Sanofi's OX40L Inhibitor Amlitelimab Shows Positive Results in Phase 3 AD Trial

Last week, Sanofi shared positive results from the COAST 1 phase 3 study (NCT06130566) evaluating amlitelimab in adults and adolescents 12 years and older with moderate to severe atopic dermatitis (AD).¹ The drug met all primary and secondary endpoints at week 24 with clinically meaningful skin clearance compared to placebo.

COAST 1 was a randomized, double-blind, placebo-controlled, parallel-group, 3-arm, global, multicenter phase 3 study that included 601 participants. It was held at sites in 15 countries across North America, Latin America, Europe, Asia-Pacific, and the Middle East. Patients were dosed to receive 250 g of amlitelimab either every 4 weeks or every 12 weeks by subcutaneous injection following a loading dose of 500 mg.

In the US and US reference countries, the primary endpoint was the proportion of patients with a Validated Investigator Global Assessment scale for AD (vIGA-AD) of 0 (clear) or 1 (almost clear) and a reduction from baseline score of ≥2 points. In the EU, EU reference countries, and Japan, the primary endpoint was the proportion of patients with vIGA-AD 0/1 and a reduction from baseline score of ≥2 points, along with the proportion of participants reaching a 75% or greater improvement in the Eczema Area and Severity Index total score (EASI-75).

In both of these arms, efficacy increased throughout the treatment period, with a high of 18.1% in those dosed every 12 weeks and 15.2% in those dosed every 4 weeks. The secondary endpoints were also achieved at week 24. These included the proportion of patients who achieved a vIGA-AD 0/1 with only barely perceptible erythema and a reduction from baseline of ≥ 2 points, and the proportion of patients who achieved a ≥4-point reduction in peak pruritus-numerical rating scale (PP-NRS) from baseline in patients with a baseline PP-NRS ≥4.

The drug was well tolerated with no new safety concerns, as the rate of treatment-emergent adverse effects in any dose arm was ≥5%. The most commonly reported events were AD, nasopharyngitis, injection site reactions, and upper respiratory tract infection. These were all more common in the placebo group, except for the injection site reactions (pooled amlitelimab 2.2%, placebo 0.7%). Rates of pyrexia and chills were low in both groups. All adverse effects were mild and patients recovered with no discontinuation of the drug.

Amlitelimab (SAR445229, KY1005) is a fully human, non-T cell-depleting monoclonal antibody that blocks OX40L. This novel mechanism of action aims to normalize the overactive immune system without depleting T cells, making it a first-in-class treatment for several immune-mediated diseases. With these results, amlitelimab has the potential to be the first and only AD therapy with possible dosing of only 4 times per year.

“Amlitelimab has the opportunity to target a broader population than some of the existing therapies," Karl Yen, executive global project head for amlitelimab at Sanofi, told Dermatology Times earlier this year. "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."²

COAST 1 is part of the OCEANA clinical development program of amlitelimab in AD, which includes 4 other phase 3 trials (SHORE, COAST 2, AQUA, and ESTUARY). Sanofi plans to read out full results through 2026 and COAST 1 findings will be shared at an upcoming medical meeting. Along with AD, the company plans to explore the use of amlitelimab in other conditions like asthma, systemic sclerosis, celiac disease, and alopecia areata.

“These positive first phase 3 results of amlitelimab reinforce the potential of targeting the OX40-ligand to normalize the overactive immune system, without depleting T cells,” said Houman Ashrafian, Executive Vice President and Head of Research & Development at Sanofi. “Amlitelimab may represent a significant advance in the treatment of atopic dermatitis with clinically meaningful and progressively increasing efficacy, with the potential of dosing only four times per year. These promising data seen in a study population that more closely resembles today’s diverse patient landscape, including a substantial proportion previously treated with advanced therapies, support our ambition to deliver a differentiated medicine. We look forward to sharing additional phase 3 results from the OCEANA clinical development program.”¹

References

1. Sanofi’s amlitelimab met all primary and key secondary endpoints in the COAST 1 phase 3 study in adults and adolescents with atopic dermatitis. Press release. Sanofi. Published September 4, 2025. Accessed September 10, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-09-04-05-00-00-3144170

2. 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 September 10, 2025. https://www.sanofi.com/en/media-room/press-releases/2024/2024-03-11-06-00-00-2843456