Data submitted to the FDA by Stealth BioTherapeutics for its ultra-rare disease drug likely aren’t sufficient for an approval or even an accelerated approval, agency staff said in briefing documents released Tuesday.
The drug, elamipretide, is meant to treat a condition called Barth syndrome, a progressive and ultimately fatal disease of mitochondrial dysfunction. It affects only about 130 people in the US.
Elamipretide was turned down by the FDA in 2021, and is likely to face a tough advisory committee Thursday when outside experts meet to discuss and vote on the drug. There are no other approved treatments for the fatal disease, but Stealth is submitting data from one Phase 2 trial that the agency previously said shouldn’t be considered as an adequate, well-controlled trial.
In its briefing document ahead of the meeting, the FDA pointed out that the placebo-controlled Phase 2 trial “failed on its primary objective to demonstrate an effect of elamipretide on both the distance walked” in a six-minute walk test and the total fatigue score on the Barth Syndrome Symptom Assessment. The assessment is based on patient-reported outcomes that can be used to evaluate the severity of symptoms.
The agency also said that the accelerated approval pathway is not appropriate for elamipretide. Regulators looked at whether there was compelling evidence of an effect on echocardiographic parameters or cardiolipin findings, which might support their use as a surrogate endpoint for accelerated approval. But “based on the significant data limitations,” the FDA said it concluded “that these data are not adequate for this use.”
Stealth and the FDA have been going back and forth on elamipretide since the first IND was submitted by the company almost a decade ago. But the agency told the company as early as 2021 that it needed to run a Phase 3 trial, according to the briefing documents, and the current data weren’t enough.
The company received a refuse-to-file letter later in 2021 for its initial application, with the FDA noting it had not submitted trial data that could establish evidence of effectiveness.
“After several additional correspondences/meetings, and FDA continuing to recommend a new phase 3 trial, the Applicant informed FDA of their intent to resubmit the NDA without conducting a new trial,” the FDA said. It added that “it cannot prevent an Applicant from submitting or resubmitting an NDA and that the Applicant should fully address our prior concerns in the resubmission.”
Stealth contends elamipretide is effective. In its own briefing documents, the Massachusetts-based company made the point that many Barth patients are willing to take some risk with a treatment.
“This conclusion regarding the benefit of elamipretide for the treatment of Barth syndrome is supported by a risk benefit analysis of the well-characterized (and generally benign) safety profile of elamipretide as well as patients’ willingness to accept some uncertainty with respect to benefit,” the company said.