Omaveloxolone is a small molecule Nrf2 activator. Nrf2 is a transcription factor that activates the activity of genes involved in promoting mitochondrial function. It has been shown to stop inflammation by reducing oxidative stress and blocking pro-inflammatory events, which are involved in the impaired function of FA patients.
Omaveloxolone is being developed by Reata in collaboration with AbbVie as a potential treatment for people with Friedreich’s ataxia. The U.S. Food and Drug Administration (FDA) granted orphan drug status to omaveloxolone for the treatment of FA in June 2017. The FDA’s orphan drug program, designed for rare diseases that affect fewer than 200,000 people in the U.S., provides tax and development incentives to companies, as well as seven years of market exclusivity in the U.S.
“Friedreich’s ataxia is a severe neurological disorder that profoundly impacts patients and their families,” Warren Huff, Reata’s CEO and president, said in a press release. “Based on the results from Part 1 of MOXIe, we are optimistic that Part 2 of the MOXIe trial could position omaveloxolone to become the first therapy approved for patients with Friedreich’s ataxia.”
“With the initiation of Part 2 of MOXIe, Reata has launched three pivotal programs in the last 12 months,” Huff added.
To evaluate the safety, effectiveness, and pharmacodynamics (the drug’s effects and mechanism of action) of oral omaveloxolone, Reata initiated MOXIe in 2015 — a two-part randomized, placebo-controlled Phase 2 clinical trial (NCT02255435). The trial is expected to be completed in 2019.
Friedreich’s ataxia patients are still being enrolled in the trial, which is being conducted at seven sites in the U.S., as well as in Australia, Austria, and the U.K. For information, visit this site.
The first part of the trial was a dose-escalation study that evaluated the safety of omaveloxolone in 69 patients. Patients were given oral, escalating doses, starting at 5 mg and ending at 300 mg, once daily for 12 weeks to determine which dose was the maximum tolerated by patients.
Results suggested that omaveloxolone induced Nrf2 with improved mitochondrial and neurological function. And all doses improved neurological function, with the 160 mg dose showing the maximum therapeutic effect.
The second part of the trial, which has now enrolled its first patient, is a parallel-group study designed to evaluate the safety and efficacy of 150 mg of omaveloxolone in nearly 100 Freidreich’s ataxia patients who will be randomized to receive either omaveloxolone or placebo.
The primary endpoint of this part of the trial will be the change from baseline in the modified Friedreich’s Ataxia Rating Scale (mFARS) of omaveloxolone compared to placebo at 48 weeks.
Additional objectives include analyzing change from baseline in peak work during maximal exercise testing, Patient Global Impression of Change, and Clinical Global Impression of Change.
Those who complete the MOXIe study will be eligible to enter an extension trial that will assess the long-term safety and tolerability of omaveloxolone. Although patients will not know which treatment they were previously given, in the extension study everyone will receive open-label omaveloxolone at 150 mg once daily.