Genentech, Inc (SOUTH SAN FRANCISCO, California), Biogen Idec (CAMBRIDGE, Massachusetts), and Roche Pharmaceuticals (BASEL, Switzerland) announced that a pivotal phase III study of rituximab (Rituxan®) met its primary endpoint of greater proportion of biologic-naïve rheumatoid arthritis (RA) patients achieving ACR20 response at week 24, compared with placebo. The randomized, double-blind, placebo-controlled, parallel group, three-arm international study enrolled patients with moderately-to-severely active RA who had an inadequate response to methotrexate (MTX) monotherapy. The study is the first to demonstrate the potential of rituximab when used earlier in the course of treatment. Data from this trial will be submitted for presentation at upcoming international scientific meetings.

The study, known as SERENE (study evaluating rituximab's efficacy in methotrexate inadequate responders), randomized 509 patients from 102 study sites across 11 countries to rituximab (500 mg or 1000 mg) plus MTX or placebo plus MTX. Patients who received a single intravenous infusion of rituximab on days 1 and 15 plus a weekly stable dose of MTX displayed a statistically significant improvement in ACR20 scores compared with patients who received placebo plus MTX. Although the study was not designed to compare the rituximab doses, treatment efficacy appears to be similar between both doses. The study also explored pharmacokinetics and long-term efficacy and safety of additional courses of the drug. Further analyses of the data are ongoing.

Preliminary analyses of the data did not reveal any unexpected safety signals. The incidence of adverse events and serious adverse events were comparable between rituximab and placebo treatment groups. There were more infusion-related reactions with the first rituximab infusion, which were primarily mild-to-moderate in severity and reversible with medical intervention; there were no serious infusion reactions.

Rituximab, discovered by Biogen Idec, is a therapeutic antibody that received US FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma. In February 2006, the drug also received FDA approval in combination with MTX to reduce signs and symptoms in adult patients with moderate-to-severe active RA who had an inadequate response to one or more TNF-antagonists. Rituximab is the first treatment for RA to selectively target CD20-positive B-cells and to have demonstrated the ability to preserve joint structure. What's more, each course of treatment offers an unprecedented duration of response of at least 6 months.

CD20 is not found on stem cells, pro-B-cells (B-cell precursors), normal plasma cells, or other normal tissues. As the drug does not target stem cells in the bone marrow, B-cells can usually regenerate and gradually return to normal levels after treatment. Rituximab is also being studied in other autoimmune diseases including systemic lupus erythematosus, lupus nephritis, antineutrophil cytoplasmic antibodies-associated vasculitis, and primary progressive multiple sclerosis.

Genentech and Biogen Idec comarket Rituxan in the US, and Roche markets MabThera in the rest of the world, except Japan, where Rituxan is co-marketed by Chugai and Zenyaku Kogyo Co, Ltd.