Activity of Research-Grade Pemivibart against Recent SARS-CoV-2 JN.1 Sublineages

This NEJM letter investigates the neutralization capacity of a lab-synthesized version of pemivibart (Vivyd), a monoclonal antibody authorized for Covid-19 prophylaxis in immunocompromised individuals. Pemivibart, derived from ADG-2 with engineered mutations for enhanced breadth, was tested against evolving SARS-CoV-2 JN.1 sublineages, including KP.2, KP.3, KP.2.3, KP.3.1.1, and LB.1. While showing strong in vitro neutralization of JN.1 and KP.2, its potency declined against KP.3, KP.2.3, LB.1, and was significantly diminished against KP.3.1.1. The IC₅₀ for KP.3.1.1 was ~25× that of JN.1, raising concerns about mucosal efficacy despite sufficient serum levels. Structural resistance appeared linked to epistatic spike mutations, notably Q493E and F456L. Findings highlight the need for ongoing clinical monitoring of pemivibart’s protective performance amid rapid viral evolution.

This NEJM letter investigates the neutralization capacity of a lab-synthesized version of pemivibart (Vivyd), a monoclonal antibody authorized for Covid-19 prophylaxis in immunocompromised individuals. Pemivibart, derived from ADG-2 with engineered mutations for enhanced breadth, was tested against evolving SARS-CoV-2 JN.1 sublineages, including KP.2, KP.3, KP.2.3, KP.3.1.1, and LB.1. While showing strong in vitro neutralization of JN.1 and KP.2, its potency declined against KP.3, KP.2.3, LB.1, and was significantly diminished against KP.3.1.1. The IC₅₀ for KP.3.1.1 was ~25× that of JN.1, raising concerns about mucosal efficacy despite sufficient serum levels. Structural resistance appeared linked to epistatic spike mutations, notably Q493E and F456L. Findings highlight the need for ongoing clinical monitoring of pemivibart’s protective performance amid rapid viral evolution.