Njira L Lugogo, Monica Kraft, Ian Pavord, Guy Brusselle, Ruchong Chen, Kazuto Matsunaga, Gautier Paux, Florian Voss, Julian Lel, Lucia De Prado Gomez, Heribert Staudinger, Benjamin T. Suratt, Megan Hardin, Sarah Chu, Bina Choi
INTRODUCTION: Lunsekimig (SAR443765), a novel pentavalent, bispecific NANOBODY® molecule, blocks thymic stromal lymphopoietin (TSLP) and IL-13.
AIM: Evaluate the efficacy and safety of lunsekimig in adults with moderate-to-severe asthma.
METHODS: AIRCULES (NCT06102005) was a phase 2b, randomized, double-blind, dose-ranging trial. Adults (18-80 yrs; N=685) on medium-to-high dose inhaled corticosteroids with 1-2 controllers, ≥1 exacerbation in the past year, and ACQ-5 ≥1.5 were randomized 2:1:2:2:2 to placebo (pbo; n=152), subcutaneous lunsekimig 60mg every 8 weeks (Q8W; n=75), 60mg Q4W (n=154), 300mg Q8W (n=151), or 300mg Q4W (n=153) for 48W. Efficacy endpoints included AAER (primary), FEV1 (key secondary), time to first exacerbation, and ACQ-5.
RESULTS: The 300mg Q4W arm showed statistically significant and clinically meaningful improvements vs pbo in AAER and FEV1 (Figure). These results were supported by numerically longer time to first exacerbation and ACQ-5 improvement. Other doses showed improvements in efficacy endpoints, though not statistically significant. Numerically greater effect sizes with lunsekimig were observed in frequent exacerbators (prespecified subgroup of ≥2 prior exacerbations; Figure). Lunsekimig was well tolerated at all doses.
CONCLUSIONS: Lunsekimig, a first-in-class molecule, demonstrated clinically meaningful improvements in exacerbations, lung function, and asthma control, and was well tolerated. These findings support dual TSLP and IL-13 targeting to address unmet need in asthma.