Long-Term Data Suggest Friedreich Ataxia Agent Omaveloxolone Slows Disease Progression Over 4 Years

New late breaking data presented at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii, from the open-label extension MOXIe trial (NCT02255435) showed that patients with Friedreich ataxia (FA) treated with omaveloxolone (Skyclarys; Biogen) for approximately 4 years experienced slower rates of disease progression compared with rates observed in natural history studies.¹ These findings, from the longest study of a disease-modifying therapy in FA, highlight omaveloxolone’s potential to alter the course of the disease.

Among 149 patients in analysis (omaveloxolone, n = 43; placebo, n = 106), those treated with omaveloxolone demonstrated a mean change from baseline in modified Friedreich Ataxia Rating Scale (mFARS) scores of 4.40 (SD, 6.26; difference, +1.1 points/year) and FA Activities of Daily Living (FA-ADL) scores of 2.79 (SD, 3.04; difference, +0.7 points/year) over 4 years. Presented by lead author Theresa Zesiewicz, MD, director of the Ataxia Research Center at University of South Florida, a comparison of natural history studies reported FA progression of approximately +1.8 to +2.0 mFARS points per year.

In this analysis of the MOXIe open-label extension, with a data cutoff of February 27, 2025, researchers assessed the long-term efficacy, safety, and tolerability of omaveloxolone in patients with FA treated beginning from extension baseline to 216 weeks. The study evaluated the mean change in mFARS and FA-ADL scores among patients who were treatment naive upon entry into the open-label extension, which include all patients from Part 1 and placebo-treated patients from Part 2 of MOXIe, those who received omaveloxolone in Part 2 and continued treatment in the open-label extension, and the pooled population.

READ MORE: Ionis Plans Application Submission for Zilganersen as Potential First Treatment for Alexander Disease Following Positive Data

Consistent with earlier treatment initiation, patients in the omaveloxolone group had lower baseline mean mFARS scores of 41.2 (SD, 12.0) versus 43.3 (SD, 12.7), and FA-ADL scores of 12.0 (SD, 5.16) versus 12.7 (SD, 4.92) compared in the placebo group, respectively. Notably, continued treatment with omaveloxolone was associated with no worsening from baseline on 2 mFARS subscales, bulbar function (mean change, –0.21; SD, 0.52) and upper limb coordination (mean change, –1.04; SD, 2.93). The open-label extension study observed that safety findings were consistent with previous results of omaveloxolone.

Omaveloxolone received FDA approval for the treatment of FA in adults and adolescents aged 16 years and older in February 2023.² The agency's decision was supported by the efficacy and safety data from the MOXIe Part 2 trial and a post hoc Propensity-Matched Analysis of the open-label MOXIe extension trial. In the supporting trial data, treatment with omaveloxolone resulted in statistically significant lower modified mFARS scores relative to placebo at 48 weeks, accounting for a placebo-corrected difference between the groups of –2.41 points (P = .0138).

In June 2025, Biogen announced that it has initiated a new phase 3 trial dubbed BRAVE (NCT06953583) to test the therapeutic potential of omaveloxolone in pediatric patients living with FDA.³ The newly initiated 52-week study, split into 2 parts, includes children with genetically confirmed FA aged 2 to 16 who will receive either omaveloxolone once a day or placebo. Part 1, the randomized controlled portion, uses change in Upright Stability Score, a part of the validated mFARS, as the primary end point. Part 2, or the open-label extension phase, lasts up to 104 weeks, giving patients from either cohort the opportunity to experience omaveloxolone treatment.

Click here for more coverage of MDS 2025.

REFERENCES
1. Zesiewicz T, Lynch DR, Delatycki MB, et al. Long-Term Efficacy and Safety of Omaveloxolone in Patients With Friedreich Ataxia: 4-Year Data From the Ongoing MOXIe Open-Label Extension. Presented at: 2025 MDS Congress; October 5-9; Honolulu, Hawaii. LBA-3.
2. 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 October 3, 2025. 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
3. Biogen Initiates Phase 3 Pediatric Study of Omaveloxolone for the Treatment of Friedreich Ataxia. News release. June 18, 2025. Accessed October 3, 2025. https://investors.biogen.com/news-releases/news-release-details/biogen-initiates-phase-3-pediatric-study-omaveloxolone-treatment