Tuesday, Apr 5, 2005
South San Francisco, Calif., Cambridge, Mass. and Basel, Switzerland -- April 5, 2005 --Genentech, Inc. (NYSE: DNA), Biogen Idec (Nasdaq: BIIB) and Roche (SWX Zurich) announced today that a Phase III clinical study of Rituxan® (Rituximab) met its primary endpoint of a greater proportion of Rituxan-treated patients achieving an American College of Rheumatology (ACR) 20 response at week 24, compared to placebo. The study included patients with active rheumatoid arthritis (RA) who have had an inadequate response or were intolerant to prior treatment with one or more anti-TNF therapies.
In this study, known as REFLEX (Randomized Evaluation of Long-term Efficacy of Rituximab in RA), patients who received a single treatment course of two infusions of Rituxan with a stable dose of methotrexate (MTX) displayed a statistically significant improvement in symptoms compared to patients who received placebo and MTX. Further analyses of the data are ongoing and will be submitted for presentation at an upcoming medical meeting.
A preliminary analysis of the data did not reveal any unexpected safety signals. The most common side effects in the Rituxan arm included headache, upper respiratory tract infection and nasopharyngitis. The reported rate of serious adverse events was comparable across the two treatment arms.
"These results continue to support the potential of Rituxan as a new therapeutic option for RA," said Burt Adelman, M.D., executive vice president, development, Biogen Idec. "We look forward to sharing the REFLEX data in our discussions with the FDA."
"These are the first Phase III Rituxan data to demonstrate clinical improvement in this difficult-to-treat RA patient population. The findings add to the growing body of evidence that selectively targeting B cells may provide an important new treatment approach for this debilitating disease," said Hal Barron, M.D., Genentech's senior vice president, development and chief medical officer. "While we are encouraged that the preliminary safety results are similar to previous studies, we recognize the importance of monitoring long-term safety in RA patients treated with Rituxan."
These new Phase III data follow recent positive preliminary findings from a Phase IIb study that evaluated the efficacy and safety of Rituxan in moderate-to-severe RA patients who failed prior treatment with at least one disease-modifying anti-rheumatic drug (DMARD).
About the Study
A total of 520 patients from the United States, Canada and Europe were randomized to receive either Rituxan (1000 mg i.v. on days one and 15) or placebo in this multi-center, double-blind, placebo-controlled study. All patients received a stable dose of MTX and a two-week course of corticosteroids.
ACR 20 indicates a 20 percent improvement in the number of swollen and tender joints, as well as a 20 percent improvement compared with baseline in three of five disease-activity measures: patient assessment, physician assessment, pain scale, Health Assessment Questionnaire and the value for one acute phase reactant (erythrocyte sedimentation rate or C-reactive protein).
RA is a debilitating autoimmune disease that affects more than two million Americans1 and hinders the daily activities of sufferers. RA occurs when the immune system inappropriately attacks joint tissue, causing chronic inflammation and irreversible destruction of cartilage, tendons and bones, often resulting in disability. While RA has traditionally been considered a T-cell mediated disease, emerging research suggests that other immune cells called B cells may play multiple roles in the pathophysiology of RA including autoantibody production, T-cell activation and cytokine production. Common RA symptoms include inflammation of the joints, swelling, fatigue, stiffness and pain. Additionally, since RA is a systemic disease, it can have effects in other tissues such as the lungs, eyes and bone marrow.
Rituxan is a therapeutic antibody that targets and selectively depletes peripheral CD20 positive B cells without targeting stem cells or existing plasma cells. B cells may play multiple roles in the pathophysiology of RA. Rituxan is also being investigated in other autoimmune diseases including lupus, multiple sclerosis and ANCA associated vasculitis.
Rituxan received initial 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 also was approved in the European Union (EU) under the trade name MabThera® in June 1998. 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 with Zenyaku Kogyo Co. Ltd. Rituxan has been used to treat more than 380,000 patients worldwide. For a copy of the Rituxan full prescribing information, including Boxed Warning, please call 1-800-821-8590 or visit http://www.gene.com.
Rituxan Safety Profile in NHL
In NHL patients, the majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include but are not limited to: flu-like fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema and hypotension. These symptoms vary in severity and generally are reversible with medical intervention. In rare instances, severe and fatal infusion-related reactions have occurred, nearly all of which have been associated with the first Rituxan infusion. These events appear as manifestations of an infusion-related complex and include hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock and tumor lysis syndrome. Patients who develop clinically significant infusion-related cardiopulmonary events should have their Rituxan infusion discontinued and receive medical treatment.
In rare instances, severe mucocutaneous skin reactions have occurred that may be associated with Rituxan therapy. Many of these reactions have been described as paraneoplastic pemphigus and are known to be associated with various B cell lymphomas, particularly NHL and chronic lymphocytic leukemia. Patients who develop a severe mucocutaneous skin reaction should have Rituxan discontinued and receive appropriate medical treatment, including a skin biopsy to guide therapy.
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 directly in the United States and licenses several additional products to other companies. The company has headquarters in South San Francisco, California and is traded 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 oncology and immunology. As a global leader in the development, manufacturing and commercialization of novel therapies, Biogen Idec transforms scientific discoveries into advances in human healthcare. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2004 sales by the Pharmaceuticals Division totaled 21.7 billion Swiss francs, while the Diagnostics Division posted sales of 7.8 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.
(1) American College of Rheumatology, 2005