*3.3. Anti-IL-5 mAbs*

Targeting BEC reduction through the inhibition of IL-5 represents an established therapeutic option in severe asthma [57]. Depemokimab (GSK3511294) is a subcutaneously administered anti-IL-5 mAb, designed for improved affinity and long-acting IL-5 suppression compared to the currently approved anti-IL-5 mAbs, and it has been evaluated in a first-in-human Phase I RCT [30,31] enrolling mild to moderate asthmatic patients with BEC ≥ 200 cells/μL at screening.

A single administration of depemokimab generally improved lung function parameters with an increase in the dose from 2 mg to 300 mg. Depemokimab 300 mg induced a greater improvement from baseline in FEV1 (240 mL (95%CI 68–412)) vs. PCB (105 mL (95%CI not calculated)) and in percent predicted normal FEV1 (7.65% (95%CI 1.76–13.54)) vs. PCB (3.85% (95%CI not calculated)). No data are available for symptoms control [30,31].

Across all doses, depemokimab markedly decreased the circulating BEC by >48.0% 24 h post-dose, and reductions of 54.0% and 53.0% were observed in patients treated, respectively, with depemokimab 100 mg and 300 mg. The duration of such marked suppression of BEC was dose dependent, and thus was maintained for longer with the increasing dose. Six months after the single-dose administration, depemokimab induced reductions in BEC of 31.0% (2 mg), 41.0% (10 mg), 72.0% (30 mg), 82.0% (100 mg), and 83.0% (300 mg) vs. PCB [30,31].
