Long-Term Survival of Participants in the CENTAUR Trial of AMX0035 for ALS (4550)

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. Disclosure: The institution of Dr. Paganoni has received research support from Amylyx. Dr. Hendrix has received personal compensation for serving as an employee of Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $100,000-$499,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Pentara Corporation. The institution of Dr. Hendrix has received personal compensation in the range of $100,000-$499,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Pentara Corporation. Dr. Hendrix has received publishing royalties from a publication relating to health care. Samuel Dickson has received personal compensation for serving as an employee of Pentara Corporation. Newman Knowlton has received personal compensation for serving as an employee of Pentara Corporation. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoparkinson Healthcare LLC. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Macklin has received research support from Amylyx Pharmaceuticals. The institution of Dr. Macklin has received research support from Biohaven. The institution of Dr. Macklin has received research support from Clene Nanomedicine. The institution of Dr. Macklin has received research support from GlaxoSmithKline. The institution of Dr. Macklin has received research support from Mitsubishi Tanabe. The institution of Dr. Macklin has received research support from Prilenia. The institution of Dr. Macklin has received research support from Ra Pharmaceuticals. Josh Cohen has received personal compensation for serving as an employee of Amylyx Pharmaceuticals Inc. Josh Cohen has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Amylyx Pharmaceuticals Inc.. Josh Cohen has received stock or an ownership interest from Amylyx Pharmaceuticals Inc.. The institution of Josh Cohen has received research support from ALS Finding a Cure Foundation. The institution of Josh Cohen has received research support from ALSA. The institution of Josh Cohen has received research support from ADDF. The institution of Josh Cohen has received research support from Alzheimer’s Association. The institution of Josh Cohen has received research support from Cure Alzheimer’s Fund. Josh Cohen has received intellectual property interests from a discovery or technology relating to health care. Justin Klee has received personal compensation for serving as an employee of Amylyx. Justin Klee has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Amylyx Pharmaceuticals. Justin Klee has received stock or an ownership interest from Amylyx Pharmaceuticals. Justin Klee has received intellectual property interests from a discovery or technology relating to health care. Kent Leslie has received personal compensation for serving as an employee of Amylyx Pharmaceuticals. Kent Leslie has received stock or an ownership interest from Amylyx Pharmaceuticals. Patrick Yeramian has received personal compensation for serving as an employee of Amylyx Pharmaceuticals. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avexis. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revalasio. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for takeda. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for aclipse. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mt pharma. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for biohaven. Dr. Cudkowicz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for sunovian. Dr. Cudkowicz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for biogen. Dr. Cudkowicz has received personal compensation in the range of $0-$499 for serving as a Consultant for anelixis. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cytokinetics. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for disarm. Dr. Cudkowicz has received personal compensation in the range of $0-$499 for serving as a Consultant for als pharma. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for RRD. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for immunitypharm. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for helixsmith. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for denali. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for wave. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for orion. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for transposon. The institution of Dr. Cudkowicz has received research support from NINDS. The institution of Dr. Cudkowicz has received research support from ALSA . The institution of Dr. Cudkowicz has received research support from ALSFAC. The institution of Dr. Cudkowicz has received research support from UCB ra. The institution of Dr. Cudkowicz has received research support from Biohaven. The institution of Dr. Cudkowicz has received research support from Clene nanomedicine. The institution of Dr. Cudkowicz has received research support from prilenia. Dr. Cudkowicz has received research support from ALS one. Dr. Cudkowicz has received publishing royalties from a publication relating to health care.