Amlitelimab Demonstrates Progressive Efficacy in Moderate to Severe AD Across Phase 3 Trials

Phase 3 data presented in a late-breaking research session at the 2026 American Academy of Dermatology Annual Meeting in Denver, Colorado, showed that amlitelimab (Sanofi), a fully human monoclonal antibody targeting OX40-ligand (OX40L), significantly improved skin clearance and disease severity in patients aged 12 years and older with moderate to severe atopic dermatitis (AD). Findings from the COAST 1 (NCT06130566), COAST 2 (NCT06181435), and SHORE (NCT06224348) studies reinforced a pattern of progressive efficacy with no evidence of plateau at week 24, supporting the potential for a dosing of once every 12 weeks from treatment initiation.^1,2

Mechanism of Action

Amlitelimab selectively blocks OX40L, a key immune regulator involved in the initiating phase of T cell–mediated inflammation. Unlike some existing therapies, it is non–T cell–depleting, meaning it modulates the inflammatory cascade without eliminating T cells. This mechanism targets what investigators describe as the inflammatory prequel, potentially normalizing immune overactivation upstream of the downstream inflammatory response characteristic of AD.¹

Key Efficacy Findings

In the monotherapy studies COAST 1 (n = 601) and COAST 2 (n = 589), amlitelimab met the primary end point of a validated Investigator Global Assessment (vIGA-AD) score of 0 or 1 with a reduction of 2 or more points from baseline for both the every-4-weeks and every-12-weeks dosing schedules vs placebo. In COAST 1, all key secondary end points reached statistical significance, including the proportion of patients reaching a 75% or greater improvement in the Eczema Area Severity Index total score (EASI 75) (35.9% every 4 weeks and 39.1% every 12 weeks vs 19.1% placebo) and an improvement of 4 or more points in Peak Pruritus Numerical Rating Scale (PP-NRS≥4) (22.5% every 4 weeks and 24.5% every 12 weeks vs 12.7% placebo). In COAST 2, EASI 75 and PP-NRS≥4 reached nominal significance, while vIGA-AD 0/1 with barely perceptible erythema did not achieve statistical significance.^1,2

The SHORE study (n = 643) evaluated amlitelimab in combination with topical corticosteroids, with or without topical calcineurin inhibitors. Both the every-4-weeks and every-12-weeks arms demonstrated statistically significant improvements across primary and key secondary end points vs placebo. Notably, the every-12-weeks combination arm achieved a vIGA-AD 0/1 rate of 32.3% compared with 16.8% for placebo, suggesting that even with less frequent dosing, a clinically meaningful benefit is achievable alongside topical therapies.^1,2

Safety Profile

The safety profile across all 3 studies was consistent with previously reported amlitelimab data. The most common treatment-emergent adverse events were nasopharyngitis, upper respiratory tract infection, and AD flares, occurring at rates generally similar to or lower than with placebo. Malignancy rates were below 1% and comparable between treatment and placebo groups. Two cases of Kaposi sarcoma were identified across the broader development program of approximately 4630 patients, both in individuals with known risk factors, and neither has led to a programwide safety signal.^1,2

Notably, Kyowa Kirin announced in March 2026 that it was discontinuing the research and development of rocatinlimab, a different investigational anti-OX40 monoclonal antibody, due to 1 confirmed case and 1 suspected case of Kaposi sarcoma.³

During the late-breaking presentation on amlitelimab, presenter and investigator Eric Simpson, MD, MCR, a dermatologist in Portland, Oregon, addressed this safety concern among OX40s: “There were no cases with Kaposi sarcoma in these 3 studies. But the reason why I bring that up is because, cumulatively, over the course of 3700 patients that have been looked at in this program, there were 2 cases of Kaposi sarcoma. Both cases were elderly [men] who had other risk factors for Kaposi sarcomas, so it’s just important to keep that in mind as something that we’re watching very closely.”¹

Looking Ahead

Longer-term safety and efficacy data from the ESTUARY phase 3 extension study, evaluating every-12-weeks maintenance dosing, are anticipated in the second half of 2026. Amlitelimab remains investigational and has not yet received regulatory approval. These results add to a growing body of evidence suggesting that OX40L inhibition may offer a meaningful, convenient treatment option for patients with moderate to severe AD in whom significant unmet need persists.²

“In conclusion, amlitelimab every 4 weeks or every 12 weeks reached clinically meaningful improvement in both skin and itch,” Simpson said. “The doses seem comparable, [every 12 weeks] or [every 4 weeks], so I think this could be [an every-12-weeks] dose. Amlitelimab was well tolerated. There were 2 cases of Kaposi sarcomas that we’re going to be watching closely, and hopefully we’ll see this progressive improvement over time in the longer treatment. Then, we’ll have to wait and see in our future studies, when we withdraw the drug, how long can we get this durable response?”¹

References

1. Simpson EL. Combined oral: efficacy and safety of monotherapy amlitelimab, a non-depleting anti-OX40 ligand antibody, in moderate-to-severe atopic dermatitis: 24-week results from the pivotal COAST 1 and COAST 2 phase 3 trials and efficacy and safety of amlitelimab, a non-depleting anti-OX40 ligand antibody, in combination with topical therapy in participants with moderate-to-severe atopic dermatitis: 24-week results from the SHORE phase 3 trial. Presented at: 2026 American Academy of Dermatology Annual Meeting; March 27-31, 2026; Denver, CO.

2. AAD: new results from Sanofi’s amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. News release. Sanofi. March 28, 2026. Accessed April 13, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-03-28-15-00-00-3264184

3. Kyowa Kirin announces discontinuation of rocatinlimab clinical trials. News release. Kyowa Kirin. March 3, 2026. Accessed April 13, 2026. https://www.globenewswire.com/news-release/2026/03/03/3248303/0/en/Kyowa-Kirin-Announces-Discontinuation-of-Rocatinlimab-Clinical-Trials.html