The encouraging results come from the first of the two-part MOXIe Phase 2 trial (NCT02255435) that is evaluating the drug’s efficacy and safety, as well as how omaveloxolone works in the body (pharmacodynamics) in FA patients.
In the first part of the MOXIe trial, 69 patients received escalating doses of omaveloxolone or placebo to evaluate the maximum tolerated dose between 5 and 300 milligrams.
In addition to the safety profile of the drug, peak workload during exercise is of primary interest. Patients will complete exercises while being monitored for workload, measured in watts per kg body weight. Clinicians are also evaluating patients using the modified Friedreich’s ataxia rating scale (mFARS), which monitors the adeptness of patients during daily activities.
The newly reported results from Part 1 of the MOXIe trial demonstrated that omaveloxolone induced Nrf2, which is suppressed in Friedreich’s ataxia patients, and that this was linked to improvements in patients’ mitochondrial and neurological function.
All doses of omaveloxolone improved patients’ neurological function as measured by the mFARS. The maximum therapeutic effect on the mFARS was observed at the 160 mg dose level. Therefore, 160 mg was determined as the optimal dose associated with pharmacodynamic measures of Nrf2 induction and improvements in patients’ mitochondrial function.
Twelve weeks of treatment at the 160 mg dose resulted in an improvement in the neurological functioning of patients without a foot deformity, which is equivalent to recovering one to two years of disease progression.
Across all patients, omaveloxolone did not improve peak work as measured during the maximal exercise test. However, in the subset of patients without foot deformity, omaveloxolone increased peak work across all doses, and again, the maximum effect was observed at the 160 mg dose level.
In the second part of the MOXIe trial, researchers hope to enroll 100 Friedreich’s ataxia patients who will be split among groups who receive 150 mg omaveloxolone or placebo. The scientists believe the 150 mg dose will produce similar effects to the 160 mg dose while decreasing the number of capsules per administration.
There were no safety issues reported in Part 1.
“We are very pleased that data from Part 1 of the MOXIe trial demonstrated clear evidence of biological activity that was associated with improvements in neurological function,” Colin Meyer, MD, chief medical officer of Reata, said in a press release.
“We believe these results are quite meaningful since omaveloxolone-treated patients had substantial improvements in mFARS scores from baseline and versus placebo with only 12 weeks of treatment,” he said. “The data suggest that omaveloxolone may not just slow disease progression but instead may promote the recovery of lost neurological function.”
Jennifer Farmer, executive director of the Friedreich’s Ataxia Research Alliance (FARA) said the alliance appreciates the work Reata and the study volunteers put into the “well-designed and robust dose-escalation study.”
“We find these results to be very exciting, and they are the ideal outcome for an early Phase 2 study,” she added. “They exceed expectations in terms of safety and by demonstrating dose-dependent and clinically meaningful activity that correlated with biological activity.”
Farmer said FARA and the FA community “encourage urgency” in advancing the trial to Part 2 for further evaluation of effectiveness and safety, “as there are no approved therapies to slow progression or improve symptoms for individuals living with FA. Every day counts for our patient families.”
These findings were recently presented by David Lynch, director of the Friedreich’s Ataxia Program at Children’s Hospital of Philadelphia, after a patient-focused drug development meeting hosted by FARA.
The second part of the MOXIe study is expected to begin in the second half of 2017.
Omaveloxolone (RTA 408) is a new treatment based on the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) signaling pathway. The drug activates Nrf2, leading to antioxidant target gene expression that may help reduce oxidative damage from Friedreich’s ataxia.
The MOXIe trial is sponsored by Reata Pharmaceuticals, with AbbVie and the Friedreich’s Ataxia Research Alliance as participating collaborators.