Phase 2/3 Trial of Elamipretide to Treat Barth Syndrome Now Enrolling Patients

A Phase 2/3 clinical trial of elamipretide, a potential treatment for a rare mitochondrial disease known as Barth syndrome, is now enrolling patients, the therapy’s developer, Stealth BioTherapeutics, announced.

The TAZPOWER study (NCT03098797) will be conducted in McKusick-Nathans Institute of Genetic Medicine, at the Johns Hopkins University School of Medicine, and is expected to include 12 patients, ages 12 or older, with genetically confirmed Barth syndrome and stable symptoms, but impaired walking ability.

“Our understanding of Barth syndrome and how it manifests has evolved significantly, but current treatment efforts are still limited to the management of symptoms,” Hilary Vernon, an assistant professor of pediatrics at the McKusick-Nathans Institute and the study’s primary investigator, said in a press release. “The initiation of TAZPOWER represents an important milestone in the potential development of a disease-specific treatment option.”

Barth syndrome is a rare inherited mitochondrial disease that is almost exclusive to males. This disease is characterized by cardiac abnormalities, skeletal muscle weakness, recurrent infections due to low white blood cell (immune cell) counts, and delayed growth. It is caused by caused by genetic mutations in the TAZ gene, which encodes the protein tafazzin that is essential for the normal functioning of mitochondria.

“The severe problems experienced by patients with Barth syndrome are caused by misshapen and dysfunctional mitochondria, which reduce the energy production in the affected tissues. The resulting muscle weakness can lead to severe fatigue, heart failure and death,” said Doug Weaver, chief medical officer at Stealth. “In this study, we hope to show that elamipretide may have clinical benefit by improving function in these affected mitochondria.”

Elamipretide was designed to restore mitochondria’s ability to work as the cell’s power source. Due to its capacity to penetrate the inner membrane of mitochondria, the therapy as the potential to reduce the levels of damaging oxidative stress produced by mitochondria’s dysfunctional activity.

TAZPOWER trial is a placebo-controlled crossover study, designed to evaluate the effects of daily administration of elamipretide in patients with Barth syndrome. All participants will receive single daily subcutaneous injections of elamipretide or placebo for 12 weeks, followed by a four-week wash-out period. This will then be followed by additional 12 weeks of therapy, but this time the patients will switch the treatment received, with those previously given elamipretide now receiving a placebo and vice-versa.

The drug’s efficacy will be measured by changes in the distance that patients are able to walk during the 6-minute walk test (6MWT). Secondary endpoints will include other functional assessments (of muscle strength, balance, etc.), patient-reported outcomes, and overall treatment safety.

“This study underscores our commitment to develop elamipretide for the treatment of rare genetic mitochondrial diseases,” said Reenie McCarthy, Stealth’s chief executive officer.