Amlitelimab Shows Efficacy Across Phase 3 AD Trials

Key Takeaways

• Amlitelimab met primary and key secondary endpoints across three Phase 3 trials, demonstrating efficacy both as monotherapy and in combination with topical therapy.
• Responses were consistent across Q4W and Q12W dosing, with evidence of progressive improvement and potential durability over time.
• Safety was comparable to placebo, with no new major safety signals, though rare cases of Kaposi sarcoma are under continued monitoring.

Late-breaking Phase 3 data presented at the American Academy of Dermatology (AAD) 2026 Annual Meeting demonstrated that amlitelimab, a nondepleting anti–OX40 ligand (OX40L) antibody, significantly improved disease severity and symptoms in patients with moderate-to-severe atopic dermatitis (AD), both as monotherapy and in combination with topical therapy.

Eric Simpson, MD, MCR, presented results from the SHORE trial (combination therapy) and the pivotal COAST-1 and COAST-2 trials (monotherapy), encompassing more than 1,800 participants globally.

Amlitelimab targets OX40L on antigen-presenting cells, modulating T-cell activation upstream of inflammatory cytokine production.

“By dampening that co-stimulatory molecule, it can reduce inflammation … not just specific for Th2m (but also) Th1, Th17, Th22,” Dr. Simpson said. 

In SHORE (NCT06224348), which evaluated amlitelimab with background topical corticosteroids and/or calcineurin inhibitors in 643 patients, both Q4W and Q12W dosing regimens significantly outperformed placebo at Week 24. vIGA-AD 0/1 response rates reached 28.7% and 32.3% vs 16.8% with placebo (P ≤ .01), with similar improvements across EASI-75 and pruritus endpoints.

Parallel findings were observed in the COAST-1 (N=601) and COAST-2 (N=589) monotherapy trials. In COAST-1, amlitelimab achieved higher vIGA-AD 0/1 response rates vs placebo (21.1%–22.5% vs 9.2%; P < .01), along with significant improvements in EASI-75 and itch. COAST-2 met its primary endpoint, though some secondary endpoints reached nominal significance.

Across studies, efficacy appeared similar between Q4W and Q12W regimens.

“The doses seem comparable. … This could be a Q12-week drug,” Dr. Simpson noted.

He also pointed to a trend of continued improvement:

“You can see that maybe the line keeps going up,” he said. “Is there going to be progressive efficacy over time?” 

Preliminary extension data suggest this may be the case, with up to 50% of patients achieving clear or almost clear skin at one year, though these findings remain uncontrolled.

Amlitelimab was well tolerated across trials, with adverse event rates comparable to placebo and low rates of serious adverse events

Dr. Simpson described the safety profile as “reassuring.” He noted that rare cases of Kaposi sarcoma were observed across the broader development program but that these occurred in patients with additional risk factors and resolved after treatment discontinuation.

Regarding clinical positioning, Dr. Simpson emphasized individualized use.

“It is patient dependent. … This is a marathon, not a sprint,” he said, noting that amlitelimab may be best suited as a long-term strategy rather than for rapid disease control.