The pharmacokinetics and safety comparison of Zamerovimab and Mazorelvimab monoclonal antibodies vs. HRIG in category III rabies post-exposure prophylaxis: a stratified analysis by wound characteristics

• Published in: Biologicals Vol. 92; p. 101852
• Main Authors: Liu, Xiaoqiang, Zha, Yongxian, Wang, Zhengxiong, Jiang, Ya, Zhang, Xiangyu, Guo, Jiangshu, Li, Jingyu, Zhang, Qingchao, Tsao, Eric
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2025
• Subjects: mAb cocktail; Rabies; RVNA; Wound characteristics; RVNA; Wound characteristics; Rabies; mAb cocktail
• ISSN: 1045-1056; 1095-8320; 1095-8320
• DOI: 10.1016/j.biologicals.2025.101852

To compare rabies virus neutralizing antibody (RVNA) kinetics and safety profiles of Zamerovimab and Mazorelvimab monoclonal antibodies (mAbs) versus human rabies immunoglobulin (HRIG) in Category III rabies-exposed patients with heterogeneous wound characteristics. In this randomized, double-blind, phase III trial, 1000 participants with Category III exposure were stratified into single-wound (n = 735) and multi-wound (n = 265) subgroups. Subjects received either 0.3 mg/kg mAbs (n = 750) or 20 IU/kg HRIG (n = 250) on Day 0, followed by Essen regimen vaccination. RVNA levels were quantified by Rapid Fluorescent Foci Inhibition Test (RFFIT) at 0, 3, 7, 14, and 42 days. Primary endpoints included RVNA geometric mean concentration (GMC), seroconversion rate (RVNA ≥0.5 IU/mL) and incidence of adverse events (AEs). The mAbs-treated subgroups exhibited significantly higher RVNA GMCs than HRIG at early timepoints (e.g., Day 3, single-wound subgroups: 4.552 vs. 0.297 IU/mL; multi-wound subgroups: 4.06 vs. 0.305 IU/mL), achieving over 99.8 % seroconversion by Day 3. The mAbs showed similar or higher RVNA seroconversion rates in multi-wound subgroup compared to single-wound subgroup, while HRIG exhibited lower serum positivity rates. AEs were more common in HRIG recipients across both single-wound and multi-wound subgroups (mAbs: 41.9 %, 42.4 %; HRIG: 55.3 %, 54.8 %). Treatment-related AEs were also higher in HRIG groups (mAbs: 26.3 %, 27.1 %; HRIG: 39.9 %, 48.4 %), particularly in multi-wound subgroups. Most local and systemic AEs were mild to moderate in severity. No suspected rabies cases or deaths occurred through the 365-day study period, and no participants withdrew due to AEs. Zamerovimab and Mazorelvimab achieves earlier and higher RVNA titers than HRIG across diverse wound types, with comparable safety. In multi-wound exposures, mAbs therapy demonstrates superior RVNA seroconversion rate and reduced reactogenicity compared to HRIG, providing robust evidence for its preferential use in high-risk rabies exposures. ClinicalTrials.gov #NCT04644484.