The global COAST 1 phase 3 trial (NCT06130566) delivered encouraging results for amlitelimab, a fully human, non–T cell depleting monoclonal antibody targeting OX40-ligand (OX40L). When administered every four weeks (Q4W) or every 12 weeks (Q12W), amlitelimab met all primary and key secondary endpoints. At Week 24, it demonstrated statistically significant and clinically meaningful improvements in skin clearance and disease severity compared to placebo in patients aged 12 years and older with moderate-to-severe atopic dermatitis (AD). Importantly, amlitelimab was well tolerated, with no new safety concerns identified.
Expert Perspective
Commenting on the findings, Houman Ashrafian, Executive Vice President, Head of Research & Development at Sanofi, stated:
“These positive first phase 3 results of amlitelimab reinforce the potential of targeting OX40-ligand to normalize the overactive immune system, without depleting T cells. Amlitelimab may represent a significant advance in the treatment of atopic dermatitis, offering clinically meaningful and progressively increasing efficacy, with the potential for dosing only four times per year. These promising results were observed in a diverse patient population, including those previously treated with advanced therapies. They strengthen our ambition to deliver a differentiated medicine. We look forward to sharing additional phase 3 results from the OCEANA program.”
Primary Endpoints Across Global Regions
The study measured its primary endpoints at Week 24:
- US and reference countries: proportion of patients achieving a validated Investigator Global Assessment for AD (vIGA-AD) score of 0 (clear) or 1 (almost clear), plus a ≥2-point reduction from baseline.
- EU, EU reference countries, and Japan: co-primary endpoints included vIGA-AD 0/1 with ≥2-point reduction and achievement of a 75% or greater improvement in the Eczema Area and Severity Index (EASI-75).
Efficacy Results
Non-responder imputation analysis:
- vIGA-AD 0/1: Q4W 21.1% (p<0.01), Q12W 22.5% (p<0.01), Placebo 9.2%.
- EASI-75: Q4W 35.9% (p<0.001), Q12W 39.1% (p<0.001), Placebo 19.1%.
Treatment policy analysis:
- vIGA-AD 0/1: Q4W 26.5% (p<0.001), Q12W 29.1% (p<0.001), Placebo 10.5%.
- EASI-75: Q4W 46.0% (p<0.001), Q12W 50.3% (p<0.001), Placebo 27.6%.
Notably, both dosing arms showed a progressive increase in efficacy without plateau throughout the treatment period.
Secondary Endpoints Achieved
Amlitelimab also met its key secondary endpoints at Week 24. These included:
- The proportion of patients with vIGA-AD 0/1 and barely perceptible erythema plus ≥2-point reduction from baseline.
- The proportion of patients with a ≥4-point reduction in peak pruritus-numerical rating scale (PP-NRS) from baseline among those with baseline PP-NRS ≥4.
Safety Profile
As per the press release, the treatment showed a favorable safety profile. The most common treatment-emergent adverse events (TEAEs), reported in ≥5% of patients in any arm, were atopic dermatitis, nasopharyngitis, and upper respiratory tract infection, all more common in the placebo group. Injection site reactions occurred more frequently with amlitelimab (2.2%) versus placebo (0.7%), but all were mild, resolved, and did not require discontinuation. Low rates of pyrexia (1.1% vs. 0.7%) and chills (0.4% vs. 0%) were also noted. Overall, TEAEs, serious adverse events, and discontinuations were comparable between amlitelimab and placebo groups.
Next Steps in Clinical Development
Sanofi will present the full results of COAST 1 at an upcoming medical meeting. Meanwhile, amlitelimab continues under evaluation in the OCEANA phase 3 development program, which includes COAST 1, COAST 2, SHORE, AQUA, and ESTUARY. These studies, expected to report through 2026, will form the basis for potential global regulatory submissions.
Current Status
Amlitelimab remains under clinical investigation. Its safety and efficacy have not yet been evaluated or approved by any regulatory authority.