Amlitelimab Meaningfully Clears Skin in Moderate-to-Severe Atopic Dermatitis

In the global COAST 1 phase 3 trial (NCT06130566), amlitelimab, a fully human, non-T-cell depleting monoclonal antibody targeting the OX40-ligand (OX40L), demonstrated statistically significant and clinically meaningful skin clearance and disease severity compared with placebo at week 24 in patients aged 12 years and older with moderate-to-severe atopic dermatitis (AD), according to a news release from Sanofi.^1,2

Atopic dermatitis can appear in moderate or severe forms. | Image Credit: © Rochu_2008 - stock.adobe.com

Amlitelimab blocks OX40L, a key immune regulator in the body. By normalizing an overactive immune system without depleting T-cells, amlitelimab utilizes a novel mechanism of action to treat AD, which is a chronic inflammatory skin condition characterized by dry and inflamed skin. Patients with AD are in sore need of novel treatment options, especially for moderate or severe forms of the condition that involve more severe itching and more frequent and serious flare-ups.^1,3

Amlitelimab Demonstrates Reduction in Itch Severity in AD

COAST 1, a randomized, double-blind, placebo-controlled, parallel-group, 3-arm, global, multicenter phase 3 study, was designed to evaluate the safety and efficacy of amlitelimab monotherapy through subcutaneous injection either every 4 weeks (Q4W) or every 12 weeks (Q12W). Investigators enrolled 601 adults and adolescents aged 12 and older with moderate-to-severe AD, with key objectives primarily featuring the measuring of the safety and efficacy of amlitelimab compared with placebo at week 24. Amlitelimab was administered at a dose of 250 mg, with dosage variations depending on body weight.¹

The study’s primary end point for patients in the US and US reference countries was the proportion of patients with a validated investigator global assessment scale for AD (vIGA-AD) of 0 (clear) or 1 (almost clear), with a corresponding score reduction by 2 or more points. For individuals in the European Union (EU) and EU reference countries, co-primary end points included the aforementioned end point, in addition to the proportion of patients achieving 75% or greater improvement in the eczema area and severity index total score (EASI-75).¹

According to data released by Sanofi, 26.5% of patients who received amlitelimab Q4W and 29.1% of patients receiving the drug Q12W reached vIGA-AD scores of 0 or 1, compared with 10.5% in the placebo group. In addition, 46% of patients dosed Q4W and 50.3% dosed Q12W achieved significant reductions in EASI-75 scores. For each treatment arm, there was a progressive increase in efficacy without a plateau, a key indicator of treatment success.¹

Furthermore, a series of key secondary end points were successfully achieved at week 24. These included the proportion of patients who achieved a vIGA-AD 0/1 with only slight erythema and a reduction from baseline of 2 or more points, and the proportion of individuals achieving a 4-point or more reduction in peak pruritus-numerical rating scale (PP-NRS) from baseline in patients with a baseline PP-NRS of 4 or more.¹

With Positive Safety, Amlitelimab Shows Great Potential in AD

A thorough safety analysis was also conducted. Common treatment-emergent adverse events (TEAEs) in COAST 1—which were those with a 5% or higher incidence in either dose arm—were AD, nasopharyngitis, and upper respiratory tract infection. Importantly, all TEAEs were more common in the placebo arm compared with amlitelimab arms (pooled amlitelimab, 2.2%; placebo, 0.7%). Importantly, all TEAEs were mild, patients were observed to recover, and amlitelimab was continued in all cases.¹

Other safety concerns were reported, including reports of pyrexia (pooled amlitelimab, 1.1%; placebo, 0.7%) and chills (pooled amlitelimab, 0.4%; placebo arm, 0%), though these appeared at low rates. The investigators observed that, overall, rates of TEAEs, serious AEs, and TEAEs resulting in treatment discontinuation were similar in the placebo and pooled amlitelimab arms.¹

Amlitelimab, if indications continue to be positive as it proceeds through phase 3 studies, has the potential to be a first-in-class treatment for not only AD but also a variety of immune-mediated diseases and inflammatory disorders. As the OCEANA clinical development of amlitelimab in AD continues—with 4 other phase 3 trials currently ongoing—pharmacists should stay aware of updates and possible regulatory actions.¹

“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,” Houman Ashrafian, executive vice president and head of research and development at Sanofi, said in the news release. “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 4 times per year.”¹

REFERENCES

1. Sanofi. Press Release: Sanofi’s amlitelimab met all primary and key secondary endpoints in the COAST 1 phase 3 study in adults and adolescents with atopic dermatitis. News Release. Released 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. A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab Monotherapy Compared With Placebo in Participants Aged 12 Years and Older With Moderate-to-severe Atopic Dermatitis (COAST 1). ClinicalTrials.gov Identifier: NCT06130566. https://www.clinicaltrials.gov/study/NCT06130566?term=NCT06130566&rank=1

3. Mayo Clinic Staff. Atopic dermatitis (eczema). Mayo Clinic. Published May 15, 2024. Accessed September 10, 2025. https://www.mayoclinic.org/diseases-conditions/atopic-dermatitis-eczema/symptoms-causes/syc-20353273