Brogidirsen Shows Sustained Motor Function Benefits in 3.5-Year Duchenne Muscular Dystrophy Trial
核心洞察
NS Pharma (搜索) and NCNP (搜索) presented 3.5-year clinical trial data for brogidirsen, an antisense oligonucleotide therapy for Duchenne muscular dystrophy (搜索) patients amenable to exon 44 (搜索) skipping.
The study demonstrated high exon 44 (搜索) skipping efficiency and sustained dystrophin (搜索) expression levels in muscle biopsies at both week 25/26 and week 99/100.
Ambulant participants maintained motor function over the long-term treatment period with no serious adverse events or treatment discontinuations reported.
NS Pharma (搜索), Inc. and the National Center of Neurology and Psychiatry (NCNP (搜索)) presented compelling 3.5-year efficacy and safety data for brogidirsen (NS-089/NCNP-02) at the 30th annual International Congress of the World Muscle Society, demonstrating the antisense oligonucleotide's potential to slow disease progression in Duchenne muscular dystrophy (搜索) (DMD (搜索)) patients with dystrophin (搜索) gene mutations amenable to exon 44 (搜索) skipping.
The investigational therapy, co-discovered by Nippon Shinyaku and NCNP (搜索), showed sustained therapeutic benefits in a small cohort of six participants who received weekly intravenous dosing throughout the extended trial period.
Sustained Dystrophin Production and Motor Function
The long-term extension study revealed consistent functional benefits, with high exon 44 (搜索) skipping efficiency and dystrophin (搜索) expression levels observed in biopsied muscles at both week 25/26 and week 99/100. This sustained protein production represents a critical therapeutic milestone, as dystrophin deficiency is the underlying cause of progressive muscle weakness in DMD (搜索).
Participants who remained ambulant after long-term brogidirsen administration maintained their motor function in evaluations including the North Star Ambulatory Assessment, a standardized measure of functional ability in DMD (搜索) patients. This maintenance of motor function over 3.5 years suggests the therapy's potential to alter the natural progression of this devastating neuromuscular disorder.
"These long-term motor function data suggest the potential for brogidirsen to slow disease progression in DMD (搜索) patients amenable to exon 44 (搜索) skipping and support the robust increases in dystrophin (搜索) production seen earlier in the trial," said NS Pharma (搜索) President Yukiteru Sugiyama, Ph.D.
Favorable Safety Profile
The extended safety analysis demonstrated an acceptable tolerability profile over the 3.5-year treatment period. No serious or severe adverse events related to long-term brogidirsen administration were reported, and importantly, no cases of anaphylaxis occurred. The therapy's safety profile was further supported by the absence of any treatment discontinuations throughout the study period.
Advancing Global Development
The presented data stem from an investigator-initiated clinical trial conducted by NCNP (搜索) and its extension study conducted by Nippon Shinyaku. These findings support brogidirsen's potential to modify DMD (搜索) progression and provide the foundation for ongoing development efforts.
A global Phase II study of brogidirsen is currently being conducted by Nippon Shinyaku and NS Pharma (搜索), representing the next critical step in the therapy's clinical development pathway. The long-term extension trial continues to investigate the efficacy and safety of extended administration periods.
Addressing Critical Unmet Need
Duchenne muscular dystrophy (搜索) primarily affects males and causes progressive weakness and loss of skeletal, cardiac, and respiratory muscles. Early signs may include delayed ability to sit, stand, or walk, with progressive loss of mobility leading to wheelchair dependence by adolescence. Cardiac and respiratory complications typically emerge during teenage years, creating life-threatening complications for patients and families.