Ziresovir Cleared by FDA for Phase 2 Trial, With Infants and Young Children With Severe RSV the Key Test

When respiratory syncytial virus (RSV) sends an infant to the intensive care unit, clinical management still largely relies on oxygen, respiratory support, and other supportive care. Shanghai Ark Biopharmaceutical said the US Food and Drug Administration (FDA) has cleared a Phase 2 trial of ziresovir, allowing this direct-acting antiviral to enter the population of infants and young children with severe disease who have the greatest need for treatment—and in whom rigorous evidence is also the hardest to obtain.

The US study will use a randomized, placebo-controlled design and enroll infants and young children hospitalized with severe RSV infection, including patients in pediatric intensive care units. A version of the company’s application submitted to the Hong Kong Stock Exchange in March this year had planned to enroll approximately 80 participants, and the company had at one point sought FDA approval to proceed directly to Phase 3. The regulator’s clearance of a Phase 2 trial now means that ziresovir must first supplement the efficacy and safety data in US children with severe disease through a smaller study.

Under the previous plan, the primary assessment tool was the Pediatric Clinical Progression Scale (CPS-Ped), which evaluates whether patients’ overall clinical course improves; the Wang bronchiolitis clinical score was to be used for secondary analysis. This design examines not only symptoms such as wheezing, respiratory rate, and chest wall retractions, but also seeks to capture clinical changes as severely ill patients move from intensive respiratory support toward recovery.

Ziresovir is an oral RSV fusion protein inhibitor that works by interfering with the virus’s entry into cells. The Phase 3 AIRFLO trial in China enrolled children aged 1 to 24 months who were hospitalized with RSV. After five days of treatment, the improvement in the Wang score on Day 3 was 0.8 points greater in the ziresovir group than in the placebo group, and the reduction in viral load was also greater on Day 5. The proportions of drug-related adverse events were 16% and 13%, respectively, but resistance-associated viral mutations were detected in 9% of participants in the treatment group.

A prespecified analysis of the more vulnerable subgroup of infants younger than 6 months likewise showed improvement in symptom scores, with no drug-related serious adverse events or deaths. The company’s application documents also stated that, after combining existing AIRFLO data, pediatric intensive care unit stays were 2.5 days shorter in the ziresovir group than in the placebo group. However, few patients in the previous Phase 3 trial were in intensive care at baseline, making this result more appropriately viewed as a signal supporting the new study rather than confirmatory evidence.

Multinational validation remains the next hurdle. The Phase 3 AIRFLO trial was conducted entirely in China, and regional differences in hospitalization criteria and supportive treatment may affect the results. The reduction in parent-reported wheezing observed during 24 months of follow-up also cannot, based on subgroup analysis alone, prove that the drug can prevent long-term respiratory sequelae. The comprehensive QT cardiac safety assessment previously requested by the FDA has been accepted, but the new trial must still clarify the actual extent of recovery in infants with severe disease, safety, and whether resistance mutations affect clinical benefit.