Incyte Corporation (Nasdaq:INCY) announced the presentation of final six-month clinical data from the dose ranging, placebo-controlled Phase IIa trial of its orally available janus kinase (JAK) inhibitor INCB28050 in patients with active rheumatoid arthritis (RA). These results were presented today at the 2010 American College of Rheumatology / Association of Rheumatology Health Professionals (ACR/ARHP) Annual Scientific Meeting being held in Atlanta, November 7 to 11, 2010.
Results from the 125-patient Phase IIa trial demonstrated that all three doses of oral INCB28050 (4 mg QD, 7 mg QD and 10 mg QD) improved on the primary endpoint, the percent of patients achieving American College of Rheumatology (ACR) 20 improvement, over the full 24-week treatment period. Importantly, ACR responses improved between week 12 and week 24 achieving up to 72% for ACR20, 44% for ACR50 and 30% for ACR70 at week 24. Results seen at 12 weeks for placebo were 32% for ACR20, 13% for ACR50 and 3% for ACR70, and for patients treated with INCB28050 the results were up to 59% for ACR20, 35% for ACR50 and 16% for ACR70.
Evidence of improvement was seen as early as the first assessment at two weeks. Responses were similar in both biologic-experienced and biologic-naïve patients and adverse events for all three doses were predominantly mild-to-moderate with frequencies similar to placebo.
"Results from the Phase IIa trial with INCB28050, an oral JAK1 and JAK2 inhibitor are encouraging, suggesting that the compound has the potential to become a welcome addition to the current armamentarium of available RA therapies. There is a clear unmet need for new oral RA therapies and we look forward to seeing INCB28050 progress through clinical development," stated Maria Greenwald, M.D., F.A.C.R., Palm Desert, California, the presenting investigator of the Phase IIa trial results.
Summary of Phase IIa Clinical Results (Study 28050-201)
ACR20, ACR50 and ACR70 response rates for the three once daily dose groups and placebo patients at 12 weeks and 24 weeks are described below:
ACR Response Rates
After 12 weeks of treatment, placebo-treated patients were randomized to receive either 7 mg QD or 10 mg QD
In addition to the ACR response rates, patients who achieved Disease Activity Scores using C-reactive protein (DAS-CRP) of less than 3.2, which corresponds to mild disease, and less than 2.6, which corresponds to remission, also improved from week 12 through week 24. At 24 weeks the remission rates for DAS-CRP<2.6 ranged from 30% to 48%.
DAS-CRP Scores
Safety
The most frequently reported adverse events during the placebo-controlled period were headache, upper respiratory tract infection, and diarrhea. Adverse events were predominantly mild-to-moderate with frequencies similar to placebo. There appeared to be no relationship between dose and total frequency of reported adverse events, with exception of reports of anemia. There were dose-related decreases in mean hemoglobin ranging from approximately 2% to 8%. Un-complicated cases of herpes zoster (shingles) were observed. HDL and LDL increased with a trend for improvement in the HDL to LDL ratio while CRP levels decreased.
Trial Design
Study 28050-201, a randomized, double-blind, placebo-controlled, dose-ranging trial, involved 125 patients with active RA with an inadequate response to any disease modifying anti-rheumatic drug (DMARD) therapy including biologics. The duration of the study was six months with the primary endpoint assessed at three months. Eligible patients were randomly assigned to one of three doses (4, 7 or 10 mg QD) of INCB28050 or placebo. At week 12, placebo patients crossed over to 7 mg QD or 10 mg QD.
Primary Outcome Measures:
- Safety and tolerability of INCB28050 as measured by adverse events, vital signs, clinical laboratory tests and ECGs at three months
- Efficacy as determined by percent of patients achieving ACR20 improvement at three months
Secondary Outcome Measures:
- Safety and tolerability of INCB28050 as measured by adverse events, vital signs, clinical laboratory tests and ECGs at six months
- Efficacy as determined by percent of patients achieving ACR20, 50, 70 and 90 improvement at six months
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