Press Releases / Notices

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NEWS 2015

March 23, 2015 R & D

An Investigator-Initiated Clinical Trial of NS-065/NCNP-01 for the Treatment of Duchenne Muscular Dystrophy Has Been Completed

In an investigator-initiated clinical trial of NS-065/NCNP-01, the first clinical trial of an antisense oligonucleotide discovered in Japan, all administrations have been completed and dystrophin protein expression has been detected. On the basis of this result, we will commit to further development of this product.

National Center of Neurology and Psychiatry (NCNP, Kodaira City; President, Teruhiko Higuchi) and Nippon Shinyaku Co., Ltd. (Nippon Shinyaku; Headquarters, Kyoto City; President, Shigenobu Maekawa) have completed all administrations in an investigator-initiated clinical trial of a jointly developed product for the treatment of Duchenne Muscular Dystrophy (DMD) (Development Code, NS-065/NCNP-01).

This is the first clinical study of an antisense oligonucleotide discovered in Japan, NS-065/NCNP-01. The study was conducted at the National Center Hospital of NCNP in 10 patients suffering from DMD, and was composed of three dose groups (low, medium, and high doses). In the study, safety as a primary endpoint and efficacy, assessed by such measures as the expression of dystrophin protein, were investigated.

Early analysis by NCNP detected dystrophin mRNA with the amino acid reading frame restored by exon 53 skipping in every dose group. Furthermore, the expression of dystrophin protein which appeared to have been translated from such a mRNA was detected in the high-dose group. On the basis of these results, NS-065/NCNP-01 is expected to have therapeutic efficacy in DMD.

In addition, no serious adverse events were observed throughout the study, and no subjects discontinued administration. Anemia and a slight effect on renal function have been reported as general adverse events.

NCNP is currently conducting detailed evaluations of safety and dystrophin protein expression. Brief reports of the results of the study will be presented at relevant academic meetings such as the 18th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) and the 56th Annual Meeting of the Japanese Society of Neurology in May 2015.

Taking the results of the investigator-initiated clinical trial, Nippon Shinyaku takes over the study from NCNP under a joint development agreement, and is preparing for the next stage of clinical development with a view to launching this product in Japan in 2018.

    * The investigator-initiated clinical trial was supported by the following grants:
    •Health and Labor Sciences Research Grants
      - 2012–2014 Grant for Clinical Trial on Development of New Drugs and Medical Devices
    (Clinical Research and Clinical Trial Coordination/Management)
      - 2011–2013 Grant for Comprehensive Research on Disability Health and Welfare
     (Nervous and Muscular Diseases)
      - 2014 Grant for Comprehensive Research and Development on Disability Health and Welfare
        (Nervous and Muscular Diseases)
    •Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP

<Duchenne Muscular Dystrophy (DMD) and Exon Skipping Treatment>
DMD is an inherited muscle disorder with the highest incidence that is limited to male children. The onset of disease is due to a deficiency in dystrophin, a protein which constitutes the framework of muscle cells. This deficiency arises from mutation of the dystrophin gene and results in muscle degeneration and eventual death. Because there is no effective treatment for DMD other than steroids, which retard progression of the disease, an effective new treatment is urgently needed.

Exon skipping is a therapeutic approach based on the use of a synthetic oligonucleotide, known as an antisense oligonucleotide, to restore the amino acid reading frame by artificially skipping certain exons of the transcription product (mRNA) to be translated into protein. Applied to DMD, this approach produces a dystrophin protein that is shorter than normal but still functional, to improve muscle function. The exon to be skipped depends on the mutation type of the patient. NS-065/NCNP-01 skips exon 53.

This product is an antisense oligonucleotide drug synthesized from morpholino compounds, so that potency and high safety are expected. It has been developed as a therapeutic agent for DMD patients with mutation of the dystrophin gene amenable to exon 53 skipping, and it is expected to be an important option for the treatment of DMD.

<Oligonucleotide drugs>
Oligonucleotide drugs have the structure of nucleic acids, which are the constituents of genes, and they target certain causative genes of a disease. They work by stopping or regulating the production of protein from the target gene. They are often called next-generation medicines because they are expected to lead to treatment of diseases that are untreatable with existing small molecules, with high specificity and high safety.