Benralizumab Prevents Recurrent Exacerbations in Patients with Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis

Abstract

Exacerbations in chronic obstructive pulmonary disease (COPD), which tend to occur in clusters and increase with disease severity, come with high societal and economic burdens. Prevention and delay of recurrent exacerbations is an unmet and significant therapeutic need for patients with COPD. GALATHEA (NCT02138916) and TERRANOVA (NCT02155660) were trials assessing efficacy of benralizumab in patients with frequent COPD exacerbations despite treatment. Although these studies found that benralizumab given as an add-on treatment did not significantly reduce annual rates of COPD exacerbations after 56 weeks of treatment, in the following exploratory post hoc analysis of the GALATHEA and TERRANOVA trials we identified a potential responder population in which treatment with benralizumab prevents recurrent COPD exacerbations during 30- and 90-day periods following an initial exacerbation, a vulnerable period for an exacerbation to occur. This responder population was characterized by high blood eosinophil counts and frequent previous exacerbations despite optimized triple therapy. These results highlight the importance of targeted therapies for high-risk populations and merit further research into the benefits of biologic therapies for COPD exacerbations.

Keywords:

• COPD
• recurrent exacerbations
• benralizumab
• eosinophil

Data Sharing Statement

Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data-sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Ethics Approval and Consent to Participate

Ethical review and approval was not required for this post hoc analysis of data from previously completed trials. As described in the previous primary publication of that study, independent ethics committees of the trial centers or central institutional review boards approved the trial protocols for the GALATHEA and TERRANOVA trials.⁹ Both trials were conducted in accordance with the principles of the Declaration of Helsinki; all patients provided written informed consent.

Acknowledgments

The authors thank Peter Barker, Ying Fan, and Yasa Reddy (AstraZeneca) for statistical discussions and programming support. Medical writing support was provided by Alexia Williams, PhD, and Dan Jackson, PhD, CMPP, of CiTRUS Health Group (United States), which was in accordance with Good Publication Practice (GPP 2022) guidelines and funded by AstraZeneca (Cambridge, UK).

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

DS has received personal fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Orion, Pulmatrix, Sanofi, Synairgen, Teva, Theravance, and Verona. GJC has received grants from NIH-NHLBI, PA-DOH, GSK, Boehringer Ingelheim, Novartis, AstraZeneca, Respironics, MedImmune, Novartis, Pearl, PneumRx, Pulmonx, Broncus, Spiration, Olympus, Fisher-Paykel Healthcare, Chiesi, Gilead, Pfizer, Corvus, Lilly, Regeneron, Genentech, and Roche and is a consultant for Almirall, AstraZeneca, Nuvaira, GSK, CSA Medical, PneumRx, BTG, Mereo, Broncus, Pulmonx, and EOLO. AA has received grants and private fees from AstraZeneca, Chiesi, GlaxoSmithKline, and Menarini and is a member of the GOLD Science Committee and Board of Directors. MB has received fees from AstraZeneca, Boehringer Ingelheim, Chiesi, and GlaxoSmithKline, and grants from AstraZeneca, Roche, and other support from Asthma & Lung UK, Albus Health and ProAxsis to the institution, outside the submitted work. JS, GLS, YS, MJ, UJM, and IP are or were employees of AstraZeneca at the time these analyses were conducted and may own stock/stock options in AstraZeneca. IL was a contractor for AstraZeneca at the time these analyses were conducted and affiliated with Cytel Inc. The authors report no other conflicts of interest in this work.

Additional information

Funding

The GALATHEA and TERRANOVA studies were funded by AstraZeneca (Södertälje, Sweden).