The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate‐to‐severe atopic dermatitis: results from a randomized double‐blind placebo‐controlled study. (1st October 2019)

• Record Type: Journal Article
• Authors: Bissonnette, R.; Maari, C.; Forman, S.; Bhatia, N.; Lee, M.; Fowler, J.; Tyring, S.; Pariser, D.; Sofen, H.; Dhawan, S.; Zook, M.; Zammit, D.J.; Usansky, H.; Denis, L.; Rao, N.; Song, T.; Pavel, A.B.; Guttman‐Yassky, E.
• Is Part Of: British journal of dermatology. Volume 181:Number 4(2019)
• Page Start: 733
• Page End: 742
• Publication Date: 2019-10-01
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.17932
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved in the pathogenesis of atopic dermatitis (AD) through their regulatory role on T helper (Th)1, Th2 and Th17/Th22 pathways. Objectives: The objectives of this study were to evaluate the efficacy, safety, pharmacokinetics and effects on systemic biomarkers of ASN002 in patients with moderate‐to‐severe AD. Methods A total of 36 patients with moderate‐to‐severe AD were randomized (3 : 1) to ASN002 or placebo in the phase Ib study. Three dosage cohorts were studied over a 28‑day period (20 mg, 40 mg and 80 mg once daily). Results: ASN002 was superior to placebo for the proportion of patients achieving Eczema Area and Severity Index (EASI) 50 (20 mg 20%, P = 0·93; 40 mg 100%, P = 0·003; 80 mg 83%, P = 0·03; placebo 22%), EASI 75 (20 mg 0%, P = 0·27; 40 mg 71%, P = 0·06; 80 mg 33%, P = 0·65; placebo 22%) and in change from baseline in pruritus (20 mg −1·3 ± 2·1, P = 0·81; 40 mg −3·1 ± 2·7, P = 0·27; 80 mg −4·7 ± 2·1, P = 0·01; placebo −1·6 ± 1·8). Adverse events were generally mild and similar across all groups. ASN002 showed dose‐dependent plasma exposure with low interpatient variability, significantly downregulated several serum biomarkers involved in Th1, Th2 and Th17/Th22 immunity, and decreased the atherosclerosis‐associated biomarker E selectin/SELE. Conclusions: In patients with moderate‐to‐severe AD, ASN002 showed strong efficacy with rapid onset of action and associated improvements in systemic inflammation.