An evaluation of sipavibart for pre-exposure prophylaxis of COVID-19 in immunocompromised individuals

INTRODUCTION: The COVID-19 pandemic has disproportionately affected immunocompromised individuals, who remain at risk for severe disease despite widespread vaccination efforts. Poor vaccine-induced humoral responses in this population necessitate additional preventive strategies. Sipavibart (AZD3152) is a next-generation long-acting monoclonal antibody designed to target the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein and provide broad-spectrum neutralization against divergent variants. AREAS COVERED: This review evaluates sipavibart's preclinical pharmacology, pivotal and supportive clinical trial data, and early real-world evidence, including the SUPERNOVA Phase 3 trial and national early-access programs. We discuss its safety profile, variant-specific activity, and resistance challenges. EXPERT OPINION: Sipavibart was the first monoclonal antibody to show efficacy and safety in preventing symptomatic COVID-19 among immunocompromised individuals, protecting for up to six months. However, the widespread circulation of variants harboring S:F456L currently limits its clinical utility, and use should be restricted. Maintaining access to Sipavibart remains justified, as future antigenic shifts could restore its activity. Its deployment should rely on genomic surveillance and local epidemiology. At the same time, next-generation mAbs should prioritize conserved spike regions and multi-epitope cocktails to counter viral evolution and prolong therapeutic value.