Efficacy of lebrikizumab: predictive biomarkers matter in selecting the appropriate study population with asthma

Published: February 13, 2024

Eosinophilic asthma is characterized by elevated eosinophils and fractional exhaled nitric oxide (FeNO). In the past decade, an increased understanding of asthma, including eosinophilic asthma, has led to the development of new treatment options and the emergence of biologic therapies. Interleukin (IL)-13 is a cytokine that plays a dominant role in type 2 allergic inflammation, and lebrikizumab is a monoclonal antibody that blocks IL-13 signaling. LAVOLTA (L)I, LII, and ACOUSTICS were Phase 3 clinical trials of lebrikizumab in patients with moderate-to-severe, poorly controlled asthma. These trials did not show consistent reductions in asthma exacerbations, possibly due to suboptimal patient selection, including no requirement for patients to have a history of prior exacerbations and the use of periostin for assessing inclusion in the trial, which was later found to be an inadequate biomarker to identify patients with eosinophilic asthma.

A recent article by Corren et al. published in The Journal of Allergy and Clinical Immunology: In Practice assessed the efficacy of lebrikizumab in a well-defined subpopulation of patients with elevated blood eosinophil counts and history of asthma exacerbation, and elevated FeNO and prior exacerbations.

Adult and adolescent patients with uncontrolled asthma received either lebrikizumab or placebo by subcutaneous injection every 4 weeks. Efficacy was assessed based on asthma exacerbation rate and lung function improvement in patients with baseline eosinophils 300 cells/µL or greater and at least 1 asthma exacerbation in the previous 12 months, or baseline FeNO 50 parts per billion or greater and at least 1 exacerbation in the same time period.

 Lebrikizumab treatment showed significant improvements in lung function and reductions in asthma exacerbation rate in adults and adolescents with elevated blood eosinophil counts and prior exacerbations compared to placebo. Similarly, adults with elevated FeNO and prior exacerbations had improvements in lung function and asthma exacerbation rates when treated with lebrikizumab. The safety profile included adverse events that were mostly mild or moderate in severity, did not lead to treatment discontinuation, and were balanced across treatment groups.
These results indicate that lebrikizumab may be effective in asthma when the appropriate population of patients with previous exacerbations and type 2 inflammation are targeted. This analysis also highlights the importance of using appropriate predictive biomarkers and targeting the optimal study population when selecting a specific biologic medication for asthma.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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