Full Press Release Details
R788 Demonstrates Significant Improvement in Rheumatoid Arthritis in Phase 2
Statistically Significant ACR20, ACR50 & ACR70 Results
SOUTH SAN FRANCICSO, Calif.,
December 13, 2007 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
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.
| Treatment Assigned | Number | ACR 20 | ACR 50 | ACR 70 | DAS28-CRP | ||||||
| po bid | (N) | %(N) | %(N) | %(N) | <2.6,% (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) |
All patients were on stable doses of methotrexate throughout the clinical trial
*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
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.
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) | 2 | 1 | 2 | 12 | |||||
| (severity moderate or greater) | |||||||||
| Hypertension (N) | |||||||||
| (severity moderate or greater) | 0 | 0 | 2 | 0 |
All patients were on stable doses of methotrexate throughout the clinical trial
period and extension.
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.
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.
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.
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