Efficacy of Omaveloxolone in Patients with Friedreich’s Ataxia: Update of the Delayed-Start Study

Topic:

Clinical Trials

Poster Number: 55

Author(s):

S H Subramony, MD, University of Florida College of Medicine, Sylvia Boesch, MD, Department of Neurology, Medical University Innsbruck, Melanie Chin, PhD, Reata Pharmaceuticals, Martin Delatycki, MD, PhD, Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Paola Giunti, MD, PhD, University College London Hospital, Angie Goldsberry, MS, Reata Pharmaceuticals, Katherine Mathews, MD, University of Iowa, Colin Meyer, MD, Reata Pharmaceuticals, Wolfgang Nachbauer, PhD, Department of Neurology, Medical University Innsbruck, Megan O'Grady, PhD, Reata Pharmaceuticals, Susan Perlman, MD, University of California Los Angeles (UCLA), George Wilmot, MD, PhD, Department of Neurology, Emory University School of Medicine, Theresa Zesiewicz, MD, University of South Florida (USF), David Lynch, MD, PhD, Division of Neurology, Children’s Hospital of Philadelphia

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).

Methods
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).

Results
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.

Conclusion
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.