Global Trajectories of Therapeutic Monoclonal Antibody Escape in SARS-CoV-2 (2020 - 2026(Projected)): Empirical Evidence of Pemivibart (VYD2311) Obsolescence

Therapeutic monoclonal antibodies (mAbs) have played a pivotal role in the clinical management of SARS-CoV-2 infection. However, the virus’s rapid evolution has systematically eroded their efficacy. Here, we present a comprehensive, global-scale analysis of escape mutation prevalence across >9.4 million Spike protein sequences (January 2020 - September 2025), tracking functional obsolescence of all major emergency-use authorized mAbs. We demonstrate that Pemivibart (VYD2311), the most recently authorized mAb (2025), has already succumbed to near-complete global escape via the co-fixation of key RBD mutations including R346T, S371F, K444T, N460K, and F486P with prevalence exceeding 98% by late 2025. Using a biologically constrained logistic growth model fitted to empirical monthly trajectories, we project that Pemivibart’s escape will reach asymptotic fixation (>99.9%) across all circulating lineages by early 2026, rendering it clinically non-viable. This dataset provides the definitive real-world evidence of Pemivibart’s functional obsolescence and serves as a quantitative foundation for therapeutic policy revision, regulatory re-evaluation, and future mAb design. Study By: [e-mail]