In April, the FDA advised Stealth BioTherapeutics to run another phase 3 clinical trial of elamipretide in a rare genetic condition before seeking approval. Stealth, having been unable to come up with a feasible design for the study, has now gone ahead and filed for approval despite the FDA’s advice.
The application covers the use of the drug candidate in Barth syndrome, a rare disease associated with heart muscle weakness, growth issues and other health problems. Stealth ran a phase 3 trial of elamipretide in the disease in the belief it could improve outcomes by restoring energy production in dysfunctional mitochondria. The trial compared data from the open-label portion of another phase 2/3 study to natural history controls.
While the study met its primary endpoint, the FDA has told Stealth it would like to see data from another phase 3 trial. The problem, as Stealth tells it, is that “neither the FDA nor the company has identified a feasible trial design due to the ultra-rare nature of this disease.”
Faced with a request for additional clinical data that it says it cannot fulfill, Stealth has decided to roll the dice on an application based on its existing evidence. Stealth believes the data could support a review by the FDA, but it acknowledges “there is no assurance” the agency will accept the filing.
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Stealth has followed the rare disease playbook in laying the groundwork for a filing on the basis of limited evidence. Earlier this year, members of the Barth community met with the FDA to educate the agency about their “willingness to accept some degree of uncertainty of clinical benefit in considering treatment options for their ultra-rare and serious disease,” Stealth said.
A positive response by the FDA would provide a boost to Stealth, which was hit by the failure of elamipretide in a phase 3 trial in the group of genetic muscle weakness disorders known as primary mitochondrial myopathy late in 2019. Alexion terminated its option on elamipretide weeks later.
Despite the failure, Stealth is still testing elamipretide in a set of other indications including dry age-related macular degeneration and Friedreich ataxia.