Long-Term Durability and Stability of Amlitelimab Efficacy in Adults With Moderate-to-Severe Atopic Dermatitis: 52-Week Post Hoc Analysis of the STREAM-AD Phase 2b Trial

Abstract

Introduction: Amlitelimab (SAR445229, KY1005) is a fully human, non-depleting, anti-OX40 ligand monoclonal antibody. In the STREAM-AD phase 2b clinical trial (NCT05131477), amlitelimab demonstrated efficacy and safety in adults with moderate-to-severe atopic dermatitis (AD). In Part 1 of the study, the primary endpoint was met, with amlitelimab significantly decreasing the percent change from baseline in Eczema Area and Severity Index (EASI) at Week 16 compared to placebo. Improvements were also observed in key secondary endpoints, including Investigator Global Assessment (IGA) score of 0/1 (clear or almost clear skin) and 75% reduction in EASI (EASI-75), at Week 16 and Week 24. In participants who achieved clinical response at Week 24 (defined as IGA 0/1 and/or EASI-75), response was maintained at Week 52 in Part 2 of the study in those who either continued or were withdrawn from amlitelimab. This post hoc analysis evaluates the stability and durability of response on and off amlitelimab during Part 2 of STREAM-AD (Week 24 to Week 52; 28 weeks) and presents the proportions of participants with minimal efficacy fluctuations during Part 2.

Methods: STREAM-AD Part 2 included clinical responders from Part 1, defined as participants achieving EASI-75 and/or IGA 0/1 at Week 24. Of 390 participants enrolled in Part 1, 190 entered Part 2. Participants were re-randomised 3:1 to amlitelimab withdrawal (switch to placebo) or continuation of their pre-Week 24 subcutaneous dose of amlitelimab every 4 weeks. Response stability was defined as the proportion of participants achieving EASI-75 or IGA 0/1 for at least 80% of visits in Part 2 of STREAM-AD.

Results: In Part 2 of STREAM-AD, amlitelimab demonstrated stable and durable efficacy. By Week 52, among Week 24 clinical responders, EASI-75 was maintained for at least 80% of STREAM-AD Part 2 visits in 72.7% of participants who continued amlitelimab and 67.7% of participants who were off amlitelimab treatment. Additionally, IGA 0/1 was maintained for at least 80% of Part 2 visits by Week 52 in 54.5% of participants who continued amlitelimab and 43.1% who were off amlitelimab treatment.

Conclusions: In the STREAM-AD study, participants who achieved clinical response at Week 24 in Part 1, whether continuing amlitelimab treatment or withdrawing in Part 2, demonstrated stable and durable clinical responses with minimal fluctuations in EASI-75 and IGA 0/1 efficacy measures. Taken together, these results suggest amlitelimab may provide sustained effects, with clinical improvements persisting even after treatment withdrawal. This is an especially meaningful outcome for AD, a condition in which durable long-term disease control is a key goal.