Early experience on omaveloxolone in adult patients with Friedreich’s ataxia: a real-world observational study

Abstract

Introduction: Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative spinocerebellar ataxia caused by a homozygous GAA triplet repeat expansion in the frataxin (FXN) gene. FRDA is a multisystem disorder involving the central and peripheral nervous systems, the musculoskeletal system, the heart, and the endocrine pancreas. In recent years, Omaveloxolone, a potent activator of nuclear factor erythroid 2-related factor 2 signaling, showed a significant neurological improvement compared to placebo, with a good safety profile. With this study, we report an early real-life experience on a cohort of FRDA patients treated with omaveloxolone. Materials and methods: Patients were assessed with an anamnestic profile, general and neurological examination, clinical scales (mFARS, SARA, and FA-ADL) and blood tests, at baseline, at 12 weeks and after 24 weeks of treatment. Inclusion criteria were genetical diagnosis of FRDA, age ≥ 18 years and mFARS < 80. Exclusion criteria included severe hepatic and renal impairment, and severe heart failure. Each patient received oral omaveloxolone at a dose of 150 mg/day. Results: Twenty patients (65% females) affected by FRDA aged 40.6 ± 12.6 years and a duration of disease of 24.9 ± 9.5 years were treated with omaveloxolone and followed up for 25.2 ± 8.0 weeks. The drug was safe with no significant adverse events during the first 24 weeks and without discontinuations. Indeed, asymptomatic, and transient liver transaminase elevation occurred in 50% of patients. Cardiac function was stable, as well as NT-proBNP and lipids. Clinical scales did not show any significant difference during follow-up, but a significant reduction in IL-6 was reported. Conclusions and discussion: Omaveloxolone seems to be safe and well-tolerated in adult FRDA patients in the real-life setting. No significant worsening of symptoms was observed with no signs of progression, as well as the improvement of inflammatory biomarkers after 24 weeks of treatment, but no predictive factors for the disease response have been identified. However, the short duration, and the small sample size limit the generalizability of the results. Further studies with longer observation are needed to clearly define the efficacy of omaveloxolone in FRDA.