Pharmacokinetics and pharmacodynamics of mepolizumab, an anti–interleukin 5 monoclonal antibody, in healthy Japanese male subjects

Interleukin 5 (IL‐5) and eosinophils are thought to play an important role in the pathology of asthma. This study evaluated the pharmacokinetics, pharmacodynamics, safety, and tolerability of mepolizumab, a humanized anti‐IL5 IgG1 monoclonal antibody, in development for the treatment of severe eosinophilic asthma. This single‐blind study randomized 35 healthy Japanese male subjects (3:1) to receive either a single mepolizumab intravenous dose (10, 75, 250, or 750 mg) or placebo. Subjects were observed for up to 151 days postdose, depending on the dose administered. Blood samples were collected to measure mepolizumab concentrations, blood eosinophils, IL‐5, and antibodies to mepolizumab. Mepolizumab exhibited dose‐proportional pharmacokinetics. The terminal phase half‐life was 19.7–34.6 days, independent of dose. Higher mepolizumab plasma concentrations were associated with lower blood eosinophil counts. Mepolizumab 75–750 mg reduced blood eosinophils for ≥3 months postdose. Mepolizumab demonstrated a favorable safety profile: of 41 reported adverse events, most were mild in severity and none were serious. No neutralizing antibodies to mepolizumab were detected. Sustained reduction in blood eosinophils after single intravenous mepolizumab doses ≥ 75 mg, along with mepolizumab pharmacokinetics and a favorable tolerability profile in healthy Japanese subjects, provides a solid foundation for future studies with mepolizumab in Japanese patients with asthma.