Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
In recent years, there has been an increase in the development of oligonucleotide therapeutics, a new modality in addition to small molecule drugs and antibody drugs. There are no ICH guidelines for the non-clinical safety assessment of oligonucleotide drugs, and Japan alone has issued domestic guidelines (Guideline for Nonclinical Safety Assessment of Nucleic Acid Pharmaceuticals, March 2020). This guideline is a hybrid of the existing biopharmaceutical guideline (ICH S6) and small molecule drug guideline (ICH M3), and provide in addition a strategy for the assessment of hybridization-dependent off-target effects, a unique challenge for nucleic acid drugs. ICH S6 and ICH M3 represent the only guidance for the non-clinical safety assessment of oligonucleotide therapeutics that we can refer to.
Viltolarsen was approved in Japan in March 2020 as the first domestically produced antisense oligonucleotide drug. It was jointly developed by the National Center of Neurology and Psychiatry and Nippon Shinyaku Co., Ltd. for the treatment of Duchenne muscular dystrophy (DMD). DMD is a lethal X-linked recessive neuromuscular disorder caused by mutations in the dystrophin gene that result in the absence or near absence of functional dystrophin protein. In patients with DMD, progressive degeneration of muscle tissue results in muscle weakness, associated motor delays, loss of ambulation, respiratory impairment, and cardiomyopathy. Yet there has been no fundamental treatment until now. Viltolarsen is expected to suppress the progression of the disease by inducing the production of new dystrophin protein.
In this presentation, we present the results of nonclinical studies of viltolarsen as an example of non-clinical safety evaluation of nucleic acid drugs in comparison with the aforementioned Japanese guideline for nucleic acid drugs.
