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

J Mark FitzGerald,1 Eugene R Bleecker,2 Arnaud Bourdin,3 William W Busse,4 Gary T Ferguson,5 Laura Brooks,6 Peter Barker,6 Ubaldo J Martin6 1Centre for Heart and Lung Health, The Lung Centre Vancouver General Hospital, UBC Institute for Heart and Lung Health, Vancouver, BC, Canada; 2Divisions of Pharmacogenomics and Genetics, Genomics and Precision Medicine, University of Arizona College of Medicine, Tucson, AZ, United States; 3Department of Respiratory Diseases, Hôpital Arnaud De Villeneuve, Montpellier, France; 4Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; 5Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, United States; 6AstraZeneca, Gaithersburg, MD, United StatesCorrespondence: J Mark FitzGeraldThe Lung Centre, Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre, 2775 Laurel Street, Vancouver BC V5Z 1M9, CanadaTel +1604-875-4122Email mark.fitzgerald@vch.caBackground: 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 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