2020 overall survival analysis of all participants randomized in CENTAUR, the mean hazard of death was 44% lower in the group originally randomized to AMX0035 versus placebo (HR, 0.56; 95% CI, 0.34–0.92; P=0.023).

Design/Methods:

CENTAUR enrolled adults with definite ALS (revised El Escorial criteria) and ≤18 months from symptom onset. Participants were randomized 2:1 to AMX0035 or matching placebo; riluzole and edaravone use was permitted. Eligible participants could enroll in the open-label extension (OLE), in which all participants received AMX0035. A survival analysis as of November 2020 (longest follow-up, 39 months post-randomization) will compare time to death (all-cause mortality) between participants originally randomized to AMX0035 vs those originally randomized to placebo. As in the July 2020 analysis, vital status for all participants including those who discontinued, were lost to follow-up, or did not enroll in the OLE, will be assessed using a participant locating service to allow for a comprehensive analysis.

Results:
Results of the November 2020 overall survival analysis will be presented.
Conclusions:

Administration of AMX0035 has shown both significant functional and survival benefits in adult people living with ALS. An updated survival analysis is planned for November 2020.