Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder with limited treatments. Omaveloxolone, an Nrf2 activator, was approved based on a phase III trial showing modified Friedreich Ataxia Rating Scale (mFARS) improvement. Real-world and long-term data now require synthesis. To perform a single-arm meta-analysis pooling mean change in mFARS from baseline across all published omaveloxolone studies and interpret findings against natural history. Four studies (MOXIe Part 1, Part 2, open-label extension, Italian observational) comprising 248 patients were included. Data were harmonised using standard conversions. A random-effects model was used with subgroup and sensitivity analyses. The pooled mean ΔmFARS was −0.05 (95% CI −2.98 to 2.88; p=0.97). Subgroup analysis showed significant improvement in controlled trials (−2.19; 95% CI −3.12 to −1.27; p<0.00001) and consistent progression in real-world studies (+2.85; 95% CI 1.62 to 4.08; p<0.00001). Sensitivity analyses confirmed robustness. Controlled trials demonstrate significant short-term improvement with omaveloxolone, while real-world data show consistent progression at rates substantially slower than natural history. These complementary findings support a disease-modifying effect of omaveloxolone in FRDA.
Ali et al. (Thu,) studied this question.