A phase 3 study published in the New England Journal of Medicine reveals that ziresovir, an investigational drug, significantly reduces symptoms of bronchiolitis in infants and young children hospitalized with respiratory syncytial virus (RSV) infection.
The multicenter trial, led by Dr. Shunying Zhao from Beijing Children’s Hospital, found that by day 3, children treated with ziresovir experienced a significantly greater reduction in their Wang bronchiolitis clinical score compared to the placebo group (−3.4 vs. −2.7 points). By day 5, the ziresovir group also showed a more pronounced reduction in RSV viral load (−2.5 vs. −1.9 log10 copies/mL). Notably, subgroups with a baseline bronchiolitis score of at least 8 and those aged 6 months or younger showed marked improvements with ziresovir treatment.
Regarding safety, the incidence of treatment-related adverse events was similar between the groups, with 16% of children in the ziresovir group and 13% in the placebo group reporting adverse events. No severe adverse effects were attributed to the drug, indicating it is generally well tolerated.
RSV is a leading global cause of respiratory infections in young children, responsible for around 30 million respiratory infections annually, 3 million hospital admissions, and over 60,000 in-hospital deaths in children under five. Efforts to develop therapies have focused on the RSV class I trimeric fusion (F) glycoprotein, a key component for viral entry into host cells.
RSV infects cells by using its F protein to fuse the viral envelope with the host cell membrane, a process essential for viral replication. Ziresovir works by targeting the F protein in its prefusion state, preventing the structural changes needed for fusion. This blocks viral entry into host cells, reducing viral replication and the spread of infection. As a result, ziresovir lowers the viral load and alleviates bronchiolitis symptoms.
The drug has shown promising results in clinical trials, demonstrating significant reductions in both RSV viral load and bronchiolitis symptoms in hospitalized infants. It has been generally well tolerated, with no severe adverse events reported, making it a potentially valuable therapeutic option for managing RSV infections, particularly in pediatric populations where effective treatments are limited. These findings suggest that ziresovir could address a critical unmet need in pediatric respiratory care by becoming a valuable therapeutic option for managing RSV in young children.
References
- Zhao S, Shang Y, Yin Y, Zou Y, Xu Y, Zhong L, et al. Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection. New England Journal of Medicine. 2024 Sep 25;391(12):1096–107.
- Walsh EE. Creeping toward Effective Antiviral Agents for RSV Infection. New England Journal of Medicine. 2024 Sep 25;391(12):1155–6.
- Zheng X, Gao L, Wang L, Liang C, Wang B, Liu Y, et al. Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor. J Med Chem. 2019 Jul 11;62(13):6003–14.