FDA Approves First Therapy for Friedreich’s Ataxia

Rare Daily Staff

The U.S. Food and Drug Administration approved Reata Pharmaceuticals’ Skyclarys as the first and only drug to treat patients with Friedreich’s ataxia, a rare and progressive neuromuscular disease.

The approval is for use in adults and adolescents aged 16 years and older with Friedreich’s ataxia. The FDA granted a rare pediatric disease priority review voucher to Reata as a result of the approval.

“The approval of Skyclarys, the first therapy specifically indicated for the treatment of Friedreich’s ataxia, is an important milestone for patients affected by this disease as well as their families and caregivers,” said Warren Huff, Reata’s CEO. “As a company, this is a transformative milestone that highlights our commitment to developing and commercializing novel therapies for patients with severe diseases with few or no approved therapies.”

Friedreich’s ataxia is an ultra-rare, inherited neurodegenerative disorder that is typically diagnosed during adolescence. Patients with Friedreich’s ataxia experience progressive loss of coordination, muscle weakness, and fatigue, which commonly progresses to motor incapacitation and wheelchair reliance by their teens or early twenties, and eventually death. Friedreich’s ataxia affects approximately 5,000 diagnosed patients in the United States.

Skyclarys (omaveloxolone) is an oral, once-daily medication that activates Nrf2 and addresses mitochondrial dysfunction, oxidative stress, and chronic inflammation. Skyclarys has received Orphan Drug, Fast Track, and Rare Pediatric Disease designations from the FDA. The company’s application to market for omaveloxolone is under review in Europe by the European Medicines Agency. The European Commission has granted Orphan Drug designation in Europe to omaveloxolone for the treatment of Friedreich’s ataxia.

The approval of Skyclarys is 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.

MOXIe Part 2 was a randomized, double-blind, placebo-controlled study. Patients with genetically confirmed Friedreich’s ataxia and baseline modified Friedreich’s Ataxia Rating Scale (mFARS) scores between 20 and 80 were randomized 1:1 to receive placebo or 150 mg of Skyclarys daily. The primary endpoint was change from baseline in mFARS score compared to placebo at Week 48 in the Full Analysis Population of patients without severe pes cavus, a foot morphology. The mFARS is a clinical assessment tool to assess patient function and is used in clinical trials to assess the efficacy of investigational products for use in Friedreich’s ataxia.

Treatment with Skyclarys resulted in statistically significant lower mFARS scores (less impairment) relative to placebo at Week 48. The placebo-corrected difference between the two groups was -2.41 points. The most common adverse reactions in MOXIe Part 2 (≥20% and greater than placebo) were elevated liver enzymes (AST/ALT), headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain.

Photo: Warren Huff, CEO of Reata Pharmaceuticals