Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial

• Type of Material: Article
• Authors: Sabrina Paganoni, Harvard Medical School; Suzanne Hendrix, Pentara Corporation; Samuel P Dickson, Pentara Corporation; Newman Knowlton, Pentara Corporation; James D Berry, Massachusetts General Hospital; Michael A Elliott, Swedish Neuroscience Institute; Samuel Maiser, Hennepin Healthcare; Chafic Karam, University of Pennsylvania; James B Caress, Wake Forest School of Medicine; Margaret Ayo Owegi, University of Massachusetts; Adam Quick, Ohio State University; James Wymer, University of Florida; Stephen A Goutman, University of Michigan; Daragh Heitzman, ALS Clinic, Texas Neurology; Terry D Heiman-Patterson, Temple University; Carlayne Jackson, University of Texas Health Science Center at San Antonio; Colin Quinn, University of Pennsylvania; Jeffrey D Rothstein, Johns Hopkins University; Edward J Kasarskis, University of Kentucky; Jonathan Katz, California Pacific Medical Center Research Institute; Lliberty Jenkins, California Pacific Medical Center Research Institute; Shafeeq S Ladha, Barrow Neurological Institute; Timothy M Miller, Washington University in St. Louis; Stephen N Scelsa, Icahn School of Medicine at Mount Sinai; Tuan H Vu, University of South Florida; Christina Fournier, Emory University; Kristin M Johnson, Ochsner Health System; Andrea Swenson, University of Iowa Health Care; Namita Goyal, University of California Irvine; Gary L Pattee, Neurology Associates; 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; Mathew Eydinov, Harvard Medical School; Jospeh Ostrow, Harvard Medical School; Lindsay Pothier, Harvard Medical School; Rebecca Randall, Worldwide Clinical Trials; Jeremy M Shefner, Barrow Neurological Institute; Alexander Sherman, Harvard Medical School; Eric Tustison, Harvard Medical School; Prasha Vigneswaran, Harvard Medical School; Hong Yu, Harvard Medical School; Joshua Cohen, Amylyx Pharmaceut Inc; Justin Klee, Amylyx Pharmaceut Inc; Rudolph Tanzi, Harvard University; Walter Gilbert, Harvard University; Patrick Yeramian, Amylyx Pharmaceut Inc; Merit Cudkowicz, Harvard Medical School
• Language: English
• Date: 2022-05-16
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/jnnp-2022-329024
• Title of Journal or Parent Work: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
• Volume: 93
• Issue: 8
• Start Page: 871
• End Page: 875
• Grant/Funding Information: The CENTAUR trial was funded by Amylyx Pharmaceuticals, Inc., ALS Finding a Cure®, and The ALS Association. The trial sponsor, Amylyx Pharmaceuticals, Inc. collaborated with the Northeast ALS Consortium network (www.neals.org) in the design and execution of the trial. Amylyx provided active drug and, during the randomised trial phase, placebo; participated in data analysis and manuscript development; and provided funding for writing support in the development of the manuscript. All other funders had no role in any aspect of the trial or in manuscript development.
• Keywords: Psychiatry; Clinical Neurology; Neurosciences & Neurology; Science & Technology; Life Sciences & Biomedicine; Surgery
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Background Coformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) was shown to prolong survival and slow functional decline in amyotrophic lateral sclerosis (ALS). Objective Determine whether PB/TURSO prolonged tracheostomy/ventilation-free survival and/or reduced first hospitalisation in participants with ALS in the CENTAUR trial. Methods Adults with El Escorial Definite ALS ≤18 months from symptom onset were randomised to PB/TURSO or placebo for 6 months. Those completing randomised treatment could enrol in an open-label extension (OLE) phase and receive PB/TURSO for ≤30 months. Times to the following individual or combined key events were compared in the originally randomised treatment groups over a period spanning trial start through July 2020 (longest postrandomisation follow-up, 35 months): death, tracheostomy, permanent assisted ventilation (PAV) and first hospitalisation. Results Risk of any key event was 47% lower in those originally randomised to PB/TURSO (n=87) versus placebo (n=48, 71% of whom received delayed-start PB/TURSO in the OLE phase) (HR=0.53; 95% CI 0.35 to 0.81; p=0.003). Risks of death or tracheostomy/PAV (HR=0.51; 95% CI 0.32 to 0.84; p=0.007) and first hospitalisation (HR=0.56; 95% CI 0.34 to 0.95; p=0.03) were also decreased in those originally randomised to PB/TURSO. Conclusions Early PB/TURSO prolonged tracheostomy/PAV-free survival and delayed first hospitalisation in ALS. Trial registration number NCT03127514; NCT03488524.