Methods: LUTE and VERSE were replicate, multicenter, double-blind studies that randomized (1:1:1:1) patients with uncontrolled asthma despite treatment with ICS and a second controller to receive lebrikizumab 37.5mg, 125mg, 250mg, or placebo subcutaneously every 4 weeks. The primary endpoint was the rate of exacerbations. Secondary endpoints included change in FEV1. The trials, initially Phase 3, were converted to Phase 2b upon identification of a process-related impurity requiring changes to the lebrikizumab manufacturing process.
Results: 463 patients were pooled for analysis. The median number of doses received was 6 (range 1–12). Compared with placebo (n=116), the exacerbation rate (95% CI) was reduced by 62% (23%–83%;n=117), 35% (-17%–65%;n=112), and 11% (-54%–49%;n=118) in all patients and by 81% (35%–97%), 77% (26%–95%), and 22% (-62%–63%) in periostin-high (≥50ng/mL) patients in the lebrikizumab 37.5mg, 125mg, and 250mg groups, respectively. At Week 12, increases in FEV1 were greater for lebrikizumab versus placebo, particularly in periostin-high patients. No important safety signals were observed.
Conclusions: Lebrikizumab treatment reduced the exacerbation rate and increased FEV1 in patients with uncontrolled asthma on ICS and a second controller, particularly those who were periostin-high, confirming the findings from the previous Phase 2 trial.