Omaveloxolone (Skyclarys; Biogen), the first FDA-approved treatment for Friedreich ataxia (FA), continues to demonstrate a positive long-term safety profile, according to recent analysis presented at the International Congress at Ataxia Research 2024. The analysis, led by David Lynch, MD, PhD, suggests that the therapy is generally well-tolerated, with most treatment-emergent adverse events (TEAEs) being manageable.
The approval of omaveloxolone was largely based on data from the phase 3 MOXIe Part 2 trial (NCT02255435), a double-blind, placebo-controlled study involving 103 patients. The study revealed statistically significant differences in Friedreich Ataxia Rating Scale (mFARS) scores over a 48-week treatment period compared to placebo (-2.41 points; P = .0138).
Safety Considerations and Management
The original approval label for omaveloxolone advises monitoring alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, B-type natriuretic peptide (BNP), and lipid parameters before and during treatment. The recent long-term analysis further supports the drug's safety, noting that common TEAEs, such as gastrointestinal issues and aminotransferase elevations, typically occur within the first 12 weeks of treatment.
Expert Insights on Tolerability
David Lynch, professor of neurology at the University of Pennsylvania Perelman School of Medicine, noted that the incidence of certain adverse events, like gastrointestinal issues, tends to decrease over time with continued omaveloxolone treatment. He emphasized that a gradual titration of the dosage over several months is effective in managing expected metabolic effects, enabling most patients to reach the full dose without significant complications. "The idea that [omaveloxolone is] basically a pretty well-tolerated drug with a very modest number of safety issues...it’s a pretty clean drug for all that considered," Lynch stated.
Clinical Implications
Omaveloxolone represents a significant advancement in the treatment of Friedreich ataxia, a neuromuscular disorder affecting approximately 1 in 40,000 individuals worldwide. Its approval fills a critical unmet need, providing the first specific therapy for this debilitating condition. The long-term safety data reinforces its role as a valuable treatment option, offering clinicians confidence in its use with appropriate monitoring and dose management strategies.
