FDA Clears NS-050/NCNP-03 for Phase 1/2 Trial of Duchenne Muscular Dystrophy

Vamshi Rao, MD

In recent news, the FDA cleared the start of a phase 1/2 study assessing NS-050/NCNP-03, NS Pharma’s investigational candidate for patients with Duchenne muscular dystrophy (DMD) amenable to exon 50 skipping therapy.¹ Clinical trial enrollment for the trial in the United States is planned to start in the second half of 2023 and will be by NS Pharma's parent company, Nippon Shinyaku.

In the planned trial, patients with DMD will be assessed on dystrophin production, muscle strength, mobility, and functional exercise capacity. Once the trial is ready to begin the enrollment of participants, NS Pharma noted that additional information will then be provided. In addition to NS-050/NCNP-03, Nippon Shinyaku has 3 investigational exon skipping candidates in different stages of preclinical development for DMD.

"This is the second trial clearance from the FDA that NS Pharma has received this year and marks the third candidate from our R&D pipeline to begin clinical trials in Duchenne," Tsugio Tanaka, MSc, president at NS Pharma, said in a statement.¹ "Our rapid development plans reflect the urgent needs of the Duchenne community and our commitment to extending the impact of our exon skipping technology."

In July 2023, the FDA granted Breakthrough Therapy Designation to NS-089/NCNP-02 (brogidirsen), another similar candidate for patients with DMD amenable to exon 44 skipping therapy.² The decision was based on findings from a first-in-human, investigator-initiated clinical trial that was performed in Japan.³ Early that month, NS-089/NCNP-02 was granted Rare Pediatric Disease Designation by the FDA.⁴ The therapy, anantisense nucleotide developed between Nippon Shinyaku and the National Center for Psychiatry and Neurological Medicine, will be assessed in a phase 2 US-based study and a phase 2 Japan-based study.

"Exon skipping therapies have the potential to treat a wide range of patients with Duchenne, but more than half of patients with Duchenne potentially amenable to exon skipping therapy have no approved treatment options that target their specific mutation," Vamshi Rao, MD, associate professor of pediatrics in neurology and epilepsy, at Northwestern University Feinberg School of Medicine, said in a statement.¹ "That is why it is exciting that this year we are beginning studies of two treatments that have the potential to reach even more patients with targeted exon skipping therapies."

In other neuromuscular news, the FDA recently placed a clinical hold on PepGen’s investigational new drug application (IND) for its phase 1 study investigating PGN-EDODM1, an antisense oligonucleotide, in patients with myotonic dystrophy type 1 (DM1). The agency plans to provide an official clinical hold letter to the company stating the reasons for its decision within 30 days.⁵ PGN-EDODM1 is designed to deliver a small molecule that binds to CUG repeats and corrects defects in RNA processing, restoring the production of DMPK and allows the muscles to function properly again.

This news comes weeks following the company’s receival of a No Objection Letter from Health Canada for its clinical trial application to initiate a phase 2 open-label trial of PGN-EDO51 in patients with DMD amenable to exon 51 skipping. Also called CONNECT1-EDO51, the multiple-ascending dose trial will not be impacted by the clinical hold placed by the FDA. The therapy is expected to evaluate the agent in 3 cohorts of ambulatory and non-ambulatory boys and young men, with doses starting at 5 mg/kg and plans to escalate to 10 mg/kg and potentially other doses following Drug Safety Monitoring Board review.⁶

REFERENCES
1. 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 August 3, 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
2. FDA Grants Breakthrough Therapy Designation to NS-089/NCNP-02 for the Treatment of Duchenne Muscular Dystrophy. News Release. NS Pharma. Published July 27, 2023. Accessed August 3, 2023. https://www.prnewswire.com/news-releases/fda-grants-breakthrough-therapy-designation-to-ns-089ncnp-02-for-the-treatment-of-duchenne-muscular-dystrophy-301886646.html
3. Study shows the efficacy of antisense oligonucleotide-based exon 44 skipping drug, NS-089/NCNP-02, for patients with Duchenne muscular dystrophy (DMD) - Investigator-initiated Clinical Trial (First-in-human Trial) may lead to the world’s first effective drug for DMD amenable to exon 44 skipping. News Release. National Center of Neurology and Psychiatry. Published March 17, 2022. Accessed August 3, 2023. https://www.ncnp.go.jp/topics/2022/20220317e.html
4. FDA Grants Rare Pediatric Disease Designation to NS-089/NCNP-02 for the Treatment of Duchenne Muscular Dystrophy. News Release. NS Pharma. Published July 7, 2023. Accessed August 3, 2023. https://www.prnewswire.com/news-releases/fda-grants-rare-pediatric-disease-designation-to-ns-089ncnp-02-for-the-treatment-of-duchenne-muscular-dystrophy-301871598.html
5. PepGen announces clinical hold in the US on IND application to initiate a phase 1 study of PGN-EDODM1 for myotonic dystrophy. News release. PepGen. May 30, 2023. Accessed August 3, 2023. https://www.globenewswire.com/news-release/2023/05/30/2678819/0/en/PepGen-Inc-Announces-Clinical-Hold-in-the-U-S-on-IND-Application-to-Initiate-a-Phase-1-Study-of-PGN-EDODM1-for-Myotonic-Dystrophy-Type-1-DM1.html
6. PepGen announces clearance by Health Canada for PGN-EDO51 to begin the phase 2 clinical trial, CONNECT1-EDO51, for the treatment of Duchenne muscular dystrophy. May 18, 2023. Accessed August 3, 2023. https://www.biospace.com/article/releases/pepgen-announces-clearance-by-health-canada-of-cta-for-pgn-edo51-to-begin-the-phase-2-clinical-trial-connect1-edo51-for-the-treatment-of-duchenne-muscular-dystrophy/