Reata Pharmaceuticals Part 2 MOXIe trial of omaveloxolone meets primary endpoint
Reata Pharmaceuticals announced that the registrational Part 2 portion of the MOXIe Phase 2 trial of omaveloxolone in patients with Friedreich's ataxia, or FA, met its primary endpoint of change in the modified Friedreich's Ataxia Rating Scale, or mFARS, relative to placebo after 48 weeks of treatment. Patients treated with omaveloxolone demonstrated a statistically significant, placebo-corrected 2.40 point improvement in mFARS after 48 weeks of treatment. Omaveloxolone treatment was generally reported to be well-tolerated. Based on these results, and subject to discussions with regulatory authorities, the company plans to proceed with the submission of regulatory filings for marketing approval in the United States and internationally. Part 2 of MOXIe, an international, multi-center, double-blind, placebo-controlled, randomized registrational Phase 2 trial, enrolled 103 patients with FA at 11 study sites in the United States, Europe and Australia. Patients were randomized 1:1 to 150 mg of omaveloxolone or placebo. The primary analysis population included patients without pes cavus, a musculoskeletal foot deformity that may interfere with the patient's ability to perform some components of the mFARS exam. Safety analyses were evaluated in the all randomized population. The primary endpoint for the study was change in the mFARS score relative to placebo after 48 weeks of treatment. The mFARS is a physician-assessed neurological rating scale used to measure FA disease progression. It includes four sections that measure the patient's performance of activities such as speaking and swallowing, upper limb coordination, lower limb coordination, and standing and walking. The FDA has indicated that mFARS is an acceptable primary endpoint to evaluate the effect of omaveloxolone for the treatment of patients with FA. Omaveloxolone treatment met the primary endpoint of the study producing a statistically significant, placebo-corrected 2.40 point improvement in mFARS. Patients treated with omaveloxolone experienced a mean improvement in mFARS of -1.55 points from baseline, while patients treated with placebo experienced a mean worsening in mFARS of +0.85 points from baseline. The observed placebo-corrected improvements in mFARS were time-dependent, increasing over the course of treatment with the largest improvement observed after 48 weeks of treatment. Omaveloxolone treatment also improved the mFARS scores of patients with pes cavus. When the pes cavus patients are included in the analysis of the mFARS scores at Week 48, omaveloxolone treatment produced a mean statistically significant, placebo-corrected 1.93 point improvement in mFARS. Omaveloxolone treatment also improved several secondary endpoints included in the study. Four omaveloxolone patients and two placebo patients discontinued study drug due to an adverse event, or AE. The reported AEs were generally mild to moderate in intensity, and the most common AEs observed more frequently compared to placebo were headache, nausea, increased aminotransferases, fatigue and abdominal pain. Increases in aminotransferases are a pharmacological effect of omaveloxolone, which increases production of aminotransferases in vitro, and believed to be related to restoration of mitochondrial function. In MOXIe, the aminotransferase increases were associated with improvements in total bilirubin and were not associated with liver injury. The overall rate of serious adverse events, or SAEs, was low, with three patients in each group reporting SAEs while receiving study drug. Two additional omaveloxolone-treated patients reported SAEs approximately two weeks after receiving their final dose.