| Rare Neurological Diseases  

Omaveloxolone approved by FDA for Friedrich ataxia

The FDA has approved Omaveloxolone for the treatment of Friedrich ataxia (FA). Omaveloxone improved neurological function assessed with the modified FA Rating Scale. A marketing authorisation application is currently under review by the EMA.

The FDA has approved Omaveloxolone for the treatment of 16 years and above-aged adults with Friedrich ataxia (FA). Despite recent advances in clinical trials for FA, this is the first approved treatment for this disease.

Omaveloxolone is an oral drug which activates the Nrf2 pathway. The support for FDA approval comes from the MOXIe study (1), an international multi-center, double blind, randomized, placebo-controlled, parallel-group, registrational phase 2 trial in patients between 16-40 years of age with genetically confirmed FA and a baseline modified FA Rating Scale (mFARS) between 20-80. A total of 103 patients were randomised either to omaveloxolone (150mg once daily, 51 patients) or placebo (52 patients) over a 48 weeks period, but only 82 (40 omaveloxolone and 42 placebo) were analyzed in the full analysis set.

The primary endpoint was the change in the score on the mFARS (a 99-point measure of physical function) from baseline at 18 months. Secondary endpoints included timed 25-foot walk test, 9-hole peg test, activities of daily living and impression of change scales, frequency of falls and peak work during maximal exercise testing.

There was a difference of -2.4 points in the mFARS score between groups and no significant differences in the secondary endpoints. The most common adverse events occurring more frequently with Omaveloxolone were headache, nausea, abdominal pain, diarrhea, fatigue and increases in alanine aspartate aminotransferase.

A delayed-start analysis of the open-label extension portion of the MOXIe study suggested that the difference in mFARS between omaveloxone and placebo at the end of the placebo-controlled portion was preserved after 72 weeks in the extension,  implying a benefit of early initiation, with the same safety profile (2).

A marketing authorisation application for Omaveloxone is currently under review by the EMA, who granted an orphan drug designation in 2018.

Key Points:

  • Omaveloxolone is the first FDA approved treatment for adult patients with FA
  • In patients with FA, Omaveloxone improved neurological function relative to placebo after 48 weeks of treatment.
  • Although generally well-tolerated, Omaveloxolone was associated with transient increases in aminotransferase levels.
  • Omaveloxolone is currently under review by the EMA.


  1. Lynch DR, Chin MP, Delatycki MB, et al. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Ann Neurol. 2021;89(2):212-225. doi:10.1002/ana.25934 pubmed.ncbi.nlm.nih.gov/33068037/
  2. Lynch DR, Chin MP, Boesch S, et al. Efficacy of Omaveloxolone in Friedreich's Ataxia: Delayed-Start Analysis of the MOXIe Extension. Mov Disord. 2023;38(2):313-320. doi:10.1002/mds.29286 pubmed.ncbi.nlm.nih.gov/36444905/


Michelangelo Mancuso, Neurological Institute, University of Pisa
Kailash Bhatia, UCL Queen Square Institute of Neurology, University College London

Publish on behalf of the Coordinating Panel on Rare Neurological Disease