Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma. Issue 2 (22nd March 2019)

• Record Type: Journal Article
• Authors: Chia, Yen Lin; Yan, Li; Yu, Binbing; Wang, Bing; Barker, Peter; Goldman, Mitchell; Roskos, Lorin
• Is Part Of: Clinical pharmacology & therapeutics. Volume 106:Issue 2(2019)
• Page Start: 383
• Page End: 390
• Publication Date: 2019-03-22
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1002/cpt.1371
• Languages: English
• ISSNs: 0009-9236

Abstract

Abstract : We evaluated the relationship between benralizumab (30 mg every 4 and 8 weeks (Q4W, Q8W)) pharmacokinetic (PK) exposure and end points of asthma exacerbation rates (AERs) and change from baseline in prebronchodilator forced expiratory volume in 1 second (FEV1 ) for patients with severe, uncontrolled eosinophilic asthma in the SIROCCO/CALIMA phase III trials. In empirical assessment, AER ratios in SIROCCO were similar across PK quartiles. However, the lowest PK quartile in CALIMA had reduced efficacy; low CALIMA placebo AER possibly confounded this result. In population modeling, estimated benralizumab 90% effective concentration for AER reduction was 927 ng/mL, below the Q8W dosage steady‐state average PK concentration (1, 066 ng/mL). Benralizumab treatment resulted in more rapid FEV1 improvement vs. placebo (estimated half‐maximum time: 7.6 vs. 18 days); this response was greater for patients with greater baseline eosinophil counts. These results confirmed 30 mg Q8W is the optimal benralizumab dosage for patients with severe eosinophilic asthma.