Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies

Nicola A Hanania, Michael Noonan, Jonathan Corren, Phillip Korenblat, Yanan Zheng, Saloumeh K Fischer, Melissa Cheu, Wendy S Putnam, Elaine Murray, Heleen Scheerens, Cecile T J Holweg, Romeo Maciuca, Sarah Gray, Ramona Doyle, Dana McClintock, Julie Olsson, John G Matthews, Karl Yen, Nicola A Hanania, Michael Noonan, Jonathan Corren, Phillip Korenblat, Yanan Zheng, Saloumeh K Fischer, Melissa Cheu, Wendy S Putnam, Elaine Murray, Heleen Scheerens, Cecile T J Holweg, Romeo Maciuca, Sarah Gray, Ramona Doyle, Dana McClintock, Julie Olsson, John G Matthews, Karl Yen

Abstract

Introduction: In a subset of patients with asthma, standard-of-care treatment does not achieve disease control, highlighting the need for novel therapeutic approaches. Lebrikizumab is a humanised, monoclonal antibody that binds to and blocks interleukin-13 activity.

Methods: LUTE and VERSE were replicate, randomised, double-blind, placebo-controlled studies, evaluating multiple doses of lebrikizumab in patients with uncontrolled asthma despite the use of medium-to-high-dose inhaled corticosteroid and a second controller. Patients received lebrikizumab 37.5, 125, 250 mg or placebo subcutaneously every four weeks. The primary endpoint was the rate of asthma exacerbations during the placebo-controlled period. Analyses were performed on prespecified subgroups based on baseline serum periostin levels. Following the discovery of a host-cell impurity in the study drug material, protocols were amended to convert from phase III to phase IIb. Subsequently, dosing of study medication was discontinued early as a precautionary measure. The data collected for analysis were from a placebo-controlled period of variable duration and pooled across both studies.

Results: The median duration of treatment was approximately 24 weeks. Treatment with lebrikizumab reduced the rate of asthma exacerbations, which was more pronounced in the periostin-high patients (all doses: 60% reduction) than in the periostin-low patients (all doses: 5% reduction); no dose-response was evident. Lung function also improved following lebrikizumab treatment, with greatest increase in FEV1 in periostin-high patients (all doses: 9.1% placebo-adjusted improvement) compared with periostin-low patients (all doses: 2.6% placebo-adjusted improvement). Lebrikizumab was well tolerated and no clinically important safety signals were observed.

Conclusions: These data are consistent with, and extend, previously published results demonstrating the efficacy of lebrikizumab in improving rate of asthma exacerbations and lung function in patients with moderate-to-severe asthma who remain uncontrolled despite current standard-of-care treatment.

Trial registration numbers: The LUTE study was registered under NCT01545440 and the VERSE study under NCT01545453 at http://www.clinicaltrials.gov.

Keywords: Asthma; Asthma Mechanisms; Cytokine Biology.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Figure 1
Figure 1
Rate of asthma exacerbations during the placebo-controlled period.
Figure 2
Figure 2
Mean (SE) percentage change in FEV1 from baseline up to week 12.
Figure 3
Figure 3
Mean values for (A) FeNO, (B) periostin and (C) blood eosinophils over 12 weeks.

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Source: PubMed

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