Fig. 5: External assessment of average overall efficacy from PROVENT ToP model using SUPERNOVA data.

*The PROVENT ToP model was developed against PROVENT data using a time-varying Cox model with adjustment for the treatment and its interaction with log₁₀(prevalence-adjusted nAb ID₅₀ titres + 1). The ToP model is used to estimate average overall efficacy (solid blue line) and two-sided 95% CI (shaded blue region) through assessment at the average prevalence-adjusted nAb ID₅₀ titre value up to each day since first dose using SUPERNOVA study data. ^†Observed efficacy was defined based on actual intervention as 100(1 – relative risk) (%) of sipavibart versus comparator, where relative risk (dashed red line) and two-sided 95% CI (shaded red region) were evaluated with Poisson regression with robust variance, which includes treatment and randomisation stratification factors as covariates and adjusted for the follow-up time at each day since first dose. Randomisation stratification factors were COVID-19 vaccination status within 6 months before randomisation (Yes or No), SARS-CoV-2 infection within 6 months before randomisation (Yes or No), and tixagevimab–cilgavimab use within 12 months before randomisation (Yes or No). The comparator group includes participants who received tixagevimab–cilgavimab followed by placebo and those who received two doses of placebo. CI confidence interval, COVID-19 coronavirus disease 2019, ID₅₀ 50% inhibitory dilution, nAb neutralising antibody, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, ToP threshold of protection.