FA Research Alliance Petitioning for Urgent Access to Omaveloxolone

With backing from a petition that is now circulating online, the Friedrich’s Ataxia Research Alliance (FARA) will ask Reata Pharmaceuticals and the U.S. Food and Drug Administration to make omaveloxolone (RTA 408) available to people living with Friedrich’s ataxia (FA) — for whom no approved treatments currently exist.

The petition — dubbed “a call to action” — asks Reata to submit a new drug application (NDA) for omaveloxolone to the FDA on an urgent basis, and for the regulatory agency to consider its approval based on evidence from existing clinical trials.

Open until Jan. 20, the petition is based on data from the MOXIe Phase 2 trial (NCT02255435), an ongoing, three-part study that demonstrated significant improvements in neurological function and in activities of daily living after nearly one year of omaveloxolone use.

“Given the positive clinical trial results, favorable safety profile of omav [omaveloxolone], and difficulty conducting clinical trials in FA especially during the current pandemic environment, we are asking FDA and Reata to work together to provide access to omav for people with FA as soon as possible,” FARA writes in its letter.

Omaveloxolone is an oral treatment candidate designed to activate Nrf2, a protein that helps restore the cellular energy production that becomes impaired over the course of FA.

MOXIe is a randomized and placebo-controlled trial evaluating the safety and efficacy of omaveloxolone in adolescents and adults with FA, ages 16-40. Part 1 of the study established the treatment’s recommended dose for further testing, and Part 2 evaluated its safety and efficacy in the longer term, for 48 weeks (nearly one year).

The Phase 2 part met its primary endpoint of improved neurological function, along with improvements in activities of daily living, among participants given the medication, compared with those in the placebo group. Neurological function was assessed by the modified Friedreich’s Ataxia Rating Scale (mFARS) and activities of daily living included walking, quality of sitting position, and swallowing.

However, the FDA determined that the results were not enough to support approval of the candidate therapy.

The agency and Reata therefore agreed on a separate, baseline-controlled study to obtain more data in support of an NDA. This crossover study involved patients who received a placebo in the first and second parts of MOXIe, and were then transitioned to the active treatment in the trial’s open-label extension study.

Because all patients received omaveloxolone and a placebo at different points in time, each participant could be used as his or her own control. The results showed that all patients showed a reversal of disease course and a significant improvement in mFARS scores when they started on omaveloxolone, compared with the placebo-period.

“Omaveloxolone improved motor function as measured by the modified Friedreich’s Ataxia Rating Scale in both Part 2 of the MOXIe study and the Baseline-Controlled study,” Warren Huff, Reata’s chairman and CEO said in a press release.

After reviewing the findings of the new study, however, the FDA remained unconvinced that the results strengthened those of Part 2 of the MOXIe study.

“Though we are disappointed in the FDA’s feedback on this program, we will carefully consider the potential paths forward for making omaveloxolone available to patients with FA,” Huff said.

The FDA has proposed additional analyses using only patients randomly selected to receive a placebo during Part 2 of the trial. But the agency has questioned the potential for such analyses to strengthen the study results, owing to the small number of patients available.

Nonetheless, the FDA remains interested in reviewing further results, as these may guide future development, according to Reata.

At the time, Reata said it intended to submit these analyses to the FDA and was considering how to proceed, including the possibility of a second pivotal study in patients with FA.

In their open letter to Reata and the FDA, however, FARA questions the need for additional trials, given the effects observed in trials to date.

“How robust of a finding in those trials must there be?” the letter asks.

The organization notes that people living with FA currently lack any approved treatment and that omaveloxolone’s observed improvements to neurological function merit its approval due to the “enormous effect on quality of life” caused by the condition’s neurological symptoms.

In their letter, FARA writes that “the patients and clinicians of the FA community are fully aware of the clinical trial results evaluating the use of omav in FA and are convinced that the results demonstrate meaningful benefit and low risk.”

FARA cites the 21st Century Cures Act in the petition.

“The voice of the patient is critical to the drug development process and FDA has been a strong advocate for identifying opportunities for the ‘patient voice’ to inform and guide drug development,” the letter says.