First Treatment Approved for Rare Neurodegenerative Disorder

The FDA approved omaveloxolone (Skyclarys) for the treatment of Friedreich’s ataxia in patients ages 16 and older, making it the first approved treatment for this rare progressive neurodegenerative disorder, the agency said Tuesday.

Friedreich’s ataxia is the most common form of hereditary ataxia in the U.S., affecting about one in every 50,000 people. Patients have progressive loss of coordination, muscle weakness, and fatigue, which can lead to motor incapacitation and, eventually, death. The average age at death is 37.5.

“Friedreich’s ataxia is a debilitating neuromuscular disease that progressively robs patients of their mobility and independence,” said Susan Perlman, MD, of the David Geffen School of Medicine at the University of California Los Angeles, in a press release from drug maker Reata Pharmaceuticals. “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.”

Omaveloxolone, an Nrf2 activator, has been shown to improve mitochondrial function, restore redox balance, and reduce inflammation in models of Friedreich’s ataxia. The drug is a once-daily oral medication.

The FDA’s decision — announced on February 28, Rare Disease Day — was based on results from the phase II MOXIe trial, which randomized patients ages 16 to 40 with genetically confirmed Friedreich’s ataxia and baseline modified Friedreich’s Ataxia Rating Scale (mFARS) scores between 20 and 80 to placebo or omaveloxolone 150 mg daily. The mFARS assesses swallowing and speech, upper limb coordination, lower limb coordination, and upright stability.

A total of 40 omaveloxolone patients and 42 placebo patients were included in the full analysis. At 48 weeks, changes from baseline in mFARS scores in the omaveloxolone group (-1.55 points) and the placebo group (0.85 points) yielded a difference between groups of -2.40 points (P=0.014).

In an open-label extension for up to 3 years, patients treated with omaveloxolone had better mFARS scores compared with a matched set of untreated patients from a natural history cohort.

Transient reversible increases in aminotransferase levels were seen in the omaveloxolone group, without increases in total bilirubin or other signs of liver injury. Headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain also occurred. Cholesterol should be monitored during treatment; full prescribing information outlined precautions and possible drug interactions.

Omaveloxolone will carry a list price of $370,000 annually, Reata Pharmaceuticals said. The company has also submitted an application for approval in Europe.

“We are hopeful that this is the first of several approved therapies,” said Jennifer Farmer, MS, chief executive officer of the Friedreich’s Ataxia Research Alliance (FARA), in a press release.

“FARA has always known that treating Friedreich’s ataxia would require a cocktail of multiple approaches,” Farmer noted. “We are excited that there is an established path to approval, and we remain committed to bringing effective therapies forward for all people living with Friedreich’s ataxia.”