Amlitelimab Demonstrates Durable Response in Atopic Dermatitis

At the 2025 American Academy of Dermatology (AAD) Annual Meeting, Sanofi shared new insights into the effectiveness of amlitelimab, an investigational drug for atopic dermatitis (AD).¹

Data from the phase 2b STREAM-AD and RIVER-AD² studies demonstrated promising findings for patients with moderate to severe AD, with results showcasing durable efficacy and a favorable safety profile.

Karl Yen, executive global project head for amlitelimab at Sanofi, spoke with Dermatology Times to share key insights from these studies, highlighting the potential of amlitelimab as a transformative treatment option for AD.

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STREAM-AD Phase 2b Study: Sustained Efficacy and Long-Term Benefits

The STREAM-AD phase 2b trial was divided into 2 parts: part 1 (24 weeks) and part 2 (28 weeks). According to Yen, the findings from the second part of the trial, presented at AAD 2024, are particularly exciting.

In the trial, a significant proportion of patients maintained their response for 28 weeks. Specifically, 74% of those who continued on amlitelimab retained a Patient-Reported Itch Numerical Rating Scale (PPRNRS) score of ≥4, indicating a meaningful reduction in itch. In total, 63% of patients who were withdrawn from treatment also maintained this score.

"In those patients continuing on amlitelimab, 74% maintain this PPNRS greater than or equal to 4 score," Yen said. "In the withdrawal arm, even more impressively, 63% of those patients still maintain their PPNRS greater than 4 score, demonstrating that amlitelimbab has the potential to provide durable, sustained efficacy, not just in patients on drug, but potentially off drug, as well."

RIVER-AD Study: Promising Results for Patients Who Initially Did Not Respond

The RIVER-AD study served as an extension to the STREAM-AD trial and included patients who did not meet response criteria in part 1. These patients were given the opportunity to continue treatment in part 2 or, for those who had been on placebo, receive active treatment in the RIVER-AD extension study.

"What we showed is that with continued treatment, the majority of these patients actually did achieve a clinical response," Yen said.

Yen also pointed out that these results highlight amlitelimab's ability to provide clinical responses even in patients who had previously not responded to treatment.

Amlitelimab’s Mechanism of Action: Targeting OX40 Ligand

One of the key factors that sets amlitelimab apart from other treatments for AD is its novel mechanism of action, Yen said. Unlike many current therapies that target cytokines involved in inflammation, amlitelimab targets the OX40 ligand (OX40L), a critical mediator in immune cell signaling.

This upstream mechanism offers several advantages, including a reduced risk of off-target effects like immunosuppression, a common concern with some biologics. Additionally, targeting OX40L, rather than the OX40 receptor itself, spares regulatory T cells, which play a crucial role in immune regulation and long-term disease modification.

Amlitelimab and the Future of AD Treatment

"Amlitelimab has the opportunity to target a broader population than some of the existing therapies," Yen said. "It also has this unprecedented opportunity to potentially have off-treatment, it can maintain off-treatment response, which is really very, very exciting for patients."

Sanofi is also exploring amlitelimab in other dermatologic conditions, including alopecia areata, hidradenitis suppurativa, and systemic sclerosis.

Looking ahead, Sanofi’s ongoing phase 3 clinical program, OCEANA, aims to further investigate the safety and efficacy of amlitelimab in AD, including its long-term benefits and potential for off-drug remission.

References

1. New phase 2b results for amlitelimab support potential for best-in-class maintenance of response in atopic dermatitis. News release. Sanofi. March 11, 2025. Accessed March 14, 2025. https://www.sanofi.com/en/media-room/press-releases/2024/2024-03-11-06-00-00-2843456
2. Health Research Authority. RIVER-AD. Accessed March 14, 2025. https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/river-ad/