Tuesday, Dec 5, 2000
San Francisco -- December 5, 2000 --Genentech, Inc. (NYSE: DNA) and IDEC (Nasdaq: IDEC) today announced positive preliminary data from small Phase II investigational studies examining the role of Rituxan® (Rituximab) in combination with chemotherapy for previously-untreated patients with chronic lymphocytic leukemia (CLL) and low-grade (indolent) non-Hodgkin's lymphoma (NHL). The studies were presented this week at the 42nd annual meeting of the American Society of Hematology (ASH).
"Results from these investigational Phase II studies show the early use of Rituxan in combination with chemotherapy provide high response rates for patients with low-grade NHL and CLL," said Susan D. Hellmann, M.D., M.Ph., Genentech's executive vice president of development and operations and chief medical officer. "Through these studies and other research presented at this meeting, it is gratifying to see that Rituxan may play an important role in improving on the benefit received from traditional cancer therapies in the common forms of lymphoma including indolent and aggressive NHL and CLL."
Rituxan in Combination with Fludarabine and Cyclophosphamide in CLL (Abstract #2214)
Researchers at the University of Texas M.D. Anderson Cancer Center, led by Dr. Michael Keating, presented preliminary data from an investigational Phase II trial designed to evaluate the combination of fludarabine, cyclophosphamide and Rituxan in previously-untreated patients with advanced CLL.
In the study, 68 patients have been enrolled and are receiving fludarabine (25 mg/m2), cyclophosphamide (250 mg/m2) and Rituxan (375 mg/m2 for first cycle; 500 mg/m2 all subsequent doses). Treatment was given over three days and repeated every four weeks for six courses with Rituxan administered on day one of each three-day cycle.
To date, 56 patients are evaluable for response, 35 of these patients have completed all six courses and 21 patients, who are still undergoing treatment, have completed three courses of therapy. The overall response rate was 94 percent (57 percent complete response rate) in the patients receiving six courses of therapy and 81 percent (14 percent complete response rate) in the patients receiving three courses of therapy.
"Historically, we have been able to achieve complete remission rates of 35 percent when we treat our patients with CLL with fludarabine alone or 43 percent with fludarabine/cyclophosphamide combination therapy," said Dr. Keating. "The initial data from this study suggests that the addition of Rituximab to fludarabine and cyclophosphamide leads to a complete remission rate that is clinically significantly higher than we have been able to achieve with chemotherapy alone. In many patients, we are currently unable to find any CLL cells using the PCR (polymerase chain reaction) technique which can identify between one and 100,000 cells."
The addition of Rituxan to fludarabine/cyclophosphamide chemotherapy did not appear to cause a clinically significant increase in adverse events to those seen with fludarabine/ cyclophosphamide alone. Neutropenia was the most commonly reported adverse event, which led to a dose reduction of fludarabine/cyclophosphamide in 21 percent of patients. Additional adverse events seen with fludarabine/cyclophosphamide were nausea (21 percent), vomiting (7 percent) and infections (13 percent). Additionally, patients experienced Grade I/II (61 percent) and Grade III/IV (14 percent) infusion-related events during the first infusion of Rituxan. Infusion-related events in the subsequent courses of Rituxan were uncommon.
Rituxan in Combination with Fludarabine in Low-Grade NHL (Abstract #3154)
A small investigational Phase II study, conducted at the Roswell Park Cancer Institute and led by Dr. Myron Czuczman, was designed to assess the safety and efficacy of combining Rituxan with fludarabine in previously-untreated (67 percent) and treated patients (33 percent) with low-grade or follicular NHL. Thirty-nine of 40 patients enrolled have received seven cycles of Rituxan (375 mg/m2) plus six cycles of fludarabine (25 mg/m2 for five days per 28-day cycle). Two infusions of Rituxan were administered at the beginning and at the end of therapy, as well as single infusions prior to the second, fourth and sixth cycles of fludarabine.
Overall response rate was 92 percent (22 of 24 evaluable patients) with 67 percent achieving complete responses and 25 percent achieving partial responses. To date, median duration of response has not yet been reached at over 15 months.
The most common adverse event attributed to Rituxan was fever and chills observed primarily during the first infusion of Rituxan. Adverse events unique to the Rituxan and fludarabine combination included significant neutropenia observed in the first 10 patients treated. This led to a 40 percent reduction in the dose of fludarabine given and subsequently only two of the next 14 patients treated needed transient growth factor support. No serious opportunistic infections or significant non-hematologic toxicities have been observed to date.
About NHL and CLL
Approximately 4.5 million people worldwide are living with various forms of lymphoma, and it is estimated that 300,000 people die each year. In the United States, approximately 54,900 people will be diagnosed with non-Hodgkinis lymphoma and an estimated 26,100 will die from the disease in 2000. In terms of incidence and death, NHL is the second fastest growing cancer in the United States and the third fastest growing cancer in the rest of the world.
Approximately 5.5 million people worldwide are living with various forms of leukemia, a cancer of the bone marrow and blood. In the United States in 2000, it is estimated that 8,100 people will be diagnosed with CLL and approximately 4,800 people will die from the disease in 2000. Chronic lymphocytic leukemia (CLL) is the second most common form of leukemia.
Rituxan is a novel approach to treating low-grade (indolent) or slow-growing NHL. It is a monoclonal antibody that works by binding to a particular protein (the CD20 antigen) on the surface of normal and malignant B cells. It then recruits the body's natural defenses to attack and kill the marked B cells. Stem cells (B-cells progenitors) in bone marrow lack the CD20 antigen, allowing healthy B cells to regenerate after treatment and return to normal levels within several months. Approximately 85 percent of all NHL cases are B-cell lymphomas.
RituxanC initially received FDA approval in November 1997 for the treatment of relapsed or refractory low-grade or follicular, CD20 positive, B-cell NHL. It was also approved in the European Union under the trade name MabTheraC in June 1998. Genentech and IDEC have marketing rights to Rituxan in the U.S. and Zenyaku Kogyo Co. Ltd. will market the drug together with Roche in Japan. Roche has marketing rights to MabThera worldwide, excluding the U.S.
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, adult respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock and tumor lysis syndrome. Patients who develop clinically significant infusion-related cardiopulmonary events should have Rituximab infusion discontinued and receive medical treatment.
Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Fourteen of the currently approved biotechnology products stem from Genentech science.
Genentech markets nine biotechnology products directly 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.
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.
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