Genentech, Inc (SOUTH SAN FRANCISCO, California) and Biogen Idec, Inc (CAMBRIDGE, Massachusetts) announced that a randomized, double-blind, placebo-controlled, multicenter phase II/III study of Rituxan^® (rituximab) for systemic lupus erythematosus (SLE) did not meet its primary endpoint defined as the proportion of Rituxan patients who achieved a major clinical response (MCR) or partial clinical response (PCR) measured by BILAG, a lupus activity response index, compared with placebo at 52 weeks. The study also did not meet any of the six secondary endpoints. Genentech and Biogen will continue to analyze the study results and will submit the data for presentation at an upcoming medical meeting. A phase III trial (LUNAR) of the drug in patients with active lupus nephritis is ongoing with results expected in the first quarter 2009.
 
The phase II/III study was designed to evaluate the efficacy and safety profile of Rituxan in patients with moderate-to-severe SLE on a background immunosuppressant. The study excluded patients with lupus nephritis. A total of 257 patients from ~55 sites in the US and Canada were randomized 2:1 to receive Rituxan plus prednisone or placebo plus prednisone in two infusions 15 days apart. The patients were retreated 6 months later with the same regimen. Patients were evaluated for efficacy every 4 weeks for 52 weeks. The majority of patients are being monitored to week 78.

The six secondary endpoints included time adjusted area-under-the-curve minus baseline of BILAG score over 52 weeks; proportion of patients who achieved a MCR, and proportion of patients who achieved a PCR (including MCR) at week 52; proportion of patients who achieved BILAG C or better in all domains at week 24; time to moderate or severe flare over 52 weeks; change in SLE Expanded Health Survey physical function score from baseline at week 52; and proportion of subjects who achieved a MCR with 10 mg prednisone/day from weeks 24 to 52.

The therapeutic antibody Rituxan, discovered by Biogen and comarketed by both companies in the US, is the first treatment for rheumatoid arthritis (RA) that selectively targets CD20-positive B-cells. CD20 is not found on stem cells, pro-B–cells, 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 with the drug in ~12 months for most patients.

In February 2006, Rituxan received US FDA approval in combination with methotrexate to reduce signs and symptoms of RA. In January 2008, the drug was approved by the FDA to slow the progression of structural damage in adult patients with moderate-to-severe active RA who have had an inadequate response to one or more TNF-antagonist therapies.