Achieves Statistically Significant ACR20, ACR50 & ACR70 Results
SOUTH SAN FRANCICSO, Calif., Dec. 13 /PRNewswire-FirstCall/ -- Rigel
Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced that its oral syk kinase
inhibitor, R788 (tamatinib fosdium), has demonstrated statistically
significant results in treating Rheumatoid Arthritis (RA) patients in a
recently completed Phase 2 clinical trial. Groups treated with R788 at 100mg
and 150mg po bid (orally, twice daily), showed higher ACR20, ACR50, ACR70 and
DAS28 response rates than the placebo group. The efficacy results for the
100mg and the 150mg dose groups were fairly comparable. Dramatically, the
onset of the effect in these dose groups occurred as early as one week after
initiation of therapy. We believe that the significant ACR scores and good
tolerability observed in this clinical trial, and the further benefit of oral
delivery may make R788 a favorable alternative to the currently marketed
biological agents.
Rigel will host a conference call today at 12:30 p.m. EST to discuss these
results (see conference call details below).
"This clinical study has shown that R788 treatment can achieve impressive
ACR response rates," said Elliott Grossbard, M.D., senior vice president of
medical development at Rigel. "In this clinical trial both the 100mg and
150mg doses improved arthritis symptoms and did so quickly. We plan to
initiate the next clinical trial with R788 in RA in 2008," he added.
Efficacy Results*
Treatment Assigned Number ACR 20 ACR 50 ACR 70 DAS28-CRP <2.6,
po bid (N) % (N) % (N) % (N) % (N)
Placebo 47 38% (18) 19% (9) 4% (2) 17% (8)
50 mg 46 32% (15) 17% (8) 2% (1) 20% (9)
100 mg 49 65% (32) 49% (24) 33% (16) 35% (17)
(p=.008) (p=.002) (p<.001) (p=.005)
150 mg 47 72% (34) 57% (27) 40% (19) 47% (22)
(p<.001) (p<.001) (p<.001) (p<.001)
Note: At 12 weeks. All patients were on stable doses of methotrexate
throughout the clinical trial and extension.
* The results presented are based on an intention to treat analysis that
includes all randomized patients, regardless of how long treatment
lasted. Any patient who dropped out of the study for any reason, or for
whom week 12 data was unavailable, was considered a treatment failure
(ACR non-responder). Disease Activity Scores are based on a 28 joint
count and CRP at week 12.
James M. Gower, chairman and chief executive officer of Rigel said, "These
very important clinical trial results are a major milestone for Rigel as we
establish the potential of R788 in RA and its value as an alternative to
current therapies. In addition, given these results and the recent results in
ITP, we believe that R788 may be a useful drug in the treatment of autoimmune
diseases."
Safety Results
The most common clinically meaningful adverse events noted in the clinical
trial were dose-related neutropenia, mild elevations of liver function tests,
and gastrointestinal (GI) side effects. Dose reduction (to one half the
assigned dose, by taking the drug once per day) was pre-specified in the
protocol, contingent on neutrophil counts and/or liver function tests.
Notably, a vast majority of the patients (19 out of 21) who had their dose
reduced, successfully completed the clinical trial with minimal safety issues.
The key safety results are shown in the table below:
Placebo 50mg 100mg 150mg
po BID N=47 po BID N=46 po BID N=49 po BID N=47
Completed Study at
Reduced Dose (N) 1 0 5 13
Dropouts (N): 11 6 6 8
Withdrew Consent 6 3 2 1
Adverse Event 2 1 3 6
Other 3 2 1 1
Neutropenia (N)
Requiring dose reduction 0 0 5 10
ALT > 3XULN (N) 2 0 0 3
Diarrhea (N)
(severity moderate
or greater) 0 3 2 10
Upper GI side effects (N)
(gastritis, nausea,
dyspepsia) (severity
moderate or greater) 2 1 2 12
Hypertension (N)
(severity moderate
or greater) 0 0 2 0
Note: At 12 weeks. All patients were on stable doses of methotrexate
throughout the clinical trial period and extension.
Study Design
The clinical trial was a multi-center, randomized, double blind, placebo
controlled, ascending dose study involving 189 patients in three approximately
equal size cohorts receiving 50, 100, or 150 mg po bid. Within each cohort,
patients were assigned on a 3:1 basis to R788 or placebo. The clinical trial
was conducted over a 12-week treatment period in patients who had RA for at
least 12 months. These patients had active disease despite receiving adequate
stable doses of methotrexate over the preceding 6 months. All of the patients
continued to receive their same stable dose of methotrexate throughout the
clinical trial period and extension. Efficacy assessments for each participant
were based on the American College of Rheumatology criteria, which denote at
least a 20% (ACR 20) improvement, at least a 50% (ACR 50) improvement, or at
least 70% (ACR 70) improvement, from the baseline assessment at the end of the
12-week treatment period. The ACR measurement factors include, reported
physician and patient global assessment of disease activity, patient reported
pain score, and any change in C-reactive protein (CRP) in the patients' blood.
The primary efficacy endpoint for the study was the percent of patients who
were ACR 20 responders at the end of week 12. Secondary efficacy endpoints
were ACR 50 and ACR 70 scores as well as Disease Activity Score (DAS) at the
end of week 12.
R788 and RA
RA is a progressive, painful and potentially debilitating disease, that
affects more than 2 million people in the U.S. It is a chronic inflammatory
disease that puts the body's immune system into overdrive where it ultimately
causes inflammation in the joints and destroys soft tissues, cartilage and
bone. Rigel's R788 is a novel, orally available syk kinase inhibitor designed
to interrupt the cellular signaling at the trigger point of inflammation,
thereby stopping the progression of the disease.
Conference Call Information
Rigel will host a conference call to discuss the R788 Phase 2 clinical
trial results today, December 13, 2007, at 12:30 p.m. EST/9:30 a.m. PST. To
access the live call, please dial 866-510-0710 (domestic) or 617-597-5378
(international) 10 minutes prior to the start time and use the passcode
54253199. A replay of the call will be available at approximately
2:30 p.m. EST/11:30 a.m. PST on December 13, 2007 until December 20, 2007. To
access the replay, please dial 888-286-8010 (domestic) or 617-801-6888
(international) and use the passcode 30990949. The conference call will also
be webcast live and can be accessed from Rigel's website at
http://www.rigel.com. Please connect to Rigel's website several minutes prior
to the start of the live webcast to ensure adequate time for any software
downloads that may be necessary. A replay of the conference call will be
available on Rigel's website, in webcast and podcast formats, approximately 2
hours after the call.Further information on R788 in RA is available at Rigel's
website: http://www.rigel.com/rigel/rheumatoid_arthritis.
About Rigel (http://www.rigel.com)
Rigel is a clinical-stage drug development company that discovers and
develops novel, small-molecule drugs for the treatment of
inflammatory/autoimmune diseases and cancer, as well as viral and metabolic
diseases. Rigel's goal is to file one new investigational new drug (IND)
application in a significant indication each year. Rigel has achieved this
goal every year since 2002. Our pioneering research focuses on intracellular
signaling pathways and related targets that are critical to disease
mechanisms. Rigel's productivity has resulted in strategic collaborations with
large pharmaceutical partners to develop and market our product candidates.
Rigel has product development programs in inflammatory/autoimmune diseases
such as rheumatoid arthritis, thrombocytopenia and asthma, as well as in
cancer.
This press release contains "forward-looking" statements, including
statements related to the potential efficacy and commercial potential of R788
and Rigel's plans to pursue further clinical development thereof. Any
statements contained in this press release that are not statements of
historical fact may be deemed to be forward-looking statements. Words such as
"believes," "plans"and similar expressions are intended to identify these
forward-looking statements. There are a number of important factors that could
cause Rigel's results to differ materially from those indicated by these
forward-looking statements, including risks associated with the timing and
success of clinical trials and the commercialization of product candidates,
potential problems that may arise in the clinical testing and approval process
and Rigel's need for additional capital, as well as other risks detailed from
time to time in Rigel's SEC reports, including its Form 10-Q for the quarter
ended September 30, 2007. Rigel does not undertake any obligation to update
forward-looking statements.
Contact: Raul Rodriguez
Phone: 650.624.1302
Email: rrodriguez@rigel.com
Media Contact: Susan C. Rogers, Alchemy Consulting, Inc.
Phone: 650.430.3777
Email: susan@alchemyemail.com
SOURCE Rigel Pharmaceuticals, Inc.
Web site: http://www.rigel.com
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