Background and Objective
Friedreich’s ataxia (FA) is a rare, degenerative neuromuscular disease with no available therapies. Omaveloxolone (Omav) is an investigational drug that activates the transcription factor Nrf2. MOXIe (NCT02255435) was a 2-part study of the safety and efficacy of Omav in patients with FA. MOXIe Part 1 was a dose-finding study, and the MOXIe Part 2 study showed that Omav significantly improved modified FA Rating Scale (mFARS) scores by 2.40 points relative to placebo after 48 weeks of treatment (p=0.014; n=82).
Patients in both MOXIe study parts were eligible to receive Omav in an open-label extension study; investigators and patients remained blinded to prior patient treatment assignments. The full analysis set included patients without severe pes cavus. The current analysis compared the difference in mFARS scores between treatment groups (placebo to Omav versus Omav to Omav) using single mixed model repeated measures (MMRM) for all available data from both the 48-week placebo-controlled period (MOXIe Part 2) and the 72-week open-label, delayed-start period (MOXIe Extension).
All patients in the full analysis set who completed MOXIe Part 2 enrolled in the MOXIe Extension study, including 42 patients previously randomized to placebo and 40 patients previously randomized to Omav. The difference in mFARS scores between the Omav and placebo groups observed at the end of the placebo-controlled MOXIe Part 2 study (-2.25 ± 1.07 points, p=0.037) was preserved at the end of the delayed-start period (-3.51 ± 1.45 points, p=0.016). Patients in the placebo to Omav group had an annualized mFARS slope (0.45 ± 0.38 points) similar to the Omav to Omav group (0.27 ± 0.59 points); both slopes were less than the expected +1.9 points per year observed in natural history data. Additionally, patients in the Omav to Omav group continued to show no worsening in mFARS scores relative to their original baseline through 120 weeks (nearly two and a half years) of treatment.
The results of this study support the positive primary endpoint findings in the pivotal MOXIe Part 2 trial and are consistent with a persistent effect of omaveloxolone treatment on disease course in Friedreich’s ataxia.