NS Pharma's investigational antisense oligonucleotide, NS-050/NCNP-03, has received rare pediatric disease designation from the FDA for the treatment of Duchenne muscular dystrophy (DMD) amenable to exon 50 skipping therapy. This designation aims to expedite the development of the therapy for this rare and severe condition affecting young boys. The company plans to investigate NS-050/NCNP-03 in a phase 1/2, first-in-human, multicenter study (NCT06053814) in the United States, which was cleared by the FDA in June 2023.
The phase 1/2 study will evaluate the safety, efficacy, tolerability, pharmacodynamics, and pharmacokinetics of NS-050/NCNP-03 in ambulant boys with DMD aged 4 to 15 years. The trial, known as METEOR50, is a two-part study. Part 1 is a randomized, double-blinded study with 9 participants receiving escalating intravenous doses of NS-050/NCNP-03 or placebo once-weekly for 2 weeks per dose level. The primary objectives for Part 1 are to assess safety, tolerability, and pharmacokinetics.
Part 2 will involve 11 additional participants, including those from Part 1, receiving the maximum-tolerated dose from Part 1 once-weekly for 24 weeks. The primary objective for Part 2 is to investigate dystrophin protein levels in skeletal muscle. Secondary objectives include assessing safety, tolerability, dystrophin mRNA induction, and strength/mobility compared to a group-matched natural history control group.
DMD is an X-linked recessive disorder resulting from mutations in the dystrophin gene, leading to a deficiency of functional dystrophin protein. Exon-skipping therapies, like NS-050/NCNP-03, aim to modify dystrophin pre-mRNA splicing, facilitating the production of a functional dystrophin protein and potentially alleviating symptoms to improve patient quality of life. Exon 50 skipping therapy may benefit approximately 4% of patients with DMD by omitting specific genetic sequences within the dystrophin gene, generating a shortened but functional dystrophin protein.
Inclusion and Exclusion Criteria
Eligible participants must have the ability to walk independently and complete the time-to-stand assessment in less than 7 seconds without assistance. Key exclusion criteria include symptomatic cardiomyopathy, recent treatment with investigational drugs or gene therapies, and recent surgery.
Mechanism of Action
NS-050/NCNP-03 is designed to target exon 50 of the dystrophin gene. By skipping this exon during mRNA splicing, the therapy aims to produce a truncated but functional dystrophin protein. This approach has the potential to slow the progression of muscle function decline in patients with DMD who are amenable to exon 50 skipping.
Significance of Rare Pediatric Disease Designation
The FDA's rare pediatric disease designation is granted for serious or life-threatening diseases primarily affecting individuals aged 18 years or younger and impacting fewer than 200,000 people in the United States. This designation can help accelerate the development and review of NS-050/NCNP-03, potentially bringing a new treatment option to patients with DMD more quickly.
