• Country: Japan
  • Official Title: Director
  • Department: Department of Molecular Therapy
  • Institute: National Institute of Neuroscience National Center of Neurology and Psychiatry
  • E-Mail: tsugu56@ncnp.go.jp

Speech Title

Development of Viltolarsen and Brogidirsen for The Treatment of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is the most prevalent and severe form of muscular dystrophy caused by a mutation in the DMD gene. The current state-of-the-art treatment involves exon-skipping therapy using antisense oligonucleotides (ASOs), an example of advanced precision medicine. Viltolarsen (Viltepso®) is an ASO developed by National Center of Neurology and Psychiatry (NCNP) in collaboration with Nippon Shinyaku to treat DMD. It specifically binds to exon 53 of the DMD pre-mRNA, enabling the skipping of exon 53 and restoring the open-reading frame. This leads to the production of a truncated but functional dystrophin protein. In 2020, viltolarsen received conditional approval in Japan and the USA for treating DMD in patients with a confirmed deletion of the DMD gene amenable to exon 53 skipping. To expand the number of patients eligible for exon-skipping treatment in DMD, we are developing brogidirsen, a novel dual-targeting ASO that uses phosphorodiamidate morpholino oligomer that targets different regions of exon 44 of the DMD gene. Brogidirsen could potentially benefit approximately 6% of all DMD patients. We have recently completed investigator-initiated Phase I/II studies to evaluate the efficacy and safety of brogidirsen in DMD patients. These studies have provided crucial data on the safety, efficacy, and pharmacokinetics of brogidirsen, supporting its further clinical development and aiming to expand treatment options for DMD and other neuromuscular disorders.