Lebrikizumab reduced exacerbations in adolescents with uncontrolled asthma and had a favorable safety profile, according to results of the ACOUSTICS study.

The study, which was stopped early by the sponsor, showed a greater treatment effect with the higher dose of lebrikizumab studied.

Stanley J. Szefler, MD, researcher in the department of pediatrics at the Children’s Hospital Colorado and University of Colorado School of Medicine, reported results from the phase 3, multicenter, randomized, double-blind, placebo-controlled ACOUSTICS study at the American Thoracic Society International Conference. The trial aimed to evaluate efficacy, safety and tolerability of lebrikizumab (Eli Lilly).

The study enrolled 346 adolescents aged 12 to 17 years with uncontrolled asthma despite daily use of an inhaled corticosteroids and at least one other controller medication. Those enrolled also had a prebronchodilator FEV₁ of 40% to 90% predicted, a bronchodilator response of 12% or more and were on stable background therapy. Patients were randomly assigned to receive lebrikizumab 125 mg (n = 75) or 37.5 mg (n = 58) or placebo (n = 91) subcutaneously once every 4 weeks. The trial was designed to be a 52-week study. Szefler presented results from 224 (65%) of adolescents who completed the 52-week placebo-controlled period.

The primary outcome was asthma exacerbation rate during the study period. Researchers also assessed time to first asthma exacerbation and safety outcomes.

At baseline, median blood eosinophil count was 295 cells/µL. Compared with the placebo group, patients assigned lebrikizumab 125 mg had a 51% (adjusted RR = 0.49; 95% CI, 0.28-0.83) reduction in exacerbation rates and those assigned 37.5 mg had a 40% (aRR = 0.6; 95% CI, 0.35-1.03) reduction, according to the data presented.

The reduction in asthma exacerbation rates with lebrikizumab compared with placebo was greatest in those with baseline blood eosinophil counts of 300 cells/µL or more. In those with blood eosinophil counts of 300 cells/µL or more, the lebrikizumab 125 mg group had a 56% (RR = 0.44; 95% CI, 0.21-0.89) reduction in asthma exacerbation rates and those assigned 37.5 mg had a 58% (RR = 0.42; 95% CI, 0.19-0.93) reduction, according to the results.

Compared with the placebo group, patients assigned lebrikizumab had increased time to first asthma exacerbation for both 125 mg dose (HR = 0.37; 95% CI, 0.21-0.66) and the 37.5 mg dose (HR = 0.4; 95% CI, 0.22-0.73).

The mean number of lebrikizumab doses was 10.2 over 41 weeks. Most adverse events that occurred during the study were non-serious, mild to moderate in severity and did not lead to discontinuation of the study drug, according to the results. Eosinophil-associated treatment-related adverse events reported included decreased neutrophil count and eosinophil; there were no cases of eosinophilic granulomatosis with polyangiitis.

“In terms of safety, it was pretty comparable to what was seen in the adult studies to date,” Szefler said.

“Looking at the data … in terms of biomarkers, there was a very positive signal,” Szefler said. “Eli Lilly purchased the drug. They’re evaluating it now; they continue to study [lebrikizumab] with atopic dermatitis … [that] used higher doses and greater frequency. So, Eli Lilly is now taking a step back looking at those studies, and then deciding whether or not to pursue this. It has been interesting when I look at the inner-city asthma consortium studies, there seems to be fairly high signals for IL-13 gene activation. So, I think there’s some promise here.”

The researchers concluded that, despite the lack of a consistent dose response, post hoc analyses of adult studies (LAVOLTA I and II, MILLY) showed similar results. In addition, recently reported data from phase 3 trials of lebrikizumab in adolescents and adults with atopic dermatitis demonstrated clinical efficacy using higher doses with greater frequency, according to the researchers. Future study in asthma may need to look at optimal use of lebrikizumab with higher and more frequent dosing in patients with type 2 inflammation at risk for exacerbations, the researchers concluded.