The US Food and Drug Administration has approved omaveloxolone (Skyclarys) to treat persons 16 years and older with Friedreich’s ataxia.
Friedreich’s ataxia is a degenerative neuromuscular disorder caused by mutations in the FXN gene which reduces the production of frataxin, a protein important for proper mitochondrial functions. The onset of symptoms varies greatly among patients but generally occurs between the ages of 5 to 18 years. Some of the more common symptoms include ataxia, fatigue, scoliosis, diabetes mellitus, and various heart conditions, including hypertrophic cardiomyopathy and arrhythmias. Omaveloxolone is the first treatment approved for Friedreich’s ataxia.
Omaveloxolone activates nuclear factor erythroid 2-related factor 2 (NrF2), a transcription factor that is impaired in patients with Friedreich’s ataxia.
The approval of omaveloxolone was largely based on 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 in which patients with Friedreich’s ataxia were randomized to receive placebo or omaveloxolone (150 mg) daily for 48 weeks. The primary endpoint was change from baseline in mFARS score and it was observed that patients treated with omaveloxolone had statistically significant lower mFARS scores compared to placebo at Week 48. The most common adverse events were elevated liver enzymes, headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain. Similar trends were observed in the open-label MOXIe Extension trial (i.e., lower mFARS scores compared to a matched set from a natural history study).
With this orphan drug approval, the developers (Reata Pharmaceuticals) received a Rare Pediatric Priority Review Voucher. The company can use this voucher for another drug under review by the FDA to have priority review. In other words, the FDA will have to review the medicine within 6 months instead of 10 months. For small companies like Reata Pharmaceuticals, this voucher is often sold to another company. Recently, Eiger Biopharmaceuticals sold their review voucher for $95 million.
Brigid Brennan of the Friedreich’s Ataxia Research Alliance (FARA) discusses Friedreich’s ataxia in the clip below.
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