Rare Daily Staff

Stealth BioTherapeutics said it submitted a New Drug Application to the U.S. Food and Drug Administration for elamipretide, the company’s lead product candidate, for the treatment of Barth syndrome, an ultra-rare genetic condition with no FDA- or EMA-approved therapies.

Barth syndrome is characterized by cardiac abnormalities often leading to heart failure and reduced life expectancy, recurrent infections, muscle weakness and delayed growth. Barth syndrome occurs almost exclusively in males and is estimated to affect one in 200,000 to 400,000 individuals worldwide.

The NDA was submitted despite FDA recommendation that additional controlled data be generated to support its review, as neither the FDA nor the company have been able to identify a feasible trial design due to the ultra-rare nature of this disease.

Stealth noted that because FDA’s view that the existing clinical data are insufficient to demonstrate substantial evidence of effectiveness and would not support NDA review, there was no assurance that the FDA will file the NDA. However, the company believes that the data could support an NDA review and so has submitted the NDA as requested by the Barth syndrome patient community.

The NDA submission is based on results from the SPIBA-001 phase 3 Retrospective Natural History Control Trial, which compared data from the open-label portion of the TAZPOWER phase 2/3 clinical trial to matched natural history controls. SPIBA-001 met its primary and most secondary endpoints, demonstrating elamipretide-mediated improvements in assessments of exercise tolerance, strength, and cardiac function that are unexpected in the natural course of this progressively debilitating disease.

In addition, improvements were observed during the TAZPOWER phase 2/3 clinical trial and open label extension in several surrogate and intermediate clinical endpoints that may be reasonably likely to predict clinical benefit for patients suffering from this serious disease, potentially supporting an accelerated approval pathway.

“Children and young adults affected by Barth syndrome are suffering from life limiting, progressive cardiomyopathy, exercise intolerance, and debilitating fatigue for which there are no approved treatment options,” said CEO Reenie McCarthy. “We initiated our Barth syndrome development efforts at the request of the Barth syndrome community. We respect the patient community’s perspective regarding its tolerance for some uncertainty of benefit in considering therapies for this ultra-rare disease, and with our NDA submission, have answered its petition that we submit our application. We know that the FDA has similarly heard the voice of these patients, and we look forward to continued dialogue with the FDA as it evaluates our submission for filing and review.”

Stealth is focused on diseases of mitochondrial dysfunction, which is involved in several rare genetic diseases as well as many common age-related diseases, typically involving organ systems with high energy demands such as the heart, the eye, and the brain. Elamipretide, the company believes, has the potential to treat both rare metabolic cardiomyopathies, such as Barth, Duchenne muscular dystrophy and Friedreich’s ataxia, rare mitochondrial diseases entailing nuclear DNA mutations, as well as ophthalmic diseases entailing mitochondrial dysfunction, such as dry age-related macular degeneration and Leber’s hereditary optic neuropathy.

Elamipretide was previously granted rare pediatric designation, fast track designation, and orphan drug designation by the FDA, and orphan drug designation by the EMA, for the treatment of Barth Syndrome. 

Photo: Reenie McCarthy, CEO of Stealth BioTherapeutics

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