Friedreich’s ataxia is a rare neuromuscular disease that affects approximately 5000 patients in the United States.
The FDA has approved omaveloxolone (Skyclarys; Reata Pharmaceuticals) for the treatment of Friedreich’s ataxia, an ultra-rare, progressive, neuromuscular disease, in patients aged 16 years and older. Additionally, the FDA granted a rare pediatric disease priority review voucher for omaveloxolone following this approval for adults and adolescents.
"The approval of [omaveloxolone], 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, CEO of Reata Pharmaceuticals, in a press release. "We are grateful to Friedreich’s ataxia patients, investigators, US regulators, and our scientists and employees who made this approval possible. 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. We look forward to delivering [omaveloxolone] to eligible patients as quickly as possible."
Typically diagnosed during adolescence, Friedreich’s ataxia is an inherited neurodegenerative disorder that causes progressive loss of coordination, muscle weakness, and fatigue and affects approximately 5000 diagnosed US patients. These patients commonly experience a progression of the disease to motor incapacitation and wheelchair reliance, which often occurs in their teens or by their early twenties.
“Friedreich's ataxia is a debilitating neuromuscular disease that progressively robs patients of their mobility and independence,” said Susan Perlman, MD, clinical professor, Department of Neurology, David Geffen School of Medicine, UCLA, in a press release. “The approval of [omaveloxolone] 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 of omaveloxolone is supported by both the results of the MOXIe Part 2 trial—a randomized, double-blind, placebo-controlled study—and a post hoc propensity-matched analysis of the open-label MOXIe Extension trial.
During the MOXIe Part 2 trial, patients who have genetically confirmed Friedreich’s ataxia with a baseline modified Friedreich’s ataxia rating scale (mFARS) score of between 20 and 80 were randomized 1:1 to receive either placebo or 150 mg of omaveloxolone daily. mFARS, a clinical assessment tool to assess patient function, is used to assess drug efficacy in the treatment of Friedreich’s ataxia during clinical trials, with lower scores signifying less impairment.
The primary endpoint of the MOXIe Part 2 trial was a change from baseline in mFARS score compared to placebo at week 48 in the full analysis population of patients without severe pes cavus (n=82). The data showed that treatment with omaveloxolone resulted in statistically significant lower mFARS scores relative to placebo at week 48. When accounting for the placebo-corrected difference between the 2 groups, the score was -2.41 points with a p-value of 0.0138. The most common adverse events during MOXIe Part 2 were elevated liver enzymes, headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain.
In the post hoc propensity-matched analysis of the open-label MOXIe Extension trial, the progression of patients—based on their mFARS score—who were treated with 150 mg of omaveloxolone daily was compared to the progression of propensity score-matched untreated patients from the Clinical Outcome Measures in Friedreich’s ataxia (FA-COMS) study. FA-COMS was the largest natural history study of Friedreich’s ataxia.
In the MOXIe Extension study, patients with at least 1 post-baseline assessment (n=136) were matched 1:1 with patients from the FA-COMS study (n=136). Lower mFARS scores were observed in patients treated with omaveloxolone after 3 years relative to the matched set of untreated patients from the FA-COMS study. However, the authors note that these exploratory analyses should be interpreted with caution due to the limitations of data being collected outside of a controlled study, which can lead to confounding.
"Today’s approval of [omaveloxolone] represents a significant milestone in our effort to advance research and achieve treatments for Friedreich’s ataxia," said Jen Farmer, CEO at Friedreich's Ataxia Research Alliance, in a press release. "The entire Friedreich's ataxia community including patients, clinicians, scientists, pharmaceutical companies, government agencies, and others have worked collaboratively for decades to enable therapeutic development for this debilitating disease. Today, we celebrate the impact of an engaged patient community, and we are grateful to the FDA and Reata for working together on the approval of [omaveloxolone], the first therapy approved in the United States for adult and adolescent patients aged 16 years and older with Friedreich's ataxia.”
Reata Pharmaceuticals Announces FDA Approval of SKYCLARYS™ (Omavaloxolone), the First and Only Drug Indicated for Patients with Friedreich’s Ataxia. Plano, TX: Reata Pharmaceuticals; February 28, 2023. Accessed March 1, 2023. https://www.businesswire.com/news/home/20230228006450/en