Postive Trial Results of Elamipretide for Primary Mitochondrial Myopathy Reported by Stealth

Boston, Massachusetts-based clinical-stage biopharma Stealth BioTherapeutics has released positive results from the MMPOWER Phase 2 trial, a double-blind, dose-ascending, placebo-controlled study investigating the safety, tolerability, and efficacy of its lead drug candidate elamipretide for treating primary mitochondrial myopathy (muscle weakness) in genetically confirmed mitochondrial disease patients.

The trial evaluated 36 patients ages 16 to 65 in three dose cohorts. Primary endpoints were improvement in distance walked in six minutes, safety, and tolerability. Trial findings showed a statistically significant improvement with elamipretide (formerly known as MTP-131) in the distance walked in six minutes — a primary efficacy endpoint of the study and a standard accepted test of functional exercise capacity.

Stealth’s research focus is on bringing mitochondrial therapies to patients to treat both rare and common diseases. Elamipretide is designed to modify disease by preserving energetics and restoring normal energy production in mitochondria, while decreasing oxidative stress. Mitochondria are tiny organelles composed of enzyme packages that transform nutrients into cellular energy, and are found in almost every cell in the body. Mitochondria are responsible for creating more than 90 percent of the cellular energy, necessary to sustain life and support growth.

The promising results of elamipretide therapy from the MMPOWER trial were presented at the United Mitochondrial Disease Foundation (UMDF) symposium Mitochondrial Medicine 2016 recently in Seattle, Washington.

“The muscle weakness, exercise intolerance, and heightened fatigue experienced by patients with primary mitochondrial disease can make simple daily tasks very challenging,” said Dr. Amel Karaa, an investigator on the trial and an internist and clinical geneticist at Massachusetts General Hospital, in a press release. “These findings demonstrate the potential for elamipretide to help improve their ability to perform everyday activities.”

She said the team looks forward to additional studies of the compound in upcoming trials of primary mitochondrial disease.

The conference presentation showed an association between elamipretide treatment at 0.25 mg/kg per hour, the highest dose studied in the trial, and a statistically significant improvement in the six-minute walk test (6 MWT). Additionally, treatment with elamipretide generated the greatest 6 MWT distance improvement in patients who had been most impaired at baseline, and a positive dose-dependent trend was indicated as dosages increased. Treatment with elamipretide was also well tolerated, and no serious adverse events were observed.

The U.S. FDA granted elamipretide fast track designation in January 2016 for the treatment of primary mitochondrial myopathy in patients with genetic mitochondrial diseases for which there are currently no FDA-approved treatments.

Genetic mitochondrial diseases are a diverse group of rare inherited disorders characterized by systemic mitochondrial dysfunction that impairs patient health and well-being. Mitochondrial disease, which can be congenital or develop later in life, causes debilitating physical, developmental, and mental disabilities. Its symptoms may include poor growth, learning disabilities, loss of muscle coordination, muscle weakness and pain, seizures, vision and/or hearing loss, gastrointestinal issues, and organ failure.

In adults, many diseases related to aging have also been associated with mitochondrial dysfunction, including type 2 diabetes, Parkinson’s disease, atherosclerotic heart disease, stroke, Alzheimer’s disease, some cancers, and other disorders.

Stealth says it plans to initiate the MMPOWER-2 extension study, “A Study to Evaluate the Safety, Tolerability, and Efficacy of Subcutaneous Injections of Elamipretide (MTP-131) in Subjects With Genetically Confirmed Mitochondrial Disease Previously Treated in the Stealth BioTherapeutics SPIMM-201 Study,“ later this year for patients who participated in MMPOWER to evaluate additional efficacy endpoints and a longer elamipretide dosing schedule. The study is currently enrolling participants by invitation only.

“Based on positive data from MMPOWER and anticipated learnings from MMPOWER-2, we will be initiating discussions with the FDA to develop a Phase 3 trial to better characterize the potential benefits of elamipretide in patients with primary mitochondrial disease,” said Stealth BioTherapeutics CEO Reenie McCarthy. “As a leader in mitochondrial medicine, we are committed to developing innovative therapies for rare primary mitochondrial diseases, as well as for common diseases of aging in which impaired mitochondrial function is a final common pathway. We look forward to sharing findings from ongoing studies in skeletal muscle and ophthalmic disorders later this year.”

“We are thrilled with the encouraging results from the MMPOWER trial presented at this year’s symposium,” said UMDF Executive Director and CEO Charles A. Mohan Jr. “The UMDF and the broader advocacy community look forward to fully supporting the upcoming Phase 3 trial.”