Elamipretide Failed to Meet Promise of Earlier Trial Results for Primary Mitochondrial Myopathy, Data Show

Treatment candidate elamipretide did not meet expectations stemming from promising early trial results in patients with primary mitochondrial myopathy (PMM), data from a Phase 3 trial show.

Elamipretide is an experimental medicine designed to treat both inherited primary mitochondrial diseases and mitochondrial dysfunction in age-related diseases. It is manufactured by Stealth BioTherapeutics.

“We are deeply grateful to our patients and families, our investigators and their teams, and our advocacy partners for their support of this study, and share their disappointment that it did not meet the promise of our earlier trials in this indication,” Reenie McCarthy, Stealth’s CEO, said in a press release. “We remain confident in the promise of our platform and committed to our mission of improving the lives of people living with diseases involving mitochondrial dysfunction.”

Mitochondria produce the energy required to power our cells and are essential to the correct functioning of the muscles, brain, and eyes. Dysfunctional mitochondria lead to inherited mitochondrial diseases (e.g., PMM, Barth syndrome) and some age-related diseases (e.g., age-related dry macular degeneration).

Dysfunctional mitochondria produce abnormally high levels of oxidative factors that can damage a lipid called cardiolipin, which helps maintain the structural integrity of mitochondria.

Elamipretide works by binding to cardiolipin, protecting it from the damaging effects of oxidative stress, thereby preventing or lessening mitochondrial membrane dysfunction and ultimately cell death.

MMPOWER-3 (NCT03323749) evaluated the efficacy and safety of elamipretide over 32 weeks in 218 patients, ages 16 to 80, with primary mitochondrial myopathy. The trial was conducted at 28 clinical sites across North America, Europe, and Australia.

The primary endpoints to assess efficacy were the six-minute walk test and the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) Total Fatigue Score.

The six-minute walk test (6MWT) measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. PMMSA is a patient-reported outcome tool developed by Stealth in which individuals with PMM report their fatigue, muscle weakness, and other symptoms on a scale from 1 (least severe) to 4 (most severe).

Safety results showed that treatment with elamipretide was well-tolerated with most adverse events mild to moderate in severity, but it did not produce significant improvements in 6MWT and PMMSA assessments.

Stealth executives plan to meet with the U.S. Food and Drug Administration in early 2020 to discuss the company’s Barth syndrome program.

“We have observed significant improvement in cardiac stroke volume during open-label extension,” McCarthy said about the program, “and continue to enroll our Phase 2b clinical trial in geographic atrophy associated with dry age-related macular degeneration, in which we observed improvement in visual function during an earlier Phase 1 study.”

“We are also progressing our pipeline of second-generation mitochondrial therapeutics, with lead pipeline compound SBT-272 entering Phase 1,” she added.