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

• Type of Material: Article
• Authors: Sabrina Paganoni, Harvard Medical School; Suzanne Hendrix, Pentara Corporation, Millcreek Utah; Samuel P Dickson, Pentara Corporation, Millcreek Utah; Newman Knowlton, Pentara Corporation, Millcreek Utah; Eric A Macklin, Harvard Medical School; James D Berry, Harvard Medical School; Micheal A Elliott, Swedish Neuroscience Institute, Seattle; Samuel Maiser, Hennepin Healthcare, Minneapolis; Chafic Karam, Oregon Health & Science University, Portland; James B Caress, Wake Forest School of Medicine; Margaret A Owegi, University of Massachusetts; Adam Quick, The Ohio State University College of Medicine, Columbus; James Wymer, University of Florida College of Medicine; Stephen A Goutman, University of Michigan, Ann Arbor; Daragh Heitzman, Texas Neurology, Dallas Texas; Terry D Heiman-Patterson, Temple University, Philadelphia; Carlayne E Jackson, The University of Texas Health Science Center at San Antonio; Colin Quinn, University of Pennsylvania, Philadelphia; Jeffrey D Rothstein, Johns Hopkins University, Baltimore; Edward J Kasarskis, University of Kentucky, Lexington; Jonathan Katz, California Pacific Medical Center Research Institute; Liberty Jenkins, California Pacific Medical Center Research Institute; Shafeeq Ladha, Barrow Neurological Institute; Timothy M Miller, Washington University School of Medicine in St. Louis; Stephen N Scelsa, Icahn School of Medicine at Mount Sinai, New York; Tuan H Vu, University of South Florida Morsani; Christina Fournier, Emory University; Jonathan Glass, Emory University; Kristin M Johnson, Ochsner Health System, New Orleans; Andrea Swenson, University of Iowa, Iowa City; Namita A Goyal, University of California, Irvine; Gary L Pattee, Lincoln Nebraska; Patricia L Andres, Independent Consultant, Nobleboro Maine; Suma Babu, Harvard Medical School; Marianne Chase, Harvard Medical School; Derek Dagostino, Harvard Medical School; Meghan Hall, Barrow Neurological Institute; Gale Kittle, Barrow Neurological Institute; Matthew Eydinov, Harvard Medical School; Michelle McGovern, Harvard Medical School; Joseph Ostrow, Harvard Medical School; Lindsay Pothier, Harvard Medical School; Randall Randall, Barrow Neurological Institute; Jeremy M Shefner, Barrow Neurological Institute; Alexender V Sherman, Harvard Medical School; Maria E St Pierre, Harvard Medical School; Eric Tustison, Harvard Medical School; Prasha Vigneswaran, Harvard Medical School; Jason Walker, Harvard Medical School; Hong Yu, Harvard Medical School; James Chan, Harvard Medical School; Janet Wittes, Statistics Collaborative, Inc.; Zi-Fan Yu, Statistics Collaborative, Inc.; Joshua Cohen, Amylyx Pharmaceuticals, Inc., Cambridge; Justin Klee, Amylyx Pharmaceuticals, Inc., Cambridge; Kent Leslie, Amylyx Pharmaceuticals, Inc., Cambridge; Rudolph E Tanzi, Harvard Medical School; Walter Gilbert, Harvard University; Patrick D Yeramian, Amylyx Pharmaceuticals, Inc., Cambridge; David Schoenfeld, Harvard Medical School; Merit E Cudkowicz, Harvard Medical School
• Language: English
• Date: 2020-10-30
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/mus.27091
• Title of Journal or Parent Work: MUSCLE & NERVE
• Volume: 63
• Issue: 1
• Start Page: 31
• End Page: 39
• Grant/Funding Information: ALS Finding A Cure Foundation; Amylyx Pharmaceuticals, Inc.; The ALS Association
• Keywords: SAFETY; ACID; Clinical Neurology; Neurosciences & Neurology; amyotrophic lateral sclerosis; survival analysis; DISEASE PROGRESSION; PATHOLOGY; Science & Technology; motor neuron disease; Life Sciences & Biomedicine; EFFICACY; DOUBLE-BLIND; taurursodiol; CENTAUR; EXPRESSION; sodium phenylbutyrate‐ Neurosciences; EDARAVONE
• Research Categories: Health Sciences, Pathology; Health Sciences, General; Health Sciences, Mental Health; Biology, Neuroscience; Health Sciences, Pharmacy; Biology, Biostatistics; Health Sciences, Medicine and Surgery

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.