Saturday, Jun 5, 2004
New Orleans -- June 5, 2004 --Genentech, Inc. (NYSE: DNA), Biogen Idec Inc. (Nasdaq: BIIB) and Roche (SWX Zurich) today announced positive data from a large, randomized Phase III trial evaluating Rituxan® (Rituximab), known as MabThera® in Europe, in combination with chemotherapy as a front-line treatment for aggressive non-Hodgkin's lymphoma (NHL). The study authors concluded that data from the MabThera International Trial (MInT) demonstrated a significant improvement in time to treatment failure (TTF), the primary endpoint of the study. At two years, 81 percent of patients who received Rituxan and chemotherapy did not experience treatment failure compared to 58 percent of patients who received chemotherapy alone. In this study, TTF was defined as documented progressive disease, failure to achieve a complete response rate (CR or CRu), relapse or death.
This trial, which was halted in December 2003 for reaching its pre-specified primary efficacy endpoint early, is the first randomized Phase III trial to evaluate whether Rituxan plus chemotherapy improves clinical outcomes in younger patients with aggressive NHL. Data from this study were highlighted in a press conference at the 40th Annual Meeting of the American Society of Clinical Oncology (ASCO) and will be presented in an oral session.
"This is the third large, randomized Phase III study supporting the use of Rituxan in combination with chemotherapy for the treatment of patients with newly diagnosed aggressive NHL," said Gwen Fyfe, M.D., Genentech's vice president, Clinical Hematology/Oncology. "In addition, this study provides the first efficacy and safety data in a randomized trial of patients under 60 with aggressive NHL."
The trial enrolled 824 previously untreated patients in 18 countries, ages 18 to 60, with diffuse, large, B-cell NHL. Patients were randomized to receive six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-like chemotherapy alone or in combination with six doses of Rituxan (375 mg/m2). The study protocol allowed the treating physician to decide which chemotherapy to give based on the standard regimen in each country. The authors reported no difference in toxicities between the two arms of the study and no unexpected adverse reactions.
At two years, the investigators reported that overall survival was 95 percent (310/326) for those treated with Rituxan and chemotherapy compared to 85 percent (278/326) for patients who received chemotherapy alone. Patients treated with Rituxan and chemotherapy had a higher rate of complete remission at 85 percent (277/326) compared to 65 percent (212/326) for patients treated with chemotherapy alone. Patients in the Rituxan and chemotherapy arm also had a lower rate of progressive disease, 6 percent (21/326) compared to 17 percent (58/326) for patients who received chemotherapy alone.
"Until now, there have been no randomized trials to evaluate the use of Rituxan and chemotherapy in a younger patient population," said Burt Adelman, M.D., executive vice president, Development, Biogen Idec. "These data contribute to our understanding of how best to treat this disease and are consistent with the results from other Phase III studies in older patients with aggressive lymphoma."
In December 2003, a pre-planned interim analysis of study data from 326 evaluable patients conducted by the trial's independent Data and Safety Monitoring Committee (DSMC) revealed the study had met its pre-specified primary endpoint, TTF, early and the trial was stopped.
About Non-Hodgkin's Lymphoma
There are more than 300,000 people in the United States with B-cell NHL. Approximately 50 percent have indolent or follicular lymphoma, while the other half are patients with aggressive NHL. According to the American Cancer Society, more than 54,000 men and women in the United States are diagnosed with NHL each year.
Rituxan Safety Profile
Rituxan is generally well tolerated by 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 (CLL). Patients who develop a severe mucocutaneous skin reaction should have Rituxan discontinued and receive appropriate medical treatment including a skin biopsy to guide therapy.
Rituxan is a therapeutic antibody that binds 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-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.
Rituxan is indicated as a single-agent treatment for relapsed or refractory low-grade or follicular, CD20-positive, B-cell NHL. More than 300,000 patients have been treated with Rituxan worldwide since approval.
Genentech and Biogen Idec co-market Rituxan in the United States. Roche markets Rituxan in the rest of the world, except Japan, where Rituxan is co-marketed by Roche, Chugai and Zenyaku Kogyo Co. Ltd.
Genentech is committed to changing the way cancer is treated by establishing a broad oncology portfolio of innovative, targeted therapies with the goal of improving patients' lives. The company is the leading provider of anti-tumor therapeutics in the United States. Genentech is leading clinical development programs for Rituxan® (Rituximab), Herceptin® (Trastuzumab), and Avastin (bevacizumab) and markets all three products in the United States either alone (Avastin, which it recently launched in the United States, and Herceptin) or with Biogen Idec Inc. (Rituxan). Genentech has licensed Rituxan, Herceptin and Avastin to Roche for sale by the Roche Group outside of the United States.
The company has a robust pipeline of potential oncology therapies with a focus on four key areas: angiogenesis, apoptosis (i.e. programmed cell death), the HER pathway and B-cell biology. Potential oncology therapies directed at the HER pathway include Tarceva (erlotinib) and a therapeutic antibody currently in Phase II trials. Also in early development are a small molecule directed at the hedgehog pathway, a therapy targeting apoptosis and a humanized anti-CD20 antibody for hematology/oncology indications.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Eighteen of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes 13 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. For press releases and 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.
Roche in Oncology
Within the last five years the Roche Group has become the world's leading provider of anti-cancer treatments, supportive care products and diagnostics. Its oncology business includes an unprecedented four marketed products with survival benefit: Herceptin, MabThera, Xeloda and Avastin (launched by Genentech in the US recently), which treat a range of malignancies such as breast cancer, non-Hodgkin's lymphoma and colorectal cancer. Other key products include NeoRecormon (anaemia in various cancer settings), Bondronat (prevention of skeletal events in breast cancer and bone metastases patients, hypercalcemia of malignancy), Kytril (chemotherapy and radiotherapy-induced nausea and vomiting) and Roferon-A (leukaemia, Kaposi's sarcoma, malignant melanoma, renal cell carcinoma). CERA is the most recent demonstration of the commitment to anaemia management. Roche's cancer medicines generated sales of more than 6 billion Swiss francs in 2003.
In a recent phase III study Tarceva met its primary endpoint of improving overall survival in patients with non-small cell lung cancer.
Roche is developing new tests, which will have a significant impact on disease management for cancer patients in the future. With a broad portfolio of tumor markers for prostate, colorectal, liver, ovarian, breast, stomach, pancreas and lung cancer, as well as a range of molecular oncology tests, we will continue to be the leaders in providing cancer focused treatments and diagnostics.
Roche Oncology has four research sites (two in the US, Germany and Japan) and four Headquarter Development sites (two in the US, UK and Switzerland).
For full prescribing information, including Boxed Warnings, please call 650-225-5873. For more information on Rituxan, visit http://www.rituxan.com.