Thursday, Jun 9, 2005
Vienna, Austria -- June 9, 2005 --Genentech, Inc. (NYSE: DNA), Biogen Idec (Nasdaq: BIIB) and Roche (SWX Zurich) announced today preliminary positive results from a large randomized clinical trial of Rituxan® (Rituximab) in rheumatoid arthritis (RA) showing that a greater proportion of patients treated with a single course of Rituxan, with a stable dose of methotrexate (MTX), achieved American College of Rheumatology (ACR) 20, 50 and 70 response rates compared to placebo. The improvement in response rates was shown to be independent of corticosteroids. This Phase IIb trial included 465 patients who were inadequately responding to MTX and who had failed prior treatment with one or more disease-modifying anti-rheumatic drugs (DMARDs), including biologics. Results from this study were presented today at a leading rheumatology meeting in Vienna, Austria.
The study, known as DANCER (Dose-Ranging Assessment International Clinical Evaluation of Rituximab in RA), evaluated the efficacy and safety of two doses of Rituxan in combination with MTX and explored the role of corticosteroids. Patients, randomized into one of nine treatment arms, received a stable dose of MTX and varying doses of Rituxan and corticosteroids. Regardless of dose, the DANCER results indicated that Rituxan provided clinically and statistically significant improvement in RA symptoms compared to placebo. In the two Rituxan groups, 54 percent and 55 percent achieved ACR 20; 33 percent and 34 percent achieved ACR 50; and 13 percent and 20 percent achieved ACR 70 compared to 28 percent, 13 percent and 5 percent for placebo respectively.
"The results of the DANCER study, which evaluated the efficacy and safety of Rituxan in a difficult-to-treat patient population, further validate selective B-cell depletion as a potentially new and viable approach to the treatment of RA, said Roy Fleischmann, M.D., University of Texas Southwestern Medical Center. For the first time, these data also showed that the benefits of Rituxan were independent of short-course corticosteroids, which were given in all previous Rituxan RA trials."
The data did not reveal any unexpected safety signals. The most frequently reported adverse events in the study were primarily infusion-related and mild-to-moderate in intensity, including headache, nausea and rigors. Intravenous corticosteroid pre-medication appeared to reduce the incidence and severity of first infusion reactions. Oral corticosteroids did not appear to provide any additional safety benefit.
The reported rate of serious adverse events was higher in the Rituxan groups, but similar to those seen in previous studies of Rituxan in RA. Across the Rituxan groups, 35 percent of patients experienced infections, compared to 28 percent of placebo patients. However, the type and severity of infections were similar between both Rituxan doses and the placebo regimen. The rate of serious infections was low and was similar across the treatment groups. In addition, Rituxan therapy had no significant impact on immunoglobulin levels or acquired immunity. The companies are committed to monitoring long-term safety of Rituxan in all clinical trials.
Although there was a trend toward higher ACR 70 responses for patients in one of the Rituxan groups, it was not statistically significant. Based on the DANCER results, the companies are planning to evaluate two doses of Rituxan in a Phase III study of patients who are inadequately responding to MTX and who have failed prior treatment with one or more DMARDs. These Phase IIb results follow recent positive findings from a Phase III study that evaluated the efficacy and safety of Rituxan in patients with active RA who had an inadequate response or were intolerant to prior treatment with one or more anti-TNF therapies.
About the Study
The primary endpoint of DANCER was ACR 20 response at 24 weeks in rheumatoid factor positive patients (n=367). Both rheumatoid factor positive and rheumatoid factor negative patients were included in the safety analysis. Of the patients enrolled, 29 percent (134/465) had inadequately responded to anti-TNF treatments.
About ACR Response
ACR 20, ACR 50 and ACR 70 indicate a 20, 50 or 70 percent improvement in the number of swollen and tender joints, as well as a 20, 50 or 70 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), respectively.
RA is a debilitating autoimmune disease that affects more than two million Americans* 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 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 U.S. Food and Drug Administration 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 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 500,000 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 http://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.
*American College of Rheumatology, 2005, http://www.rheumatology.org/public/factsheets/ra.asp?aud=pat