Assessing Omaveloxolone’s Positive Long-Term Safety Profile: David Lynch, MD, PhD

WATCH TIME: 4 minutes

"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."

In early 2023, the FDA made a landmark approval, giving greenlight to omaveloxolone (Skyclarys; Biogen) as the first treatment specific for patients with Friedreich ataxia (FA), a neuromuscular disorder impacting 1 in 40,000 people globally. Most of the approval was based on data from the phase 3 MOXIe Part 2 trial (NCT02255435), a 103-patient cohort double-blind, placebo-controlled study. In the study, omaveloxolone demonstrated statistically significant differences in the primary end point of Friedreich Ataxia Rating Scale (mFARS) scores over a 48-week treatment period (vs placebo, –2.41 points; P =. 0138).¹

In its original approval label, it states that alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, B-type natriuretic peptide (BNP), and lipid parameters should be obtained prior to and during omaveloxolone treatment. More than a year after its approval, investigators presented a long-term analysis at the International Congress at Ataxia Research 2024 assessing the safety of the therapy. Led by David Lynch, MD, PhD, the therapy was considered safe and well-tolerated treatment-emergent adverse events (TEAEs), including gastrointestinal issues and aminotransferase elevations, occurring within 12 weeks.²

Following the conference, NeurologyLive® sat down with Lynch to discuss the reasons behind the analysis and the safety considerations behind omaveloxolone. Lynch, professor of neurology at the University of Pennsylvania Perelman School of Medicine, provided comment on how the incidence of certain AEs, such as gastrointestinal issues, subsides over time with omaveloxolone treatment. For clinicians, Lynch stressed that a gradual titration of the dosage over several months has been effective in managing expected metabolic effects, allowing most patients to reach the full dose without significant complications.

REFERENCES
1. Reata Pharmaceuticals Announces FDA Approval of SKYCLARYS™ (Omavaloxolone), the First and Only Drug Indicated for Patients with Friedreich’s Ataxia. Reata Pharmaceuticals. News release. February 28, 2023. Accessed November 25, 2024. https://www.reatapharma.com/investors/news/news-details/2023/Reata-Pharmaceuticals-Announces-FDA-Approval-of-SKYCLARYS-Omavaloxolone-the-First-and-Only-Drug-Indicated-for-Patients-with-Friedreichs-Ataxia/default.aspx
2. Lynch D, Boesch S, Delatycki M, et al. The MOXIe trial of omaveloxolone in Friedreich ataxia: exploring the transient nature of treatment-emergent adverse events. Presented at: International Congress at Ataxia Research 2024