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.

Abstract

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.

• Authors: R Bissonnette, C Maari, S Forman, N Bhatia, M Lee, J Fowler, S Tyring, D Pariser, H Sofen, S Dhawan, M Zook, D J Zammit, H Usansky, L Denis, N Rao, T Song, A B Pavel, E Guttman-Yassky
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 181 Issue 4 Pg. 733-742 (10 2019) ISSN: 1365-2133 [Electronic] England
• PMID: 30919407 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Chemical References

• Acetonitriles
• Biomarkers
• E-Selectin
• Janus Kinase Inhibitors
• Piperidines
• Placebos
• Pyridazines
• SELE protein, human
• gusacitinib
• Janus Kinases
• SYK protein, human
• Syk Kinase

Topics

• Acetonitriles (administration & dosage, adverse effects, pharmacokinetics)
• Adult
• Biomarkers (blood)
• Dermatitis, Atopic (blood, diagnosis, drug therapy, immunology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Down-Regulation (drug effects, immunology)
• E-Selectin (blood)
• Female
• Humans
• Janus Kinase Inhibitors (administration & dosage, adverse effects, pharmacokinetics)
• Janus Kinases (antagonists & inhibitors, metabolism)
• Male
• Middle Aged
• Piperidines (administration & dosage, adverse effects, pharmacokinetics)
• Placebos (administration & dosage, adverse effects)
• Pyridazines (administration & dosage, adverse effects, pharmacokinetics)
• Severity of Illness Index
• Signal Transduction (drug effects, immunology)
• Syk Kinase (antagonists & inhibitors, metabolism)
• Treatment Outcome
• Young Adult