Amlitelimab: Effective also alongside topical anti-inflammatory treatment

Findings from the phase 3 COAST-1 (NCT06130566), COAST-2 (NCT06181435), and SHORE (NCT06224348) trials show that the non-depleting anti-OX40L antibody amlitelimab produced steadily improving outcomes in skin signs, lesion severity, and pruritus in adults with moderate-to-severe atopic dermatitis (AD). The first 2 trials evaluated amlitelimab as monotherapy, while SHORE assessed the agent in combination with topical corticosteroids (TCS).

Amlitelimab is designed to block OX40L without depleting T cells, aiming not merely to suppress cytokines but to induce a broader “reset” of pathogenic T-cell–mediated inflammation. This mechanism was evaluated across 3 phase 3 trials presented during a late-breaking research session [1].

COAST-1 and COAST-2 were replicate monotherapy trials enrolling 610 and 589 patients, respectively, while SHORE included 643 patients receiving amlitelimab on a background of TCS with or without calcineurin inhibitors. As Prof. Eric Simpson (Oregon Health and Science University, OR, USA) explained, participants in all 3 studies were randomised 2:1:1 to receive subcutaneous amlitelimab every 4 weeks (Q4W) with a loading dose, every 12 weeks (Q12W) with a loading dose, or placebo for 24 weeks [1].

The primary endpoint was the proportion of patients achieving a validated Global Assessment score of 0 or 1 (vIGA-AD 0/1) at week 24. Key secondary endpoints included vIGA-AD 0/1, allowing minimal erythema, the Eczema Area and Severity Index (EASI) 75, and a ≥4-point reduction in the Peak Pruritus Numerical Rating Scale (PP-NRS ≥4), considered clinically meaningful. In the monotherapy trials, rescue medication use or early discontinuation due to lack of efficacy was counted as non-response.

In COAST-1, every prespecified endpoint was met. vIGA-AD 0/1 was achieved by 17.4% (Q4W) and 18.5% (Q12W) of patients versus 7.9% on placebo (P<0.02), increasing to 21.1% and 22.5% versus 9.2% when minimal erythema was allowed (P<0.01). EASI 75 was reached by 35.9% and 39.1% versus 19.1% (P<0.001), and a PP-NRS ≥4 response by 22.5% and 24.5% versus 12.7% (P≤0.02).

COAST-2 met its primary endpoint, with vIGA-AD 0/1 achieved in 25.3% (Q4W) and 25.7% (Q12W) of amlitelimab-treated patients versus 14.8% with placebo (P≤0.025). The endpoint allowing minimal erythema (21.6% and 20.3% vs 13.2%) did not reach significance, whereas EASI 75 (41.8% and 40.5% vs 24.2%) and PP-NRS ≥4 (26.8% and 27.2% vs 17.1%) achieved nominal significance.

SHORE confirmed efficacy in combination with TCS across all primary and key secondary outcomes, including vIGA-AD 0/1 (25.3% Q4W and 29.1% Q12W vs 13.7% placebo; P≤0.01), the endpoint allowing minimal erythema (28.7% and 32.3% vs 16.8%; P≤0.01), EASI 75 (48.1% and 46.8% vs 32.3%; P≤0.025), and PP-NRS ≥4 (38.2% and 33.3% vs 21.5%; P≤0.025).

Across all 3 trials, response curves continued to improve through week 24 without evidence of a plateau, and treatment was well tolerated.

“These data, which show that amlitelimab delivers progressively increasing efficacy over time, further illustrate the potential of non-T cell-depleting OX40L inhibition to reduce disease severity and burdensome symptoms with less frequent dosing,” Prof. Simpson concluded.

Simpson E, et al. Combined Oral: Efficacy and Safety of Monotherapy Amlitelimab, a Non-Depleting Anti-OX40 Ligand Antibody, in Moderate-to-Severe Atopic Dermatitis: 24-Week Results From the Pivotal COAST 1 and COAST 2 Phase 3 Trials and Efficacy and Safety of Amlitelimab, a Non-Depleting Anti-OX40 Ligand Antibody, in Combination With Topical Therapy in Participants With Moderate-to-Severe Atopic Dermatitis: 24-Week Results From the SHORE Phase 3 Trial. S023: Late-Breaking Research: Session 1. AAD 2026, 27–31 March, Denver, CO, USA.