Background and Objective
MOXIe Part 2 (NCT02255435) was a randomized, double-blind, placebo-controlled trial evaluating omaveloxolone (omav) 150 mg once daily for 48 weeks in patients with Friedreich’s ataxia (FA). Upon study completion, patients could enter an open-label extension (OLE). Here, we present analyses of laboratory parameters associated with hepatic function.
In these studies, adverse events (AEs) of omav and hepatic safety parameters, including alanine and aspartate aminotransferase (ALT and AST, respectively), gamma-glutamyl transferase (GGT) and bilirubin levels were monitored at baseline and in-person visits (every 6-8 weeks after weeks 2 and 4).
The majority of AEs were mild to moderate in severity. There were no deaths. The distribution of hepatobiliary disorder AEs was similar between treatment groups, with 2 events in the omav group (n=51) and 1 in the placebo group (n=52). ALT increases were reported as AEs in 37.3% of patients in the omav group versus 1.9% of patients in the placebo group. AST increases were reported as AEs in 21.6% of patients in the omav group versus 1.9% of patients in the placebo group. GGT increases were reported in 5.9% of patients in the omav group versus no patients in the placebo group. Discontinuations due to ALT or AST elevation occurred in one patient in the omav group (2%) and no patients in the placebo group. Among omav-treated patients, most (68.6%) had maximum ALT and AST increases of ≤ 3 times the upper limit of normal (ULN). None had ALT and AST increases of ≥10 times the ULN. ALT and AST elevations were mild to moderate, transient, and reversible after drug discontinuation. Maximal values occurred within the first 12 weeks of treatment. No aminotransferase increase was associated with concurrent increases in total bilirubin, and no Hy’s Law cases were observed. Nonclinical data show omav modulates aminotransferase gene expression. No new safety signals were observed in the OLE, at the last data-cut (March 24th, 2022).
Omav was well tolerated and had a manageable hepatic safety profile in clinical studies in patients with FA.