Post-Hoc Analyses Support Efficacy of Lebrikizumab in Patients With Moderate-to-Severe Uncontrolled Eosinophilic Asthma and Prior Exacerbations

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Jonathan Corren
Stanley J. Szefler
Ellen Sher
Phillip Korenblat
Weily Soong
Nicola A. Hanania
Gary Berman
Guy Brusselle
Ralph Zitnik
Chitra R. Natalie
Kimberly Siu
Wen-Shuo Wu
Meihua Qiao
Peter Lio
April W. Armstrong

Keywords

Lebrikizumab, asthma, efficacy, eosinophilic

Abstract

Introduction: Lebrikizumab, a novel, high-affinity monoclonal antibody selectively targeting interleukin-13, has demonstrated efficacy and safety in moderate-to-severe atopic dermatitis at higher doses than studied in asthma. Clinical trials of lebrikizumab in moderate-to-severe uncontrolled asthma have not demonstrated consistent exacerbation reductions, possibly due to suboptimal patient selection and premature understanding of asthma phenotypes. We describe post-hoc analyses in adults with uncontrolled eosinophilic asthma with a history of ≥1 asthma exacerbation in the past 12 months from 2 phase 3 lebrikizumab clinical trials (LAVOLTA I and II) completed in 2016.


Methods: Patients were randomly assigned to receive lebrikizumab (37.5mg or 125mg), or placebo (all N=716) every 4 weeks. Adjusted exacerbation rate (AER) at week 52 (W52), presented as rate reduction, and placebo-corrected mean change in prebronchodilator forced expiratory volume in 1 second (FEV1) at weeks 24 (W24) and 52 were assessed in patients with elevated fractional exhaled nitric oxide (FeNO [≥50 mean parts per billion]; 37.5mg [n=105], 125mg [n=107], placebo [n=109]) and in those with both elevated FeNO and elevated blood eosinophils (≥300 cells/µL; 37.5mg [n=60], 125mg [n=66], placebo [n=62]) at baseline.


Results: Lebrikizumab significantly reduced the AER versus placebo at W52 in the elevated FeNO (37.5mg, 47.5%; 125mg, 45.5%) and elevated FeNO and blood eosinophils (37.5mg, 52.3%; 125mg, 52.9%) subgroups. Significant FEV1 improvement was observed in patients with elevated FeNO at W24 (improvement for 37.5mg, 205.4mL; 125mg, 240.9mL) and W52 (37.5mg, 189.8mL; 125mg, 212.0mL). In patients with elevated FeNO and elevated blood eosinophils, FEV1 significantly improved at W24 (37.5mg, 274.8mL; 125mg, 234.1mL) and for the lower dose at W52 (37.5mg, 209.5mL), while a numeric increase was observed for the higher dose (125mg, 139.2mL).


Conclusion: Lebrikizumab could be beneficial in patients with uncontrolled asthma with type 2 inflammation (elevated FeNO and/or elevated blood eosinophils) and a history of recent exacerbations.  

References

1. Hanania NA, et al. Lancet Respir Med. 2016;4:781-796.​

2. Corren J, et al. J Allergy Clin Immunol Pract. 2024;12:1215-1224.

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