Safety and efficacy of Brogidirsen in patients with Duchenne muscular dystrophy: an open-label extension study

Topic:

Clinical Trials

Poster Number: P88

Author(s):

Hirofumi Komaki, MD, PhD, National Center of Neurology and Psychiatry, Eri Takeshita, MD, PhD, National Center Of Neurology And Psychiatry, Katsuhiko Kunitake, MD, PhD, National Center Of Neurology And Psychiatry, Yuko Shimizu-Motohashi, MD, PhD, National Center Of Neurology And Psychiatry, Shinsuke Maruyama, MD, PhD, Kagoshima University Hospital, Eisuke Hida, PhD, Osaka University Graduate School of Medicine, RENA MIYAGI, DVM, NIPPON SHINYAKU CO., LTD, He Zhang, MD, PhD, Nippon Shinyaku, Yoshitsugu Aoki, MD, PhD, National Center Of Neurology And Psychiatry

Duchenne muscular dystrophy (DMD) is an X-chromosome-linked progressive hereditary muscle disease caused by mutations in the DMD gene, which codes for dystrophin, a protein expressed underneath the muscle-cell membrane. NS-089/NCNP-02 (Brogidirsen) is the world’s first exon 44 skipping drug developed by NCNP in collaboration with Nippon Shinyaku. Brogidirsen was developed based on a novel sequence design. Since it induced highly efficient exon 44 skipping and dystrophin protein expression in cells from DMD patients with exon deletion(s) in the dystrophin gene amenable to exon 44 skipping, we expect that it could slow the progression of the disease.
In a previous Phase 1/2 study (Study ID: NCNP/DMT02; NCT04129294), the six participants were enrolled and skeletal muscle dystrophin levels increased significantly after 24 weeks of Brogidirsen treatment. The ongoing study is the extension study (NCT05135663) of Brogidirsen, which is designed to assess the safety, tolerability and efficacy of Brogidirsen in patients with Duchenne muscular dystrophy (DMD).
We evaluated the safety, tolerability, pharmacokinetics, efficacy (e.g. dystrophin expression levels and motor function) up to Visit 99 (99 weeks from part 2 initiation of study NCNP/DMT02). There was no severe adverse events related to the Brogidirsen and no discontinuation of administration due to adverse events during the study. In addition, no anaphylaxis has been reported. At Visit 99, 4 out of 6 participants showed a maintenance or improvement trend of the motor function.
The results suggest the potential of Brogidirsen treatment to slow the disease progression. The extension study is ongoing, and the six participants are under treatment to evaluate long-term efficacy and safety. Phase 2 study (Study ID: NS-089/NCNP-02-201; NCT05996003) sponsored by NS Pharma, Inc (US subsidiary of Nippon Shinyaku) is also ongoing to warrant the safety and efficacy of Brogidirsen.