Reata Pharmaceuticals reported positive results from its registrational trial of omaveloxolone in patients with Freidreich’s Ataxia, a rare and progressive neuromuscular disease.
The results were reported less than a week after Reata bought back its rights to omaveloxolone and bardoxolone from AbbVie for $330 million, a move that was welcomed by the investment community.
Friedreich’s ataxia (FA) is an inherited autosomal recessive disorder caused by mutations in the FXN gene. Signs and symptoms usually begin in puberty and lead to progressive impaired muscle coordination, gradual loss of muscle strength and sensation in the arms and legs, muscle stiffness, and impaired speech. FA affects approximately 5,000 children and adults in the United States and 22,000 globally. Currently, there are no treatments approved by the U.S Food and Drug Administration for FA.
Omaveloxolone is an experimental, oral, once-daily activator of Nrf2, a transcription factor that induces molecular pathways that promote restoration of mitochondrial function, reduction of oxidative stress, and inhibition of pro-inflammatory signaling. The FDA and the European Commission have granted orphan drug designation to omaveloxolone for the treatment of Friedreich’s ataxia.
“The results of MOXIe represent a truly historic moment for the patients, families, and caregivers that comprise the Friedreich’s ataxia community,” said Ronald Bartek, president of the Friedreich’s Ataxia Research Alliance (FARA). “Based on the results reported today for omaveloxolone, we are hopeful that our community will finally have its first approved therapy that can slow this relentlessly progressive disease.”
FARA’s natural history study of FA was important in designing of the trial, and the advocacy group also participated in the trial.
The MOXIe pivotal trial of omaveloxolone in 103 patients with FA is an international, multi-center, double-blind, placebo-controlled, randomized phase 2 study. Patients treated with omaveloxolone demonstrated a statistically significant, placebo-corrected 2.40 point improvement in mFARS after 48 weeks of treatment compared to placebo, and the drug was generally reported to be well-tolerated. Based on these positive results, and subject to discussions with regulatory authorities, the company plans to proceed with the submission of regulatory filings for marketing approval in the United States and internationally.
The primary endpoint for the study was change in the mFARS score relative to placebo after 48 weeks of treatment. The mFARS is a physician-assessed neurological rating scale used to measure FA disease progression. It includes four sections that measure the patient’s performance of activities such as speaking and swallowing, upper limb coordination, lower limb coordination, and standing and walking. The FDA has indicated that mFARS is an acceptable primary endpoint to evaluate the effect of omaveloxolone for the treatment of patients with FA.
Omaveloxolone treatment met the primary endpoint of the study producing a statistically significant, placebo-corrected 2.40-point improvement (decrease) in mFARS. Patients treated with omaveloxolone experienced a mean improvement in mFARS of -1.55 points from baseline, while patients treated with placebo experienced a mean worsening in mFARS of +0.85 points from baseline. The observed placebo-corrected improvements in mFARS were time-dependent, increasing over the course of treatment with the largest improvement observed after 48 weeks of treatment.
Full results will be presented at a future meeting.
“The MOXIe trial with omaveloxolone is the first study to demonstrate a significant improvement in neurological function in patients with FA,” said Warren Huff, president and CEO of Reata. “We believe that the MOXIe findings announced today bring us closer to our goal of providing an urgently needed therapy to patients with FA.”
Photo: Warren Huff, president and CEO of Reata