Elamipretid (MTP-131) improves the fitness of people with Barth syndrome, compared to the natural course of the disease, according to a new comparison using data from the TAZPOWER phase 2/3 clinical trial.
Stealth BioTherapeutics, the company that develops elamipretid and funded TAZPOWER, plans to meet with the FDA later this quarter to discuss these results.
Barth syndrome is a rare mitochondrial disease caused by mutations in the gene tafazzine (TAZ). Such mutations lead to low levels of cardiolipin, a lipid (fatty compound) necessary for the production of energy by the mitochondria. As such, common symptoms of Barth syndrome include muscle weakness and fatigue.
Elamipretid can enter mitochondria and protect cardiolipin, which can restore cellular energy production. It is given by subcutaneous injection (under the skin).
The TAZPOWER clinical trial (NCT03098797) enrolled 12 people with genetically confirmed Barth syndrome. The trial was conducted in two parts: in the first, participants received daily injections under the skin of 40 mg of elamipretid for 12 weeks, then 12 weeks of placebo, or vice versa, with a wash- out ”of four weeks. period between. This trial design is called a crossover study, and it allows for greater statistical power because there is both treatment and placebo data for all participants.
Following the crossover portion of the trial, 10 of the participants enrolled in an open-label extension, during which they all received elamipretid and were followed up to 168 weeks (3.2 years ).
Results previously reported by TAZPOWER suggested that elamipretid improved heart function.
In the new analysis, data from the trial was compared to data from 19 untreated people with Barth syndrome, which were collected from 2012 to 2019 by investigators at the Johns Hopkins Kennedy-Krieger Institute in Baltimore, Maryland. These data were used to create a model of the natural course of Barth syndrome.
To minimize bias, Stealth did not have access to this natural evolution data while the TAZPOWER trial was ongoing, and the statistical team that developed the natural evolution model was separate from the team that analyzed the results of TAZPOWER.
The main focus of TAZPOWER was the Six Minute Walk Test (6MWT), which, as the name suggests, measures how far a person can walk in six minutes. This is commonly used to assess physical condition in ambulatory people.
TAZPOWER participants (including open-label extension) receiving elamipretid for up to a year had an average improvement of 6MWT over 80 meters (approximately 260 feet). In contrast, in the natural course of the disease, improvement was less than one meter (less than three feet). This difference was statistically significant, meaning that it was unlikely to be due to chance.
There were also statistically significant improvements, compared to the natural course, in muscle strength tests and in sit-stand assessments (ease of getting up from a seated position).
According to Stealth, more detailed results will be presented at future medical meetings.
“We are grateful to have access to such recent and carefully collected natural history data to serve as a control for our open-label TAZPOWER extension, demonstrating the enormous potential of elamipretid,” said Reenie McCarthy, CEO of Stealth , in a press release. “Thanks to the foresight and commitment of our researchers at Johns Hopkins and the Barth Syndrome Foundation, we were able to show that the effect of elamipretid on important functional parameters associated with Barth is not only striking, but far beyond what one would expect based on the natural course of the disease.
“Our patient community is in desperate need of therapy that addresses the complex, multi-system challenges that arise as a result of Barth Syndrome,” said Emily Milligan, Executive Director of the Barth Syndrome Foundation. “In our meetings with the FDA, the Agency has stressed the importance of natural history data to support therapeutic development in this ultra-rare disease, and we are optimistic that elamipretid will demonstrate such measurable improvements in several key markers of the disease which have also been demonstrated. persist over time.