Elampretide Fails to Meet Primary End Points in Primary Mitochondrial Myopathy Trial


After promising results in prior phase 2 study, Stealth BioTherapeutics’ elampretide has failed to show change in the 6-minute walk test and Primary Mitochondrial Myopathy Symptom Assessment total fatigue score in the MMPOWER-3 trial.

Reenie McCarthy

Reenie McCarthy, CEO, Stealth BioTherapeutics

Reenie McCarthy

Stealth BioTherapeutics has announced that elampretide, its small mitochondrial-targeting tetrapeptide, has failed to achieve the primary end points in the phase 3 MMPOWER-3 clinical trial (NCT03323749) in primary mitochondrial myopathy (PMM).1

The co-primary end points assessed the changes in the 6-minute walk test (6MWT) and Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) total fatigue score. Although these marks were not met, the safety data suggest that treatment with elamipretide was well tolerated, with mostly mild to moderate adverse events (AEs).

"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," said Reenie McCarthy, CEO, Stealth BioTherapeutics, in a statement. "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.”

READ MORE: MMPOWER-3 Seeks to Resolve Cell Dysfunction in Primary Mitochondrial Myopathy

McCarthy added that Stealth is planning to meet with the FDA in early 2020 to continue conversations about moving forward in its Barth syndrome program, as well as dry age-related macular degeneration (AMD). In Barth syndrome, they observed significant improvement in cardiac stroke volume during an open-label extension study. In AMD, enrollment is ongoing for a phase 2b clinical trial in geographic atrophy after observing improvement in visual function during phase 1 study.

“We are also progressing our pipeline of second-generation mitochondrial therapeutics, with lead pipeline compound SBT-272 entering phase 1,” McCarthy said.

In November 2017, shortly after the FDA granted the treatment an orphan drug designation and days before it was awarded fast track designation for Barth syndrome, Stealth BioTherapeutics announced it was initiating the MMPOWER-3 a dose of 40 mg administered as a 0.5-mL injection for 24 weeks. It was to be followed by an open-label extension where patients may receive the treatment for up to 144 weeks.

At the time the MMPOWER-3 trial was announced in early 2019, Bruce H. Cohen, MD, the director of the Neurodevelopmental Science Center at Akron Children’s Hospital and investigator in the MMPOWER clinical program, emphasized that due to the lack of FDA-approved therapies, patients are left with little to address the debilitating muscle weakness and fatigue that impact their ability to go about their day-to-day tasks.2

“Although the early trial was not designed primarily to show benefits, there were some clues of benefit, again, to the point that there was a benefit when we were doing a phase 1 phase 2 study—the data was pointing in the right direction,” Cohen said. “The most recent [phase 2] trial demonstrated improvement in patient-reported outcomes, although did not show benefit in terms of the 6-minute walk test.”

He explained that the encouraging results from those prior phase 2 clinical trials in this population made the group optimistic about the investigational compound’s potential to treat patients with PMM. Thus, news of elampretide failing to meet these end points is a painful pill to swallow for clinicians who treat PMM, due to the lack of efficacious options available. Cohen noted that the vitamin regimens which physicians have relied on in the past have begun to fall to the wayside as data have suggested little to no efficacy for them.

“The clinical trials that have been done—and there haven’t been a lot of them—and the comprehensive reviews of some of those clinical trials have suggested that, in groups of patients, these supplements provide limited, if any, benefit,” he said. “That doesn’t mean that an individual patient wouldn’t benefit from a particular vitamin, cofactor or other supplements, only that in the studies done in groups of patients have failed to show any demonstrated benefit. Don’t read anything between these words—there’s nothing between the lines, that’s just the fact. A Cochrane review and other reviews demonstrate the lack of proven efficacy and many experts are walking slowly away from using these vitamins, supplements, and cofactors as treatment.”


1. Stealth BioTherapeutics Provides Update on Phase 3 Trial of Elamipretide in Primary Mitochondrial Myopathy [press release]. Boston, MA: Stealth BioTherapeutics; Published December 20, 2019. prnewswire.com/news-releases/stealth-biotherapeutics-provides-update-on-phase-3-trial-of-elamipretide-in-primary-mitochondrial-myopathy-300978082.html. Accessed December 23, 2019.

2. Stealth BioTherapeutics Initiates Phase 3 Study of Elamipretide in Patients with Primary Mitochondrial Myopathy [press release]. Boston, MA: Stealth BioTherapeutics; Published November 6, 2017. stealthbt.com/2017/11/06/stealth-biotherapeutics-initiates-phase-3-study-elamipretide-patients-primary-mitochondrial-myopathy. Accessed December 23, 2019.

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