FDA shoots down a biotech’s last-stand patient pitch after faulting data
Stealth BioTherapeutics appeared unsure its pitch for an ultra-rare disease would be accepted when submitting an NDA in August, and on Wednesday its fears came to pass.
The FDA issued Stealth a refusal to file letter for a candidate looking to treat Barth syndrome, the biotech announced Wednesday morning. It’s a move not entirely unexpected, given Stealth’s own admission earlier this year that the agency didn’t find existing data to support NDA review.
Though this may have always been in the cards, Stealth has said numerous times it submitted the application not on the basis of new data but because Barth syndrome patient advocates petitioned the company. The Barth Syndrome Foundation asked Stealth to do so in November 2020 despite knowing the FDA’s hesitation, noting seven Barth patients — or 3% of the world’s Barth population — died in the preceding 13-month period.
Regardless, investors turned their thumbs down at the news, sending Stealth’s penny stock shares $MITO 11% lower in early Wednesday trading.
According to Stealth’s recounting, regulators gave the biotech the same reason it had previously explained, finding the NDA to be lacking an adequate and well-controlled trial that would support evidence of efficacy. Stealth had submitted data from an open-label extension and compared it with a retrospective natural history study.
Regulators had insisted, however, that Stealth conduct an additional Phase III trial. Data from the open-label extension likely would not “add meaningfully to the evidence to support an NDA,” Stealth revealed in April. But to conduct such a study in an ultra-rare disease with so few patients wouldn’t be feasible, Stealth and the advocates argued.
The drug in question is known as elamipretide, Stealth’s former lead drug that flopped a Phase III for mitochondrial disease in late 2019. Elamipretide failed the two key endpoints on the 6-minute walk test and a score on fatigue symptoms for patients with primary mitochondrial myopathy, Stealth said at the time.
But the company insisted it saw a potential efficacy signal for Barth syndrome and filed with the FDA after being asked by the patient community.
Stealth was trying to follow the path laid out by Sarepta several years ago when the company convinced the FDA to approve its Duchenne drug with limited clinical data. In that instance, the vigor and persuasiveness of advocates proved a key element in winning over regulators, something that echoed in this summer’s controversial approval of Biogen’s new Alzheimer’s drug.
The balance between needing controlled trials, tiny patient populations and Big Pharma’s business incentives continues to stifle drug development in a wide range of ultra-rare diseases, often leaving it up to biotechs to try to fill the void. Earlier this month, the biotech Retrotope said its program for infantile neuroaxonal dystrophy didn’t achieve statistical significance but researchers saw enough positive survival data to potentially continue studies.
Social image: Reenie McCarthy, Stealth BioTherapeutics CEO