L. Yan,1 L. Roskos,2 C. K. Ward,2 D. She,2 R. Merwe,3 B. Wang1; 1MedImmune, Mountain View, CA, 2MedImmune, Gaithersburg, MD, 3MedImmune, Cambridge, United Kingdom
BACKGROUND: Benralizumab is a humanized afucosylated monoclonal antibody that specifically binds to interleukin-5 receptor α and depletes eosinophils by antibody dependent cell cytotoxicity. Pharmacokinetics (PK) and pharmacodynamics (PD) of benralizumab were assessed in adult subjects with chronic obstructive pulmonary disease (COPD).
METHODS: In a double-blind, placebo controlled phase IIa study, adult subjects with moderate-to-severe COPD were randomized to receive subcutaneous injections of placebo or 100 mg benralizumab at weeks 1, 4, 8, 16, 24, 32, 40 and 48. Blood samples for serum PK evaluation and eosinophil count were collected at designated timepoints throughout the study. Empirical demographic covariate assessments were conducted based on the steady-state trough benralizumab concentrations (Ctrough,ss).
RESULTS: In COPD subjects the PK steady-state was reached at Week 16. The observed Ctrough,ss decreased with increasing body weight, although the majority of the PK variability was not explained by weight. Age, gender, baseline blood eosinophil count, and smoking status had no effect on benralizumab PK. Blood eosinophil counts were substantially reduced after the first dose of benralizumab and the suppression was maintained during the treatment period. The PK and PD of benralizumab in subjects with COPD were similar to those in asthma subjects receiving 100 mg benralizumab as previously investigated in another phase II study.
CONCLUSION: None of the demographic covariates except body weight impacted benralizumab PK in subjects with COPD. Comparable PK and PD of benralizumab in COPD and asthma subjects suggest that the 30 mg optimal benralizumab dose for asthma be further evaluated in phase III COPD pivotal trials.