Efficacy and Safety of Omaveloxolone in Friedreich Ataxia: Real‐World Data from an Advanced Disease Cohort

BACKGROUND: Friedreich ataxia (FRDA) is a rare, inherited neurodegenerative disorder. Omaveloxolone is the first disease-modifying treatment approved for FRDA. To date, real-world data remain limited. OBJECTIVES: To report short-term efficacy and safety data from a real-world FRDA cohort of advanced patients and explore potential predictors of treatment response. METHODS: We conducted a prospective study on 27 consecutive genetically-confirmed FRDA patients treated with Omaveloxolone for 3-6 months. Scores at the modified Friedreich-Ataxia-Rating-Scale (mFARS), peripheral neuropathy severity, cardiac involvement, cognitive-affective syndrome, ambulatory status, and the presence of pes cavus were assessed at baseline. Wilcoxon test was used to compare baseline vs. follow-up mFARS scores. mFARS changes in ambulatory and non-ambulatory patients were evaluated using a two-way ANOVA. Patient Global Impression of Change (PGI-C) was collected and adverse events (AEs) and laboratory data monitored. RESULTS: Twenty-six patients (median age and disease duration 42.5 and 24.5 years respectively) remained on therapy for at least 3 months. Total mFARS scores improved by 1.5 points (P = 0.007), with significant changes in the subscore of lower limb coordination (-1.5, P = 0.022). PGI-C indicated a perception of improvement in 42.3% of patients. Baseline demographic-clinical features did not correlate with the percentage improvement in mFARS score, and no differences were observed between ambulatory and non-ambulatory patients. No serious AEs occurred. CONCLUSIONS: Our findings support the efficacy and safety of Omaveloxolone in a real-world setting, being in line with data observed in the MOXIe trial, although our cohort is highly different in terms of age, disease duration, and severity.