SAN DIEGO – DEC. 7, 2003 –Genentech, Inc. (NYSE: DNA) and Biogen Idec, Inc. (Nasdaq: BIIB) announced today the initial results of a Phase III (E4494) randomized study of Rituxan Ò (Rituximab) as a front-line and maintenance therapy in the treatment of newly diagnosed, diffuse, large, B-cell, or aggressive non-Hodgkin’s lymphoma (NHL). The study was designed to evaluate Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone ( CHOP) chemotherapy compared with CHOP alone as a front-line therapy, followed by Rituxan maintenance therapy or observation . The trial was a U.S. Intergroup study led by the Eastern Cooperative Oncology Group (ECOG) in collaboration with the Southwest Oncology Group (SWOG) and the Cancer and Leukemia Group B (CALGB).
The study, presented during a plenary session at the 45 th Annual American Society of Hematology (ASH) meeting by Thomas Habermann, M.D., of Mayo Clinic was designed with two distinct randomizations: the first, called the induction phase, evaluated 546 patients age 60 and older who were randomized to receive either six-to-eight cycles of CHOP chemotherapy alone (n=279), or CHOP in combination with four-to-five doses of Rituxan (n=267). After completing the induction phase, 352 evaluable patients whose tumors responded to Rituxan
plus CHOP (R-CHOP) or CHOP alone were re-randomized to receive either Rituxan maintenance therapy (four doses of Rituxan weekly, every six months for two years) or no further therapy (observation).
For the analysis of the primary endpoint of the induction phase of the study –
time to treatment failure (TTF) – patients who received R-CHOP chemotherapy followed by Rituxan maintenance therapy or observation demonstrated a trend toward prolongation of TTF, as compared to patients who received CHOP alone followed by Rituxan maintenance therapy or observation. The addition of Rituxan to CHOP did not influence the overall response rate (ORR) in the induction phase (78 percent for R-CHOP vs. 77 percent for CHOP alone).
Due to the observed interaction between Rituxan maintenance and induction therapy, additional analyses (“weighted analyses”) were performed to compare induction therapy with R-CHOP versus CHOP alone, removing the effects of subsequent Rituxan maintenance therapy. Based on the weighted analyses, the investigators concluded that patients who received R-CHOP induction therapy experienced a significant prolongation of both TTF (hazard ratio of 0.63 or a 59 percent increase in failure-free survival) and overall survival (OS) (hazard ratio 0.69 or a 45 percent increase) compared to patients who received induction therapy with CHOP alone.
With regard to the primary endpoint for the maintenance phase of the study, patients treated with Rituxan maintenance for up to an additional two years after completing induction therapy had a statistically significant prolongation in TTF compared to patients who did not receive Rituxan maintenance therapy following induction. This advantage appeared predominantly confined to patients who received CHOP alone during the induction phase of the study. At this time, there is no difference in OS between the Rituxan maintenance and observation arms, though the investigators concluded that additional follow-up is necessary.
“The weighted analyses for the induction phase have helped us see more clearly the potential role of Rituxan plus CHOP as a front-line treatment in newly diagnosed patients with aggressive NHL,” said Gwen Fyfe, M.D., Genentech’s vice president of Clinical Hematology/Oncology. “We look forward to the availability of mature maintenance data that will allow us to more completely analyze the role of Rituxan in this setting.”
There were no differences in grade 3/4 toxicities in patients receiving R-CHOP compared to those receiving CHOP alone in the induction arm of the study. The most common toxicities included grade 3/4 neutropenia, anemia, thrombocytopenia, and infection.
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. Overall, NHL is the second fastest growing cancer in terms of incidence and deaths in the United States and is diagnosed in more than 56,000 men and women each year.
Rituxan Safety Profile
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 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.
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 and Zenyaku Kogyo Co. Ltd.
The Eastern Cooperative Oncology Group (ECOG) was established in 1955 as one of the first cooperative groups launched to perform multi-center cancer clinical trials. A cooperative group is a large network of researchers, physicians, and health care professionals at public and private institutions across the country who are members of the group. Funded primarily by the National Cancer Institute (NCI), ECOG has evolved from a five member consortium of institutions on the East Coast to one of the largest clinical cancer research organizations in the United States with almost 6000 physicians, nurses, pharmacists, statisticians, and clinical research associates (CRAs) from the United States, Canada, and South Africa.
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 12 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 .
About Biogen IdecBiogen 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 . For full prescribing information, including Boxed Warnings, please call 650-225-5873. For more information on Rituxan, visit www.rituxan.com .