Stealth's not so sneaky strategy to file unprepared drug application foiled by FDA

It was a bold strategy, filing a drug the FDA clearly said was not ready for prime time, but Stealth BioTherapeutics did it anyway. Today, its chickens have come home to roost.

The FDA has rejected the application for Barth syndrome drug elamipretide in a refusal to file letter just under two months after the Hail Mary application was submitted. The agency had asked Stealth in April for another phase 3 trial.

Stealth is seeking approval for elamipretide in Barth syndrome, a rare disorder that causes heart muscle weakness, growth issues and other health problems. The drug met the main goal of a phase 3 trial, with the data compared to an open-label portion of a different phase 2/3 study and natural history controls.

The FDA was not happy with this approach, hence the request for another trial. But Stealth said “neither the FDA nor the company has identified a feasible trial design due to the ultra-rare nature of this disease.” And so, they moved to file for approval anyway.

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The inevitable rejection sent Stealth’s shares into the red by 15% to $1.17 in premarket trading Wednesday.

According to Stealth, the FDA informed the company the application “was not sufficiently complete to permit a substantive review.” The application did not contain “an adequate and well-controlled trial”—the standard for weighing a drug approval—that could prove efficacy.

“Stealth and the FDA have previously discussed the challenges of conducting additional clinical trials in Barth syndrome, which is an ultra-rare genetic disease affecting fewer than 130 individuals in the U.S.,” the statement said.

Stealth is considering next steps and will provide an update in early November. The FDA did not say why the phase 3 trial is not considered adequate and well controlled but did commit to continuing to work with the company to find a path forward for a new trial.

The company admitted when filing the application in August that there was "no assurance” the agency would accept the filing.

RELATED: Alexion bags option on Stealth's phase 3 rare disease drug

"We submitted our [new drug application] at the request of the Barth syndrome patient community, which petitioned us and the FDA to gain access to elamipretide and shared with the FDA its tolerance of risk of uncertainty of benefit based on the data from the small clinical trials we were able to conduct in this ultra-rare disease," said Stealth CEO Reenie McCarthy.

This is not the first indication Stealth has struggled in with elamipretide. The therapy also failed a phase 3 clinical trial in the group of genetic muscle weakness disorders known as primary mitochondrial myopathy late in 2019. The drug was previously part of a partnership with Alexion, which terminated its option following the failure.

Elamipretide is also being tested in other indications including dry age-related macular degeneration and Friedreich ataxia. The therapy, which was granted rare pediatric, fast-track and orphan-drug designations by the FDA, is believed to work by restoring energy production in dysfunctional mitochondria.