ATx201 is a small molecule, which decolonizes
Staphylococcus aureus and improves the diversity of the skin microbiome in patients with mild-to-severe
atopic dermatitis (AD) (DECOLAD). We now report the safety and immune-modulatory effect
of ATx201 in patients with moderate AD. In this randomized, double-blind, intraindividual,
and vehicle-controlled Phase 2 trial, thirty-one patients received ATx201 CREAM 2%
and matching vehicle (1:1) once daily for 3 weeks (NCT03304470), with a 12-day follow-up
period. Analysis of the safety data revealed that ATx201 CREAM 2% was generally safe
and well-tolerated in subjects with moderate AD lesions. The histological and transcriptional
profiling analysis (IHC, microarray and RT-PCR) demonstrated that treatment with ATx201
CREAM 2% significantly (p < 0.05) increased expression of biomarkers related to skin
barrier function (PNPLA3, ACOX2, DGAT2, FAXDC2, etc.), and decreases expression levels
of markers related to inflammation including Th17 (S100A7, S100A9, CCL20, PI3, CXCL1,
IL17C, STAT3), Th2 (IL10, IL4R, CCL26, CCL18, etc.), Th1 (CCL2, CCR1, etc.) and inflammatory
cells (Langerin/CD207) compared to vehicle at Day 22. Finally, several biomarkers
that were significantly modulated by ATx201 CREAM 2% were significantly correlated
with improvement in TSS, TAA scores and the TSS component scores (p < 0.05), such
as S100A8 (ρ
TSS = 0.83), KRT16 (ρ
TSS = 0.77), PI3 (ρ
TSS = 0.69), IL13 (ρ
TSS = 0.68), IL22 (ρ
TSS = 0.67) and MMP12 (ρ
TSS = 0.55). IHC analysis further revealed that 15/29 (51.7%) subjects were classified
as histological responders receiving ATx201 CREAM 2% versus 9/29 (31.0%) receiving
vehicle. These data suggest that topical application of ATx201 is safe and improves
biomarkers of skin barrier function and suppresses biomarkers of AD-associated inflammation
across multiple T helper cell pathways.
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© 2020 Published by Elsevier Inc.