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

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

Acknowledgments

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 provided by Alan Saltzman, PhD (JK Associates, Inc., Conshohocken, PA, United States), and Michael A. Nissen, ELS (AstraZeneca, Gaithersburg, MD, United States). This support was funded by AstraZeneca. Some of these data were presented in a poster at the American Thoracic Society (ATS) International Conference, May 17–22, 2019, Dallas, TX, USA, as a poster presentation. The poster abstract was published in American Journal of Respiratory and Critical Care Medicine: 2019;199:A2676. https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2019.199.1_MeetingAbstracts.A2676.

Abbreviations

100-PYs, 100-patient-years; ACQ-6, Asthma Control Questionnaire 6; ADA, anti-drug antibody; AER, asthma exacerbation rate; APS, all patients set; AQLQ(S)+12, Asthma Quality of Life Questionnaire [standardized] for 12 years and older; ED, emergency department; EOT, end of treatment; FAS, full analysis set; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; LABA, long-acting β₂-agonists; OCS, oral corticosteroids; Q4W, every 4 weeks; Q8W, every 8 weeks; SD, standard deviation.

Data-Sharing Statement

Data underlying the findings described in this manuscript may be requested in accordance with AstraZeneca’s data-sharing policy described at https://astrazenecagroup-dt.pharmacm.com/DT/Home.

Author Contributions

JMF, ERB, AB, WWB, GTF, and UJM conceived and designed the study. LB, PB, and UJM acquired the data. All authors made substantial contributions to the analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

JMF is an advisory board member for AstraZeneca, Boehringer Ingelheim, Novartis, Sanofi-Regeneron, reports research grants from AstraZeneca, Sanofi Regeneron, and Teva and has received honoraria for lectures from AstraZeneca, Sanofi Regeneron, Boehringer Ingelheim, GlaxoSmithKline, and Novartis during the conduct of this study. ERB has performed clinical trials through his former employer, the Wake Forest School of Medicine, the University of Arizona, and Genentech, and has served as a paid consultant for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, MedImmune, Novartis, Regeneron, Sanofi-Aventis, Sanofi Genzyme, and TEVA. AB has received personal fees from Actelion, AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, GlaxoSmithKline, Novartis, Regeneron, Roche, and Teva; received grants from Boehringer Ingelheim and GlaxoSmithKline; received non-financial support from Actelion, AstraZeneca, Biogen, Boehringer Ingelheim, Galapagos, Novartis, Chiesi Pharmaceuticals, Roche, and Vertex; and has been an advisory board member for Actelion, AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, Gilead, GlaxoSmithKline, Novartis, Regeneron, and Teva outside of the submitted work. WWB reports personal fees from AstraZeneca, Boston Scientific, Genentech, GlaxoSmithKline, Novartis, Sanofi, GlaxoSmithKline, Gossamer Bio, Elsevier, Arrowhead, resTORbio, Medscape and Teva, outside of the submitted work. GTF reports grants, personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pearl Therapeutics and Sunovion; grants and personal fees from Verona, Theravance, Mylan and Sanofi; grants from Altavant; and personal fees from Innoviva, CSL Behring and Circassia. LB, PB, and UJM are employees of AstraZeneca Pharmaceuticals. The authors report no other conflicts of ineterestin this work.

Additional information

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.