Amlitelimab Meets Primary Endpoints in Phase 3 Atopic Dermatitis Trials

Results from three phase 3 trials evaluating amlitelimab in moderate to severe atopic dermatitis show the investigational drug met primary endpoints in two monotherapy studies and demonstrated stronger efficacy in combination therapy. The combination therapy SHORE trial produced the highest response rates of the three studies, with EASI-75 approaching 48% in the every-4-week dosing arm.

All three 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, with or without topical calcineurin inhibitors. Across all trials, patients were randomized to receive amlitelimab 250 mg (125 mg for those under 40 kg) either every 4 weeks or every 12 weeks, following a loading dose, or placebo.

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 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. The combination therapy data from SHORE were notably stronger, with vIGA-AD 0/1 rates of 28.7% (Q4W) and 32.3% (Q12W) against 16.8% for placebo with 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.

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 disclosed a second cumulative case of Kaposi sarcoma 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.

Amlitelimab is a fully human monoclonal antibody targeting OX40-ligand, 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.

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.