Safety and efficacy of amlitelimab, a fully human, non-depleting, non-cytotoxic anti-OX40Ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomised placebo-controlled trial.

BACKGROUND: Atopic dermatitis is an inflammatory skin disease with significant unmet need. Blockade of the OX40/OX40Ligand co-stimulation pathway by targeting OX40Ligand on antigen-presenting cells with a fully human, non-cytotoxic, non-depleting anti-OX40Ligand monoclonal antibody (amlitelimab; SAR445229; KY1005) is a novel way to modulate persistent inflammation.

OBJECTIVES: To assess the safety and efficacy of amlitelimab over 16 weeks in adults with atopic dermatitis in a phase IIa, double-blind, placebo-controlled study.

METHODS: The study was conducted at 19 hospitals in Germany, Poland, Spain and the United Kingdom. Eligible patients with moderate-to-severe atopic dermatitis were randomised (1:1:1) to intravenous amlitelimab low dose (200 mg), high dose (500 mg) or placebo, followed by 3 maintenance doses (50% of loading dose) at 4, 8 and 12 weeks with safety follow-up to week 36. The co-primary endpoints were incidence of treatment-emergent adverse events (all patients who received ≥1 dose of study drug) and mean percentage change in Eczema Area and Severity Index (EASI) to week 16 (full analysis set).

RESULTS: Between 13 Dec, 2018, and 12 May, 2020, 89 patients (37 [42%] women, 51 [58%] men; mean age 33.6 years [SD 11.95]) were randomly assigned to amlitelimab low or high dose or placebo (N=29, 30 and 29, respectively). Amlitelimab was generally well tolerated with an unremarkable safety profile and no hypersensitivity events were reported. For the primary endpoint, the least square mean percentage change in EASI (95% confidence interval) from baseline to week 16 was -80.12% (-95.55 to -64.68; P=0.009 versus placebo) and -69.97% (-85.04 to -54.60; P=0.072 versus placebo) for low- (N=27) and high-dose (N=27) amlitelimab groups, respectively, compared with -49.37% (-66.02 to -32.72) for placebo (N=24). Numerically greater reductions in EASI were observed for amlitelimab compared with placebo from weeks 2 to 16.

CONCLUSIONS: Novel targeting of OX40Ligand-expressing antigen-presenting cells with amlitelimab was well tolerated and resulted in clinically meaningful improvements in atopic dermatitis. The study is registered with ClinicalTrials.gov, NCT03754309.

© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.

PMID: 37463508