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Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)

OBJECTIVE: Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxol...

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Autores principales: Lynch, David R., Chin, Melanie P., Delatycki, Martin B., Subramony, S. H., Corti, Manuela, Hoyle, J. Chad, Boesch, Sylvia, Nachbauer, Wolfgang, Mariotti, Caterina, Mathews, Katherine D., Giunti, Paola, Wilmot, George, Zesiewicz, Theresa, Perlman, Susan, Goldsberry, Angie, O'Grady, Megan, Meyer, Colin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894504/
https://www.ncbi.nlm.nih.gov/pubmed/33068037
http://dx.doi.org/10.1002/ana.25934
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author Lynch, David R.
Chin, Melanie P.
Delatycki, Martin B.
Subramony, S. H.
Corti, Manuela
Hoyle, J. Chad
Boesch, Sylvia
Nachbauer, Wolfgang
Mariotti, Caterina
Mathews, Katherine D.
Giunti, Paola
Wilmot, George
Zesiewicz, Theresa
Perlman, Susan
Goldsberry, Angie
O'Grady, Megan
Meyer, Colin J.
author_facet Lynch, David R.
Chin, Melanie P.
Delatycki, Martin B.
Subramony, S. H.
Corti, Manuela
Hoyle, J. Chad
Boesch, Sylvia
Nachbauer, Wolfgang
Mariotti, Caterina
Mathews, Katherine D.
Giunti, Paola
Wilmot, George
Zesiewicz, Theresa
Perlman, Susan
Goldsberry, Angie
O'Grady, Megan
Meyer, Colin J.
author_sort Lynch, David R.
collection PubMed
description OBJECTIVE: Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA. METHODS: We conducted an international, double‐blind, randomized, placebo‐controlled, parallel‐group, registrational phase 2 trial at 11 institutions in the United States, Europe, and Australia (NCT02255435, EudraCT2015‐002762‐23). Eligible patients, 16 to 40 years of age with genetically confirmed FA and baseline modified Friedreich's Ataxia Rating Scale (mFARS) scores between 20 and 80, were randomized 1:1 to placebo or 150mg per day of omaveloxolone. The primary outcome was change from baseline in the mFARS score in those treated with omaveloxolone compared with those on placebo at 48 weeks. RESULTS: One hundred fifty‐five patients were screened, and 103 were randomly assigned to receive omaveloxolone (n = 51) or placebo (n = 52), with 40 omaveloxolone patients and 42 placebo patients analyzed in the full analysis set. Changes from baseline in mFARS scores in omaveloxolone (−1.55 ± 0.69) and placebo (0.85 ± 0.64) patients showed a difference between treatment groups of –2.40 ± 0.96 (p = 0.014). Transient reversible increases in aminotransferase levels were observed with omaveloxolone without increases in total bilirubin or other signs of liver injury. Headache, nausea, and fatigue were also more common among patients receiving omaveloxolone. INTERPRETATION: In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FA. ANN NEUROL 2021;89:212–225
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spelling pubmed-78945042021-03-02 Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study) Lynch, David R. Chin, Melanie P. Delatycki, Martin B. Subramony, S. H. Corti, Manuela Hoyle, J. Chad Boesch, Sylvia Nachbauer, Wolfgang Mariotti, Caterina Mathews, Katherine D. Giunti, Paola Wilmot, George Zesiewicz, Theresa Perlman, Susan Goldsberry, Angie O'Grady, Megan Meyer, Colin J. Ann Neurol Research Articles OBJECTIVE: Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA. METHODS: We conducted an international, double‐blind, randomized, placebo‐controlled, parallel‐group, registrational phase 2 trial at 11 institutions in the United States, Europe, and Australia (NCT02255435, EudraCT2015‐002762‐23). Eligible patients, 16 to 40 years of age with genetically confirmed FA and baseline modified Friedreich's Ataxia Rating Scale (mFARS) scores between 20 and 80, were randomized 1:1 to placebo or 150mg per day of omaveloxolone. The primary outcome was change from baseline in the mFARS score in those treated with omaveloxolone compared with those on placebo at 48 weeks. RESULTS: One hundred fifty‐five patients were screened, and 103 were randomly assigned to receive omaveloxolone (n = 51) or placebo (n = 52), with 40 omaveloxolone patients and 42 placebo patients analyzed in the full analysis set. Changes from baseline in mFARS scores in omaveloxolone (−1.55 ± 0.69) and placebo (0.85 ± 0.64) patients showed a difference between treatment groups of –2.40 ± 0.96 (p = 0.014). Transient reversible increases in aminotransferase levels were observed with omaveloxolone without increases in total bilirubin or other signs of liver injury. Headache, nausea, and fatigue were also more common among patients receiving omaveloxolone. INTERPRETATION: In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FA. ANN NEUROL 2021;89:212–225 John Wiley & Sons, Inc. 2020-11-05 2021-02 /pmc/articles/PMC7894504/ /pubmed/33068037 http://dx.doi.org/10.1002/ana.25934 Text en © 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Lynch, David R.
Chin, Melanie P.
Delatycki, Martin B.
Subramony, S. H.
Corti, Manuela
Hoyle, J. Chad
Boesch, Sylvia
Nachbauer, Wolfgang
Mariotti, Caterina
Mathews, Katherine D.
Giunti, Paola
Wilmot, George
Zesiewicz, Theresa
Perlman, Susan
Goldsberry, Angie
O'Grady, Megan
Meyer, Colin J.
Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)
title Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)
title_full Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)
title_fullStr Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)
title_full_unstemmed Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)
title_short Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)
title_sort safety and efficacy of omaveloxolone in friedreich ataxia (moxie study)
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894504/
https://www.ncbi.nlm.nih.gov/pubmed/33068037
http://dx.doi.org/10.1002/ana.25934
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