Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis.
Eric Tustison, Gary L Pattee, Patricia L Andres, Suma Babu, Marianne Chase, Derek Dagostino, Meghan Hall, Gale Kittle, Matthew Eydinov, Michelle McGovern, Joseph Ostrow, Lindsay Pothier, Rebecca Randall, Jeremy M Shefner, Alexander V Sherman, Maria E St Pierre, Namita A Goyal, Prasha Vigneswaran, Jason Walker, Hong Yu, James Chan, Janet Wittes, Zi-Fan Yu, Joshua Cohen, Justin Klee, Kent Leslie, Rudolph E Tanzi, Walter Gilbert, Patrick D Yeramian, David Schoenfeld, Merit E Cudkowicz, Terry D Heiman-Patterson, Suzanne Hendrix, Samuel P Dickson, Newman Knowlton, Eric A Macklin, James D Berry, Michael A Elliott, Samuel Maiser, Chafic Karam, James B Caress, Margaret Ayo Owegi, Adam Quick, James Wymer, Stephen A Goutman, Daragh Heitzman, Sabrina Paganoni, Carlayne E Jackson, Colin Quinn, Jeffrey D Rothstein, Edward J Kasarskis, Jonathan Katz, Liberty Jenkins, Shafeeq Ladha, Timothy M Miller, Stephen N Scelsa, Tuan H Vu, Christina N Fournier, Jonathan D Glass, Kristin M Johnson, Andrea Swenson
Journal: Muscle & nerve
2021;63(1):31-39
PMID: 33063909
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.
© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.
Address:
Sean M. Healey & AMG Center for ALS & the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts.; Pentara Corporation, Millcreek, Utah.; Department of Medicine, Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.; Swedish Neuroscience Institute, Seattle, Washington.; Departments of Neurology and Medicine, Hennepin Healthcare, Minneapolis, Minnesota.; Department of Neurology, Oregon Health & Science University, Portland, Oregon.; Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina.; Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts.; Department of Neurology, The Ohio State University College of Medicine, Columbus, Ohio.; Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.; Department of Neurology, University of Michigan, Ann Arbor, Michigan.; Texas Neurology, Dallas, Texas.; Department of Neurology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.; Department of Neurology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.; Brain Science Institute and Department of Neurology, Johns Hopkins University, Baltimore, Maryland.; Department of Neurology, University of Kentucky College of Medicine, Lexington, Kentucky.; California Pacific Medical Center Research Institute and Forbes Norris MDA/ALS Research and Treatment Center, San Francisco, California.; Department of Neurology, Gregory W. Fulton ALS Center, Barrow Neurological Institute, Phoenix, Arizona.; Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.; Department of Neurology, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, Florida.; Departments of Neurology and Pathology, Emory University School of Medicine, Atlanta, Georgia.; Department of Neurology, Ochsner Health System, New Orleans, Louisiana.; Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa.; Department of Neurology, University of California, Irvine School of Medicine, Irvine, California.; Neurology Associates, Lincoln, Nebraska.; Independent Consultant, Nobleboro, Maine.; Statistics Collaborative, Inc., Washington, District of Columbia.; Amylyx Pharmaceuticals, Inc., Cambridge, Massachusetts.; Harvard University, Cambridge, Massachusetts.
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MeSH Terms:
Adolescent,
Adult,
Aged,
Aged, 80 and over,
Amyotrophic Lateral Sclerosis,
Double-Blind Method,
Female,
Humans,
Male,
Middle Aged,
Neuroprotective Agents,
Phenylbutyrates,
Taurochenodeoxycholic Acid,
Time,
Young Adult