Genentech, Inc. and Biogen Idec, Inc. posted a phase II/III study of Rituxan (rituximab) for primary-progressive multiple sclerosis (PPMS) did not meet its primary endpoint as measured by the time to confirmed disease progression during the 96-week treatment period. Genentech and Biogen Idec will continue to analyse the study results and will submit the data for presentation at an upcoming medical meeting.
"We are disappointed in the outcome of the primary endpoint, but not surprised given the significant clinical challenges presented by PPMS," said Hal Barron, M.D., senior vice president development and chief medical officer, Genentech,. "There was some evidence of biologic activity, and we will continue to review all the data to better understand the role of B cells in MS."
This phase II/III randomised, double-blind, placebo-controlled, multi-centre study was designed to evaluate the efficacy, safety and tolerability of four courses of Rituxan in patients with PPMS. A total of 439 patients from approximately 60 sites in the US and Canada were randomised 2:1 to receive either four treatment courses of Rituxan six months apart or placebo. MRI evaluations were conducted at baseline, weeks 6, 48, 96 and 122.
Detailed safety data from the study is currently being evaluated. The incidence of overall adverse events was comparable between Rituxan and placebo treatment groups. Serious adverse events were 16.4 per cent in the Rituxan arm versus 13.6 per cent in the placebo arm, with an incidence of serious infections of 4.5 per cent compared with <1.0 per cent respectively. Infectious events reported in at least 10 per cent of patients in either group included upper respiratory and urinary tract infections. Most infectious events in the Rituxan arm were reported as mild to moderate in severity, though events of greater severity were reported more frequently in patients receiving Rituxan. There were more infusion-related reactions with Rituxan, the majority of which were mild to moderate in severity. The companies continue to monitor the long-term safety of Rituxan treatment.
"While the primary results are not what we had hoped, we continue to believe in the potential of B cell therapy for patients living with MS," said Michael Panzara, M.D., MPH, vice president and chief medical officer, neurology strategic business unit, Biogen Idec. "PPMS is widely considered a difficult form of MS to treat and historically no therapy has proven efficacy in this disease state."
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 RA who have had an inadequate response to one or more TNF-antagonist therapies. Rituxan is the first treatment for RA that selectively targets immune cells known as CD20-positive B cells. Rituxan does not target the entire immune system.
CD20 is not found on stem cells, pro-B cells (B cell precursors), normal plasma cells, or other normal tissues. Rituxan does not target plasma cells. These cells make antibodies that help fight infections.
Rituxan does not target stem cells in the bone marrow, and B cells can usually regenerate and gradually return to normal levels after treatment with Rituxan in about 12 months for most patients.
In addition, Rituxan received FDA approval in February 2006 for first-line treatment of previously-untreated patients with follicular NHL in combination with CVP (cyclophosphamide, vincristine and prednisolone) chemotherapy and in September 2006, also was approved for the treatment of non-progressing low-grade, CD20-positive, B cell NHL as a single agent, in patients with stable disease or who achieve a partial or complete response following first-line treatment with CVP chemotherapy, and for previously untreated diffuse large B cell, CD20-positive, NHL in combination with CHOP or other anthracycline-based chemotherapy regimens.