Friedreich’s ataxia is the most common type of hereditary ataxia affecting one in 50,000 people in the US. But with Skyclarys (omaveloxolone), the first and only drug to treat Friedreich’s ataxia in patients aged 16 years and older, Reata Pharmaceuticals has developed a new treatment option to improve neurological function. This US Food and Drug Administration (FDA)-approved drug was also awarded a rare pediatric disease priority review voucher.
“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,” said Dr. Susan Perlman, a clinical professor in the Department of Neurology at the David Geffen School of Medicine, UCLA, in a press release.
Skyclarys has received Fast Track, Orphan Drug and Pediatric Rare Disease designations in the US. In the EU, Skyclarys has been granted the Orphan Drug designation and is under review by the European Medicines Agency (EMA).
What is Friedreich’s Ataxia?
Friedreich’s ataxia is an ultra-rare, progressive, neuromuscular disease that causes damage to the nervous system and affects the body’s movements. It is caused by a mutation in the FXN gene, which is responsible for the production of the protein frataxin.
Patients with this disease experience impaired muscle coordination (ataxia), difficulty walking, poor balance and fatigue. Usually diagnosed during adolescence (10-15 years), Friedreich’s ataxia shortens life expectancy, causing the patient to be wheelchair bound within the first 10 to 20 years of diagnosis and most often leading to death.
“Friedreich’s ataxia is a debilitating neuromuscular disease that progressively robs patients of their mobility and independence,” added Dr. Perlman in the same press release.
Omaveloxolone Clinical Trials
Skyclarys is an oral medication that contains omaveloxolone, an activator of the nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway. Previous animal model studies of Friedreich’s ataxia showed a dysfunction in the regulation of Nrf2 signaling, a pathway associated with reduced inflammatory response and improved mitochondrial function. Another study showed that omaveloxolone restored mitochondrial function in fibroblasts from Friedreich’s ataxia patients.
Skyclarys was approved based on the results of the MOXIe Part 2 clinical trial. This was followed by the post-hoc extension study, which assessed the long-term safety and tolerability of omaveloxolone in eligible patients. In the MOXIe Part 2 trial, 82 patients with Friedreich’s ataxia (as confirmed by genetic testing) were randomized 1:1 to receive either 150 mg omaveloxolone or placebo.
A modified version of the Friedreich’s Ataxia Rating Scale (mFARS) was used as the primary endpoint. Clinicians use the mFARS clinical assessment tool to measure neurological function in patients. Patients who received Skyclarys showed significantly lower impairment compared with placebo as evidenced by low mFARS scores at week 48.
In addition, 136 patients from the extension study were matched one on one with patients from the multicenter natural history FA-COMS study. Over a period of three years, patients treated with Skyclarys displayed improved mFARS scores compared with matched untreated patients from the FA-COMS study.
Though Reata has been in business for over two decades, Skyclarys is the company’s first FDA-approved product. The company’s other disease targets include another neurological condition, diabetic peripheral neuropathic pain, and two forms of hereditary kidney disease, autosomal dominant polycystic kidney disease and Alport syndrome.
Reata Pharmaceuticals expects Skyclarys to be available for commercial supply in the second quarter of 2023. “We look forward to delivering Skyclarys to eligible patients as quickly as possible, ” said Warren Huff, chief executive officer of Reata Pharmaceuticals.