Sanofi reported late-stage data for amlitelimab, a fully human non-T cell depleting monoclonal antibody targeting the OX40-ligand (OX40L), described as reinforcing its potential as a treatment for patients aged 12 years and older with moderate-to-severe atopic dermatitis (AD).

Results were mixed: Sanofi said the Phase III SHORE study – assessing amlitelimab in combination with topical therapy – met all primary and key secondary endpoints for both US and EU analyses, however, the COAST 2 monotherapy study delivered statistically significant primary endpoint results in the US population but failed to meet co-primary endpoints under the EU estimand. With the divergence driven by regional analysis rather than safety or consistency of effect, Sanofi views the data as supporting plans for global regulatory submissions.

Trials summary

The SHORE study enrolled 596 participants in a randomized, double-blind, placebo-controlled, three-arm, multinational Phase III design evaluating amlitelimab in combination with medium-potency topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI). Patients received a loading dose followed by either every four-week (Q4W) or every 12-week (Q12W) subcutaneous dosing of amlitelimab, with efficacy measured at Week 24. Across both US and EU estimands, both dosing schedules met all primary and key secondary endpoints versus placebo plus TCS/TCI with statistical significance on validated Investigator Global Assessment for AD (vIGA-AD 0/1) and Eczema Area and Severity Index 75 (EASI-75).

In the COAST 2 Phase III monotherapy study, 547 adults and adolescents with moderate-to-severe AD were randomized to amlitelimab Q4W or Q12W versus placebo. At Week 24, the primary endpoint — proportion of patients achieving vIGA-AD 0/1 with a ≥2-point reduction — was statistically significant for the US and US reference populations with both dosing schedules. However, the co-primary endpoints for the EU and EU reference populations (vIGA-AD 0/1 and EASI-75) did not achieve statistical significance under EU estimand analysis, limiting interpretability in those regions under hierarchical testing.

There was also preliminary analysis from the open-label Phase II ATLANTIS study, assessing long-term safety, which showed continued and progressive improvements through Week 52, with no plateau in response. Across the Phase III studies, amlitelimab was well tolerated with a safety profile aligned with previous data.

Research context

Amlitelimab is a fully human, non-T cell depleting monoclonal antibody that selectively blocks the OX40 ligand (OX40L), a key immune regulator involved in T-cell activation and survival. By inhibiting OX40L, amlitelimab aims to normalize overactive immune responses without broadly depleting T cells, distinguishing it mechanistically from other immunosuppressive biologics. This targeted approach is hypothesized to reduce inflammation while minimizing immunosuppression-related risks. Sanofi acquired the molecule via the USD 1.1 billion acquisition of Kymab completed in 2021.

The mixed results for amlitelimab in COAST 2 and SHORE follow the September 2025 release of COAST 1 data, a Phase III study of similar design to COAST 2. In COAST 1, amlitelimab demonstrated statistically significant and clinically meaningful efficacy, however, its efficacy rates – particularly for the most stringent endpoints – appeared numerically lower than those reported for Sanofi’s Dupixent (dupilumab).

Houman Ashrafian, Executive Vice President and Head of R&D at Sanofi, said the totality of data bolstered confidence in amlitelimab’s potential to deliver 12-week dosing from the start and to normalize immune function without depleting T cells. In contrast, Sanofi’s Dupixent typically requires dosing every 2 weeks. Pending data from additional Phase III studies (AQUA and ESTUARY) anticipated in H2 2026, Sanofi aims to leverage this dataset in planned global regulatory filings for amlitelimab later in 2026.

Amlitelimab’s development comes amid broader efforts to address unmet needs in moderate-to-severe AD, a chronic inflammatory skin disease affecting millions worldwide. Existing therapies like dupilumab require more frequent dosing and have set a high efficacy bar, making differentiated profiles an important factor for new entrants.