A LARGE Phase III trial has found that onradivir, a novel PB2 polymerase inhibitor, significantly shortens recovery time in adults with uncomplicated influenza A, offering a promising alternative to oseltamivir.
Onradivir (ZSP1273) previously showed potential in a Phase II trial, where a 600 mg daily dose reduced time to recovery when administered within 48 hours of symptom onset. In this new randomised, double-blind, placebo- and oseltamivir-controlled Phase III study, researchers assessed the efficacy and safety of onradivir in a broader population. Conducted across 68 clinical sites in China, the trial enrolled adults aged 18–64 years who tested positive for influenza A via rapid antigen testing, had a fever ≥38°C, and reported at least one moderate systemic and one moderate respiratory symptom. Participants were randomly assigned in a 2:1:1 ratio to receive onradivir (600 mg once daily), oseltamivir (75 mg twice daily), or placebo for 5 days.
Of 943 patients screened, 702 tested positive for influenza A and were included in the intention-to-treat infection analysis: 349 received onradivir, 177 oseltamivir, and 176 placebo. Median time to alleviation of symptoms was significantly shorter in the onradivir group compared to placebo (38.83 hours [95% CI: 35.32–41.18] vs 63.35 hours [55.48–68.48], p<0.0001), with a hazard ratio of 1.53 (95% CI: 1.27–1.85). Time to alleviation of symptoms for onradivir was similar to that of oseltamivir (42.17 hours [38.27–52.83], p=0.092). Adverse events were reported in 67% of onradivir recipients, 55% of placebo, and 47% of oseltamivir participants. Diarrhoea was more frequent with onradivir (49%), though most cases were mild, lasted a median of 2 days, and resolved without intervention.
These findings support onradivir as a clinically effective alternative to oseltamivir for uncomplicated influenza A. Its efficacy and tolerable safety profile may make it a valuable option in the face of rising antiviral resistance.
Reference
Yang Z et al. Efficacy and safety of onradivir in adults with acute uncomplicated influenza A infection in China: a multicentre, double-blind, randomised, placebo-controlled and oseltamivir-controlled, phase 3 trial. Lancet Respir Med. 2025; DOI: 10.1016/S2213-2600(25)00046-3.
