Onset of Effect, Changes in Airflow Obstruction and Lung Volume, and Health-Related Quality of Life Improvements with Benralizumab for Patients with Severe Eosinophilic Asthma: Phase IIIb Randomized, Controlled Trial (SOLANA)
Received 26 November 2019
Accepted for publication 18 January 2020
Published 17 February 2020 Volume 2020:13 Pages 115—126
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Amrita Dosanjh
Reynold A Panettieri Jr, 1 Tobias Welte, 2 Kartik V Shenoy, 3 Stephanie Korn, 4 Margret Jandl, 5 Edward M Kerwin, 6 Rosa Feijoo, 7 Peter Barker, 8 Richard F Olsson, 9 Ubaldo J Martin 8
On behalf of the SOLANA Study Investigators
1Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA; 2Department of Respiratory Medicine, Member of the German Center of Lung Research, Medizinische Hochschule Hannover, Hannover, Germany; 3Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; 4Pulmonary Department, Universitätsmedizin Mainz, Langenbeckstr, Mainz, Germany; 5Hamburger Institut Für Therapieforschung, Hamburg, Germany; 6Clinical Trials Division, Clinical Research Institute of Southern Oregon (Crisor), Medford, OR, USA; 7Departamento De Medicina Interna Oriente, Universidad De Chile, Santiago, Chile; 8Research and Development, AstraZeneca, Gaithersburg, MD, USA; 9R&D, Innovative Medicines and Early Development, Early Clinical Development, AstraZeneca, Gothenburg, Sweden
Correspondence: Reynold A Panettieri
University of Pennsylvania, 125 South 31st Street, Philadelphia, PA 19104, USA
Tel +1 215 573-9860
Fax +1 215 746-1224
Objective: In the SOLANA trial, we sought to physiologically characterize benralizumab’s onset of effect and maintenance of that effect for patients with severe eosinophilic asthma.
Methods: SOLANA (NCT02869438) was a multicenter, randomized, double-blind, parallel-group, placebo-controlled, Phase IIIb study conducted at 49 centers in six countries (Chile, Germany, Hungary, the Philippines, South Korea, and the United States). Eligible patients with baseline blood eosinophil counts ≥ 300 cells/μL were randomized to subcutaneous benralizumab (30 mg) or placebo administered at Days 0, 28, and 56. The primary endpoint was the average change from baseline in prebronchodilator forced expiratory volume in 1 s (pre-BD FEV 1) during the Day 28‒Day 84 period for benralizumab vs placebo. Secondary endpoints included patient-reported outcomes (PROs). A subset of patients participated in a whole-body plethysmography substudy. Safety was also assessed.
Results: In total, 233 patients were randomized to benralizumab (n=118) or placebo (n=115). Improvement from baseline in pre-BD FEV 1 with benralizumab 30 mg was not statistically significant compared with placebo (least-squares mean change difference [95% confidence interval] 57 mL [− 22 to 135]; p=0.16). Compared with placebo, benralizumab demonstrated early (Day 7) nonstatistically significant improvements in whole-body plethysmography assessments of hyperinflation and clinically meaningful improvements in PRO measures (Asthma Control Questionnaire 6 at Day 14 and St. George’s Respiratory Questionnaire at Day 28), which were maintained over the treatment period. Benralizumab’s safety profile was commensurate with previously reported studies.
Conclusion: The observed early changes in lung volume despite relatively small improvements in airflow obstruction suggest that the anti-inflammatory effect of benralizumab may be manifested as deflation over time for patients with hyperinflation, who potentially have a greater degree of airway remodeling. This early effect could partially explain the rapid PRO improvements observed for certain patients.
Keywords: anti–IL-5Rα, benralizumab, interleukin-5, randomized controlled trial, eosinophilic, severe asthma
Corrigendum for this paper has been published
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