Rare Daily Staff
Avidity Biosciences reported positive topline data from a phase 1/2 trial of its experimental therapy antibody-oligonucleotide therapy del-zota in people living with the rare neuromuscular disease Duchenne muscular dystrophy who are amenable to exon 44 skipping.
The study demonstrated consistent, statistically significant improvements in dystrophin, exon skipping, and creatine kinase, as well as favorable safety and tolerability across the dose cohorts, the company said. The data will be highlighted in an oral and poster presentation at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference in Dallas, Texas.
“These data are a true testament to the power of our AOC platform and the potential of del-zota to change the course of this relentless and devastating rare disease,” said Sarah Boyce, president and CEO of Avidity. “Based on our interactions with FDA on accelerated approval, we believe dystrophin data from EXPLORE44 combined with the safety data from our fully enrolled EXPLORE44-OLE trial will support our planned BLA submission at the end of this year.”
Avidity said its commercial preparations for a potential U.S. launch of del-zota in DMD44 are well underway.
Duchenne muscular dystrophy (DMD) causes a lack of functional dystrophin that leads to stress and tears of muscle cell membranes, resulting in muscle cell death and the progressive loss of muscle function. The dystrophin protein maintains the integrity of muscle fibers and acts as a shock absorber through its role as the foundation of a group of proteins that connect the inner and outer elements of muscle cells.
People living with DMD suffer from progressive muscle weakness that typically starts at a very young age. Over time, people with DMD will develop problems walking and breathing, and eventually, the heart and respiratory muscles will stop working. Those living with the condition often require special aid and assistance throughout their lives and have significantly shortened life expectancy.
Del-zota is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal muscle and heart tissue to specifically skip exon 44 of the dystrophin gene to enable dystrophin production in people living with Duchenne muscular dystrophy with mutations amenable to exon 44 skipping (DMD44). Del-zota consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a PMO targeting exon 44.
The phase 1/2 EXPLORE44 trial of del-zota has been completed, and the EXPLORE44 Open-Label Extension trial of del-zota is currently ongoing.
Topline data from the completed del-zota Phase 1/2 EXPLORE44 trial demonstrated unsurpassed delivery of PMOs to skeletal muscle, robust increases in dystrophin production, significant increases in exon 44 skipping, and significant and sustained decreases of creatine kinase levels to near normal in people living with DMD44.
Del-zota has received Rare Pediatric Disease, Orphan Drug and Fast Track designations by the FDA and Orphan designation by the European Medicines Agency.
Del-zota’s anticipated launch sets the foundation for sequential launches of Avidity’s three neuromuscular programs, including del-desiran for myotonic dystrophy type 1 (DM1) and del-brax for facioscapulohumeral muscular dystrophy (FSHD).
“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,” said Aravindhan Veerapandiyan, associate professor of pediatrics at the 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.”
Photo: Sarah Boyce, president and CEO of Avidity
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