Amlitelimab Demonstrates Efficacy With Q12W Dosing in AD Trials

Atopic dermatitis (AD) remains a chronic, heterogeneous inflammatory disease that challenges both patients and clinicians despite an expanding therapeutic armamentarium. While current biologics and small molecules have transformed care, unmet needs persist, particularly around durability of response, dosing convenience, and long-term immune modulation. Amlitelimab, a fully human monoclonal antibody targeting OX40-ligand (OX40L), has generated interest as a potential addition to the treatment landscape.¹ Recent results from the SHORE and COAST 2 phase 3 trials, together with earlier COAST 1 findings and preliminary long-term data from the ATLANTIS phase 2 study, provide a growing body of evidence to evaluate.²

Amlitelimab selectively blocks OX40L, a costimulatory molecule involved in T-cell activation and survival, without depleting T cells. This approach differs from agents that broadly suppress immune pathways or directly eliminate immune cell populations. The proposed advantage is a more gradual normalization of immune responses rather than rapid suppression, which could theoretically translate into sustained disease control and a favorable safety profile. Whether this mechanistic distinction results in clinically meaningful differences over time remains an important question as longer-term data mature.

SHORE: Combination Therapy with Topicals

The SHORE study evaluated amlitelimab in combination with medium-potency topical corticosteroids (with or without topical calcineurin inhibitors) in adolescents and adults with moderate to severe AD. At week 24, both dosing regimens, every 4 weeks (Q4W) and every 12 weeks (Q12W), met primary and key secondary endpoints across US and EU statistical frameworks.

Clinically, approximately 29–32% of patients receiving amlitelimab achieved clear or almost clear skin (vIGA-AD 0/1) compared with 16.8% on placebo. EASI-75 responses approached 47–50% with amlitelimab versus roughly one-third with placebo. While these effect sizes are in line with other systemic therapies when used alongside topicals, the consistency across dosing schedules is notable, particularly for the Q12W regimen starting early in treatment.

Common adverse events included nasopharyngitis and upper respiratory tract infections, with overall rates of treatment-emergent and serious adverse events similar between amlitelimab and placebo arms. Importantly, no new safety signals emerged.

COAST 2: Monotherapy and Regional Differences

COAST 2 explored amlitelimab as monotherapy, offering insight into its standalone efficacy. In US and US reference countries, both Q4W and Q12W dosing met the primary endpoint at week 24, with vIGA-AD 0/1 responses of approximately 25% compared with 14.8% on placebo. However, key secondary endpoints, including a stricter erythema assessment, did not consistently reach statistical significance.

In contrast, for EU and EU reference countries, the co-primary endpoints (vIGA-AD 0/1 and EASI-75) were not met. Although nominal improvements in EASI-75 were observed, the hierarchical testing framework limits formal interpretation of these findings. These regional discrepancies underscore the challenges of global AD trials, where differences in patient populations, background care, and expectations may influence outcomes.

From a clinician’s perspective, the COAST 2 results suggest that amlitelimab monotherapy has measurable activity but may be more variable than when used with topical therapies. This raises practical questions about optimal positioning—whether amlitelimab is best viewed primarily as an add-on to optimized topical care rather than a replacement.

Durability Signals from ATLANTIS

The open-label ATLANTIS phase 2 study offers an early look at longer-term outcomes. In this uncontrolled setting, response rates continued to increase between week 24 and week 52, with vIGA-AD 0/1 rising from 35% to 50% and EASI-75 from 63% to 77%. While open-label data must be interpreted cautiously, the progressive improvement over time aligns with the hypothesized mechanism of immune normalization rather than rapid maximal suppression.

Safety through one year remained generally consistent, though an isolated case of cutaneous Kaposi’s sarcoma was reported in a patient with known risk factors, highlighting the need for continued vigilance as exposure lengthens.

Looking Ahead

Taken together, the SHORE and COAST 2 trials support amlitelimab as an effective and generally well-tolerated therapy for moderate to severe AD in patients aged 12 years and older. The ability to maintain efficacy with Q12W dosing from early in treatment is particularly appealing in a chronic disease where treatment burden matters. At the same time, mixed results in monotherapy and regional variability emphasize that amlitelimab is not a panacea and will need to be carefully contextualized among existing options.

With additional phase 3 studies (AQUA and ESTUARY) expected to report in 2026 and global regulatory submissions planned thereafter, clinicians will soon have a clearer picture of where OX40L inhibition fits into real-world AD management. For now, amlitelimab represents a promising, mechanistically distinct candidate whose ultimate value will depend on durability, safety, and how it complements established therapies in everyday practice.

References

1. Bieber T. Atopic dermatitis: an expanding therapeutic pipeline for a complex disease. Nat Rev Drug Discov. 2022;21(1):21-40. doi:10.1038/s41573-021-00266-6
2. Sanofi's amlitelimab confirms its potential in atopic dermatitis. News release. Sanofi. Published January 23, 2026. Accessed January 23, 2026. https://www.sanofi.com/en/media-room/press-releases/2026/2026-01-23-06-00-00-3224400