Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)
Objective: Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatments. Omaveloxolone, an Nrf2 activator, has demonstrated the ability to improve mitochondrial function, restore redox balance, and reduce inflammation in FA models. This study aimed to evaluate the safety and efficacy of omaveloxolone in patients with FA.
Methods: We conducted a double-blind, randomized, placebo-controlled, parallel-group phase 2 trial across 11 institutions in the United States, Europe, and Australia (NCT02255435, EudraCT2015-002762-23). Eligible participants, aged 16 to 40 with genetically confirmed FA and baseline modified Friedreich’s Ataxia Rating Scale (mFARS) scores between 20 and 80, were randomly assigned in a 1:1 ratio to receive either 150 mg per day of omaveloxolone or a placebo. The primary outcome was the change from baseline in mFARS scores at 48 weeks.
Results: Out of 155 screened patients, 103 were randomized to receive either omaveloxolone (n = 51) or placebo (n = 52). A full analysis set included 40 patients in the omaveloxolone group and 42 in the placebo group. The change in mFARS scores from baseline was -1.55 ± 0.69 for the omaveloxolone group compared to 0.85 ± 0.64 for the placebo group, resulting in a significant difference of -2.40 ± 0.96 (p = 0.014). Omaveloxolone was associated with transient, reversible increases in aminotransferase levels but did not lead to elevated total bilirubin or other signs of liver damage. Additionally, headache, nausea, and fatigue were more frequently reported among patients receiving omaveloxolone.
Interpretation: The MOXIe trial demonstrated that omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. These findings suggest that omaveloxolone holds promise as a potential therapeutic option for FA.