Reata Submits New Data to FDA to Support Omaveloxolone Application

The agency has expressed concerns about the therapy's effectiveness

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Note: This story was updated on Aug. 10, 2022, to add the U.S. Food and Drug Administration has extended its review of the omaveloxolone application through the end of February.

Following a meeting with the agency, Reata Pharmaceuticals has submitted new data to the U.S. Food and Drug Administration (FDA) in support of its application to approve omaveloxolone, an experimental once-daily oral treatment for Friedreich’s ataxia.

The new data include long-term findings for up to nearly three years of treatment in the MOXIe clinical trial and comparative analyses that show omaveloxolone slows Fiedreich’s ataxia’s progression compared to what would be expected in patients without treatment.

Reata completed its submission of a new drug application (NDA) for omaveloxolone earlier this year. The FDA gave the application priority review and stated it plans to hold an advisory committee meeting to discuss the application. A decision from the FDA was originally expected by the end of November, but the administration is extending its review to account for the new data, so a decision is now expected by Feb. 28, 2023.

Reata recently completed a mid-cycle communication meeting with the FDA. The aim of this type of meeting is for the FDA to give an update on the NDA’s status and identify any issues.

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According to a press release from Reata, the FDA didn’t identify any significant new issues in the meeting. There are so far no significant clinical safety issues, though the agency’s review of omaveloxolone’s effects on heart health is still ongoing. The FDA “continues to have concerns regarding the strength of the efficacy evidence,” according to Reata.

Reata proposed submitting new data to help address these concerns and the FDA agreed that the company could submit the data to the updated NDA.

“We have submitted these additional data and analyses to the FDA and are continuing to prepare for the upcoming Advisory Committee meeting,” Warren Huff, CEO of Reata, said.

The NDA for omaveloxolone was supported by data from a clinical trial called MOXIe (NCT02255435). The first part of the study determined the optimum dose of the therapy, then 103 people with Friedreich’s ataxia were given either omaveloxolone or placebo for 48 weeks, nearly a year.

Results showed omaveloxolone outperformed a placebo on the modified Friedreich’s Ataxia Rating Scale (mFARS), a standardized measure of disease progression. On average, mFARS scores increased (worsened) by 0.85 points for patients on a placebo, whereas they decreased by 1.55 points for those on omaveloxolone — a between-group difference of more than 2 points.

At the trial’s end, participants had the option to enter an open-label extension where all are being treated with omaveloxolone.

The newly submitted data include data up through March 2022 that show this between-group difference was maintained over nearly three years of treatment. At 144 weeks (almost 2.8 years), mFARS scores were on average 2.58 points lower for patients who had been on omaveloxolone since the study’s start, compared to those who took a placebo in the main trial before switching to omaveloxolone in the open-label extension. Similar between-group differences also were seen at earlier timepoints.

The new data also include a propensity-matched analysis, where each participant in MOXIe was matched up with a similar person in FA-COMS (NCT03090789), a natural history study that tracked Friedreich’s ataxia’s progression in the absence of treatment. This was a post hoc analysis, meaning it was designed after trial data had already been collected.

Results showed that, after three years, the average mFARS score increased by 3 points for patients on omaveloxolone in MOXIe, compared to 6.61 for patients without treatment in FA-COMS. Statistical analyses showed the rate of progression was significantly slower, by approximately 55%, with omaveloxolone.

Omaveloxolone is designed to activate a protein called Nrf2 that’s important for the health of mitochondria, the cellular energy factories that are impaired in Friedreich’s ataxia.

The new data submitted to the FDA also include mechanistic data supporting Nrf2 activation as a therapeutic strategy in Friedreich’s ataxia, including data from MOXIe showing omaveloxolone boosted Nrf2 activity, and that the protein’s higher activity was associated with larger improvements in mFARS scores.

“We look forward to continuing to work with FDA on its review of our NDA for omaveloxolone for the treatment of patients with Friedreich’s ataxia, a rare, genetic, debilitating, and degenerative neuromuscular disorder with no approved therapies,” Huff said.