FDA Grants Orphan Drug Designation to Exon 44 Skipping AOC for Duchenne Muscular Dystrophy

AOC 1044 (Avidity Biosciences, San Diego, CA), an antibody oligonucleotide conjugate (AOC), was granted orphan drug designation by the Food and Drug Administration (FDA) for the treatment of patients with Duchenne muscular dystrophy (DMD) with mutations amenable to exon 44 skipping therapy. In April 2023, Avidity Biosciences announced that the FDA granted Fast Track Designation to AOC 1044.

AOC 1044 is currently under evaluation to test the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending doses of this AOC in a phase 1/2 clinical trial that is actively recruiting called EXPLORE44 (NCT05670730). EXPLORE44 is a randomized, placebo-controlled, double-blind study split into 2 cohorts, a healthy control cohort and a cohort with clinical diagnosis of DMD amenable to exon 44 skipping therapy. Participants in the healthy cohort will receive a single dose of either AOC 1044 or placebo, while participants in the DMD cohort will receive multiple ascending doses of either AOC 1044 or placebo. The primary outcome is the incidence of treatment-emergent adverse events (TEAEs), with secondary outcomes measuring for plasma, urine, and skeletal muscle tissue pharmacokinetics as well as change in level of dystrophin protein.

“AOC 1044 is designed to specifically skip exon 44 of the dystrophin gene to enable the production of functional dystrophin protein,” said Steve Hughes, MD, Chief Medical Officer at Avidity. “We look forward to advancing AOC 1044 in clinical development and bringing this very important treatment to patients as quickly and safely as possible."

DMD is an incurable form of muscular dystrophy associated with progressive skeletal, cardiac, and respiratory muscle weakness; individuals with DMD have an average life expectancy of 26 years. In DMD, a genetic mutation in specific gene exons, or regions, prevents the production of the dystrophin protein essential for proper muscle function.

The FDA grants orphan drug designation to agents that prevent, diagnose, or treat rare diseases and conditions with the aim of supporting their clinical development and evaluation. The company expects to release results from the first part of the EXPLORE44 study by the end of 2023.