FDA Approves First Therapy for Rare Neuromuscular Disease

The FDA has approved Skyclarys (omaveloxolone) to treat patients with Friedreich’s ataxia in adults and adolescents aged 16 years and older. With this approval, the FDA granted a rare pediatric disease priority review voucher.

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 and eventually death. Friedreich’s ataxia affects about 5,000 diagnosed patients in the United States.

Developed by Reata Pharmaceuticals, Skyclarys oral, once-daily activator of Nrf2, a transcription factor that induces molecular pathways that promote the resolution of inflammation by restoring mitochondrial function, reducing oxidative stress, and inhibiting pro-inflammatory signaling.

Skyclarys will be available in the second quarter of 2023 with a wholesale acquisition cost of $370,000. The company is offering Skyclarys through a patient support program, ReataReach, which will provide insurance and access support and commercial copay support. The company anticipates Skyclarys will be placed on a specialty tier, Dawn Bir, chief commercial officer, said in a conference. They anticipate that 60% of patients will have commercial insurance Reata will offer a $0 copay card, but regardless of coverage, no patient will face more than a nominal copay, Bir said.

Susan Perlman, M.D.

“Friedreich's ataxia is a debilitating neuromuscular disease that progressively robs patients of their mobility and independence,” Susan Perlman, M.D., clinical professor, department of Neurology, David Geffen School of Medicine, UCLA, said in a press release. “The approval of Skyclarys represents an important step forward in the treatment of Friedreich's ataxia, providing physicians with the first disease-specific treatment option approved for patients living with this ultra-rare and progressive disease.”

The approval 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 placebo-controlled study. The primary endpoint was change from baseline in Friedreich’s Ataxia Rating Scale score compared with placebo at week 48. The Friedreich’s Ataxia Rating Scale 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 most common adverse reactions in MOXIe Part 2 were elevated liver enzymes, headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain.

While there is no black box warnings or Risk Evaluation and Mitigation Strategies program associated with Skyclarys, the FDA has required post-marketing studies that include an assessment of drug-drug interaction, thorough QT, and a pregnancy lactation study. Reata will also sponsor a post-market registry study to assess long-term safety.