Pharmacokinetic/pharmacodynamic drug evaluation of benralizumab for the treatment of asthma

ABSTRACT

Introduction: In many severe asthmatics, eosinophils cause inflammation and airways hyperresponsiveness, resulting in frequent exacerbations, impaired lung function, and reduced quality of life. Interleukin-5 (IL-5) is a key cytokine for eosinophil growth, differentiation, recruitment, activation, and survival. Anti-IL-5-based therapies (mepolizumab and reslizumab are humanized monoclonal antibodies (hmAbs) that recognize free IL-5, benralizumab is a hmAb directed at the α subunit of the IL-5R) target the IL-5-signaling in eosinophilic asthma.

Areas covered: The pharmacodynamic/pharmacokinetic profile of benralizumab and how it provided indications that permitted optimization of the design and timelines of the pivotal trials are described.

Expert opinion: Benralizumab has the advantage over other anti-IL-5 therapies to target the IL-5Rα itself. Afucosylation enhances its interaction with its binding site and facilitates its pharmacological activity. Other benefits of benralizumab are fast (within 24 h) depletion of peripheral blood eosinophils, potent suppressive activity of bone marrow eosinophils and eosinophil precursors, tissue eosinophil apoptosis regardless of the presence of eosinophil survival factors and even at low IL-5R densities. The fact that benralizumab is dosed subcutaneously and is equally effective when given every eight weeks instead than every four weeks provides patients with convenience of self-administration and make it appealing for patients who dislike injections.

KEYWORDS:

• Asthma
• benralizumab
• eosinophils
• humanized monoclonal antibodies
• interleukin-5

Declaration of interest

M Cazzola and MG Matera have participated as a speaker, and advisor in scientific meetings and courses under the sponsorship of AstraZeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.