Background and Objective
Approximately 66% of patients with Friedreich’s ataxia (FA) develop cardiomyopathy. Natural history studies in patients with FA show that cardiac dysfunction is the most common cause of death (60%). In MOXIe Part 2 (NCT02255435), a randomized, double-blind, placebo-controlled study evaluating omaveloxolone (omav) 150 mg once daily for 48 weeks in patients with FA, those with mild to moderate cardiomyopathy were included. Here, we present post-hoc analyses of cardiac safety assessments performed during MOXIe Part 2.
In addition to standard adverse event collection, electrocardiogram, heart rate, blood pressure and BNP assessments were performed at baseline and at periodic in-person visits. Echocardiogram was performed at baseline and every 6 months until Week 48. Clinical chemistry tests included lipid panel assessments. After completion of MOXIe Part 2, patients were eligible to enroll in an ongoing open-label extension (OLE) trial.
Cardiac adverse events (AEs) occurred in 9.8% of patients receiving omav (n=51) as compared to 13.5% of those receiving placebo (n=52). A standardized medical query revealed no imbalances for arrhythmia-related AEs (5 in omav group and 5 in placebo group). In patients with a medical history of cardiomyopathy, no imbalances in cardiovascular AEs were observed (12% in omav group and 13.3% in placebo group). Only one cardiac serious AE (SAE), atrial fibrillation, was reported in more than one patient, and it was reported in one patient each in placebo and omav groups. Two additional patients in the omav group reported cardiac SAEs. No clinically significant changes were observed between groups in echocardiogram, electrocardiogram, heart rate and blood pressure assessments. Slight increases in BNP and NT-Pro-BNP were observed only in the omav-treatment group but occurred without signs or symptoms of fluid retention. Mean values remained below the ULN of 100 pg/mL. Although mean cholesterol values were higher in the omav group than in the placebo group, the values remained within normal limits. The OLE trial is ongoing, with data in MOXIe accrued up to 4.3 years, as of the last data-cut of March 24th, 2022. No new cardiac safety signals have been observed. There were no deaths in the study and the majority of all adverse events were mild to moderate in severity.
Omav was well tolerated and had a manageable cardiac safety profile in MOXIe Part 2.