Lebrikizumab in Uncontrolled Asthma: Reanalysis in a Well-Defined Type 2 Population. (2024)

Afiliação

• Corren J; David Geffen School of Medicine at UCLA, Los Angeles, Calif. Electronic address: jcorren@ucla.edu.
• Szefler SJ; Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colo.
• Sher E; Allergy Partners of NJ, Ocean, NJ.
• Korenblat P; Phillip Korenblat LLC, St Louis, Mo.
• Soong W; Allervie Clinical Research-Alabama Allergy & Asthma Center, Birmingham, Ala.
• Hanania NA; Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, Texas.
• Berman G; Clinical Research Institute and Allergy & Asthma Specialists, Minneapolis, Minn.
• Brusselle G; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
• Zitnik R; Valerio Consulting, LLC, Santa Barbara, Calif.
• Natalie CR; Eli Lilly and Company, Indianapolis, Ind.
• Sun L; Eli Lilly and Company, Indianapolis, Ind.
• Siu K; Eli Lilly and Company, Indianapolis, Ind.
• Wu WS; Eli Lilly and Company, Indianapolis, Ind.
• Lio P; Northwestern University Feinberg School of Medicine, Medical Dermatology Associates of Chicago, Chicago, Ill.
• Armstrong AW; Keck School of Medicine at University of Southern California and Clinical Research for the Southern California Clinical and Translational Research Institute (SC CTSI), Los Angeles, Calif.

ABSTRACT

BACKGROUND:

LAVOLTA (L)I, LII, and ACOUSTICS were randomized, placebo-controlled, Phase 3 trials of lebrikizumab, a monoclonal antibody targeting IL-13 in patients with uncontrolled asthma. Failure to demonstrate efficacy may have been related to patient selection in those trials.

OBJECTIVE:

To assess the efficacy in a well-defined subpopulation of patients with elevated blood eosinophil counts and a minimum number of prior asthma exacerbations. We performed an additional analysis in a subpopulation of patients with elevated FeNO and prior exacerbations.

METHODS:

Adult (LI and LII) and adolescent patients (aged 12-17 years weighing ≥40 kg, ACOUSTICS) with uncontrolled asthma received lebrikizumab (125 mg, n= 832; or 37.5 mg, n= 829) or placebo (n= 833) subcutaneously every 4 weeks. Post hoc analysis of the annualized adjusted exacerbation rate (AER) was performed in a subpopulation of patients with baseline blood eosinophils of 300 cells/µL or greater and history of one or more exacerbations. In this subpopulation, there were 227 patients in the placebo group, 222 in the lebrikizumab 37.5-mg group, and 217 in the lebrikizumab 125-mg group. We summarized safety in patients who received at least one dose of lebrikizumab using adverse events.

RESULTS:

Lebrikizumab significantly reduced AER compared with placebo in adults (AER reduction 125 mg [38%]; and 37.5 mg [41%]) and adolescents (AER reduction125 mg [59%]; 37.5 mg [64%]) with baseline blood eosinophils of 300 cells/µL or greater and one or more exacerbations. Most adverse events were mild or moderate in severity and did not lead to treatment discontinuation.

CONCLUSION:

Lebrikizumab significantly reduced asthma exacerbations in a subpopulation of patients with elevated blood eosinophils, elevated FeNO, and a history of asthma exacerbation.