Stealth BioTherapeutics Corp (NASDAQ:MITO), a clinical-stage biotechnology company focused on the discovery, development, and commercialization of novel therapies for diseases involving mitochondrial dysfunction, today reported an update on its pre-IND meeting with the FDA’s Division of Cardiology and Nephrology (DCN) regarding its Duchenne muscular dystrophy (DMD) development program, including reaching alignment on Stealth’s proposal to assess the progression of myocardial fibrosis as a surrogate endpoint for its planned clinical trial.
“We applaud DCN for recognizing the importance of assessing myocardial fibrosis in DMD, where progressive fibro-fatty infiltration starting as early as middle childhood is associated with a loss of left ventricular function and adverse cardiovascular events,” said Reenie McCarthy, Chief Executive Officer at Stealth. “This progressive cardiomyopathy can lead to heart failure, which is the leading cause of early mortality in DMD, and remains an important unmet need in this devastating disease. We look forward to continued dialogue with DCN regarding a proposed approval pathway on the basis of this surrogate endpoint, which will include ascertaining elamipretide’s effect on this biomarker in our proposed clinical trial and designing an appropriate postmarketing confirmatory study.”
The purpose of the pre-investigational new drug (IND) meeting was to discuss Stealth’s proposed development plan in DMD. DCN agreed that myocardial fibrosis assessed by magnetic resonance imaging (MRI) using late gadolinium enhancement (LGE) could serve as a primary endpoint for Stealth’s proposed new clinical trial. DCN also outlined the steps that could support an eventual determination that reducing the progression of fibrosis is reasonably likely to lead to clinical benefit in DMD, which would be necessary for an Accelerated Approval based on this endpoint. DCN signaled alignment with other key aspects of the clinical trial design, while recommending that additional information be submitted with Stealth’s planned IND on others. Stealth expects to engage in further dialogue with DCN early next year as it moves toward an IND submission during the first half of the year and a potential trial initiation during the second half of the year, subject to further regulatory feedback and financing.
“End-stage heart failure is the main cause of death in DMD, so that even as we applaud the introduction of new therapies and treatment modalities to address other aspects of the disease, we have been asking ourselves: Is the DMD heart ‘built to last’?” explained Pat Furlong, founding president and chief executive officer, Parent Project Muscular Dystrophy (PPMD). “We appreciate the FDA’s willingness to listen to the voice of the DMD community by outlining novel pathways to speed the development of therapies for the devastating cardiomyopathy that affects young boys and men living with DMD, and we are pleased to welcome Stealth to the dedicated community of researchers, clinicians and industry who have partnered with us over the last 25+ years to find treatments for all people living with DMD.”
Stealth has also recently reported new preclinical data demonstrating that administration of elamipretide with an exon-skipping phosphorodiamidate morpholino oligomer (PMO), a therapeutic class that has already garnered regulatory approval and commercialization for its effects in skeletal muscle, significantly improves dystrophin expression levels in the X-linked muscular dystrophy (mdx) mouse model.