Serum Virus-Neutralizing Antibody Titers in Clinical Trial Participants With and Without Immunocompromise Receiving Pemivibart, a Long-Acting Monoclonal Antibody for COVID-19

BACKGROUND: Pemivibart received emergency use authorization for COVID-19 prevention in certain individuals with immunocompromise based on immunobridging calculated serum virus-neutralizing antibody (csVNA) titers. We report an analysis of measured (msVNA) titers against SARS-CoV-2 variants before and after receipt of pemivibart in a SARS-CoV-2 immune-experienced population (CANOPY) and compare the relationship between csVNA and msVNA titers in 2 clinical trials. METHODS: The trials were conducted during 2023-2024. In the phase 3 CANOPY trial, participants with (cohort A) or without (cohort B) significant immunocompromise received 2 intravenous 4500-mg pemivibart or placebo infusions 90 days apart. In the phase 1 trial, healthy adults received a single intravenous dose of pemivibart (1500, 2500, or 4500 mg). msVNA titers were determined using a SARS-CoV-2 spike pseudotyped assay; csVNA titers were calculated as serum pemivibart concentrations divided by variant-specific IC50 values from in-vitro neutralization assays. RESULTS: In CANOPY, predose msVNA geometric mean titers (GMTs) to the dominant circulating XBB.1.5 lineage were low across cohorts (range, 78.6-119.8), suggesting inadequate protection. msVNA titers were substantially higher against earlier Delta (B.1.617.2) and BA.4/5 variants. Pemivibart increased the day-28 msVNA GMT >55-fold against XBB.1.5, with similar levels in both cohorts. Across trials, csVNA titers were significantly correlated with msVNA titers (all Spearman correlation coefficients ≥0.73, P < .0001). CONCLUSIONS: These data show that previous immune experience to earlier pandemic variants provided limited cross-protection and demonstrate that pemivibart increased protective titers against newly circulating SARS-CoV-2 in individuals with and without immunocompromise. Notably, csVNA titers effectively predicted pemivibart's neutralization potential.