Promising Early Results of Investigational Duchenne Muscular Dystrophy Therapy

Avidity Biosciences, Inc. announced positive results from their phase 1/2 EXPLORE44 trial of del-zota in 23 patients living with Duchenne muscular dystrophy amenable to exon 44 skipping (DMD44), according to a recent news release. Results include a 25% increase in dystrophin production and an increase of approximately 40% in exon 44 skipping, the release explains. The company says it is on track to submit an application for accelerated biologics license application approval by the end of 2025. Del-zota has already been granted orphan designation by the FDA.

Avidity also announced that enrollment in the ongoing EXPLORE44 open label extension study has been completed. During this phase, 38 patients will receive a 5 milligram (mg) per kilogram of body weight dose of del-zota every six weeks for approximately 24 months.

"Del-zota has shown remarkable improvements across multiple measures, including a substantial increase in dystrophin production and a significant reduction in serum creatine kinase levels to near normal after just three doses,” Aravindhan Veerapandiyan, M.D., associate professor of pediatrics at the University of Arkansas for Medical Sciences and Arkansas Children's Hospital, said in the news release. “These results bring new hope for patients and families affected by DMD who are in urgent need of targeted therapies that can preserve muscle integrity and possibly prevent or delay the progression of muscle weakness and loss of function associated with this disease.”

Duchenne muscular dystrophy is the most severe and most common form of childhood muscular dystrophy. It is characterized by a loss of muscle function, caused by a lack of dystrophin, a protein in muscle cells that maintains muscle structure and function. The disease can begin as early as age 2 or 3 and primarily affects boys. Worldwide, approximately one in 3,500 to 5,000 boys is born with DMD, the news release said.

Del-zota is part of a new class of RNA therapies called antibody oligonucleotide donjugates. It is designed to deliver phosphorodiamidate morpholino oligomers to skeletal and cardiac muscle tissue to specifically skip the exon 44 dystrophin gene, which is mutated in DMD patients. This enables the production of near-full-length dystrophin.

During the first phase of the Explore44 trial, participants received three doses of either 5 mg/kg del-zota or placebo every six weeks, or 10 mg/kg del-zota or placebo every eight weeks. Twenty-eight days after the third dose, data was also gathered on muscle delivery and creatine kinase levels.

Results showed that creatine kinase levels were reduced to near normal with more than 80% of reductions when compared to baseline. Additionally, tissue concentrations of del-zota reached approximately 200nM in skeletal muscle, the release states. Del-zota demonstrated favorable safety and tolerability at both doses.

Avidity was scheduled to share the EXPLORE44 data this week at the Muscular Dystrophy Association Clinical and Scientific Conference, being held March 16-19, 2025, in Dallas, Texas.