Amlitelimab Phase 2b data show potential best-in-class profile in atopic dermatitis: Sanofi

In this dose-ranging study, subcutaneous treatment with amlitelimab resulted in statistically significant improvements in the primary endpoint of percent change in Eczema Area and Severity Index (EASI) score from baseline at 16 weeks compared to placebo for all four doses that were studied. Among these, patients treated with amlitelimab 250 mg Q4W with 500 mg loading dose (LD) had the numerically highest response versus placebo, showing a 61.5% reduction in EASI from baseline at week 16 (P<0.0001) and a 64.4% reduction at week 24 (P<0.0001) vs. 29.4% at week 16 and 27.6% at week 24 for placebo.

Professor Stephan Weidinger, M.D, Ph.D, Director, Professor, Chair of Department of Dermatology and Allergy, University Hospital Schleswig-Holstein said, “These results are exciting news for patients with moderate-to-severe atopic dermatitis who continue to suffer from symptoms including persistent itch and skin lesions, despite available treatment options. Across all four doses studied, we saw consistent improvements in important signs and symptoms of the disease with an unremarkable safety profile. These data also add to the growing body of evidence that targeting OX40-Ligand potentially stops the inflammatory cascade across multiple pathways resulting in significant benefit for patients.”

Across amlitelimab doses, clinically meaningful and nominally significant improvements were seen in all key secondary endpoints at weeks 16 and 24, including Investigator Global Assessment response of 0 (clear) or 1 (almost clear skin) (IGA 0/1), 75% reduction from baseline in EASI (EASI-75) and weekly average reduction of Peak Pruritus Numerical Rating Scale ≥4 points from baseline (PP-NRS ≥4), with the exception of the 250 mg (no LD) in IGA 0/1 at Week 16 (p=0.0562).

22.1% and 45.5% of patients treated with amlitelimab 250 mg with LD achieved IGA 0/1 at weeks 16 and 24, respectively, compared to 5.1% and 11.4% of placebo patients (P=0.0022 and P<0.0001). Of patients treated with that same dose, 40.3% and 54.5% achieved EASI-75 at weeks 16 and 24, respectively, versus 11.4% and 17.7% on placebo (both P<0.0001).

Across all doses at weeks 16 and 24, amlitelimab treatment substantially reduced levels of biomarkers elevated in atopic dermatitis, including Th2-related IL-13 and TARC, Th17/Th22-related IL-17A and IL-22, and blood eosinophil counts, with significant reduction observed as early as week 4 in the 250 mg with LD arm.

Houman Ashrafian, M.D., Ph.D., Global Head of Research & Development, Sanofi said, “The data presented at EADV provide more detailed insight into amlitelimab’s potential as a best-in-class therapy for people with atopic dermatitis. In addition, our ability to pursue a differentiated dosing regimen could be very meaningful to patients. We look forward to initiating a larger Phase 3 development program for amlitelimab in atopic dermatitis in the first half of 2024, which further underscores our commitment to delivering a diverse range of solutions for this chronic condition.”

Amlitelimab was well-tolerated in the study across all dose arms and no new safety concerns were identified. 

Amlitelimab is a fully human non-depleting monoclonal antibody that binds to OX40-Ligand, a key immune regulator, and has the potential to be a first-in-class treatment for a range of immune-mediated diseases and inflammatory disorders, including moderate-to-severe atopic dermatitis and asthma. By targeting OX40-Ligand, amlitelimab aims to restore balance between pro-inflammatory and regulatory T cells.

Amlitelimab is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.