Two-Year Integrated Efficacy And Safety Analysis Of Benralizumab In Severe Asthma

J Mark FitzGerald; Eugene R Bleecker; Arnaud Bourdin; William W Busse; Gary T Ferguson; Laura Brooks; Peter Barker; Ubaldo J Martin

doi:10.2147/JAA.S227170

Two-Year Integrated Efficacy And Safety Analysis Of Benralizumab In Severe Asthma

J Asthma Allergy. 2019 Dec 9:12:401-413. doi: 10.2147/JAA.S227170. eCollection 2019.

Authors

J Mark FitzGerald¹, Eugene R Bleecker², Arnaud Bourdin³, William W Busse⁴, Gary T Ferguson⁵, Laura Brooks⁶, Peter Barker⁶, Ubaldo J Martin⁶

Affiliations

¹ Centre for Heart and Lung Health, The Lung Centre Vancouver General Hospital, UBC Institute for Heart and Lung Health, Vancouver, BC, Canada.
² Divisions of Pharmacogenomics and Genetics, Genomics and Precision Medicine, University of Arizona College of Medicine, Tucson, AZ, United States.
³ Department of Respiratory Diseases, Hôpital Arnaud De Villeneuve, Montpellier, France.
⁴ Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.
⁵ Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, United States.
⁶ AstraZeneca, Gaithersburg, MD, United States.

Abstract

Background: Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody. Treatment with benralizumab significantly reduces exacerbations and improves lung function after 1 year for patients with severe, uncontrolled eosinophilic asthma.

Objective: We explored whether benralizumab efficacy was sustained after an additional year of treatment while maintaining an acceptable safety profile.

Methods: Data from the pivotal 48-week SIROCCO and 56-week CALIMA studies were integrated with data from the predefined 56-week adult phase of the BORA extension study to provide a 2-year integrated efficacy and safety analysis of benralizumab. BORA enrolled patients who had completed SIROCCO or CALIMA. Patients receiving benralizumab 30 mg subcutaneously, either every 4 weeks (Q4W) or every 8 weeks (Q8W; first three doses Q4W), were assessed. Efficacy was evaluated based on baseline blood eosinophil counts from the pivotal studies (≥300 and <300 cells/μL).

Results: Mean treatment exposures were 24.3 (Q4W, n=518) and 24.6 (Q8W, n=512) months. Exacerbation frequency reductions observed in SIROCCO/CALIMA were maintained; 50% of the patients had no exacerbations during the 2-year study period (crude exacerbation rate, Q8W: 0.56 exacerbations/year for patients with blood eosinophil counts ≥300 cells/μL). Lung function improvements with benralizumab were maintained for 2 years, as represented by increases in mean prebronchodilator forced expiratory volume in 1 second from baseline of 0.343 L and 0.364 L with 1 and 2 years of benralizumab Q8W treatment, respectively, for patients with blood eosinophil counts ≥300 cells/μL. Health-related quality of life improvements with benralizumab observed in the pivotal studies were also sustained. Adverse events and serious adverse event rates were similar between the BORA extension and SIROCCO/CALIMA periods, with no new or unexpected occurrence of adverse events.

Conclusion: This benralizumab 2-year integrated analysis further supports long-term use of benralizumab for patients with severe, uncontrolled eosinophilic asthma.

Keywords: asthma; benralizumab; clinical features; eosinophilic inflammation; interleukin-5 receptor; safety.

Grants and funding

AstraZeneca and Kyowa Hakko Kirin funded the SIROCCO, CALIMA, ZONDA, and BORA studies. Writing and editing support, including preparation of the draft manuscript under the direction and guidance of the authors, incorporating author feedback and manuscript submission, was funded by AstraZeneca.