33781 Sustained and durable response up to 24 weeks after last dose observed in a phase 2a study (NCT03754309) of amlitelimab (KY1005, SAR445229) a novel nondepleting anti-OX40Ligand (OX40L) mAb in patients with moderate to severe atopic dermatitis (AD)

Abstract

Introduction: Amlitelimab (KY1005) is novel human nondepleting IgG4 monoclonal antibody blocking OX40Ligand which is found on antigen presenting cells (APCs) including dendritic cells. By targeting APCs it was hypothesised amlitelimab could potentially have long and durable anti-inflammatory effect in AD. Materials and methods: Kymab, a Sanofi Company, funded a Ph2a RCT (NCT03754309) in 89 moderate-to-severe AD patients (EASI>16, vIGA-AD>2 at baseline (BL)) with an inadequate response or intolerance of topical treatments. 1:1:1 randomization to intravenous amlitelimab low dose (LD, 200 mg loading/100 mg maintenance every 4 weeks), high dose (HD, 500 mg/250 mg Q4W) or placebo (PBO). Last dose was at Week 12. To assess long-term durability of response in patients achieving vIGA-AD0/1 at Week 16 efficacy assessments were collected to Week 36. Co-primary endpoints were % change in EASI from baseline and incidence of TEAEs at Week 16. Results: 88 patients received study medication. 59 evaluable patients competed Week 16. Both co-primary endpoints were met. 24 patients (12 LD (44%), 10 HD (37%) and 2 PBO (8%)) achieved a vIGA-AD 0/1 at Week 16. At Week 24, 83% (n = 10) LD, 90% (n = 9) HD, and 50% (n = 1) PBO maintained vIGA-AD0/1. 3 patients withdrew by Week 36 (2 LD, 1 HD). 21 patients remained with 67% (n = 8) LD, 70% (n = 7) HD, and 50% (n = 1) PBO maintaining a vIGA-AD0/1. Conclusions: This Ph2a study has demonstrated that Amlitelimab monotherapy targeting APCs is not only associated with a marked clinical improvement at Week16 but in patients achieving ‘clear’ or ‘almost clear’ skin (vIGA0/1) a sustained response up to 24 weeks after the last dose was maintained. A Phase 2b study is planned.