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

BACKGROUND: LAVOLTA (L)I, LII, and ACOUSTICS were randomized, placebo-controlled, Phase 3 trials of lebrikizumab, a monoclonal antibody targeting interleukin-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. An additional analysis in a subpopulation of patients with elevated fractional exhaled nitric oxide (FeNO) and prior exacerbations was performed.

METHODS: Adult (LI and LII) and adolescent patients (12-17 years weighing ≥40kg, ACOUSTICS) with uncontrolled asthma received lebrikizumab (125mg, N=832 or 37.5mg, 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 ≥300 cells/μL and history of ≥1 exacerbation. In this subpopulation, there were 227 patients in the placebo group, 222 patients in the lebrikizumab 37.5mg group, and 217 patients in the lebrikizumab 125mg group. Safety in patients who received at least 1 dose of lebrikizumab was summarized using adverse events (AEs).

RESULTS: Lebrikizumab significantly reduced AER vs. placebo in adults (AER reduction:125mg, 38%; 37.5mg, 41%) and adolescents (AER reduction:125mg, 59%; 37.5mg, 64%) with baseline blood eosinophils ≥300 cells/μL and ≥1 exacerbation. Most AEs 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.