FDA Grants Breakthrough Therapy Status to Avidity Biosciences' Del-zota for DMD44

Avidity Biosciences has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for its investigational therapy, delpacibart zotadirsen (del-zota). 

This designation applies to the treatment of Duchenne muscular dystrophy (DMD) in patients who have mutations amenable to exon 44 skipping—a specific genetic subgroup referred to as DMD44.

Del-zota is being evaluated in an ongoing Phase 2 open-label extension study, EXPLORE44-OLE™, which builds upon the findings from a prior Phase 1/2 trial. 

It represents the first Antibody Oligonucleotide Conjugate (AOC™) in Avidity’s pipeline for DMD treatment.

DMD is a severe genetic disorder characterized by progressive muscle weakening due to the absence of functional dystrophin, a key structural protein. Symptoms typically emerge in early childhood.

The therapeutic approach of del-zota involves targeted delivery of phosphorodiamidate morpholino oligomers (PMOs) to both skeletal and cardiac muscles. 

These PMOs are designed to promote exon 44 skipping, thereby restoring the production of a truncated yet functional form of the dystrophin protein.

Data from the initial EXPLORE44® trial demonstrated that treatment with del-zota resulted in a notable increase in both exon skipping and dystrophin protein levels, along with a sustained decrease in creatine kinase, a biomarker of muscle damage. Additionally, the treatment was generally well tolerated, with a favorable safety profile.

Del-zota is part of Avidity’s expanding portfolio of RNA-targeted therapies aimed at treating neuromuscular conditions. 

The company is also progressing del-desiran for myotonic dystrophy type 1 (DM1) and del-brax for facioscapulohumeral muscular dystrophy (FSHD).