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

Business Wire, Oct 26, 2008

Complete Results from 28-day Phase IIa Clinical Trial Presented at the 2008 American College of Rheumatology Annual Scientific Meeting

A Webcast and Conference Call to Discuss These Results Are Scheduled for Tonight at 10:30 P.M. Eastern Time / 7:30 P.M. Pacific Time

WILMINGTON, Del. -- Incyte Corporation (Nasdaq:INCY) announced today the presentation of clinical results from a 28-day Phase IIa trial of INCB18424, its orally available janus kinase (JAK) inhibitor, in patients with rheumatoid arthritis (RA).

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 (see data summary below). 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:

           >       >           >          >          >





           >       >      (N)  >          >   ACR20  >
ACR50

ACR70

ACR90
           >       >           >          >   % (N)  >
% (N)

% (N)

% (N)
           >       >           >          >          >





Placebo    >       >        9  >          >  33 (3)  >
11 (1)

0 (0)

0 (0)
5 mg BID   >       >        9  >          >  33 (3)  >
11 (1)

0 (0)

0 (0)
15 mg BID  >       >       12  >          >  83 (1-  >
50 (6)

25 (3)

17 (2)
25 mg BID  >       >       10  >          >  50 (5)  >
40 (4)

30 (3)

10 (1)
50 mg QD   >       >       10  >          >  60 (6)  >
50 (5)

30 (3)

10 (1)
           >       >           >          >          >

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.

           >       >                    >







           >       >               (N)  >
DAS28CRP <3.2

DAS28CRP <2.6




           >       >                    >
% (N)

% (N)




           >       >                    >







Placebo    >       >                 9  >
0 (0)

0 (0)




5 mg BID   >       >                 9  >
0 (0)

0 (0)




15 mg BID  >       >                12  >
50 (6)

25 (3)




25 mg BID  >       >                10  >
30 (3)

10 (1)




50 mg QD   >       >                10  >
50 (5)

30 (3)




           >       >                    >

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.

Safety:

INCB18424 was safe and well tolerated. Adverse effects (AEs) were seen in similar frequency in patients receiving INCB18424 or placebo. In general, AEs were mild and self-limited during continued dosing. There were no changes in mean hemoglobin or platelet counts and mean neutrophil counts remained completely within the normal range even with the expected transient margination effects common to drugs that inhibit the activity of IL-6. There was one margination-induced grade 3 neutropenia which improved during continued dosing and rapidly resolved after the last dose (50 mg QD) and one reversible grade 3 thrombocytopenia in a patient with a history of recurrent immune-mediated thrombocytopenia (50 mg QD). In future studies, the rare patient with immune-mediated thrombocytopenia or other causes of recurrent thrombocytopenia will be excluded. There were no serious infections in any patient group. Minor infections were infrequent and similar in occurrence in the placebo and INCB18424 treated patients.

Trial Design:

This was a 28-day, double-blind, placebo-controlled study in patients with active RA as defined by six or more tender and four or more swollen joints and erythrocyte sedimentation rate (ESR) 28 mm/h or C-reactive protein (CRP) 15 mg/L. Patients in the trial could remain on stable doses of methotrexate, sulfasalazine, antimalarials and/or low dose prednisone. Patients could not have received treatment with biological agents or other DMARDs for at least 12 weeks. Patient assessments were conducted at weeks 1, 2 and 4.