A Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose Ranging Study to Assess the Efficacy, Safety, and Tolerability of Subcutaneous Lunsekimig in Adult Participants With Moderate-to-severe Asthma (AIRCULES)

AIRCULES

Patient / Population Intervention / Exposure Comparison Outcome

In 685 adults with moderate-to-severe asthma, subcutaneous lunsekimig 300 mg every 4 weeks reduced the annualised asthma exacerbation rate over 48 weeks compared with placebo.

N

685patients

Design

Phase 2b, multicentre, randomised, double-blind, placebo-controlled dose-ranging trial (NCT06102005); adults aged 18 to 80 on medium to high dose inhaled corticosteroids with one or two controllers, at least one exacerbation in the past year and an ACQ-5 of 1.5 or more, randomised 2:1:2:2:2 to placebo (152) or subcutaneous lunsekimig 60 mg every 8 weeks (75), 60 mg every 4 weeks (154), 300 mg every 8 weeks (151) or 300 mg every 4 weeks (153) for 48 weeks

Endpoint

Annualised asthma exacerbation rate over 48 weeks; key secondary the change from baseline in FEV1 at week 48

Relevance

2Important — one of several pillars.

ResultAnnualised asthma exacerbation rate with lunsekimig 300 mg every 4 weeks 0.314 vs 0.702 with placebo, a relative reduction of 55.3% (95% CI 27.8 to 72.3; adjusted P = 0.0016). FEV1 at week 48 rose by 0.190 L vs 0.066 L (difference 0.125 L, 95% CI 0.036 to 0.214; adjusted P = 0.0183). A first exacerbation occurred in 22.2% vs 34.9% (hazard ratio 0.601, 95% CI 0.382 to 0.944), which did not hold after multiplicity adjustment, and ACQ-5 fell by 1.347 vs 0.994 (difference 0.353, 95% CI 0.130 to 0.575), not formally tested. Among the 194 patients with two or more prior exacerbations the rate reduction was 62.9% (95% CI 35.0 to 78.8). The three lower dose regimens improved the same endpoints without reaching significance, and all doses were well tolerated.

Lugogo NL, Kraft M, Pavord I, et al. Presented at ERS Congress 2026, ALERT 2, 8 September. Not yet published.

Discussion & critique

A bispecific nanobody that blocks thymic stromal lymphopoietin and IL-13 at once cut exacerbations by more than half at its top dose, in patients chosen by symptoms and exacerbation history rather than by type 2 markers. One of the four regimens cleared the multiplicity gate, so this is a dose-finding read and not yet an effect estimate: 153 patients carried the winning arm and the interval on the rate reduction runs from 28% to 72%. Lung function moved with it, the time to first exacerbation did not survive adjustment, and the symptom score was never formally tested. Whether blocking both pathways beats blocking either one is the question phase 3 has to answer, and this trial was not built to.