A Phase 3 clinical trial conducted in China indicates that ziresovir, an investigational oral antiviral drug, significantly reduces the severity of bronchiolitis in infants and young children hospitalized with respiratory syncytial virus (RSV) infection. The multicenter, double-blind, randomized, placebo-controlled trial, published in The New England Journal of Medicine, found that ziresovir improved clinical outcomes and reduced viral load compared to placebo.
The AIRFLO trial enrolled 244 infants aged 1 to 24 months hospitalized with RSV. Participants were randomly assigned in a 2:1 ratio to receive either ziresovir (10 to 40 mg, based on body weight) or placebo, administered twice daily for five days. The primary outcome was the change in the Wang bronchiolitis clinical score from baseline to day 3, with secondary outcomes including reductions in RSV viral load by day 5.
Significant Improvement in Clinical Outcomes
The trial demonstrated that ziresovir significantly improved clinical outcomes. The reduction in the Wang bronchiolitis clinical score by day 3 was significantly greater in the ziresovir group compared to the placebo group (-3.4 points vs -2.7 points; P = .002). Additionally, ziresovir led to a larger reduction in RSV viral load by day 5 (-2.5 vs -1.9 log10 copies/mL), indicating enhanced antiviral activity.
"RSV infection has long been a serious medical challenge in pediatric health care," said Xin Ni, MD, PhD, a leading principal investigator at Beijing Children's Hospital, Capital Medical University. "This virus not only poses a threat to children's health, but also places a heavy burden on our health care system. For a long time, we have been searching for a safe and effective treatment."
Safety and Tolerability
Adverse events were comparable between the ziresovir and placebo groups. Common adverse events included diarrhea (4% in the ziresovir group vs 2% in the placebo group), elevated liver enzyme levels (3% in both groups), and rash (2% vs 1%). Notably, 9% of participants in the ziresovir group developed resistance-associated mutations, but no significant safety concerns were identified overall.
Limitations and Future Directions
The researchers acknowledged limitations, including the fact that the Wang bronchiolitis clinical score is not fully validated in studies of RSV infections, and the study was conducted exclusively in China. Edward Walsh, MD, of the University of Rochester in New York, noted that it remains to be seen whether changes in the bronchiolitis score correlate with important outcomes such as earlier hospital discharge or fewer ICU admissions.
Despite these limitations, the researchers believe these findings suggest ziresovir could offer an effective therapeutic option for RSV in young children. Jim Wu, PhD, CEO of ArkBio, which is developing ziresovir, stated, "Under the guidance of the regulatory agencies, we will continue to develop the drug in collaboration with the medical community. We are committed to the research and development of innovative medicines to safeguard the wellbeing and healthy growth of children."
