Antisense oligonucleotide (ASO) drugs have shown significant progress in clinical development, targeting a wide range of diseases, from rare genetic disorders to more common conditions. Since the approval of the first ASO drug, Fomivirsen, in 1998, the pipeline has expanded substantially. Here are some key ASO drugs currently in clinical stages: 

Approved ASO Drugs 

     ●      Nusinersen (Spinraza): Approved in 2016 by the FDA for treating spinal muscular atrophy (SMA). It enhances the production of functional SMN protein. 

     ●      Eteplirsen: Approved for Duchenne muscular dystrophy (DMD), it promotes exon skipping to restore functional dystrophin protein. 

     ●      Inotersen: Approved for hereditary transthyretin-mediated amyloidosis (hATTR), it reduces transthyretin protein levels to slow disease progression. 

ASO Drugs in Clinical Trials 

     ●      Tominersen: Designed for Huntington’s disease, it reduces mutant huntingtin protein levels. Currently in Phase II clinical trials. 

     ●      ON363: Targets FUS-related amyotrophic lateral sclerosis (ALS) by decreasing FUS protein production. It has reached Phase III clinical trials. 

     ●      ALG-020572: A novel ASO for chronic hepatitis B (CHB) treatment, currently in Phase I trials. 

     ●      IONIS-TTR-LRx: A liver-targeting ASO for hATTR amyloidosis, improving delivery efficiency with GalNAc conjugation. 

Global and Regional Progress

ASO development is advancing globally, with contributions from leading biotechnology companies and institutions. In China, domestic enterprises such as Hengrui Medicine are developing ASO drugs, with 16 oligonucleotide-based candidates approved for clinical studies, marking a significant milestone in local innovation. 

The ASO clinical pipeline has grown to address diverse diseases, including neurodegenerative disorders, rare genetic diseases, and viral infections. Advances in chemical modifications, delivery systems, and disease-specific targeting continue to drive the evolution of ASO therapeutics. These developments promise to bring more ASO drugs to market, benefiting patients worldwide.