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/microL 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 FEV1) during the Day 28Day 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 FEV1 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.
- Panettieri, R. A., Jr.
- Welte, T.
- Shenoy, K. V.
- Korn, S.
- Jandl, M.
- Kerwin, E. M.
- Feijoo, R.
- Barker, P.
- Olsson, R. F.
- Martin, U. J.
- Solana Study Investigators
Keywords
- *anti-IL-5Ralpha
- *benralizumab
- *eosinophilic
- *interleukin-5
- *randomized controlled trial
- *severe asthma
- Theravance, Avillion, Sanofi/Regeneron, MedImmune, RIFM, Equillium, Genentech,
- and Oncoarendi, during the conduct of the study. Reynold A Panettieri also
- receives grants and personal fees from AstraZeneca, Equillium, MedImmune, and
- Sanofi/Regeneron
- personal fees from Avillion, Genentech, Novartis, Teva,
- Theravance, and Boehringer Ingelheim
- and grants from Oncoarendi, Theratrophix,
- Amgen, RFIM, Vertex, Bristol Myers Squibb, Genentech, Gilead, and Boston
- Scientific, outside of the submitted work. Tobias Welte has received honoraria
- for lectures and advisory boards from AstraZeneca, Berlin Chemie, Chiesi,
- GlaxoSmithKline, Sanofi Aventis, and Novartis, and his institution has received
- research grants from AstraZeneca, Chiesi, GlaxoSmithKline, and Novartis. Kartik V
- Shenoy has participated in consulting, advisory boards, or received travel
- reimbursement from AstraZeneca and GlaxoSmithKline. Stephanie Korn has received
- honoraria for lectures and advisory board attendance from AstraZeneca,
- GlaxoSmithKline, Novartis, Sanofi, and Teva. Margret Jandl has received honoraria
- for lectures from AstraZeneca. Edward M Kerwin has participated in consulting,
- advisory boards, speaker panels, or received travel reimbursement from Amphastar,
- AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Mylan,
- Novartis, Oriel, Pearl, Sunovion, Teva, and Theravance. He has also conducted
- multicenter clinical research trials for approximately 40 pharmaceutical
- companies. Rosa Feijoo reports personal fees from AstraZeneca, during the conduct
- of the study. Peter Barker, Richard F Olsson, and Ubaldo J Martin are employees
- of AstraZeneca. The authors report no other conflicts of interest in this work.
