Journal article
Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)
Annals of neurology, Vol.89(2), pp.212-225
02/2021
DOI: 10.1002/ana.25934
PMID: 33068037
Abstract
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
Details
- Title: Subtitle
- Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)
- Creators
- David R Lynch - Children's Hospital of PhiladelphiaMelanie P Chin - Reata PharmaceuticalsMartin B Delatycki - Victorian Clinical Genetics Services, Murdoch Children's Research InstituteS. H Subramony - McKnight Brain Institute, University of Florida Health SystemManuela Corti - University of Florida Health SystemJ. Chad Hoyle - Ohio State University College of MedicineSylvia Boesch - Medical University InnsbruckWolfgang Nachbauer - Medical University InnsbruckCaterina Mariotti - Istituto di Ricovero e Cura a Carattere Scientifico–Carlo Besta Neurological InstituteKatherine D Mathews - University of Iowa Carver College of MedicinePaola Giunti - University College London HospitalGeorge Wilmot - Emory University School of MedicineTheresa Zesiewicz - University of South Florida Ataxia Research CenterSusan Perlman - University of California, Los AngelesAngie Goldsberry - Reata PharmaceuticalsMegan O'Grady - Reata PharmaceuticalsColin J Meyer - Reata Pharmaceuticals
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.89(2), pp.212-225
- DOI
- 10.1002/ana.25934
- PMID
- 33068037
- NLM abbreviation
- Ann Neurol
- ISSN
- 0364-5134
- eISSN
- 1531-8249
- Publisher
- John Wiley & Sons, Inc; Hoboken, USA
- Number of pages
- 14
- Language
- English
- Date published
- 02/2021
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984071607802771
Metrics
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