Current evidence demonstrates that omaveloxolone, a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, has therapeutic benefit in Friedreich ataxia (FA) and could be the first approved treatment for the disease.

“The data from [omaveloxolone] are at present superior to that assembled for other agents. Agents such as idebenone did not reach their endpoints, while the data on PTC743, elamipretide, and leriglitazone in adults are inconclusive at present,” explained Profeta et al, experts from the Children’s Hospital of Philadelphia, Pennsylvania, in a review article recently published in Expert Opinion on Investigational Drugs.

Patients treated with 150 mg per day of omaveloxolone showed improved modified Friedreich ataxia rating scale (mFARS) scores, while those on placebo performed worse, at 48 weeks after treatment initiation. The positive effects were particularly noticeable in younger participants and those with longer GAA repeats.

The clinical efficacy of omaveloxolone in FA has been assessed through the MOXIe trial, which was split into 2 parts: a randomized, placebo-controlled, double-blind dose escalation study (part 1, n=69) and a pivotal double-blind single dose-level study (part 2, n=103).

Part 1 determined the optimal dose of omaveloxolone to be 160 mg. Therefore, 150 mg was selected as an optimal convenient dose for part 2.

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In general, omaveloxolone was well tolerated among FA patients. The most commonly reported adverse event was an increased number of upper respiratory tract infections in part 1. Moreover, patients reported headache, nausea, increased alanine aminotransferase and aspartate aminotransferase, fatigue, diarrhea, and abdominal pain, but most of these events attenuated or even resolved after the first 12 weeks of treatment.

In addition, all participants were given the opportunity to continue into an open-label extension phase (ongoing, 58 subjects enrolled) to monitor the safety and tolerability of omaveloxolone in long-term use. The results from the MOXIe extension phase suggest a potential benefit to starting treatment with omaveloxolone earlier, but this requires further elucidation.

Omaveloxolone was the first agent targeting downstream events in FA to reach New Drug Application submission stage. It is currently under review by the US Food and Drug Administration, with a Prescription Drug User Fee Act date of February 28, 2022.


Profeta V, McIntyre K, Wells M, Park C, Lynch DR. Omaveloxolone: an activator of Nrf2 for the treatment of Friedreich ataxia. Expert Opin Investig Drugs. Published online February 8, 2023. doi:10.1080/13543784.2023.2173063