Duchenne MD therapy brogidirsen shows long-term benefit in boys
Study: Investigational drug sustained motor function over 3.5 years
Brogidirsen (NS-089/NCNP-02), NS Pharma’s investigational therapy for people with Duchenne muscular dystrophy (DMD) who are amenable to exon 44 skipping, has been shown to sustain motor function and maintain a favorable safety profile over 3.5 years of treatment in an open-label extension study.
The therapy is designed to restore the production of a functional version of dystrophin, a protein that protects muscle fibers from damage. It was first evaluated in a 24-week Phase 1/2 study (NCT04129294) that enrolled six boys with DMD in Japan, which was followed by an ongoing extension study (NCT05135663) that allowed the boys to continue treatment to assess long-term safety and efficacy. The extension study is sponsored by Nippon Shinyaku, the parent company of NS Pharma.
Long-term findings were presented at this year’s International Congress of the World Muscle Society, held earlier this month in Vienna, Austria.
“These long-term motor function data suggest the potential for brogidirsen to slow disease progression in DMD patients amenable to exon 44 skipping and support the robust increases in dystrophin production seen earlier in the trial,” Yukiteru Sugiyama, PhD, NS Pharma president, said in a company press release. “We are proud to offer hope to families and continue to demonstrate our commitment to the DMD community.”
Increases in dystrophin levels sustained over 3.5 with brogidirsen
A form of muscular dystrophy, DMD is caused by mutations in the DMD gene, which provides the instructions for making dystrophin. In most cases, these mutations delete one or more sections of the gene called exons, the protein-coding regions.
When these sections are missing, the gene’s remaining instructions fall out of alignment, and cells produce a shortened, unstable dystrophin protein that’s quickly broken down. Without enough functional dystrophin, muscle cells weaken and gradually degenerate, leading to DMD symptoms.
Brogidirsen is a type of small, lab-made molecule called an antisense oligonucleotide. Similar to other exon-skipping therapies, it prompts the cells to skip over, or exclude, a whole exon — in this case, exon 44 — so that the remaining ones can align correctly. This allows the body to produce a shorter but still functional form of dystrophin.
Data from 24 weeks of treatment in the Phase 1/2 study showed that once-weekly intravenous, or into-the-vein, infusions of brogidirsen led to significant increases in dystrophin levels in boys’ muscle tissue that reached up to 15.8% of normal at the higher dose (80 mg/kg).
Motor function, based on changes in North Star Ambulatory Assessment (NSAA) scores, tended to improve. The NSAA is a standardized test used to evaluate motor abilities in children with DMD who can walk.
Long-term data now confirm that these benefits were maintained over 3.5 years of continued treatment. Increases in dystrophin levels were sustained, and participants who were still able to walk preserved their motor abilities. No treatment discontinuations or serious or severe side effects were reported.
Overall, these results support the therapy’s potential to modify disease progression of DMD, according to the company.
A global Phase 2 study (NCT05996003) is now underway, with sites in the U.S., Canada, Japan, and South Korea either recruiting now or in the future. The trial aims to enroll up to 20 boys, ages 4 to 14, with DMD mutations amenable to exon 44 skipping. After a first part where multiple dose levels will be tested, the second part will assess the maximum tolerated dose of brogidirsen, given weekly for 24 weeks. The therapy’s safety, tolerability, pharmacological profile, and efficacy, including its effects on dystrophin production and motor function, will be analyzed.
The therapy received both rare pediatric disease and breakthrough therapy designations for DMD from the U.S. Food and Drug Administration in 2023.
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