FDA Grants Breakthrough Therapy Designation to Delpacibart Zotadirsen for Duchenne Muscular Dystrophy

Del-zota (delpacibart zotadirsen; Avidity Biosciences, San Diego, CA) has been granted Breakthrough Therapy designation by the Food and Drug Administration (FDA) as an investigational therapy for the treatment of people with Duchenne muscular dystrophy (DMD) with mutations amenable to exon 44 skipping (DMD44). The FDA previously granted Orphan Drug, Rare Pediatric Disease, and Fast Track designations to del-zota for the treatment of DMD44, and according to a statement from Avidity Biosciences, the company plans to submit a biologics license application (BLA) for the drug by the end of 2025.

Treatment with del-zota is intended to induce exon 44 skipping of the dystrophin gene through the delivery of phosphonodiamidite morpholino oligomers (PMOs) to heart and skeletal muscle tissue, thereby enabling production of near full-length dystrophin proteins. Del-zota treatment was evaluated in the completed phase 1/2 EXPLORE44 clinical trial (NCT05670730), which included 26 participants with DMD44 who received treatment with del-zota as a single-dose IV infusion, del-zota as 3 ascending doses, or placebo.

Participants who received del-zota demonstrated:

• Significantly increased exon skipping
• Increased dystrophin protein production
• Significant and sustained reductions in creatine kinase to near normal levels
• Consistent and favorable safety and tolerability

The therapy is now being evaluated in the ongoing Phase 2 EXPLORE44-OLE open-label extension study, with topline results expected in late 2025.

“Breakthrough Therapy designation further underscores the FDA's appreciation for the significant potential of del-zota to address the underlying cause of DMD44 and the urgent need to bring innovative treatment options to the DMD community,” said Steve Hughes, MD, Chief Medical Officer at Avidity Biosciences. “With the remarkable, consistent improvements we've seen in multiple biomarkers including dystrophin in the Phase 1/2 EXPLORE44 trial, we are focused on bringing del-zota to people living with DMD44 as quickly as possible and remain on track for our planned BLA submission at year end 2025.”