"There remains a great need for safe and effective treatments for patients with RRMS," said Stephen Hauser, MD, Professor and Chair, Department of Neurology, University of California, San Francisco. "These Phase II results are very encouraging and suggest B-cells play a key role in MS. They also lend support to the concept that selective targeting of B-cells may be an important approach to treating this debilitating disease."
In this Phase II double-blind, placebo-controlled study that evaluated the safety and efficacy of Rituxan in adult patients with RRMS, 104 patients were randomized to receive either a single treatment course of Rituxan (two infusions separated by two weeks) or placebo. The primary endpoint was defined as the total number of gadolinium-enhancing T1 lesions at weeks 12, 16, 20 and 24, as measured by serial MRI scans of the brain. The total number of gadolinium lesions at weeks 12, 16, 20 and 24 was statistically significantly reduced in patients receiving Rituxan compared to those receiving placebo (p less than 0.0001). At week 24, the total cumulative mean number of gadolinium lesions per patient was reduced by 91 percent, to 0.5 in the Rituxan-treated group from 5.5 in the placebo group.
In addition, the proportion of patients with relapses over 24 weeks in the Rituxan-treated arm was 14.5 percent compared to 34.3 percent in the placebo arm (58 percent relative reduction) (p = 0.0238).
With the exception of infusion associated adverse events, the percentage of patients with overall adverse events and serious adverse events were comparable between the two treatment groups during this 24-week period (97.1 percent of patients in both treatment groups experienced an adverse event and 10.1 percent of Rituxan-treated patients compared with 14.3 percent of placebo-treated patients experienced a serious adverse event). There were more first infusion-associated adverse events in Rituxan-treated patients (78.3 percent compared to 40.0 percent in placebo-treated patients), the majority (greater than 95 percent) were mild to moderate in severity and managed with appropriate medical intervention. The second infusion associated adverse events were 20.9 percent in Rituxan-treated patients versus 40.0 percent in placebo-treated patients. The overall percent of patients with infection were comparable in Rituxan-treated patients (65.2 percent) and placebo-treated patients (62.9 percent). Efficacy and safety data in this study will be collected and analyzed through 48 weeks.
About MS and RRMS
MS is a chronic autoimmune disease of the central nervous system (CNS) in which the immune system is thought to attack the body's own myelin, a fatty substance that surrounds and protects the nerve fibers of the brain, spinal cord and optic nerves. There are four types of MS with a wide variety of symptoms and different courses of disease progression. RRMS is the most common form of MS, accounting for approximately 65 percent of all cases. It is characterized by inflammatory events leading to loss of myelin (demyelination), variable levels of recovery between events, and irregular periods of remission. When recovery from relapse is incomplete, patients with RRMS gradually accumulate irreversible neurological damage and disability.
MS is the leading cause of neurological disability in young adults. Neurological disability typically accumulates over time and includes muscle weakness and spasticity, balance and coor dination problems, as well as memory impairment and depression. Other symptoms include numbness, pain, slurred speech and blurred vision. Many patients experience fatigue and problems with bladder, bowel or sexual function.
While MS has traditionally been considered a T-cell mediated disease, recent research suggests that B-cells may play multiple roles in the initiation and development of MS.
Rituxan Safety Profile in Rheumatoid Arthritis and Oncology
The safety profile of Rituxan in rheumatoid arthritis and non-Hodgkin's lymphoma (NHL) has been evaluated through a number of clinical trials.
The most common adverse events observed in rheumatoid arthritis (RA) patients treated with Rituxan in clinical studies of up to 24 weeks were infection and infusion reactions. Among non-Hodgkin's lymphoma patients treated with Rituxan in clinical studies, the most common adverse events were infusion reactions and cytopenias (low blood cell counts).
The majority of patients experiencing an infusion-related reaction do so during their first Rituxan infusion. These symptoms include but are not limited to: flu-like illness, fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema, hypotension and hypoxia. These symptoms vary in severity and generally are reversible.
Severe infusion reactions have been reported in patients treated with Rituxan, some with fatal outcomes. These severe reactions typically occur during the first infusion. The most severe manifestations and sequelae include hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation and cardiogenic shock.
Acute renal failure requiring dialysis with instances of fatal outcome has been reported in the setting of tumor lysis syndrome following treatment with Rituxan in patients with NHL.
Severe mucocutaneous skin reactions, some with fatal outcome, have been reported in association with Rituxan treatment. Abdominal pain, bowel obstruction and perforation, in some cases leading to death, were observed in patients receiving Rituxan in combination with chemotherapy for diffuse large B-cell (DLBCL), CD20-positive NHL. Other serious or potentially life-threatening adverse reactions that have been reported following Rituxan therapy include cardiac arrhythmias, hepatitis B reactivation with fulminant hepatitis, and other viral infections.
JC virus infection resulting in PML and death has been reported in Rituxan-treated patients including those with hematologic malignancies or with certain autoimmune diseases such as systemic lupus erythematosus (SLE), an indication for which Rituxan has not been approved.
Rituxan is a therapeutic antibody being studied in primary progressive MS, for which there is currently no FDA-approved therapy. Rituxan is also being studied in other autoimmune diseases with significant unmet medical needs, including SLE, lupus nephritis and ANCA-associated vasculitis.
Rituxan, discovered by Biogen Idec, first received FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma. It was also approved in the European Union under the trade name MabThera(R) in June 1998. Rituxan received FDA approval in February 2006 for the treatment of diffuse large B-cell lymphoma (DLBCL) in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens in previously untreated patients. In February 2006, Rituxan also received FDA approval in combination with methotrexate to reduce signs and symptoms in adult patients with moderately-to-severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor antagonist therapies. In addition, Rituxan received FDA approval in September 2006 for first-line treatment of previously-un treated patients with follicular NHL in combination with CVP (cyclophosphamide, vincristine, and prednisolone) chemotherapy and also for the treatment of low-grade NHL in patients with stable disease or who achieve a partial or complete response following first-line treatment with CVP chemotherapy.
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. Rituxan has more than 1,000,000 patient exposures worldwide across all indications. For a copy of the Rituxan full prescribing information, including Boxed Warning, please call 1-800-821-8590 or visit http://www.gene.com.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes multiple biotechnology products and licenses several additional products to other companies. The company has headquarters in South San Francisco, California and is listed on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit http://www.gene.com.
About Biogen Idec
Biogen Idec creates new standards of care in therapeutic areas with high unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the discovery, development, manufacturing, and commercialization of innovative therapies. Patients in more than 90 countries benefit from Biogen Idec's significant products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis. For product labeling, press releases and additional information about the company, please visit http://www.biogenidec.com.
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