Amlitelimab Meets Primary Endpoints in 2 of 3 Phase 3 AD Trials

Results from 3 phase 3 trials evaluating amlitelimab in moderate to severe atopic dermatitis (AD) were presented during a late-breaking research session at the 2026 American Academy of Dermatology Annual Meeting in Denver, reinforcing what has emerged as a key theme for this investigational agent: efficacy that continues to build over the treatment course without evidence of plateauing by week 24.¹

Amlitelimab is a fully human monoclonal antibody targeting OX40-ligand (OX40L), a co-stimulatory molecule involved in the activation and differentiation of T helper cell subsets implicated in type 2 inflammation. Unlike biologics that deplete T cells directly, its mechanism is designed to modulate the upstream inflammatory cascade while preserving the broader T cell compartment — a distinction that has drawn attention from researchers interested in long-term immunologic effects.²

Study Designs and Populations

All 3 studies — COAST 1, COAST 2, and SHORE — enrolled adults and adolescents aged 12 and older with moderate to severe AD. COAST 1 (n=601) and COAST 2 (n=589) evaluated amlitelimab as monotherapy, while SHORE (n=643) assessed the drug in combination with topical corticosteroids (TCS), with or without topical calcineurin inhibitors (TCI). Across all trials, patients were randomized to receive amlitelimab 250 mg (125 mg for those under 40 kg) either every 4 weeks (Q4W) or every 12 weeks (Q12W), following a loading dose, or placebo. The primary endpoint for US and US-reference countries was achievement of a validated Investigator Global Assessment (vIGA-AD) score of 0 or 1 with a reduction from baseline of at least 2 points at week 24.

Efficacy Findings

In both COAST 1 and COAST 2, amlitelimab met the primary vIGA-AD 0/1 endpoint at both dosing intervals. In COAST 1, Q4W and Q12W arms achieved vIGA-AD 0/1 rates of 21.1% and 22.5%, respectively, versus 9.2% with placebo. EASI-75 response rates were 35.9% (Q4W) and 39.1% (Q12W) versus 19.1% for placebo, and clinically meaningful itch reduction (PP-NRS ≥4) was achieved in approximately 22–24% of treated patients versus 12.7% on placebo.

COAST 2 produced largely similar results, with vIGA-AD 0/1 rates of 25.3% and 25.7% for Q4W and Q12W, respectively, compared to 14.8% for placebo. EASI-75 and PP-NRS ≥4 reached nominal significance, though vIGA-AD 0/1 with barely perceptible erythema (BPE) — a more stringent endpoint — did not meet statistical significance in this cohort.

The combination therapy data from SHORE were notably stronger. vIGA-AD 0/1 rates were 28.7% (Q4W) and 32.3% (Q12W) against 16.8% for placebo with TCS/TCI background therapy. EASI-75 approached 47–48% in treated arms versus 32.3% for placebo, and itch responder rates exceeded 33–38% versus 21.5%.

One clinically notable observation across all three studies was the performance of Q12W dosing, which was numerically comparable to — and in several endpoints marginally higher than — Q4W dosing. Investigators have suggested this may reflect the mechanism's upstream, durable modulation of T cell activation, though longer-term data will be needed to fully characterize this pattern.

Safety

The safety profile was broadly consistent with previously reported amlitelimab data. The most common treatment-emergent adverse events across studies were nasopharyngitis, upper respiratory tract infection, and worsening of AD — the latter occurring at notably higher rates in placebo groups. Injection site reactions were not a significant concern, and malignancy rates remained below 1%, generally similar between treated and placebo cohorts.

Sanofi also disclosed a second cumulative case of Kaposi sarcoma (KS) in the broader development program, identified in the blinded ESTUARY phase 3 extension study. Both KS cases occurred in patients with known risk factors, and both patients discontinued treatment and are in recovery. Across an estimated 4,630 patients exposed to amlitelimab across all indications, no further KS cases have been identified. The company indicated it continues to monitor closely.

Context and Next Steps

Amlitelimab remains investigational, with no regulatory approvals to date. Longer-term safety and the feasibility of Q12W maintenance dosing are being evaluated in the ongoing ESTUARY extension study, with results anticipated in the second half of 2026. For clinicians managing patients with moderate to severe AD who have had inadequate responses to existing biologics or JAK inhibitors, the emerging profile of amlitelimab, particularly its infrequent dosing potential, may represent a meaningful addition to the treatment landscape, pending regulatory review.

References

1. AAD: new results from Sanofi's amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. News release. Sanofi. Published March 28, 2026. Accessed March 31, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-03-28-15-00-00-3264184
2. Weidinger S, Blauvelt A, Papp KA, et al. Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2025;155(4):1264-1275. doi:10.1016/j.jaci.2024.10.031