Reata Begins Rolling Submission of Omaveloxolone for FA
In a rolling submission, companies can submit individual sections of the application for review by the U.S. Food and Drug Administration (FDA) as soon as they are completed, rather than waiting to file the entire document at once, as is typical.
“Today’s announcement marks an important milestone in our efforts to advance the first therapy for patients with Friedreich’s ataxia, a serious and devastating disease,” Warren Huff, Reata’s president and CEO, said in a press release.
Omaveloxolone was granted fast track designation in late November, which provided Reata with access to more frequent communication with the FDA about the therapy’s development plan and approval path, as well as to a rolling submission. Additionally, if other criteria are met, the therapy may be eligible for accelerated approval and/or priority review.
Reata expects to complete the rolling submission by the end of March, which may then be followed by a review period of six months, rather than 10 months, if priority review is granted by the agency.
“We appreciate the FDA’s recognition of the potential of omaveloxolone for patients with Friedreich’s ataxia through its Fast Track Designation and guidance on the contents of the [application],” Huff said.
Omaveloxolone also received orphan drug designation in both the U.S. and European Union (EU) for the treatment of FA, which is meant to accelerate the therapy’s development and regulatory review by providing relevant support and financial benefits. It also ensures marketing exclusivity for seven years in the U.S. and 10 years in the EU upon regulatory approval, if granted.
Friedreich’s ataxia is caused by low levels of frataxin, an essential protein for the normal functioning of mitochondria, the cells’ powerhouses. Frataxin deficiency leads to mitochondrial problems and impaired energy production, oxidative stress, and chronic inflammation, ultimately resulting in progressive neurodegeneration.
A type of cellular damage, oxidative stress, results from an imbalance between the production of potentially harmful oxidant molecules and cells’ ability to clear them.
Omaveloxolone is a small, orally available molecule that works by activating Nrf2, a protein involved in restoring mitochondrial function, increasing antioxidant levels, and blocking inflammation. Nrf2’s function is impaired in FA patients.
As such, the therapy is expected to slow or prevent further neurodegeneration in people with FA.
The regulatory submission will be based on data from a global, two-part Phase 2 clinical trial, called MOXIe (NCT02255435), which tested omaveloxolone in 172 adolescents and adults, ages 16–40, with FA.
The study’s Part 1, involving 69 participants, established the therapy’s recommended dose at 150 mg once a day, while Part 2 assessed that dose’s safety and effectiveness against a placebo in 103 patients for 48 weeks (nearly one year).
Results from the second part showed that omaveloxolone was generally safe and well-tolerated and that it resulted in significant improvements in multiple measures of neurological function and in patients’ ability to perform daily activities.
Participants who completed the trial were given the opportunity to enroll in an open-label extension study, in which all are receiving the experimental therapy, at a dose of 150 mg, for a longer period. The trial is expected to conclude in December.
“I want to thank all the patients, families, and investigators who participated in the MOXIe trial and the extension phase of the study,” Huff said.
While the FDA initially declared MOXIe’s results were not strong enough to merit regulatory approval, the Friedreich’s Ataxia Research Alliance issued a petition — signed by more than 74,000 people worldwide — asking Reata to submit omaveloxolone for approval and the agency to consider its approval based on existing evidence.
After a preliminary meeting with the FDA to discuss the approval pathway of omaveloxolone, Reata announced it was planning to seek standard approval for the therapy, and that no additional clinical trial was planned prior to regulatory submission, planned for the beginning of this year.
In that meeting, the agency also said that, given FA’s seriousness and lack of treatment, Reata may be allowed to submit additional clinical and nonclinical data even after the application is officially submitted.