A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis

Abstract

INCB039110 produced significant improvements in sPGA, demonstrating proof of concept in chronic plaque psoriasis.

Evaluation of a Janus kinase 1 inhibitor, PF‐04965842, in healthy subjects: A phase 1, randomized, placebo‐controlled, dose‐escalation study

“…There were no incidences of anaemia or thrombocytopenia during this study and the incidence of infections was low. Changes in lipid parameters were observed in this study, as has been reported in some studies with other JAK inhibitors . The most dramatic effects on HDL and LDL cholesterol were observed in subjects receiving PF‐04965842 BID.…”

Efficacy and safety of the Janus kinase 1 inhibitor PF-04965842 in patients with moderate-to-severe psoriasis: phase II, randomized, double-blind, placebo-controlled study

“…In this study, infections occurred more frequently in the PF‐04965842 vs. placebo groups, but there were no serious infections or bleeding events related to neutropenia or thrombocytopenia, respectively. Infections were also reported more frequently for patients treated with INCB039110 compared with placebo, but not for those treated with GSK2586184 compared with placebo . Recent data from studies of tofacitinib treatment in patients with psoriasis showed that nasopharyngitis and upper respiratory tract infections were the most frequent infections and the authors noted increased occurrence of herpes zoster …”

“…Dose‐dependent reduction in psoriasis severity has been reported with two other JAK1 inhibitors. Treatment with INCB039110 resulted in reductions from baseline in static PGA at day 28 (mean 22·2–42·4% for 100 mg OD, 200 mg OD, 200 mg TD and 600 mg OD, respectively) . Similarly, dose‐dependent changes from baseline in PASI scores were observed following 12 weeks of treatment with GSK2586184 100 mg TD, 200 mg TD and 400 mg TD .…”

“…In terms of notable AEs reported for other JAK inhibitors, severe thrombocytopenia was reported in a patient who received GSK2586184 100 mg TD; however, there were no statistically significant changes in mean haemoglobin, neutrophils, monocytes, reticulocytes, leucocytes or platelets . Minor decreases in platelet counts and elevations in mean lipid values were observed with INCB039110 treatment but these were not considered clinically meaningful . Similar to other JAK inhibitors, dose‐dependent changes in lipoprotein cholesterol were observed for PF‐04965842 in the current study but were not considered clinically relevant.…”

“…Key cytokines implicated in the pathophysiology of psoriasis require Janus kinase (JAK) 1 for signal transduction, suggesting that JAK1 inhibition could be effective for the treatment of chronic plaque psoriasis . This concept is supported by data from phase II trials of two oral JAK1‐selective inhibitors, GSK2586184 and INCB039110, which have demonstrated clinical improvement in patients’ psoriasis …”