Long‐term survival of participants in the CENTAUR trial of sodium phenylbutyrate‐taurursodiol in amyotrophic lateral sclerosis
Open accessAbstract
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.
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Oral combination of TUDCA and sodium phenylbutyrate (AMX0035) slows functional decline and prolongs overall survival in amyotrophic lateral sclerosis patients.
“Notably, an oral combination of TUDCA and sodium phenylbutyrate (AMX0035) is effective in slowing functional decline and prolonging the overall survival of ALS patients.400–402”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [400]
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- Authors
- Paganoni, S., Hendrix, S., Dickson, S. P., Knowlton, N., Macklin, E. A., Berry, J. D., Elliott, M. A., Maiser, S., Karam, C., Caress, J. B., Owegi, M. A., Quick, A., Wymer, J., Goutman, S. A., Heitzman, D., Heiman‐Patterson, T. D., Jackson, C. E., Quinn, C., Rothstein, J. D., Kasarskis, E. J., Katz, J., Jenkins, L., Ladha, S., Miller, T. M., Scelsa, S. N., Vu, T. H., Fournier, C. N., Glass, J. D., Johnson, K. M., Swenson, A., Goyal, N. A., Pattee, G. L., Andres, P. L., Babu, S., Chase, M., Dagostino, D., Hall, M., Kittle, G., Eydinov, M., McGovern, M., Ostrow, J., Pothier, L., Randall, R., Shefner, J. M., Sherman, A. V., St Pierre, M. E., Tustison, E., Vigneswaran, P., Walker, J., Yu, H., Chan, J., Wittes, J., Yu, Z., Cohen, J., Klee, J., Leslie, K., Tanzi, R. E., Gilbert, W., Yeramian, P. D., Schoenfeld, D., & Cudkowicz, M. E.
- Affiliations
- Harvard University (US)
- Pentara Corporation Millcreek Utah
- Swedish Medical Center (US)
- Hennepin County Medical Center (US)
- Oregon Health & Science University (US)
- Wake Forest University Health Sciences (US)
- UMass Memorial Medical Center (US)
- The Ohio State University Wexner Medical Center (US)
- University of Florida Health (US)
- University of Michigan (US)
- Texas Neurology (US)
- Department of Neurology, Lewis Katz School of Medicine Temple University Philadelphia Pennsylvania
- The University of Texas at San Antonio Health Science Center (US)
- University of Pennsylvania (US)
- Johns Hopkins University (US)
- University of Kentucky (US)
- California Pacific Medical Center (US)
- Barrow Neurological Institute (US)
- Washington University in St. Louis (US)
- Mount Sinai Beth Israel (US)
- University of South Florida (US)
- Emory University (US)
- Ochsner Health System (US)
- University of Iowa (US)
- University of California, Irvine (US)
- Neurology Associates Lincoln Nebraska
- Independent Consultant Nobleboro Maine
- Sean M. Healey & AMG Center for ALS & the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts
- Statistics Collaborative (US)
- Amylyx Pharmaceuticals, Inc. (United States) (US)
- Corresponding author
- Paganoni, Sabrina
- ORCID
- Paganoni, Sabrina
- Hendrix, Suzanne
- Dickson, Samuel P.
- Macklin, Eric A.
- Berry, James D.
- Maiser, Samuel
- Karam, Chafic
- Caress, James B.
- Quick, Adam
- Wymer, James
- Goutman, Stephen A.
- Jackson, Carlayne E.
- Quinn, Colin
- Rothstein, Jeffrey D.
- Kasarskis, Edward J.
- Ladha, Shafeeq
- Miller, Timothy M.
- Scelsa, Stephen N.
- Vu, Tuan H.
- Fournier, Christina N.
- Swenson, Andrea
- Goyal, Namita A.
- Pattee, Gary L.
- Babu, Suma
- Pothier, Lindsay
- Randall, Rebecca
- Shefner, Jeremy M.
- Sherman, Alexander V.
- Yu, Hong
- Chan, James
- Cohen, Joshua
- Tanzi, Rudolph E.
- Schoenfeld, David
- Cudkowicz, Merit E.
- Venue
- Muscle & Nerve
- Publisher
- Wiley
- Published
- 2020-10-30
- Volume
- 63
- Issue
- 1
- Pages
- 31-39
- ISSN
- 0148-639X (ISSN-L)
- 1097-4598
- PMC
- PMC7820979
- OpenAlex
- W3092893535
- Cited by
- 180
- References
- 35
- Citations by year
- 2026: 21 · 2025: 22 · 2024: 38 · 2023: 48 · 2022: 34 · 2021: 15 · 2020: 1 · 2019: 1
- FWCI
- 10.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Muscle & Nerve (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- Funders
- Amyotrophic Lateral Sclerosis Association
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- amyotrophic lateral sclerosis, 4-phenylbutyric acid, long-term survival, all-cause mortality, open-label extension, functional decline
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Double-Blind Method, Female, Humans, Male, Middle Aged, Phenylbutyrates, Taurochenodeoxycholic Acid, Time, Neuroprotective Agents, Young Adult
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