The pharmacodynamic response (blood eosinophil reduction) following repeat doses of mepolizumab administered subcutaneously or intravenously was evaluated in adult subjects with asthma and blood eosinophil levels >200 cells/mcL. Subjects received 1 of 4 mepolizumab treatments (administered every 28 days for a total of 3 doses): 12.5 mg subcutaneous, 125 mg subcutaneous, 250 mg subcutaneous, or 75 mg IV. Sixty-six of the 70 randomized subjects completed the trial. Compared with baseline levels, blood eosinophils decreased in a dose-dependent manner. A reduction in blood eosinophil levels was observed in all treatment groups by Day 3 (48 hours post-dose). On Day 84 (4 weeks post‑last dose), the observed geometric mean reduction from baseline in blood eosinophils was 64%, 78%, 84%, and 90% in the 12.5-mg subcutaneous, 75-mg IV, 125-mg subcutaneous, and 250-mg subcutaneous treatment groups, respectively. The model-predicted subcutaneous doses providing 50% and 90% of maximal reduction of blood eosinophils at Day 84 were estimated to be 11 and 99 mg, respectively. These results, along with the clinical efficacy data from the dose-ranging exacerbation trial in adult and adolescent subjects with severe asthma (Trial 1) supported the evaluation of mepolizumab 75 mg IV and 100 mg subcutaneous in the confirmatory severe asthma trials [see Clinical Studies (14.1)]. Following subcutaneous administration of mepolizumab 100 mg every 4 weeks for 32 weeks in adult and adolescent subjects with severe asthma (Trial 2), blood eosinophils were reduced to a geometric mean count of 40 cells/mcL, which corresponds to a geometric mean reduction of 84% compared with placebo.

The pharmacodynamic response (blood eosinophil reduction) was also evaluated in children aged 6 to 11 years with severe asthma. Following subcutaneous administration of mepolizumab 40 mg every 4 weeks for 52 weeks, blood eosinophils were reduced to a geometric mean count of 48 cells/mcL. This corresponds to a geometric mean reduction from baseline of 85%. 

The magnitude of reduction in adults, adolescents, and children was observed within 4 weeks of treatment and was maintained throughout the treatment periods.

For adults with CRSwNP, following subcutaneous administration of mepolizumab 100 mg every 4 weeks for 52 weeks, blood eosinophils were reduced to a geometric mean count of 60 cells/mcL. There was a geometric mean reduction of 83% compared with placebo. This magnitude of reduction was observed within 4 weeks of treatment and was maintained throughout the treatment period [see Clinical Studies (14.2)].

For adults with EGPA, following subcutaneous administration of mepolizumab 300 mg every 4 weeks for 52 weeks, blood eosinophils were reduced to a geometric mean count of 38 cells/mcL. There was a geometric mean reduction of 83% compared with placebo, and this magnitude of reduction was observed within 4 weeks of treatment [see Clinical Studies (14.3)].

For adults and adolescents with HES, following subcutaneous administration of mepolizumab 300 mg every 4 weeks for 32 weeks, blood eosinophils were reduced to a geometric mean count of 70 cells/mcL. There was a geometric mean reduction of 92% compared with placebo [see Clinical Studies (14.4)].