Infect Dis Ther. 2026 Feb 16. doi: 10.1007/s40121-026-01315-6. Online ahead of print.
ABSTRACT
INTRODUCTION: Neutralizing antibody titers are recognized as an acceptable surrogate efficacy endpoint for immunobridging next-generation monoclonal antibodies (mAbs) to those with demonstrated clinical efficacy for the prevention of COVID-19. However, titers measured at early time points after dosing overestimate levels required for clinical protection. Long-term efficacy data are limited due to continued evolution of SARS-CoV-2 and loss of activity of previously effective mAbs against emerging variants. We aimed to develop a predictive tool for efficacy using neutralizing titers to provide a framework for dose selection, target efficacy, and immunobridging of mAbs for the prevention of COVID-19.
METHODS: Drug concentration and clinical efficacy data collected over 12 months following pemivibart administration in the phase 3 CANOPY trial were used to develop a Cox proportional hazards model with time-varying covariate as a statistical immune correlates of protection model. The time-varying covariate was estimated serum virus neutralizing antibody activity, estimated at 2-week intervals by integrating drug concentration with weighted average IC50 (half-maximal inhibitory concentration) values of the circulating variant population. Clinical efficacy was predicted in immunocompromised and non-immunocompromised populations.
RESULTS: Efficacy increased with antibody titer in a non-linear manner, with smaller incremental gains at higher concentrations. Predicted efficacy was lower at all titer levels in the immunocompromised cohort. Model-derived estimates aligned well with observed infection outcomes and external analyses, supporting model validity. A titer of 1:500 predicted an estimated efficacy of 50% (immunocompromised) and 70% (non-immunocompromised).
CONCLUSION: The Cox model enables evaluation of suitable neutralizing titer targets to guide dosing, predict estimated clinical benefit for related mAbs derived from the same platform, and support immunobridging in both immunocompromised and non-immunocompromised populations.
TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT06039449.
PMID:41697535 | DOI:10.1007/s40121-026-01315-6
