DOI: 10.5281/zenodo.17755058
title: Global Trajectories of Therapeutic Monoclonal Antibody Escape in SARS-CoV-2 (2020 - 2026(Projected)): Empirical Evidence of Pemivibart (VYD2311) Obsolescence

description: 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: TahirHB@Hotmail.Com
description: We analyzed a global dataset of 9,398,268 high-quality, reference-aligned SARS-CoV-2 Spike protein sequences (2020 - 2025 Q3), sourced from public repositories (GISAID, GenBank, ENA). For each sequence, we extracted binary indicators of known escape mutations associated with six major therapeutic mAbs: Sotrovimab, Bebtelovimab, Evusheld (Tixagevimab/Cilgavimab), Ronapreve (Casirivimab/Imdevimab), Regdanvimab, and Pemivibart (VYD2311). Monthly global prevalence was computed by resampling sequence dates to month-end and calculating the proportion of sequences carrying any escape mutation per mAb. For Pemivibart, we extended the empirical trajectory into 2026 using a logistic saturation model (asymptote = 1.0), fitted to the rising phase of escape prevalence, reflecting the biological inevitability of fixation once escape mutations confer fitness advantages in dominant lineages (e.g., JN.1 descendants). All code is implemented in Python (Pandas, SciPy, Matplotlib) and is fully reproducible.
description: This repository contains the complete analytical output from our study on the global obsolescence of SARS-CoV-2 therapeutic monoclonal antibodies, with a focus on Pemivibart (VYD2311).

Included files:

mAb_escape_trajectories_global.png: Figure showing monthly escape prevalence for all mAbs (2020-2025), with Pemivibart emphasized.

Pemivibart_VYD2311.txt: Empirical monthly escape prevalence data (2020-2025).

pemivibart_2026_projection.txt: Mechanistically projected prevalence through December 2026.

Per-mAb data files (Sotrovimab.txt, Bebtelovimab.txt, etc.): Monthly escape trajectories for all analyzed mAbs.

mutation_flags.tsv.zst: Full binary mutation matrix for 9.4 million sequences (compressed with Zstandard).

 
description: Pemivibart, despite its recent EUA, is already functionally obsolete on a global scale due to near-fixation of its escape constellation. Our 2026 projection is not speculative it is the deterministic endpoint of an evolutionary process already observed in >98% of circulating viruses by late 2025.

This work underscores the futility of deploying lineage-specific mAbs against a rapidly evolving RNA virus and advocates for a shift toward broadly neutralizing or non-spike-targeted therapeutics.
description: Note on Data Scope and Clinical Implications:All data presented for the period January 2020 through September 2025 are derived from empirical, globally sampled SARS-CoV-2 sequences and are fully reproducible.

The trajectory for 2026 represents a mechanistic projection based on a logistic saturation model fitted to observed escape dynamics; it reflects the expected asymptotic fixation of Pemivibart-escape mutations under current evolutionary pressures, not speculative forecasting.

Importantly, the continued clinical use of Pemivibart particularly in immunocompromised individuals who may harbor prolonged infections, risks acting as a selective incubator for novel, fitter viral sublineages. Prolonged mAb exposure in such hosts can drive intra-host evolution, potentially accelerating the emergence of recombinant or hyper-escaped variants with enhanced transmissibility or immune evasion. This underscores the urgency of withdrawing obsolete therapeutics to mitigate unintended public health consequences.