Patients previously randomized to omaveloxolone in the core study period continued to show no worsening on modified Friedrich Ataxia Rating Scale relative to their original baseline after nearly 2.5 years of treatment.
Results of the delayed-start study presented at the International Parkinson and Movement Disorders Society (MDS) Virtual Congress 2021, September 17-22, showed continued positive effect of treatment with omaveloxolone (Reata Pharmaceuticals) in patients with Friedrich ataxia (FA).1
The results, presented by David R. Lynch, MD, PhD, professor of neurology, University of Pennsylvania Perelman School of Medicine, showed a difference in modified Friedrich’s Ataxia Rating Scale (mFARS) of –2.18 points (±0.96) between the omaveloxolone and placebo groups at the end of the end of the placebo-controlled MOXIe Part 2. These differences were preserved at the end of the delayed-start period (–2.92 points [±2.13]).
MOXIe (NCT02255435), a 2-part study designed to evaluate the safety and efficacy of omaveloxolone, is the largest global interventional trial ever conducted in FA. After completing either part of the study, patients were invited to join the open-label extension study, where investigators and patients remained blinded to prior patient treatment assignments. Here, Lynch and colleagues report all available data from both the 48-week placebo-controlled period (MOXIe Part 2) and the 72-week open-label, delayed-start period (MOXIe extension).
In total, 97% (73 of 75) of patients in the Full Analysis Set who completed MOXIe Part 2 enrolled in the extension study, of which 39 were previously randomized to placebo and 34 were previously randomized to omaveloxolone. Similar annualized mFARS slopes were observed between the placebo to omaveloxolone (0.29 points [±0.68]) groups and omaveloxolone to omaveloxolone groups (0.17 points [±0.61]); however, both slopes were less than the expected gain of 1.9 points per year observed in natural history data. After nearly 2 and a half years of treatment, investigators noticed that patients previously randomized to omaveloxolone in MOXIe Part 2 continued to show no worsening in mFARS relative to their original baseline.
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Adverse events (AEs) recorded were generally mild to moderate in intensity. In total, 8 patients (5.4%) discontinued study due to AEs. ALT increase (n = 26; 18%), headache (n = 22; 15%), upper respiratory tract infection (n = 23; 15%), nausea (n = 22; 15%), fatigue (n = 15; 10%), and abdominal pain (n = 15; 10%) were the AEs documented. In total, 9 patients (6.1%) reported serious AEs that were considered treatment-emergent; however, no new safety signals were observed in the extension study to date.
Original topline results from MOXIe published in 2019 showed a statistically significant 2.40-point improvement in mFARS score for those treated with the investigational agent compared with placebo (P = .014).2 A mean improvement of 1.55 points in mFARS score from baseline was recorded in the treatment group, while patients treated with placebo experienced a mean worsening of +0.85 points. When patients without pes cavus were included in the analysis (n = 103), a statistically significant mean 1.93-point improvement on mFARS was recorded compared with placebo (P = .034).
After a preliminary review of briefing materials for an upcoming Type C meeting, the FDA told Reata that a pre-NDA meeting is the most appropriate format for a discussion of the development program for omaveloxolone in FA.3 The company announced in May that it plans to follow the FDA’s request to withdraw the current request for a Type C meeting and submit a request for a pre-NDA meeting as soon as practicable. The announcement follows a petition from the Friedrich’s Ataxia Research Alliance, which was signed by more than 74,000 people worldwide, asking that Reata submit a new drug application for omaveloxolone on an urgent basis and that the FDA consider its approval based on existing evidence from the MOXIe clinical trial.
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