Efficacy of Omaveloxolone in Friedreich's Ataxia: Delayed‐Start Analysis of the MOXIe Extension.

Background: MOXIe was a two‐part study evaluating the safety and efficacy of omaveloxolone in patients with Friedreich's ataxia, a rare, progressive neurological disease with no proven therapy. MOXIe part 2, a randomized double‐blind placebo‐controlled trial, showed omaveloxolone significantly improved modified Friedreich's Ataxia Rating Scale (mFARS) scores relative to placebo. Patients who completed part 1 or 2 were eligible to receive omaveloxolone in an open‐label extension study. Objective: The delayed‐start study compared mFARS scores at the end of MOXIe part 2 with those at 72 weeks in the open‐label extension period (up to 144 weeks) for patients initially randomized to omaveloxolone versus those initially randomized to placebo. Methods: We performed a noninferiority test to compare the difference between treatment groups (placebo to omaveloxolone versus omaveloxolone to omaveloxolone) using a single mixed model repeated measures (MMRM) model. In addition, slopes of the change in mFARS scores were compared between both groups in the open‐label extension. Results: The noninferiority testing demonstrated that the difference in mFARS between omaveloxolone and placebo observed at the end of placebo‐controlled MOXIe part 2 (−2.17 ± 1.09 points) was preserved after 72 weeks in the extension (−2.91 ± 1.44 points). In addition, patients previously randomized to omaveloxolone in MOXIe part 2 continued to show no worsening in mFARS relative to their extension baseline through 144 weeks. Conclusions: These results support the positive results of MOXIe part 2 and indicate a persistent benefit of omaveloxolone treatment on disease course in Friedreich's ataxia. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]