Shanghai-based Ark Biopharmaceutical's novel RSV antiviral drug ziresovir has demonstrated significant clinical efficacy and long-term respiratory benefits in hospitalized infants under six months of age, according to Phase III trial results published in The Lancet Child & Adolescent Health.
The findings represent a potential paradigm shift in RSV treatment, as ziresovir becomes the first direct-acting antiviral therapy to show efficacy in this high-risk population. The detailed subgroup analysis follows primary results previously published in The New England Journal of Medicine in September 2024.
Addressing a Critical Unmet Need
Respiratory syncytial virus (RSV) remains a leading cause of hospitalization and mortality in young children, particularly those under six months of age. Current treatment options are limited to supportive care, with no approved direct-acting antivirals available for this vulnerable population.
"This pivotal Phase III trial provides the first solid evidence of an effective antiviral treatment for RSV in high-risk infants," said Prof. Xin Ni, principal investigator of the Airflo study and professor at Beijing Children's Hospital, Capital Medical University. "Following our initial publication in The New England Journal of Medicine, this deeper analysis in infants under six months further validates ziresovir's safety, efficacy, and long-term benefit."
Trial Design and Key Efficacy Findings
The multicenter, randomized, double-blind, placebo-controlled Phase III trial was conducted across 30 sites in 28 hospitals throughout China. Infants were randomized in a 2:1 ratio to receive either ziresovir or placebo orally for five days, with a comprehensive 24-month follow-up period.
By day three, infants treated with ziresovir showed a 3.5-point reduction in Wang Bronchiolitis Clinical Score (WBCS), compared to just 2.2 points in the placebo group—representing a 54.5% relative improvement (p<0.001). Statistically significant improvements were also observed in respiratory rate, wheezing, and chest retractions (p<0.05).
The antiviral activity of ziresovir was confirmed through viral load measurements, with treated infants experiencing a 2.51 log₁₀ copies/mL reduction by day five, versus 1.87 log₁₀ in the placebo group (p=0.024).
Time to symptom resolution was notably faster in the treatment group, with hazard ratios of 1.53 for wheezing resolution (p=0.021) and 1.49 for retraction relief (p=0.018). While trends toward shorter hospital stays and reduced oxygen use were observed, these differences did not reach statistical significance.
Long-Term Respiratory Benefits
Perhaps most striking were the long-term respiratory health benefits observed during the 24-month follow-up period. Infants who received ziresovir experienced:
- 3.6 times lower incidence of recurrent wheezing (0.18% vs. 0.65%, p=0.0048)
- 2.6 times fewer wheezing episodes overall (1.2 vs. 3.1)
- Lower asthma rates (3% vs. 5%)
These findings suggest that early antiviral intervention during RSV infection may significantly reduce the risk of developing chronic respiratory conditions, addressing a major concern for pediatricians and parents alike.
Safety Profile
The treatment was generally well-tolerated, with treatment-emergent adverse events occurring in 18% of the ziresovir group compared to 11% in the placebo group. Importantly, no drug-related severe adverse events or deaths were reported during the study.
Mechanism of Action
Ziresovir represents a first-in-class approach to RSV treatment. The oral small-molecule inhibitor targets the RSV fusion (F) protein, preventing viral entry and cell-to-cell transmission by blocking syncytia formation—a hallmark of RSV infection.
This mechanism differs fundamentally from existing RSV treatments that focus solely on symptom relief, potentially explaining the drug's ability to not only improve acute symptoms but also reduce long-term respiratory sequelae.
Regulatory Status and Future Outlook
The promising results have already earned ziresovir Breakthrough Therapy Designation from China's National Medical Products Administration (NMPA). The drug is the first oral RSV antiviral to successfully complete a pivotal Phase III trial with positive results.
Dr. Jim Wu, CEO of ArkBio, presented these findings at the 13th International RSV Symposium in Brazil, where they received recognition from the global RSV research community.
Global Impact
The burden of RSV is substantial worldwide. According to the Centers for Disease Control and Prevention, RSV causes approximately 2.1 million outpatient visits in pediatric patients under five years of age annually, with an additional 600,000 hospitalizations. It is the most common cause of hospital admission in children under one year of age.
If approved, ziresovir would address a significant gap in the treatment landscape for RSV, potentially reducing hospitalization duration, improving clinical outcomes, and preventing long-term respiratory complications in the most vulnerable infant population.
ArkBio has established strategic partnerships with several multinational pharmaceutical companies and academic institutes, including Roche, Genentech, and the Scripps Research Institute, positioning the company to potentially bring this innovative therapy to patients globally.
