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

Sabrina Paganoni; 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; Terry D. Heiman-Patterson; 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; Namita A. Goyal; 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; Eric Tustison; 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

doi:10.1002/mus.27091

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

Sabrina Paganoni, 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, Terry D. Heiman-Patterson, Carlayne E. Jackson, Colin Quinn, Jeffrey D. Rothstein, Edward J. KasarskisJonathan 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, Namita A. Goyal, 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, Eric Tustison, 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

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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.

Original language	English
Pages (from-to)	31-39
Number of pages	9
Journal	Muscle and Nerve
Volume	63
Issue number	1
DOIs	https://doi.org/10.1002/mus.27091
State	Published - Jan 2021

Keywords

CENTAUR
amyotrophic lateral sclerosis
motor neuron disease
sodium phenylbutyrate-taurursodiol
survival analysis

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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., ... Cudkowicz, M. E. (2021). Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. Muscle and Nerve, 63(1), 31-39. https://doi.org/10.1002/mus.27091

@article{985787e72d604c4f92379aa9f899794e,

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

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.",

keywords = "CENTAUR, amyotrophic lateral sclerosis, motor neuron disease, sodium phenylbutyrate-taurursodiol, survival analysis",

author = "Sabrina Paganoni and Suzanne Hendrix and Dickson, {Samuel P.} and Newman Knowlton and Macklin, {Eric A.} and Berry, {James D.} and Elliott, {Michael A.} and Samuel Maiser and Chafic Karam and Caress, {James B.} and Owegi, {Margaret Ayo} and Adam Quick and James Wymer and Goutman, {Stephen A.} and Daragh Heitzman and Heiman-Patterson, {Terry D.} and Jackson, {Carlayne E.} and Colin Quinn and Rothstein, {Jeffrey D.} and Kasarskis, {Edward J.} and Jonathan Katz and Liberty Jenkins and Shafeeq Ladha and Miller, {Timothy M.} and Scelsa, {Stephen N.} and Vu, {Tuan H.} and Fournier, {Christina N.} and Glass, {Jonathan D.} and Johnson, {Kristin M.} and Andrea Swenson and Goyal, {Namita A.} and Pattee, {Gary L.} and Andres, {Patricia L.} and Suma Babu and Marianne Chase and Derek Dagostino and Meghan Hall and Gale Kittle and Matthew Eydinov and Michelle McGovern and Joseph Ostrow and Lindsay Pothier and Rebecca Randall and Shefner, {Jeremy M.} and Sherman, {Alexander V.} and {St Pierre}, {Maria E.} and Eric Tustison and Prasha Vigneswaran and Jason Walker and Hong Yu and James Chan and Janet Wittes and Yu, {Zi Fan} and Joshua Cohen and Justin Klee and Kent Leslie and Tanzi, {Rudolph E.} and Walter Gilbert and Yeramian, {Patrick D.} and David Schoenfeld and Cudkowicz, {Merit E.}",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.",

year = "2021",

month = jan,

doi = "10.1002/mus.27091",

language = "English",

volume = "63",

pages = "31--39",

journal = "Muscle and Nerve",

issn = "0148-639X",

number = "1",

}

Paganoni, S, Hendrix, S, Dickson, SP, Knowlton, N, Macklin, EA, Berry, JD, Elliott, MA, Maiser, S, Karam, C, Caress, JB, Owegi, MA, Quick, A, Wymer, J, Goutman, SA, Heitzman, D, Heiman-Patterson, TD, Jackson, CE, Quinn, C, Rothstein, JD, Kasarskis, EJ, Katz, J, Jenkins, L, Ladha, S, Miller, TM, Scelsa, SN, Vu, TH, Fournier, CN, Glass, JD, Johnson, KM, Swenson, A, Goyal, NA, Pattee, GL, Andres, PL, Babu, S, Chase, M, Dagostino, D, Hall, M, Kittle, G, Eydinov, M, McGovern, M, Ostrow, J, Pothier, L, Randall, R, Shefner, JM, Sherman, AV, St Pierre, ME, Tustison, E, Vigneswaran, P, Walker, J, Yu, H, Chan, J, Wittes, J, Yu, ZF, Cohen, J, Klee, J, Leslie, K, Tanzi, RE, Gilbert, W, Yeramian, PD, Schoenfeld, D & Cudkowicz, ME 2021, 'Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis', Muscle and Nerve, vol. 63, no. 1, pp. 31-39. https://doi.org/10.1002/mus.27091

TY - JOUR

T1 - Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis

AU - Paganoni, Sabrina

AU - Hendrix, Suzanne

AU - Dickson, Samuel P.

AU - Knowlton, Newman

AU - Macklin, Eric A.

AU - Berry, James D.

AU - Elliott, Michael A.

AU - Maiser, Samuel

AU - Karam, Chafic

AU - Caress, James B.

AU - Owegi, Margaret Ayo

AU - Quick, Adam

AU - Wymer, James

AU - Goutman, Stephen A.

AU - Heitzman, Daragh

AU - Heiman-Patterson, Terry D.

AU - Jackson, Carlayne E.

AU - Quinn, Colin

AU - Rothstein, Jeffrey D.

AU - Kasarskis, Edward J.

AU - Katz, Jonathan

AU - Jenkins, Liberty

AU - Ladha, Shafeeq

AU - Miller, Timothy M.

AU - Scelsa, Stephen N.

AU - Vu, Tuan H.

AU - Fournier, Christina N.

AU - Glass, Jonathan D.

AU - Johnson, Kristin M.

AU - Swenson, Andrea

AU - Goyal, Namita A.

AU - Pattee, Gary L.

AU - Andres, Patricia L.

AU - Babu, Suma

AU - Chase, Marianne

AU - Dagostino, Derek

AU - Hall, Meghan

AU - Kittle, Gale

AU - Eydinov, Matthew

AU - McGovern, Michelle

AU - Ostrow, Joseph

AU - Pothier, Lindsay

AU - Randall, Rebecca

AU - Shefner, Jeremy M.

AU - Sherman, Alexander V.

AU - St Pierre, Maria E.

AU - Tustison, Eric

AU - Vigneswaran, Prasha

AU - Walker, Jason

AU - Yu, Hong

AU - Chan, James

AU - Wittes, Janet

AU - Yu, Zi Fan

AU - Cohen, Joshua

AU - Klee, Justin

AU - Leslie, Kent

AU - Tanzi, Rudolph E.

AU - Gilbert, Walter

AU - Yeramian, Patrick D.

AU - Schoenfeld, David

AU - Cudkowicz, Merit E.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

KW - CENTAUR

KW - amyotrophic lateral sclerosis

KW - motor neuron disease

KW - sodium phenylbutyrate-taurursodiol

KW - survival analysis

UR - http://www.scopus.com/inward/record.url?scp=85094653246&partnerID=8YFLogxK

U2 - 10.1002/mus.27091

DO - 10.1002/mus.27091

M3 - Article

C2 - 33063909

AN - SCOPUS:85094653246

SN - 0148-639X

VL - 63

SP - 31

EP - 39

JO - Muscle and Nerve

JF - Muscle and Nerve

IS - 1

ER -

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

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