Pharmacodynamic effect of benralizumab on blood basophils and serum biomarkers in adults with COPD with sputum eosinophilia

Rationale: Benralizumab is a humanized, afucosylated anti-IL-5Rα monoclonal antibody shown to reduce sputum and blood eosinophils and improve FEV₁ in a Phase 2a study in adults with GOLD II-IV COPD¹. An exploratory analysis investigated its effect on blood basophils and potential serum pharmacodynamic markers. Methods: The randomized, double-blind, placebo-controlled study was conducted in subjects on standard of care(n=101) with >1 COPD exacerbation and >3.0% sputum eosinophils in previous year¹. Subjects received subcutaneous benralizumab (100 mg) or placebo every 28-days (3 doses) then every 56-days (5-doses). Blood and serum were collected at Day 1 (baseline) and Days 29, 113, and 225. Blood basophils were evaluated using a hematology analyzer; serum was analyzed for biomarkers using multi-analyte protein profiling. Results: In comparison with placebo, benralizumab significantly suppressed (p<0.05) mean absolute blood–basophil count at Days 29 (23 vs 50 cells/μL), 113 (24 vs 54 cells/μL), and 225 (35 vs 56 cells/μL), with no significant effect on neutrophil counts, and was associated with significant (p<0.05) increases in CCL11/eotaxin-1 and CCL24/eotaxin-2 at Day 225 (105% and 45% respective increases relative to baseline). Conclusion: Eosinophils, blood basophils and the eosinophil chemokines were modulated with benralizumab administration and could serve as serum markers of treatment. Increased levels of the chemokines are not unexpected and may result from accumulation following removal of eosinophils. Other mechanisms may be involved. ¹Brightling CE et al. Lancet Resp Med. 2014. doi: 10.1016/S2213-2600(14)70187-0.