Avidity Biosciences Announces Positive Topline Del-zota Data Showing Consistent, Statistically Significant Improvements in Dystrophin, Exon Skipping, and Creatine Kinase in Phase 1/2 EXPLORE44® Trial Participants with Duchenne Muscular Dystrophy Amenable to Exon 44 Skipping.
The data will be highlighted in an oral and poster presentation at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, being held March 16-19, 2025, in Dallas, Texas.
Avidity Biosciences EXPLORE44 (Del-zota) Clinical Trials
“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. The consistency of these results in such a short time frame, coupled with favorable safety and tolerability, underscores the potential of del-zota to become a groundbreaking treatment for individuals living with DMD with genetic variants amenable to exon 44 skipping,” said Aravindhan Veerapandiyan, M.D., Associate Professor of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital.
“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.”
What is Del-Zota?
Del-zota is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal and cardiac muscle tissue to specifically skip exon 44 of the dystrophin gene and enable production of near-full length dystrophin. Del-zota has been granted Orphan designation by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA has also granted del-zota Rare Pediatric Disease and Fast Track designations. Del-zota is the first of multiple AOCs currently in development at Avidity for the treatment of DMD.
The data presented at MDA highlight the consistent data across all parameters in both the 5 mg/kg and 10 mg/kg cohorts of del-zota, including:
- Targeted delivery of PMOs resulting in tissue concentrations of approximately 200nM in skeletal muscle;
- Statistically significant increases of approximately 40% in exon 44 skipping;
- Statistically significant increase of approximately 25% of normal in dystrophin production and restored total dystrophin up to 58% of normal;
- Reduction in creatine kinase levels to near normal with greater than 80% reductions compared to baseline:
- Similarly, placebo participants demonstrated a reduction in creatine kinase levels to near normal upon treatment with del-zota;
- Significant reductions in creatine kinase levels were sustained in the EXPLORE44-OLE trial with continued treatment up to one year; and,
- Del-zota demonstrated favorable safety and tolerability at both doses, with most treatment emergent adverse events (TEAEs) mild or moderate.
Learn More: Next Generation Exon Skipping Therapies Developed for the Treatment of Duchenne Muscular Dystrophy
