Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS)

Abstract

Background: Lebrikizumab is a monoclonal antibody that modulates activity of interleukin-13. The Phase 3 ACOUSTICS study assessed lebrikizumab efficacy and safety in adolescents with uncontrolled asthma despite standard-of-care treatment.

Methods: Adolescents (aged 12-17 years) with uncontrolled asthma, prebronchodilator forced expiratory volume in 1 s 40%-90% predicted, and stable background therapy were randomised 1:1:1 to receive lebrikizumab 125 or 37.5 mg or placebo subcutaneously once every 4 weeks. Primary efficacy endpoint was asthma exacerbation rate over 52 weeks.

Results: Between August 2013 and July 2016, 579 patients were screened and 346 were randomised; 224 (65%) completed the study with 52 weeks of treatment. Lebrikizumab 125 mg (n = 116) reduced the exacerbation rate at 52 weeks versus placebo (n = 117; adjusted rate ratio [RR] 0.49 [95% CI 0.28-0.83]; 51% rate reduction). Lebrikizumab 37.5 mg (n = 113) was less effective at reducing exacerbations (RR 0.60 [95% CI 0.35-1.03]; 40% rate reduction). In patients with blood eosinophil counts ≥300 cells/μl, both lebrikizumab doses reduced exacerbations (125 mg: RR 0.44 [95% CI 0.21-0.89]; 37.5 mg: 0.42 [95% CI 0.19-0.93]). Treatment-emergent adverse events, serious adverse events, and adverse events leading to study discontinuation occurred in 155 (68%), 7 (3%), and 5 (2%) of 229 patients who received lebrikizumab (both 125 and 37.5 mg doses) and in 72 (62%), 4 (3%), and 1 (1%) of 117 who received placebo, respectively. No deaths occurred.

Conclusion: Lebrikizumab 125 mg reduced asthma exacerbation rates in adolescents with uncontrolled asthma. However, the study was prematurely terminated (sponsor's decision) potentially limiting interpretation of results.

Clinical trial registration: NCT01875003 (www.ClinicalTrials.gov).

Keywords: IL‐13; adolescents; lebrikizumab; uncontrolled asthma.

Conflict of interest statement

Stanley J. Szefler reports consultancy during the time of this report and currently for Aerocrine, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Genentech, Inc., Merck, Novartis, Propeller Health, Regeneron, Roche, Sanofi and Teva and research support from the US National Institutes of Health; US National Heart, Lung, and Blood Institute; US National Institute of Allergy and Infectious Diseases; US National Institute of Environmental Health Sciences; US Environmental Protection Agency; Cancer, Cardiovascular and Pulmonary Disease Program; and GlaxoSmithKline. Graham Roberts was the lead investigator in the United Kingdom for this study. Adalberto S. Rubin reports fees from AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Roche, Bristol, and Sanofi. Stefan Zielen reports grants and personal fees from bene‐Arzneimittel GmbH, grants from ALK Arzneimittel, personal fees from Novartis GmbH, Boehringer Ingelheim, Lofarma GmbH, IMS HEALTH GmbH and Co. OHG, GSK, Stallergen, Procter and Gamble, Allergopharma GmbH, AstraZeneca, Sanofi/Pasteur, and Aimmune outside the submitted work. Piotr Kuna reports personal fees from Astra, Boehringer Ingelheim, Berlin Chemie Menarini, GSK, Lekam, Novartis, Polpharma, Mylan, Orion, Teva, Adamed. Oral Alpan reports no disclosures that pertain to this submission. Cécile T J Holweg, and Wendy S. Putnam are former employees of Genentech, Inc. (a member of the Roche Group). Qiang Chen is an employee of Roche (China) Holding Ltd. Janusz Kaminski is a former employee of Roche Products Ltd. John G. Matthews is a former employee of Genentech, Inc. Judith Anzures‐Cabrera and Nikhil Kamath are employees of Roche Products Ltd.

© 2022 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

Figures

FIGURE 1

Study design schematic. Lebri, lebrikizumab; R, masked randomisation. *After the last dose of study drug during the optional active‐treatment extension (or during the placebo‐controlled period for patients who opt not to participate in the active‐treatment extension), all patients were to be followed‐up for safety for 24 weeks. This includes the 4 weeks after the final dose during the placebo‐controlled period or the active‐treatment extension and a 20‐week safety follow‐up period

FIGURE 2

Trial profile

FIGURE 3

Adjusted rate of asthma exacerbations over 52 weeks in all patients and by eosinophil group

FIGURE 4

Time to first asthma exacerbation