Abstract Rationale Amlitelimab (SAR445229; KY1005) is a fully human, nondepleting, anti-OX40 ligand (OX40L) monoclonal antibody that binds OX40L on antigen-presenting cells, preventing interaction with OX40 on activated T cells. In adults with moderate-to-severe asthma, amlitelimab was well tolerated, reduced annualized rate of severe exacerbation events, and improved forced expiratory volume in 1 second (FEV1) and asthma control. Furthermore, patients with mixed inflammation at baseline, characterized by elevated blood eosinophils (≥300 cells/µL) and neutrophils (≥4000 cells/µL), achieved marked improvements with amlitelimab, consistent with a mechanism of action targeting type 2 inflammation and other immune pathways. Here, the effects of amlitelimab on blood and serum biomarkers were evaluated up to week 48 of the TIDE-Asthma study. Methods TIDE-Asthma (NCT05421598) was a phase 2, 60-week, randomized, double-blind, placebo-controlled, dose-ranging trial. Adults (N = 437; 18-75 years of age) with moderate-to-severe asthma were randomized 2:2:1:2 to subcutaneous amlitelimab 250 mg + 500 mg loading dose (LD), 125 mg + 250 mg LD, 62.5 mg + 125 mg LD, or placebo given every 4 weeks (Q4W) for 24 weeks, then Q12W up to week 60. The annualized rate of severe exacerbation events over 48 weeks was the primary endpoint. Changes in blood and serum biomarkers from baseline were evaluated across all dose regimens vs placebo (fold change from baseline from mixed models for repeated measures) at weeks 24 and 48. Results Amlitelimab at doses of 125 mg and 250 mg led to a consistent reduction in multiple biomarkers associated with type 2 inflammation from baseline to week 48 vs placebo. Significant reductions in blood eosinophil count, serum total immunoglobulin E, interleukin (IL)-13, and thymus and activation-regulated chemokine were seen at week 24 (p 0.05) and week 48 (p 0.05) following Q4W and Q12W dosing, respectively. Significant reductions in blood eosinophil count and IL-5 vs placebo (p 0.05) were observed as early as week 4 in the 250 mg dose arm. The effect of amlitelimab on non‒type 2 inflammation-associated biomarkers was also evaluated, with amlitelimab demonstrating a meaningful reduction in IL-17A from baseline to week 24 and week 48 vs placebo in the 250 mg and 125 mg arms (p 0.05). Conclusions Amlitelimab significantly reduced biomarkers associated with type 2 inflammation as well as IL-17A in adults with moderate-to-severe asthma. This further supports OX40L blockade as a relevant target for the treatment of asthma-related inflammation. This abstract is funded by: Sanofi
Akuthota et al. (Fri,) studied this question.