Medera Inc. and the University of Kansas Medical Center have achieved a significant milestone in treating Duchenne muscular dystrophy (DMD) by successfully administering the first dose of AAV1.SERCA2a gene therapy to a patient in the landmark MUSIC-DMD Phase 1b clinical trial. This represents the first-in-human gene therapy approach specifically targeting cardiomyopathy secondary to DMD.
The patient was treated via left radial artery access using Medera's proprietary minimally invasive intracoronary infusion methodology. The procedure was well-tolerated, and the patient was discharged following an overnight hospital stay for observation.
Addressing a Critical Unmet Medical Need
"This milestone represents a pivotal advancement in the treatment of DMD-associated cardiomyopathy," said Ronald Li, PhD, CEO and co-founder of Medera. "As survival rates improve due to respiratory interventions, cardiac complications have emerged as the leading cause of mortality in DMD patients. Our Sardocor division's innovative, first-in-human gene therapy offers a promising solution to address this critical unmet medical need through our proprietary intracoronary infusion methodology that has been shown in other indications to safely and reliably deliver the therapeutic gene directly to affected heart tissue."
DMD affects over 300,000 people worldwide, including 40,000 patients in the US and EU. With improved respiratory care extending survival, cardiac complications have become increasingly prevalent as patients live longer. Nearly all patients develop cardiomyopathy by age 18, characterized by widespread fibrosis of the heart muscle leading to heart failure and potentially fatal arrhythmias.
Novel Gene Therapy Mechanism
The MUSIC-DMD Phase 1b trial is an open-label, controlled study evaluating the safety and efficacy of AAV1.SERCA2a, an adeno-associated virus serotype 1 (AAV1) gene therapy that delivers the SERCA2a gene directly to heart muscle cells in adult males with DMD-associated cardiomyopathy. The study will enroll up to 12 participants across low-dose, high-dose, and control groups.
DMD-associated cardiomyopathy is characterized by calcium overload in heart muscle cells, leading to progressive fibrosis and heart failure. AAV1.SERCA2a aims to restore calcium handling in DMD-CM patients by increasing SERCA2a protein production, potentially reversing the underlying disease process.
"The successful initiation of this trial marks an important step forward in addressing the cardiac complications that ultimately affect nearly all patients with Duchenne muscular dystrophy," said Pradeep Mammen, MD, Division Chief for Advanced Heart Failure Therapeutics & Cardiac Transplantation and the Maureen and Marvin Dunn Professor of Cardiovascular Medicine at the University of Kansas Medical Center, who serves as the principal investigator of the MUSIC-DMD study. "This innovative gene therapy approach targets the fundamental calcium handling defects that drive heart muscle deterioration in DMD patients."
Limited Current Treatment Options
Current treatments for DMD-associated cardiomyopathy rely on standard heart failure medications, which have shown limited effectiveness in this patient population. The gene therapy approach represents a potentially transformative treatment modality for a condition with few therapeutic options.
"Cardiac dysfunction affects all patients with Duchenne," noted Pat Furlong, Founding President and CEO of Parent Project Muscular Dystrophy (PPMD), who has been a vocal advocate for advancing cardiac care in Duchenne muscular dystrophy. "This novel gene therapy modality targeted to the cardiac muscle promises to have important effects on cardiac care in Duchenne by repairing hearts."
Company Pipeline and Development
Medera operates through its clinical development division Sardocor, which has received Investigational New Drug (IND) clearances from the FDA for three ongoing AAV-based cardiac gene therapy clinical trials. These target Heart Failure with Reduced Ejection Fraction (HFrEF), Heart Failure with Preserved Ejection Fraction (HFpEF) with Fast Track Designation, and Duchenne Muscular Dystrophy-associated Cardiomyopathy (DMD-CM) with Orphan Drug Designation.
The company's pipeline includes four preclinical gene therapy and three preclinical small molecule candidates targeting various cardiac, pulmonary, and vascular diseases. Medera also operates Novoheart, which utilizes "mini-Heart" technology for disease modeling and drug discovery.
Additional information about the MUSIC-DMD trial is available on ClinicalTrials.gov using the study identifier NCT06224660. Medera announced in September 2024 that it had entered into a definitive merger agreement with Keen Vision Acquisition Corporation (NASDAQ: KVAC, KVACW).
