The Lancet Publishes Ziresovir Phase III RSV Trial in Infants Under 6 Months

SHANGHAI, April 16, 2025 /PRNewswire/ -- The Lancet Child & Adolescent Health, a leading international journal in pediatric and adolescent medicine, has published the Phase III clinical trial results of ziresovir, a novel RSV-targeted antiviral drug developed by Shanghai Ark Biopharmaceutical Ltd. The article, titled "Efficacy and safety of ziresovir in hospitalised infants aged 6 months or younger with respiratory syncytial virus infection in China: findings from a phase 3 randomised trial with 24-month follow-up", presents detailed subgroup analysis of infants under six months of age, following the primary results published in The New England Journal of Medicine in September 2024.

Image credit: The Lancet Child & Adolescent Health

RSV: An Urgent Unmet Medical Need

Respiratory syncytial virus (RSV) is a leading cause of hospitalization and mortality in children under six years old. With millions of cases annually worldwide, especially among infants under six months, RSV imposes a significant burden on families and healthcare systems. Current treatments are limited to symptomatic and supportive care, with no approved direct-acting antiviral therapies available.

Ziresovir's Phase III results mark a significant milestone, representing the first clinical validation of an antiviral's efficacy in hospitalized infants ≤6 months, and demonstrating long-term benefits in reducing recurrent wheezing and asthma.

Study Design

This multicenter, randomized, double-blind, placebo-controlled Phase III trial was conducted at 30 sites in 28 hospitals across China. The trial included two parts:

• Part 1 assessed safety and pharmacokinetics
• Part 2 evaluated clinical efficacy and antiviral effects

Infants were randomized in a 2:1 ratio to receive ziresovir or placebo for five days, with a 24-month follow-up. The latest publication focuses on infants aged six months or younger.

Key Findings

1. Significant Efficacy

• Improved Bronchiolitis Symptoms: By Day 3, ziresovir-treated infants had a 3.5-point reduction in Wang Bronchiolitis Clinical Score (WBCS), compared to 2.2 points in the placebo group—a 54.5% difference (p<0.001). Improvements in respiratory rate, wheezing, and retractions were also statistically significant (p<0.05).
• Rapid Viral Load Reduction: By Day 5, viral load decreased by 2.51 log₁₀ copies/mL in the treatment group, versus 1.87 log₁₀ in the placebo group (p=0.024), confirming ziresovir's antiviral activity.
• Faster Symptom Relief: Time to wheezing resolution (HR=1.53, p=0.021) and retraction relief (HR=1.49, p=0.018) were shorter in the treatment group. Hospital stay and oxygen use showed a reduction trend, though not statistically significant.

2. Long-Term Safety and Respiratory Health Benefits

• Favorable Safety Profile: Treatment-emergent adverse events (TEAEs) occurred in 18% of the treatment group vs. 11% in placebo. No drug-related severe adverse events or deaths were reported.
• Reduced Risk of Recurrent Wheezing and Asthma:
  • Wheezing incidence was 3.6 times lower in the treatment group (0.18% vs. 0.65%, p=0.0048).
  • Wheezing episodes were reduced by 2.6 times (1.2 vs. 3.1 episodes).
  • Asthma rates were also lower (3% vs. 5%).

These long-term benefits suggest early antiviral intervention may reduce the risk of chronic respiratory conditions.

A New Era in RSV Treatment

Unlike existing RSV treatments focused solely on symptom relief, ziresovir is the first RSV-targeted antiviral therapy with demonstrated clinical efficacy in infants under six months—those most at risk of severe complications. These findings introduce a new therapeutic paradigm for RSV treatment and prevention of long-term sequelae.

The results were presented by Dr. Jim Wu, CEO of ArkBio, at the 13th International RSV Symposium in Brazil, receiving recognition from the global RSV research community.

Prof. Xin Ni, principal investigator of the Airflo study and professor at Beijing Children's Hospital, Capital Medical University, commented:

"This pivotal Phase III trial provides the first solid evidence of an effective antiviral treatment for RSV in high-risk infants. Following our initial publication in The New England Journal of Medicine, this deeper analysis in infants under six months published in The Lancet Child & Adolescent Health further validates ziresovir's safety, efficacy, and long-term benefit. We are proud of our team's commitment and look forward to bringing this drug to patients in China and worldwide."

For public readers, the article can be accessed at the following link:
https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(25)00067-7/fulltext