Sunday, Oct 26, 2003
Orlando -- October 26, 2003 --Genentech (NYSE: DNA), IDEC Pharmaceuticals Inc. (NYSE: IDPH) and Roche announced positive follow-up results from a Phase II study showing that a single, short course of treatment (two infusions during the first 15 days of treatment) with Rituxan® (rituximab), alone or in combination with either methotrexate (MTX) or cyclophosphamide (CTX), improved symptoms in patients with moderate to severe rheumatoid arthritis (RA) for up to 48 weeks compared to MTX alone. These data will be presented during an oral session at the annual American College of Rheumatology (ACR) meeting on October 26, 2003. The 24-week data was first presented at ACR in 2002 and updated at the European League Against Rheumatism (EULAR) earlier this year.
In the study, investigators followed patients who had completed the 24-week clinical trial in order to assess duration of response with Rituxan beyond the initial endpoint of 24 weeks. Patients in the four-arm, placebo-controlled trial were randomized to receive Rituxan alone or in combination with MTX or CTX, as compared to patients receiving MTX alone. At 48 weeks, patients receiving the combination of Rituxan and MTX had the greatest improvement in symptoms: 65 percent (26/40 patients) showed at least a 20 percent improvement in symptoms (ACR20), 35 percent (14/40 patients) showed at least a 50 percent improvement (ACR50) and 15 percent (6/40 patients) showed at least a 70 percent improvement (ACR70). The study was blinded through the 48-week period.
"These data indicating a durable response with just two infusions of Rituxan are encouraging," said Charles Johnson, Genentech senior director, Specialty Biotherapeutics. "Rituxan represents a potentially novel approach to treating this disease by selectively targeting B-cells which appear to be a significant contributing factor in the development of rheumatoid arthritis."
About the Study
The study included 161 patients with active, long-standing RA (mean 10.4 years) who had not responded or responded inadequately to multiple other therapies. Patients were randomized into one of four treatment groups. The first group continued receiving methotrexate (MTX) alone (10 mg weekly), the second group received Rituxan alone (2 infusions of 1g), the third group received Rituxan (2 infusions of 1g) in combination with cyclophosphamide (CTX) (2 infusions of 750 mg) and the fourth group received Rituxan (2 infusions of 1g) in combination with MTX (10 mg weekly). Each group also received a 17-day course of corticosteroids (total dose of 910 mg). Rituxan was infused intravenously on days one and 15 of the study -- no further treatment with Rituxan was given.
Results from the other three arms of the study include:
"These data contribute to our knowledge of the role of B-cells in immune-mediated inflammatory diseases such as RA," continued Johnson. "With two doses of Rituxan in combination with methotrexate, some patients in this study were able to maintain their responses for nearly one year. Based on the data from this study, we, together with our partners IDEC and Roche, are enrolling patients worldwide into pivotal Phase III and Phase IIb studies to determine the potential for Rituxan in the treatment of RA."
According to a second abstract submitted by the authors, the study's safety profile indicates that all three Rituxan regimens were well tolerated with similar levels and types of adverse events compared to MTX alone. The majority of events were reported during the first Rituxan infusion and were of mild-to-moderate intensity. At week 48, the incidence and types of events, including infections, were evenly balanced between all groups. Since week 24 and up to week 48, a total of four additional serious adverse events were reported. These included two serious infections (arytenoiditis in the Rituxan+CTX group and viral gastroenteritis in the Rituxan alone group). The other events were goiter (Rituxan alone) and replacement of a renal stent (Rituxan+MTX).
There are approximately eight other poster presentations on Rituxan at ACR this year, including studies in systemic lupus erythmatosus (SLE) and refractory lupus nephritis.
Based on earlier results from this study, the companies initiated global randomized studies evaluating Rituxan in the treatment of RA, including a pivotal Phase III study known as REFLEX, for patients who have had an inadequate response to tumor necrosis factor (TNF) inhibitor therapies and a Phase IIb study known as DANCER, for patients who have had an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs). Both of these studies are currently enrolling patients. For more information on these studies in the United States, please call 888-662-6728.
About RA and B-Cells
RA is a debilitating autoimmune disease that affects 2.1 million Americans and hinders the daily activities of sufferers. RA occurs when the body's own immune system inappropriately attacks joint tissue and causes chronic inflammation that destroys healthy tissue and damage within the joints. Symptoms include inflammation of the joints, swelling, 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. Fewer than 50 percent of patients who have had RA for more than 10 years can continue to work or function normally on a day-to-day basis.
Both genetics and environmental factors play a role in RA, and there is no known cure. Treatments include a variety of steroidal and non-steroidal anti-inflammatory drugs, immunosuppressive agents, and DMARDs. All of these treatments target the immune system's T-cells or inflammatory signals.
The role of immune dysfunction in RA has predominantly focused on T-cells. However, the evidence from this study reinforces the importance of B-cells in the pathogenesis of RA. Research in 1987 and 1988 established that B-cells are indeed present and proliferate in the synovium when it is inflamed.
Rituxan is a therapeutic antibody that targets B-cells, which are thought to play a key role in the inflammatory cascade of RA -- a series of reactions inflaming the synovia (joint fluid) and leading to the cartilage loss and bone erosion that is characteristic of the disease.
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 IDEC co-market Rituxan in the United States and Roche markets Rituxan in the rest of the world, except Japan where Rituxan is co-marketed with Zenyaku Kogyo Co. Ltd. In March 2002, the EU approved MabThera in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy for the treatment of aggressive NHL, and in Japan Rituxan was approved for this indication in September 2003. More than 300,000 patients have been treated with Rituxan for NHL worldwide.
In NHL patients, based on clinical trials and post-marketing experience, 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.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Sixteen of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes 11 biotechnology products in the United States. 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.
Headquartered in Basel, Switzerland, Roche is an innovation driven global healthcare leader focused on pharmaceuticals and diagnostics. Roche is world-wide number one in diagnostics, oncology and transplantation and has a leading position in virology. With products and services that address the prevention, diagnosis and treatment of diseases, the company contributes broadly to the enhancement of people's health and quality of life. Roche employs some 62,000 people in more than 150 countries around the world. The company has business alliances and R&D relationships with numerous partners, including majority ownership interests in Genentech and Chugai, which are both members of the Roche Group.
IDEC Pharmaceuticals focuses on the commercialization and development of targeted therapies for the treatment of cancer and autoimmune diseases. IDEC's antibody products act chiefly through immune system mechanisms, exerting their effect by binding to specific, readily targeted immune cells in the patient's blood or lymphatic systems. IDEC is headquartered in San Diego, California, and is traded on the NASDAQ National Market System under the stock symbol, IDPH.
For more information about Rituxan, please visit http://www.gene.com.