Genentech, Inc. and Biogen Idec, Inc. said a phase II/III study of Rituxan (rituximab) for systemic lupus erythematosus (SLE, commonly called lupus) did not meet its primary endpoint defined as the proportion of Rituxan treated patients who achieved a major clinical response (MCR) or partial clinical response (PCR) measured by BILAG, a lupus activity response index, compared to placebo at 52 weeks.
The study also did not meet any of the six secondary endpoints. Genentech and Biogen Idec will continue to analyze the study results and will submit the data for presentation at an upcoming medical meeting, the companies said in a recent press statement.
"We are disappointed in the results of this phase II/III study, but we understood from the outset the significant challenges in developing treatments for systemic lupus erythematosus," said Hal Barron, M.D., senior vice president, development and chief medical officer, Genentech,. "We believe the ongoing Phase III trial in lupus nephritis (LUNAR) remains an important study as it evaluates the potential of Rituxan in a different patient population."
"There is a critical need to discover new therapeutic pathways in lupus as no new therapy has been approved in more than 30 years. We will analyze the full set of data from this trial in the coming months, share the findings with regulatory authorities, and apply the key insights to our continued research in lupus," said Evan Beckman, M.D., senior vice president, Immunology Research and Development, Biogen Idec.
This phase II/III randomised, double-blind, placebo-controlled, multi-center study was designed to evaluate the efficacy and safety profile of Rituxan in patients with moderate-to-severe SLE on a background immunosuppressant. This study excluded patients with lupus nephritis (LN). A total of 257 patients from approximately 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 six months later with the same regimen. Patients were evaluated for efficacy every four weeks for 52 weeks. The majority of patients are being monitored to Week 78.
The primary endpoint of the study was the proportion of patients who achieved either a Major Clinical Response (MCR) or Partial Clinical Response (PCR) using the BILAG instrument at 52 weeks. Additional endpoints included: time adjusted area-under-the-curve minus baseline of BILAG score over 52 weeks; proportion of patients who achieve a MCR, and proportion of patients who achieve a PCR (including MCR) at Week 52; proportion of patients who achieve 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 achieve a MCR with 10 mg prednisone per day from Weeks 24 to 52.
Detailed safety data from the study is currently being evaluated. The incidence of overall adverse events and serious adverse events were comparable between Rituxan and placebo treatment groups. Side effects occurring more frequently in the Rituxan arm included: herpes viral infections (15.4 per cent in the Rituxan arm versus 8.0 per cent in the placebo arm), and neutropenia (3.6 per cent in the Rituxan arm versus 0 per cent in the placebo arm). Overall, infusion reactions were mild to moderate in severity. The companies continue to monitor the long-term safety of Rituxan treatment.
This is the first of two studies evaluating the safety and efficacy of Rituxan in patients with lupus. The second, an ongoing phase III trial (LUNAR) is evaluating Rituxan in patients with active lupus nephritis with results expected in Q1- 2009.
Rituxan, discovered by Biogen Idec, is a therapeutic antibody that first received Food and Drug Administration (FDA) approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B cell non-Hodgkin's lymphoma (NHL). It was also approved in the European Union under the trade name MabThera in June 1998. In February 2006, Rituxan also received FDA approval in combination with methotrexate to reduce signs and symptoms and, in January 2008, to slow the progression of structural damage in adult patients with moderately-to-severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more TNF-antagonist therapies.
Genentech and Biogen Idec co-market Rituxan in the United States, and Roche markets MabThera in the rest of the world, except Japan, where Rituxan is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.