Incyte’s JAK Inhibitor Demonstrates Rapid and Marked Clinical Improvement in Rheumatoid Arthritis Patients

Results from the 50-patient placebo-controlled trial demonstrated that three of the four doses of INCB18424 evaluated (15 mg BID, 25 mg BID and 50 mg QD) produced impressive clinical benefits and all of the doses were well tolerated. American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 response rates in the three most effective dose groups ranged from 50% to 83%, 40% to 50%, 25% to 30%, 10% to 17% respectively, and were achieved in one month, with responses seen as early as one week. Although there have been no head-to-head comparator trials, ACR 20/50/70 response rates with existing injectable biologic agents in larger studies typically average 60%/40%/20%, respectively, after 3 to 6 months of therapy.

The results were presented today in an oral presentation by Larry Moreland, M.D., Margaret Jane Miller Endowed Professor of Arthritis Research, Chief, Division of Rheumatology and Clinical Immunology, University of Pittsburgh, and principal investigator of the study, during the “RA Treatment: Small Molecules and Gene Therapy” session at the 2008 American College of Rheumatology / Association of Rheumatology Health Professionals (ACR/ARHP) Annual Scientific Meeting.

Dr. Moreland stated, “Results from this initial Phase IIa trial suggest that INCB18424, a novel oral JAK inhibitor, has the potential to be at least as effective as currently available RA therapies, including the widely used injectable biologicals. I look forward to participating in the next phase of clinical trials and seeing this new class of potent oral anti-inflammatory agents with an exciting mechanism of action progress through clinical development.”

Summary of Phase IIa Trial
Key Efficacy Results:

The patients in this study had highly active disease at baseline with tender and swollen joint counts averaging from 11-20 using a 28 joint count, and Disease Activity Scores (DAS) in the 6-7 range. Below is a summary of the ACR scores on day 28 and DAS28 scores using C-Reactive Protein (DAS28CRP) on day 28:

The ACR 20/50/70 response rates for placebo and the 5 mg BID dose group were similar, 33% ACR20 and 11% ACR50. The response rates for the three higher doses, 15 mg BID, 25 mg BID and 50 mg QD, achieved ACR20 rates of 50% to 83%, ACR50 rates of 40% to 50%, ACR70 rates of 25% to 30% and ACR90 rates of 10% to 17%. All the individual components of the ACR assessments showed similar trends for improvement, including marked improvement in the Health Assessment Questionnaire, a measure of functional status which typically can take several months to show improvement.

Patients who achieved a DAS28CRP score less than 3.2, which corresponds to mild disease, and less than 2.6, which corresponds to remission if sustained, were only seen in the three higher dose groups, 15 mg BID, 25 mg BID and 50 mg QD. In these three dose groups, the proportion of subjects achieving a DAS28CRP below 3.2 ranged from 30% to 50% of subjects, and the proportion achieving a score less than 2.6 ranged from 10% to 30% in 28 days.