52-Week Safety and Efficacy of Amlitelimab in Participants with Moderate-to-Severe Atopic Dermatitis: Preliminary Analysis from the Open-Label Long-Term ATLANTIS Trial

Abstract

Introduction Amlitelimab, a fully human, nondepleting, anti-OX40 ligand (OX40L) monoclonal antibody, blocks OX40L–OX40 interactions upstream of T-cell expansion and inflammatory cytokine production in atopic dermatitis (AD). In STREAM-AD (NCT05131477), a Phase 2b, randomized, double-blind, placebo-controlled trial, amlitelimab was well-tolerated, and demonstrated clinically meaningful and statistically significant improvements through Week 24 compared to placebo, with responses sustained up to Week 52 on- and off-therapy. To further assess the consistency of these results and evaluate longer term safety, a preliminary analysis of the ATLANTIS trial (NCT05769777) was conducted in participants with 52-week data.

Methods ATLANTIS is an ongoing Phase 2, open-label, single-arm, long-term study evaluating the safety and efficacy of amlitelimab in participants with moderate-to-severe AD over 268 weeks (~5 years). Enrolled participants aged ≥12 years (n=963, including 321 adolescents) receive amlitelimab 250mg every-4-weeks (Q4W; 125mg for participants ≥25kg and <40kg) following a loading dose. Concomitant topical corticosteroids and/or topical calcineurin inhibitor use is allowed as needed, and short-term (<4 weeks) oral corticosteroids rescue therapy is permitted. This preliminary analysis used a data cut-off of November 3, 2025, and included 591 participants (38 adolescents) who reached week 52. Safety assessments included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESI), and TEAE-related discontinuations. Efficacy endpoints included the proportion of participants achieving a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 (vIGA-AD 0/1), Eczema Area and Severity Index responses ≥50% improvement from baseline (EASI-50), EASI-75, and EASI-90, the percentage change in EASI score from baseline, and the proportion achieving a ≥4-point reduction in Peak Pruritus Numerical Rating Scale (PP-NRS≥4). The analysis population includes all 591 subjects at all timepoints. Missing data are imputed as non-responders regardless of reasons; all observed data were included in the analysis.

Results Amlitelimab was generally well-tolerated. The most frequently reported TEAEs (≥5%) included nasopharyngitis, headache, influenza, AD, upper respiratory tract infection, and accidental overdose (related to dose scheduling). TEAEs resulting in treatment discontinuation were low (2.9%), and no deaths were reported. One case of Kaposi’s sarcoma, determined to be cutaneous, was reported in a participant with known risk factors. At Week 24 of ATLANTIS, 35.4% of participants achieved vIGA-AD 0/1 increasing to 50.3% at Week 52. Mean percentage change from baseline in EASI score was -77.3% at Week 24 and further improved to -87.1% at Week 52. At Week 24, EASI-50, EASI-75 and EASI-90 response rates were 84.6%, 62.9% and 32.5%, respectively. Continued improvement was observed through Week 52, with EASI-75 and EASI-90 rates reaching 76.5% and 52.3% respectively. PP-NRS≥4 response rates also increased consistently/steadily through Week 24, with continued improvements among participants with available Week 52 data.

Conclusion In this preliminary analysis of the ATLANTIS trial, amlitelimab administered Q4W was generally well-tolerated and demonstrated sustained and progressive clinical improvements without plateau up to week 52 in participants with moderate-to-severe AD. These findings provide robust data supporting a sustained and durable therapeutic benefit with long-term amlitelimab treatment.