Orphan Drug Designation Granted by FDA for First Exon 44 Skipping Drug for Duchenne Muscular Dystrophy

Investigational antisense oligonucleotide brogidirsen (NS-089/NCNP-02; NS Pharma, Paramus, NJ) has been granted orphan drug designation by the Food and Drug Administration (FDA) for the treatment of patients with Duchenne muscular dystrophy amenable to exon 44 skipping therapy. Previously, brogidirsen received rare pediatric disease designation from the FDA in June 2023 and received breakthrough therapy designation in July 2023.

FDA orphan drug designation was granted to brogidirsen based on results from a Japanese, investigator-initiated, first-in-human clinical trial evaluating the safety and efficacy of brogidirsen. This study demonstrated that treatment with the investigational agent was associated with maintenance or improvement in motor function and increased expression of the dystrophin protein in participants with DMD, indicating potential therapeutic efficacy.

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. Brogidirsen is designed as an exon skipping therapy, intended to bypass mutated exons to restore dystrophin production. Brogidirsen represents the world’s first exon 44 skipping drug, targeting exon 44.

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. Two phase 2 trials are planned: one to be conducted in the United States by NS Pharma, and a second to be conducted in Japan by Nippon Shinyaku.