Market intelligence: Genentech's Rituxan fails late stage trials in Lupus

Genentech, Inc. (NYSE: DNA) and Biogen Idec, Inc. (Nasdaq: BIIB) announced today that 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 Phase II/III randomized, 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 U.S. 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.

The news has not pleased investors and the stocks are diving as a result because the negative result has implications beyond Rituxan. The company has been developing a second-generation anti-CD20 antibody, ocrelizumab, which has the same mechanism as Rituxan, and is currently in Phase III for RA and Phase II for MS. This drug is being developed as a more benign version of Rituxan for use in patients witw non-life-threatening conditions, including the autoimmune diseases. Rituxan, a more potent drug, was unable to meet a single endpoint in this trial, and failed in MS, so the lupus news does not instill confidence in the prospects for the next-generation version, making investors wary and nervous about the future of the pipeline. In addition, there have been no new significant treatments for this debilitating disease for nearly 30 years.