The U.S. Food and Drug Administration (FDA) agreed that Reata Pharmaceuticals can use the modified Friedreich’s Ataxia Rating Scale (mFARS) as a primary endpoint for the second part of its possibly pivotal Phase 2 clinical trial assessing omaveloxolone in treating Friedreich’s ataxia, the company announced.
This decision followed Reata’s request that the FDA confirm its earlier guidance that, depending on trial results, mFARS could support omaveloxolone approval. The oral therapy is in line to possibly become the first FDA-approved treatment for people with Friedreich’s ataxia (FA).
The FDA also indicated it may grant either accelerated or full approval based on the trial’s overall results and the strength of its data. It recommended that Reata extend treatment duration in this part of the MOXIe trial, and add a patient-reported or performance-based outcome to the study as another measure of effectiveness.
“This communication from the FDA confirms our view that mFARS could support approval in Friedreich’s ataxia, and we believe that it leaves open an opportunity for full approval if the trial produces robust clinical results,” Colin Meyer, MD, Reata’s chief medical officer, said in a press release. “We remain committed to rapidly advancing omaveloxolone so that it could be the first approved treatment for this serious, debilitating and life-shortening condition.”
Part 2 of the MOXIe trial is a double-blind, randomized, placebo-controlled, and multi-center study to evaluate the safety, tolerability and effectiveness of omaveloxolone in patients with FA, a rare inherited nervous system disorder.
The trial will enroll about 100 FA patients, ages 16 to 40, randomized evenly to either 150 mg of omaveloxolone or placebo (the total enrollment goal is about 170). Its primary goal is the change from baseline in mFARS of patients treated with omaveloxolone or placebo at 48 weeks. Additional goals include the change from baseline in peak work during maximal exercise testing, Patient Global Impression of Change, and Clinical Global Impression of Change.
Results from Part 1 of the MOXIe trial demonstrated that omaveloxolone activated a protein called Nrf2 — which is suppressed in FA patients — and this was linked to improvements in their mitochondrial and neurological functions. Omaveloxolone targets this transcription factor to restore mitochondrial function, reduce oxidative stress, and resolve inflammation.
In that first part, 69 FA patients received escalating doses of omaveloxolone or placebo, between 5 and 300 milligrams, to evaluate the maximum tolerated dose. Researchers determined that a 160 mg dose had the strongest therapeutic effect. Results showed improved neurological functions at 12 weeks of treatment at that dose in patients without foot deformities. This is equivalent to recovering one to two years of disease progression, the company announced in June.
Reata has initiated screening patients for study, and plans to randomize participants later this year, with the trial to finish by February 2019. Researchers will conduct the study in five states — California, Florida, Georgia, Iowa, Ohio and Pennsylvania — as well as at sites in Australia, Austria, and the U.K.
Omaveloxolone, formerly known as RTA 408, was developed specifically to target FA’s biological features by activating a protein called Nfr2, which is less active in FA patients.
Earlier this month, Reata, based in Irving, Texas, announced that a stock sale had generated $115.9 million to support the clinical development of omaveloxolone and other drugs in its pipeline. The FDA granted orphan drug status to omaveloxolone in late June to treat FA.