FDA Grants NS-050/NCNP-03 Rare Pediatric Disease Designation in Duchenne Muscular Dystrophy

Yukiteru Sugiyama, PhD

(Credit: NS Pharma)

According to a recent company announcement, the FDA has granted rare pediatric disease designation to NS Pharma’s NS-050/NCNP-03, an investigational antisense oligonucleotide treatment in development for patients with Duchenne muscular dystrophy (DMD) amenable to exon 50 skipping therapy.¹ The company will investigate NS-050/NCNP-03 in a phase 1/2, first-in-human, multicenter, 2-part study (NCT06053814) in the United States, which the agency cleared for initiation in June 2023.²

"The journey from first symptom to diagnosis and finally treatment can be long and challenging for patients with rare diseases and their caregivers," Yukiteru Sugiyama, PhD, the president at NS Pharma, said in a statement.¹ "We are grateful for this designation which can help us accelerate the development of this therapy for Duchenne."

The phase 1/2 study will assess the safety, efficacy, tolerability, pharmacodynamics, and pharmacokinetics of NS-050/NCNP-03 in ambulant boys with DMD aged at least 4 years to less than 15 years. The study outline, presented at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 3-6, in Orlando, Florida, by lead investigator Vamshi Rao, MD, revealed that eligible participants must have the ability to walk independently and complete the time-to-stand assessment in less than 7 seconds without any needed assistance.³ Investigators also noted that key exclusion criteria include symptomatic cardiomyopathy, recent treatment with investigational drugs or gene therapies, and recent surgery.

READ MORE: Avidity Biosciences Initiates Biomarker Cohort in Phase 1/2 FORTITUDE Trial, Seeks Accelerated Approval Path for AOC 1020

In Part 1, researchers will conduct a randomized, double-blinded study with 9 participants who will be randomized to receive escalating intravenous doses of NS-050/NCNP-03 or placebo once-weekly for 2 weeks/dose level. The primary objectives for this part of the study are assessing safety, tolerability, and pharmacokinetics of the investigational therapy. In Part 2, 11 additional participants, including participants from Part 1, will receive 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, with secondary objectives including assessment of safety, tolerability, dystrophin mRNA induction, and strength/mobility versus a group-matched natural history control group.

Duchenne is an X-linked recessive disorder caused by mutations in the dystrophin gene, leading to a deficiency of functional dystrophin protein. Exon-skipping therapies aim to modify dystrophin premRNA splicing, facilitating the production of a functional dystrophin protein and potentially alleviating symptoms to improve patient quality of life. Exon 50 skipping therapy, such as NS-050/NCNP-03, may benefit approximately 4% of patients with DMD by omitting specific genetic sequences within the dystrophin gene. This approach generates a shortened but functional dystrophin protein, which is anticipated to slow the progression of muscle function decline.

In a previous interview with NeurologyLive^®, Rao, an associate professor of pediatrics in neurology and epilepsy at Northwestern University Feinberg School of Medicine, discussed about how exon skipping therapies like NS-050/NCNP-03 work to address the mutations responsible for DMD. He also talked about the primary focus of the phase 1/2 trial, and why safety is considered a crucial aspect at this stage of the study. In addition, Rao spoke about how researchers hope to correlate changes in dystrophin protein levels with improvements in muscle function among patients with DMD using NS-050/NCNP-03 during the trial.

REFERENCES
1. FDA Grants Rare Pediatric Disease Designation to NS-050/NCNP-03 for the Treatment of Duchenne Muscular Dystrophy. News Release. NS Pharma. Published September 10, 2024. Accessed December 4, 2024. https://www.nspharma.com/pdfs/FDA-Grants-Rare-Pediatric-Disease-Designation-to-NS-050.pdf
2. NS Pharma Announces FDA Clearance to Initiate a Phase I/II Study for NS-050/NCNP-03, an Exon 50 Skipping Candidate for the Treatment of Duchenne Muscular Dystrophy. News Release. NS Pharma. Published June 15, 2023. Accessed December 4, 2023. https://www.prnewswire.com/news-releases/ns-pharma-announces-fda-clearance-to-initiate-a-phase-iii-study-for-ns-050ncnp-03-an-exon-50-skipping-candidate-for-the-treatment-of-duchenne-muscular-dystrophy-301851575.html
3. Rao VK, Finanger EL, Previtera ML, et al. T A Phase 1/2 study of NS-050/NCNP-03, an investigational exon 50 skipping therapy, in boys with Duchenne muscular dystrophy (Meteor50): Trial design. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Poster M160. Accessed December 4, 2024. https://www.mdaconference.org/abstract-library/a-phase-1-2-study-of-ns-050-ncnp-03-an-investigational-exon-50-skipping-therapy-in-boys-with-duchenne-muscular-dystrophy-meteor50-trial-design/