Stealth Clinches Orphan Drug Designation in DMD

Duchenne muscular dystrophy genetic test

Stealth BioTherapeutics has received Orphan Drug Designation from the U.S. Food and Drug Administration for elamipretide. The candidate received this designation for its potential to treat patients with Duchenne Muscular Dystrophy (DMD), a rare neurologic disease that affects muscles. In addition, the FDA’s Division of Neurology has agreed to a pre-IND meeting to evaluate the path to regulatory approval of elamipretide.

DMD is typically diagnosed primarily in males between the ages of two and eleven years old, according to the National Institutes of Health’s Genetic and Rare Disease Information Center. Early signs of DMD include difficulty sitting, standing, walking and learning how to speak. As the disease progresses, muscles begin to weaken and degrade, leading to atrophy in skeletal and heart muscles. Patients often die in early adulthood, once respiratory or cardiac issues become too severe for treatment. The disease is hereditary, passed through an X-linked recessive chromosome pattern.

To combat the progression of DMD, elamipretide’s peptide compound composition allows it to penetrate the cellular membrane to bind to cardiolipin. After binding, elamipretide induces an increase in mitochondrial respiration and ATP production. Increased ATP production interrupts and potentially reverses oxidative stress. Oxidative stress is a factor in DMD, along with various other dry age-related macular degeneration and primary mitochondrial diseases.

Stealth Chief Executive Officer Reenie McCarthy commented on the designation’s significance.

"We are pleased that the FDA has recognized the high unmet need for innovative treatments for DMD," she said. We look forward to further discussions with the FDA regarding our development initiatives, which we hope will bring new options to patients suffering from this devastating disease."

Treatment, as well as regulatory approval, would be a combination therapy of elamipretide and an exon-skipping phosphorodiamidate morpholino oligomer (PMO). Preclinical data with mouse models have demonstrated the efficacy of elamipretide with a PMO, as dystrophin expression improved significantly.

Additional indications for elamipretide are being evaluated, including for Barth Syndrome, primary mitochondrial myopathy due to nDNA mutations (nPMM), cardiomyopathy and extra-foveal geographic atrophy (GA), associated with dry age-related macular degeneration. A New Drug Application (NDA) is expected to be filed for the Barth Syndrome treatment indication in the second half of 2022.

A pre-IND meeting was held with the FDA for a cardiomyopathy indication, in which the two parties agreed upon a path of development. For extra-foveal GA, a Phase-II ReCLAIM-2 clinical trial is in the end stages, with the final patient dosed in February of this year.

Earlier this year, Stealth announced that Orphan Drug Designation was granted for elamipretide indicated to treat Friedreich’s Ataxia. A Phase-IIa study is currently underway at the Children’s Hospital of Philadelphia, evaluating the treatment’s safety.

The company remains focused on the discovery and development of therapies for mitochondrial dysfunction diseases. Stealth has another candidate, SBT-272, that may be suitable for the treatment of rare diseases such as frontotemporal dementia and amyotrophic lateral sclerosis. Preclinical data for this candidate is promising.

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