brogidirsen (NS-089/NCNP-02) / Nippon Shinyaku, National Center of Neurology and Psychiatry - LARVOL DELTA

Brogidirsen -The First Dual-Targeting Exon 44 Skipping Drug for Duchenne Muscular Dystrophy Safety, Tolerability, and High Dystrophin Restoration in Long-Term Clinical Studies (ASGCT 2025) - P1/2, P2 | "These findings underscore Brogidirsen's safety and potential to modify the progression of DMD. The extension study is ongoing, and a Phase 2 trial in the USA (NCT05996003), sponsored by NS Pharma, Inc., is also in progress to further evaluate its safety and efficacy. Disease Focus of Abstract:Muscular Dystrophy (all forms)"

Clinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Psychiatry • MYOD1

Phase 1/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy. (PubMed, Cell Rep Med) - P1/2 | "These promising results warrant a subsequent trial for DMD. This study was registered at ClinicalTrials.gov (NCT04129294)."

Journal • P1/2 data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • TTN

Brogidirsen, an investigational exon 44 skipping agent for the treatment of Duchenne muscular dystrophy: Clinical trial design (Phase 2) (MDA 2024) - P2 | "Background: Brogidirsen (NS-089/NCNP-02) is being studied for the treatment of Duchenne muscular dystrophy (DMD) in patients with a dystrophin gene mutation amenable to exon 44 skipping... The design of this 2-part Phase 2 study was informed by the results of the previous Phase 1/2 trial that showed brogidirsen induced significant dystrophin production. The Phase 2 study has begun recruitment."

Clinical • P2 data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

NS-089/NCNP-02-201 in Boys With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: NS Pharma, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: May 2025 ➔ Sep 2025 | Initiation date: Aug 2023 ➔ Jan 2024 | Trial primary completion date: May 2025 ➔ Sep 2025

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

NS-089/NCNP-02 Receives Orphan Drug Designation from the European Commission for the Treatment of Duchenne Muscular Dystrophy (PRNewswire) - "NS Pharma, Inc...announced that, on December 13, 2023, the European Commission (EC) has granted orphan drug designation for NS-089/NCNP-02, which is being developed for the treatment of Duchenne muscular dystrophy (Duchenne), a rare and deadly genetic disorder that occurs primarily in males. There are various genetic mutations that cause Duchenne, and NS-089/NCNP-02 targets a gene mutation that can be treated by exon 44 skipping."

European regulatory • Duchenne Muscular Dystrophy • Genetic Disorders

Exon 44 skipping in Duchenne muscular dystrophy: NS-089/NCNP-02, a dual-targeting antisense oligonucleotide. (PubMed, Mol Ther Nucleic Acids) - "NS-089/NCNP-02 induced exon 44 skipping in skeletal and cardiac muscle of cynomolgus monkeys. In conclusion, NS-089/NCNP-02, an antisense oligonucleotide with a novel connected-sequence design, showed highly efficient exon skipping both in vitro and in vivo."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

NS-089/NCNP-02 Preclinical Data Published in Molecular Therapy Nucleic Acids (PRNewswire) - "The article, co-authored with the National Center of Neurology and Psychiatry, describes the process that led to the discovery of NS-089/NCNP-02 and its molecular properties, including nucleic acid sequences that target two separate sites within exon 44 of the dystrophin pre-mRNA sequence. The article also presents in vitro and in vivo preclinical efficacy data regarding dystrophin protein expression."

Preclinical • Duchenne Muscular Dystrophy

NS-089/NCNP-02-201 in Boys With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: NS Pharma, Inc.

New P2 trial • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

FDA Grants Orphan Drug Designation to NS-089/NCNP-02 for the Treatment of Duchenne Muscular Dystrophy (PRNewswire) - "NS Pharma, Inc. announced today the U.S. Food & Drug Administration (FDA) has granted Orphan Drug Designation to NS-089/NCNP-02, an investigational candidate for patients with Duchenne muscular dystrophy amenable to exon 44 skipping therapy. The FDA issues Orphan Drug Designations to support the development and evaluation of new treatments to prevent, diagnose, or treat a rare disease or condition."

Orphan drug • Duchenne Muscular Dystrophy • Genetic Disorders

FDA Grants Breakthrough Therapy Designation to NS-089/NCNP-02 for the Treatment of Duchenne Muscular Dystrophy (PRNewswire) - "NS Pharma, Inc. announced today the U.S. Food & Drug Administration (FDA) has granted Breakthrough Therapy Designation to NS-089/NCNP-02, an investigational candidate for patients with Duchenne muscular dystrophy amenable to exon 44 skipping therapy...The Breakthrough Therapy Designation for NS-089/NCNP-02 is based on results from a first-in-human, investigator-initiated clinical trial conducted in Japan...In July 2023, NS-089/NCNP-02 was granted Rare Pediatric Disease Designation by the FDA....Clinical development of NS-089/NCNP-02 includes a planned Phase 2 study in the United States conducted by NS Pharma and a Phase 2 study conducted in Japan by Nippon Shinyaku. Additional details will be provided once the trials are ready to begin enrolling participants."

Breakthrough therapy designation • FDA event • Duchenne Muscular Dystrophy • Genetic Disorders

Systemic administration of the antisense oligonucleotide NS-089/NCNP-02 for skipping of exon 44 in patients with Duchenne muscular dystrophy: Study protocol for a phase I/II clinical trial. (PubMed, Neuropsychopharmacol Rep) - "Exon-skipping therapy using ASOs shows promise in selected patients, and this first-in-human study is expected to provide critical information for subsequent clinical development of NS-089/NCNP-02."

Clinical protocol • Journal • P1/2 data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Recent Trends in Antisense Therapies for Duchenne Muscular Dystrophy. (PubMed, Pharmaceutics) - "These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown."

Journal • Review • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Extension Study of NS-089/NCNP-02 in DMD (clinicaltrials.gov) - P2 | N=6 | Active, not recruiting | Sponsor: Nippon Shinyaku Co., Ltd. | Trial completion date: Jul 2023 ➔ Jul 2026 | Trial primary completion date: Jan 2023 ➔ Jan 2026

Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Restoring Dystrophin Expression with Exon 44 and 53 Skipping in the DMD Gene in Immortalized Myotubes. (PubMed, Methods Mol Biol) - "In particular, PMOs for skipping exon 44 have been developing in clinical trials, such as the drug NS-089/NCNP-02. Two exon 53 skipping PMOs, golodirsen and viltolarsen, have received conditional approval for treating patients due to their ability to restore dystrophin protein expression...We introduce how to quantify exon-skipping efficiencies and dystrophin rescue levels represented by RT-PCR and western blotting, respectively. The screening methods using immortalized patient myotubes can serve to find exon-skipping PMO drug candidates."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

A Phase I/II study of NS-089/NCNP-02, Exon 44 skipping drug, in patients with Duchenne muscular dystrophy (WMS 2022) - "All motor function scales including NSAA consistently tend to decrease in part 1 stage, but their functions tend to improve in part 2 stage. Our first-in-human studies shall provide critical data of safety, potential efficacy and pharmacokinetics of NS-089/NCNP-02 for subsequent clinical development of NS-089/NCNP-02, with the ultimate aim of expanding treatment capacity for DMD and other neuromuscular conditions."

Clinical • P1/2 data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Exploratory Study of NS-089/NCNP-02 in DMD (clinicaltrials.gov) - P1/2 | N=6 | Completed | Sponsor: National Center of Neurology and Psychiatry, Japan | Enrolling by invitation ➔ Completed

Trial completion • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

A Phase I/II Study of NS-089/NCNP-02, Exon 44 Skipping Drug, in Patients with Duchenne Muscular Dystrophy (ASGCT 2022) - "We then compared the efficiency of exon 44 skipping induced by NS-089/NCNP-02 in differentiated MYOD1-UDCs (UDC-myotubes) and muscle biopsy samples from all the subjects. Our first-in-human studies shall provide critical data of safety, efficacy and pharmacokinetics of NS-089/NCNP-02 for subsequent clinical development of NS-089/NCNP-02, with the ultimate aim of expanding treatment capacity for DMD and other neuromuscular conditions."

Clinical • P1/2 data • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy • MYOD1

Exploratory Study of NS-089/NCNP-02 in DMD (clinicaltrials.gov) - P1/2 | N=6 | Enrolling by invitation | Sponsor: National Center of Neurology and Psychiatry, Japan | Trial completion date: Dec 2021 ➔ May 2022 | Trial primary completion date: Sep 2021 ➔ May 2022

Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Extension Study of NS-089/NCNP-02 in DMD (clinicaltrials.gov) - P2; N=6; Active, not recruiting; Sponsor: Nippon Shinyaku Co., Ltd.

Clinical • New P2 trial • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Exploratory Study of NS-089/NCNP-02 in DMD (clinicaltrials.gov) - P1/2; N=6; Enrolling by invitation; Sponsor: National Center of Neurology and Psychiatry, Japan; Trial primary completion date: Mar 2021 ➔ Sep 2021

Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy