Phase 3 trials support amlitelimab efficacy for atopic dermatitis in patients 12 years and older

Sanofi announced positive results from two global phase 3 clinical trials evaluating amlitelimab, an investigational monoclonal antibody targeting OX40-ligand (OX40L), in adolescents and adults with moderate-to-severe atopic dermatitis.¹

Data from the SHORE and COAST 2 studies demonstrated statistically significant efficacy at Week 24 across several primary and key secondary endpoints, with a safety profile consistent with previously reported findings. Based on the totality of evidence, the company plans to proceed with global regulatory submissions.¹

Amlitelimab is a fully human, non–T cell depleting monoclonal antibody designed to selectively block OX40L signaling, a pathway involved in T cell–mediated inflammation. The agent is being studied in patients aged 12 years and older with moderate-to-severe atopic dermatitis. According to Sanofi, the clinical program is evaluating both every-4-week (Q4W) and every-12-week (Q12W) dosing regimens, including the potential for initiating treatment with Q12W dosing.

“Importantly, these results validate amlitelimab’s novel mechanism of action to block OX40-ligand without T-cell depletion and its promise to normalize the immune system over time,” said Houman Ashrafian, Executive Vice President and Head of Research & Development at Sanofi. “The totality of data seen to date reinforce our confidence in amlitelimab’s potential to deliver both Q12W dosing from the start and progressive efficacy through Week 52.”

SHORE phase 3 study

The SHORE study (NCT06224348) was a randomized, double-blind, placebo-controlled phase 3 trial evaluating amlitelimab in combination with background topical therapies, including medium-potency topical corticosteroids with or without topical calcineurin inhibitors.² The study enrolled 596 participants aged 12 years and older with moderate-to-severe atopic dermatitis.

At Week 24, amlitelimab met all primary and key secondary endpoints across both US and European estimands. The primary endpoint was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear) with a reduction of at least 2 points from baseline. Secondary endpoints included the proportion of patients achieving at least a 75% improvement in the Eczema Area and Severity Index (EASI-75).

In the US estimand analysis using non-responder imputation, 28.7% of patients receiving amlitelimab Q4W and 32.3% receiving Q12W achieved vIGA-AD 0/1 at Week 24, compared with 16.8% in the placebo group. For EASI-75, response rates were 48.1% in the Q4W group and 46.8% in the Q12W group, compared with 32.3% with placebo. Results using the European treatment policy estimand were consistent across both dosing regimens.

COAST 2 phase 3 study

The COAST 2 study (NCT06181435) evaluated amlitelimab as monotherapy in a randomized, double-blind, placebo-controlled phase 3 design involving 547 adolescents and adults with moderate-to-severe atopic dermatitis.³ For the US and US reference countries, amlitelimab met the primary endpoint of achieving vIGA-AD 0/1 with a reduction of at least 2 points from baseline at Week 24.

In the non-responder imputation analysis, 25.3% of patients receiving amlitelimab Q4W and 25.7% receiving Q12W achieved the primary endpoint, compared with 14.8% in the placebo group. For the European and EU reference countries, amlitelimab did not meet statistical significance for the co-primary endpoints of vIGA-AD 0/1 and EASI-75, and subsequent analyses were reported as nominal without adjustment for multiplicity.

Safety findings

Across both phase 3 studies, amlitelimab was generally well-tolerated. The most common treatment-emergent adverse events in SHORE included nasopharyngitis, upper respiratory tract infection, and atopic dermatitis, with similar overall rates of adverse events, serious adverse events, and treatment discontinuations between amlitelimab and placebo groups. Safety findings in COAST 2 were consistent, with no new safety signals identified.

Supporting phase 2 data and next steps

Sanofi also reported a preliminary analysis from the ongoing ATLANTIS phase 2 open-label study, which showed continued improvement in skin clearance and disease severity through Week 52, with no evidence of a treatment plateau. In this analysis, 50.3% of patients achieved vIGA-AD 0/1 and 76.5% achieved EASI-75 at Week 52.

Additional phase 3 studies, including AQUA and ESTUARY, are expected to report results in the second half of 2026. Amlitelimab remains investigational, and its safety and efficacy have not yet been evaluated by regulatory authorities. Global regulatory submissions are planned for the second half of 2026.

References

1. Sanofi. Sanofi's amlitelimab confirms its potential in atopic dermatitis. Sanofi. January 23, 2026. Accessed January 23, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-01-23-06-00-00-3224400
2. NIH. A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab in Participants Aged 12 Years and Older With Moderate-to-severe Atopic Dermatitis on Background Topical Corticosteroids (SHORE). ClinicalTrials.gov. 2025. Accessed January 23, 2026. https://clinicaltrials.gov/study/NCT06224348
3. NIH. A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab Monotherapy Compared With Placebo in Participants Aged 12 Years and Older With Moderate-to-severe Atopic Dermatitis (COAST 2). ClinicalTrials.gov. 2025. Accessed January 23, 2026. https://clinicaltrials.gov/study/NCT06181435