Amlitelimab meets primary endpoints in Phase 3 atopic dermatitis trials, enabling Sanofi regulatory submissions | iPharmaCenter

Sanofi has reported new phase 3 and phase 2 data indicating that amlitelimab continues to build its profile as a potential treatment option for adolescents and adults with moderate-to-severe atopic dermatitis.

Amlitelimab: Phase 3 program overview

Amlitelimab is a fully human, non–T‑cell–depleting monoclonal antibody that selectively targets OX40 ligand, designed to modulate immune pathways involved in atopic dermatitis. The late-stage program includes three global studies, COAST 1, SHORE, and COAST 2, evaluating amlitelimab given every four weeks (Q4W) or every 12 weeks (Q12W) in patients aged 12 years and older who are candidates for systemic therapy.

Across SHORE and COAST 2, primary and key secondary endpoints were assessed at Week 24. For the US and aligned countries, the primary endpoint was the proportion of patients achieving a validated Investigator Global Assessment score for atopic dermatitis (vIGA‑AD) of 0 (clear) or 1 (almost clear) with at least a 2‑point improvement from baseline, analyzed using a non‑responder imputation approach.

For the EU, EU reference countries, and Japan, co‑primary endpoints combined vIGA‑AD 0/1 with a ≥2‑point improvement and achievement of at least 75% improvement in Eczema Area and Severity Index (EASI‑75), analyzed using a treatment‑policy framework.

SHORE: combination with topical therapy

In SHORE, amlitelimab was administered either Q4W or Q12W on top of medium‑potency topical corticosteroids, with or without topical calcineurin inhibitors, and compared with placebo plus the same topical regimen.

At Week 24, both dosing schedules met all primary and key secondary endpoints versus placebo across US and EU analytic frameworks:

• For the US estimand (non‑responder imputation), 28.7% of patients on amlitelimab Q4W and 32.3% on Q12W achieved vIGA‑AD 0/1 with at least a 2‑point improvement, compared with 16.8% on placebo; both active arms met prespecified significance thresholds.

• Under the EU estimand (treatment policy), vIGA‑AD 0/1 responses were 29.9% with Q4W dosing and 32.9% with Q12W, again versus 16.8% on placebo, with statistically significant differences in favor of amlitelimab.

• For EASI‑75, 48.1% of patients on Q4W and 46.8% on Q12W achieved at least 75% improvement under the US estimand, compared with 32.3% on placebo.

• Using the EU estimand, EASI‑75 rates were 50.9% for Q4W and 48.1% for Q12W versus 34.2% for placebo, with robust significance for both dosing intervals.

• Efficacy increased progressively over the 24‑week period, with some patients experiencing clinical improvement as early as Week 2. Amlitelimab was generally well tolerated in SHORE, with a safety profile consistent with earlier studies.

COAST 2: monotherapy outcomes

COAST 2 evaluated amlitelimab as monotherapy, administered either Q4W or Q12W, compared with placebo.

For the US and US reference countries:

• Using the US estimand, 25.3% of patients in the Q4W arm and 25.7% in the Q12W arm achieved vIGA‑AD 0/1 with at least a 2‑point improvement at Week 24, versus 14.8% with placebo, with both doses reaching statistical significance.

• EASI‑75 was achieved by 41.8% of patients on Q4W and 40.5% on Q12W, compared with 24.2% on placebo, with highly significant differences favoring amlitelimab.

• Under the EU estimand, vIGA‑AD 0/1 responses were 28.8% for Q4W and 27.7% for Q12W, versus 18.8% with placebo. The Q4W arm reached nominal statistical significance, while the Q12W arm did not meet the prespecified threshold.

• EASI‑75 rates were 49.7% for Q4W and 45.9% for Q12W, compared with 30.2% for placebo, with statistically significant improvements for both amlitelimab regimens.

The key secondary endpoint in the US region – vIGA‑AD 0/1 with barely perceptible erythema – did not meet statistical significance, and for the EU region the co‑primary endpoints were not consistently met across arms. As a result, subsequent secondary endpoints in COAST 2 are interpreted as nominal.

ATLANTIS: long-term phase 2 findings

A preliminary analysis from the open‑label ATLANTIS phase 2 study provides longer‑term data for amlitelimab given Q4W. The analysis included 591 patients aged 12 years and older with moderate‑to‑severe atopic dermatitis.

• At Week 24, 35.4% of participants achieved vIGA‑AD 0/1; by Week 52, this proportion increased to 50.3%.

• EASI‑75 responses rose from 62.9% at Week 24 to 76.5% at Week 52, indicating continued improvement without evidence of plateau over one year.

Amlitelimab remained generally well tolerated through Week 52 in this interim assessment.

These data suggest that OX40‑ligand inhibition may offer sustained, progressive benefit over time in chronic atopic dermatitis.