Friedreichs Ataxia Treatment, Omaveloxolone, Receives EU Orphan Drug Designation

This week in the European Union, Friedreich’s ataxia received an orphan drug designation for omaveloxolone from the European Commission, which largely based its decision on the positive opinion from the Committee for Orphan Medicinal Products of the European Medicines Agency’s (EMA).

“Orphan drug designation from the EMA is an important recognition of the potential for omaveloxolone to become the first approved therapy for patients affected by this devastating disease,” said Warren Huff, Reata’s president and chief executive officer, in a recent statement.

Omaveloxolone is a second-generation member of the synthetic oleanane triterpenoid compounds put out by Reata Pharmaceuticals, Inc. In in vitro models, it displayed abilities to restore mitochondrial transmembrane potential in fibroblasts isolated from Friedreich’s ataxia patients.

Since Nrf2 signaling is significantly impaired in Friedreich’s ataxia, which is characterized by progressive nervous system damage due to degeneration in the nerve fibers in the spinal cord and peripheral nerves, omaveloxolone’s ability to cause Nrf2 activation has the potential to cause clinical benefits in patients with the disease.

The efficacy of omaveloxolone is further supported by the first part of the 2-part, international, multi-center, randomized, double-blind, placebo-controlled phase 2 trial, referred to as MOXIe.

"There are no currently-approved therapies for the treatment of FA," said Vineet Jindal, vice president, Strategy at Reata exclusively to Rare Disease Report®. "Results from part 1 of the Phase 2 MOXIe trial have shown that treatment of FA patients with omaveloxolone produced dose- and time-dependent improvements in their modified Friedreich’s Ataxia Rating Scale (mFARS) scores, which are a measure of the neurologic function of FA patients."

The trial consists of 172 Friedreich’s ataxia patients ranging in age from 16 to 40 years who are being administered omaveloxolone or placebo. For the first part of the study, investigators sought to evaluate the safety of omaveloxolone at various doses in patients with the disease. The various experimental arms include those receiving 2.5 mg orally once-daily for 2 weeks and then 5 mg once-daily for the duration of 10 weeks; and oral once-daily administration of10 mg, 20 mg, 40 mg, 80 mg, 150 mg, 160 mg, or 300 mg for the duration of 12 weeks. The second part of the trial aims to assess the safety and efficacy of the drug administered in a 150 mg dose. For this portion of the trial, patients will be randomized 1:1 to either receive omaveloxolone 150 mg or placebo.

Primary outcome measures for the trial include the change in the modified Friedreich's ataxia rating scale (FARS) as measured in the timeframe of 24 weeks and the change of peak workload (in watts/kg) during exercise testing as measured in the time frame of 12 weeks.

Furthermore, secondary outcomes measures include the change of peak workload (in watts/kg) during exercise testing as measured in the time frame of 24 weeks and the change in the modified Friedreich's ataxia rating scale (FARS) as measured in the time frame of 12 weeks.

Updated results from part 1 of the study indicate dose- and time-dependent improvements in the participants’ modified Friedrich’s Ataxia Rating Scale (mFARS) scores in those who were treated with omaveloxolone.

Reata is currently in the process of enrolling about 100 patients with Friedreich's ataxia for part 2 of the MOXIe trial; results are expected in second half of 2019.