Rigel Pharmaceuticals, Inc (SOUTH SAN FRANCISCO, California) is a clinical-stage drug development company that has small-molecule product development programs in inflammatory/autoimmune diseases such as rheumatoid arthritis (RA), thrombocytopenia, and asthma. The company announced the initiation of two phase IIb clinical trials of its lead product candidate, R788 (fostamatinib disodium), an orally bioavailable spleen tyrosine kinase (Syk) inhibitor, in patients with RA. The trials will be conducted concurrently at a number of clinical research centers throughout the US, Latin America, and Europe in order to evaluate the efficacy of R788 compared with placebo in distinct RA patient groups
 
The first trial (TASKI 2) will evaluate approximately 420 RA patients receiving 100 mg of the agent PO bid (orally, twice daily) or 150 mg PO qd (orally, once daily), compared with those receiving placebo in a multicenter, randomized, double-blind, placebo-controlled, parallel-dose study of R788 in patients who have failed to respond to methotrexate (MTX). Patients will continue to receive a stable dose of MTX throughout the course of the 6-month clinical trial. Primary outcome results are expected in November 2009, and the estimated study completion date is March 2010.

The second trial (TASKI 3) will evaluate a group of RA patients receiving 100 mg of R788 PO bid compared with a group receiving placebo in a multicenter, randomized, double-blind, placebo-controlled, parallel-dose study of the agent in patients who have failed at least one marketed biologic agent. Approximately 195 patients will be enrolled in the trial, each of whom will receive R788 or placebo over a 3-month treatment period. Patients may continue on their stable dose of MTX and/or other (nonbiologic) therapies. Primary outcome results are expected in August 2009, and the estimated study completion date is November 2009.

The primary objectives for both TASKI 2 and TASKI 3 are to measure the efficacy of R788 as determined by ACR20 scores at 6 and 3 months, respectively. Secondary objectives will include comparing higher ACR response rates (ACR50 and ACR70) and DAS28 rates, in addition to evaluating various safety measures. TASKI 3 will also assess the radiologic response of the agent 100 mg PO bid compared with placebo as determined by magnetic resonance imaging using the modified RAMRIS scoring system of hands and wrists at baseline and month 3.

In December 2007, Rigel announced the results of a phase II clinical trial of R788 in RA patients simultaneously receiving MTX. That trial found that doses of 100 mg and 150 mg bid produced statistically significant improvement in RA symptoms. The two new clinical trials will seek to demonstrate similar results in larger numbers of patients and for a longer treatment period.

R788 has a novel mechanism of action that blocks IgG receptor (Fc receptor (FcR)) signaling in macrophages and B-cells, and addresses multiple inflammatory mechanisms including TNFα, IL-1, and IL-6. The agent has shown clinically significant results in treating patients with immune thrombocytopenic purpura in clinical trials and has slowed progression and prolonged survival in a murine model of lupus.