Pharmacokinetics and safety of HIV fusion inhibitor Lipovirtide in non-human primates

Abstract

Lipovirtide, also known as LP-80, is a lipopeptide-based HIV fusion inhibitor with potent broad-spectrum and long-lasting antiviral activity. We recently reported the pharmacokinetics and safety of Lipovirtide in rats (Zhu et al. 2025); herein, its pharmacokinetics and safety profiles in cynomolgus macaques were systematically evaluated. Lipovirtide was rapidly absorbed after subcutaneous administration, with absolute bioavailability (F) of 110.11 % in male and 92.33 % in female. The time to reach maximum plasma concentration (T_max) ranged from 4 to 8 h, and the terminal half-life (T_1/2) was between 10.18 and 13.51 h. Comprehensive safety assessments revealed no significant effects on cardiovascular or respiratory functions in conscious macaques after a single subcutaneous administration. General toxicity studies demonstrated its excellent tolerability, with a maximum tolerated dose above 150 mg/kg for single dosing; the 4-week and 39-week repeated dosing determined the no-observed-adverse-effect level (NOAEL) to be 15 mg/kg. Toxicokinetic analyses confirmed that long-term administration did not lead to drug accumulation in both male and female animals. No anti-drug antibody (ADA) formation was observed throughout the study schedule. Collectively, our preclinical characterizations provide compelling data to support the clinical development of Lipovirtide, which has already progressed to a phase III clinical trial.