Pfizer’s Oral JAK Inhibitor Demonstrates Response In Patients With Active Rheumatoid Arthritis

Final Phase 2 Analyses Presented at the American College of Rheumatology/ Association of Rheumatology Health Professionals (ACR/ARHP) Annual Scientific Meeting

Pfizer Inc announced that 24-week data from two clinical studies of the oral JAK inhibitor, CP-690,550, confirmed statistically significant ACR20 response and DAS28 remission rates for several doses versus placebo when given alone or in combination with methotrexate for patients with active rheumatoid arthritis (RA). The findings, which were presented at the 2009 ACR/ARHP Annual Scientific Meeting in Philadelphia, represent the final analyses from two Phase 2 trials evaluating the effect of CP-690,550 over 24 weeks.

“These data suggest that CP-690,550 could represent a promising advance for patients with rheumatoid arthritis,” said Michael Berelowitz, MD, senior vice president Clinical Development and Medical Affairs for Pfizer Specialty Care. “Our Phase 3 program is currently underway with enrollment progressing as planned, and we are hopeful that data from these trials will validate the Phase 2 results.”

Efficacy as Monotherapy at 24 weeks

Data presented from a six-month, double-blind, placebo-controlled Phase 2B study (Study A3921035), which evaluated 384 patients with active RA who had not responded to disease-modifying anti-rheumatic drugs (DMARDs), showed that patients treated with 5, 10 and 15 mg twice-daily doses of CP-690,550 dosed without background methotrexate experienced statistically significant ACR response rates and DAS28 remission rates at week 24 as compared to placebo. These results were consistent with the previously reported primary analysis of ACR response at week 12.

24-Week efficacy results are as follows:
	Treatment		ACR20(%)		ACR50(%)		ACR70(%)		DAS28 Remission(%)
	1 mg		24.1		7.4		5.6		5.8
	3 mg		37.3		27.5*		13.7		13.7*
	5 mg		51.0*		34.7*		20.4*		14.6*
	10 mg		65.6***		44.3***		37.7***		21.3**
	15 mg		66.7***		54.4***		33.3**		21.1**
	Placebo		25.4		10.2		6.8		1.8
*p≤0.05 **p≤0.01 *** p≤0.0001

All patients were randomized to either placebo or one of the studied doses of CP-690,550. This study also included adalimumab (40 mg subcutaneously every other week) as an active control in the first 12 weeks of the study.

Efficacy in Combination with Methotrexate at 24 weeks

Data from a second six-month, double-blind, placebo-controlled Phase 2b study (Study A3921025) evaluating 507 patients whose RA was active despite ongoing treatment with methotrexate demonstrated that patients treated with 3, 10 and 15 mg twice-daily and 20 mg once-daily doses of CP-690,550 in addition to stable background methotrexate experienced statistically significant ACR response rates and DAS28 remission rates at week 24 as compared to placebo. These results were consistent with previously reported primary analysis of ACR response at week 12.

24 week efficacy results are as follows:
	Treatment		ACR20(%)		ACR50(%)		ACR70(%)		DAS28 Remission(%)
	1 mg		41.4		31.4		20.0*		13.2
	3 mg		52.9*		27.9		19.1*		23.9*
	5 mg		47.9		33.8		19.7*		28.6*
	10 mg		55.4*		35.1		17.6		29.6*
	15 mg		58.7*		44.0*		30.7**		29.7*
	20 mg		52.5*		38.8*		23.8*		22.8*
	Placebo		34.8		23.2		7.3		10.5
*p≤0.05 **p≤0.01

This study evaluated CP-690,550 doses of 1, 3, 5, 10 and 15 mg twice daily and 20 mg once daily. All patients were maintained on their stable background of methotrexate and randomized to either addition of placebo or one of the studied doses of CP-690,550.

In both studies, the most commonly-reported treatment-emergent adverse events were urinary tract infections, headache, and diarrhea. Most adverse events were mild or moderate in severity. Serious adverse events and adverse events leading to discontinuation were infrequent. Dose-dependent decreases in mean neutrophil counts and increases in mean LDL, HDL, and total cholesterol were consistent with what has been observed in previous studies of CP-690,550 in RA. For patients dosed on background methotrexate, transaminase increases were also consistent with what had been reported in interim analyses in previous studies of CP-690,550 in RA.

All studies were sponsored by Pfizer Inc.

ORAL Trials: Advancing Clinical Research for RA

The Phase 3 program, which is known as the ORAL (Oral CP-690,550 Rheumatoid Arthritis Phase 3 TriaLs) Program, consists of six Phase 3 studies at more than 350 locations in 35 countries worldwide (www.ORALtrials.com.)

About CP-690,550

CP-690,550 is an oral, selective, potent inhibitor of the JAK family of enzymes. In cell-based assays, CP-690,550 has been shown to inhibit JAK-3 and JAK-1 with functional selectivity over JAK-2. By inhibiting these enzymes, which affect the signaling of multiple cytokines (proteins released by cells to communicate with other cells) that are involved in a broad spectrum of inflammatory and autoimmune diseases, treatment with CP-690,550 may lead to clinically meaningful improvement for patients.

CP-690,550 is also being evaluated as a potential treatment for psoriasis, Crohn’s disease, ulcerative colitis and solid organ transplant.