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FDA Approves Rituxan Plus CHOP for Non-Hodgkin's Lymphoma

FDA Approves Rituxan Plus CHOP or Other Anthracycline-Based Chemotherapy Regimens for First-Line Treatment of Diffuse Large B-cell Non-Hodgkin's Lymphoma

Treatment Offers the First Significant Improvement in Survival for Patients with Diffuse Large B-cell Lymphoma in More than 25 Years

SOUTH SAN FRANCISCO, Calif. and CAMBRIDGE, Mass., February 10, 2006 -- Genentech, Inc. and Biogen Idec, Inc. today announced that the U.S. Food and Drug Administration (FDA) has approved Rituxan (Rituximab) for use in the first-line treatment of patients with diffuse large B-cell, CD20-positive, non-Hodgkin's lymphoma, in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens. Rituxan has previously been approved as a single agent for use in relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma.

"Diffuse large B-cell lymphoma can be fatal within as little as six months to two years without aggressive treatment," said Sandra J. Horning, M.D., chair, lymphoma group for the Eastern Cooperative Oncology Group. "With this approval, Rituxan in combination with chemotherapy becomes the first FDA- approved treatment to improve survival for patients with this type of non- Hodgkin's lymphoma since the introduction of the CHOP chemotherapeutic regimen more than 25 years ago."

An estimated 360,000 Americans have non-Hodgkins lymphoma (NHL) and more than 58,000 new cases are diagnosed annually. Diffuse large B-cell lymphoma (DLBCL), an aggressive subtype of NHL, divides and multiplies rapidly in the body, and if left untreated, can be fatal. However, early diagnosis and treatment can improve chances of long-term survival. Of those diagnosed with NHL, about 50 percent have an aggressive form of the disease, the most common type being DLBCL. The other 50 percent of patients have a slow-growing, but usually incurable or indolent form of the disease, of which the most common type is follicular lymphoma.

Clinical Studies

The approval was based on efficacy and safety data from three randomized, controlled, multicenter studies of Rituxan in combination with CHOP or other anthracycline-based chemotherapy induction regimens in 1,854 previously untreated (first-line) patients with DLBCL. In each study, hazard ratios for the time-to-event comparison, as well as the overall survival benefit, favored the Rituxan-containing arms. Results were generally consistent across subgroups, including age, gender and disease prognostic variables. With two years of follow-up, more patients were alive in the Rituxan-containing versus control arms for each study. In one of the studies with five years of follow-up, the GELA trial, R-CHOP improved overall survival by 47 percent compared to CHOP alone (a hazard ratio of 0.68, which is equivalent to a 32 percent decrease in the risk of death).

The studies included in the submission to the FDA were GELA/LNH 98-5 (the Group d'Etude des Lymphome d'Adulte also known as the GELA trial), E4494 (a National Cancer Institute-sponsored Intergroup trial led by the Eastern Cooperative Oncology Group) and MInT (MabThera International Trial M39045). Rituxan is known as MabThera in Europe.

The GELA trial was designed to evaluate the efficacy and safety of Rituxan in combination with induction CHOP chemotherapy in 399 patients 60 years of age or older with DLBCL. Patients were randomized to receive chemotherapy or Rituxan plus chemotherapy. At five years, an estimated 58 percent of patients who received Rituxan plus chemotherapy were alive versus 46 percent of patients who received chemotherapy alone. Results of this trial were previously presented publicly in 2000 at the American Society of Hematology annual meeting and in 2001 at the American Society of Clinical Oncology annual meeting and were published in the New England Journal of Medicine in January 2002.

In addition to GELA, the MInT and E4494 trials demonstrated an overall survival benefit with the addition of Rituxan to chemotherapy in a wide range of patients. In the MInT trial, the addition of Rituxan significantly increased survival in younger (<60 years) DLBCL patients. Ninety five percent of patients who received Rituxan in addition to chemotherapy survived two years versus 86 percent of patients who received chemotherapy alone. In the E4494 study of older (greater than or equal to 60 years) DLBCL patients, 74 percent of patients who received Rituxan plus chemotherapy survived two years versus 63 percent who received chemotherapy alone.

"The approval of this new indication underscores our continued commitment to help advance the treatment of B-cell malignancies," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer. "This approval is the result of an extraordinary collaboration between Genentech and Biogen Idec, and among clinical investigators, the FDA, and most importantly, the patients who participated in the clinical trials."

"The best chance to achieve treatment success is in the first-line setting and these data demonstrate that first-line treatment with up to eight cycles of Rituxan plus chemotherapy resulted in a significant survival advantage in patients with diffuse large B-cell lymphoma," said Arturo Molina, M.D., Biogen Idec's acting head of Medical Research, Hematology/Oncology.

Rituxan Safety Profile

The safety profile of Rituxan has been established in more than 730,000 patient exposures over a period of eight years.

In NHL, the majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include but are not limited to: flu-like illness, fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema and hypotension. These symptoms vary in severity and generally are reversible with medical intervention.

Severe infusion reactions, some with fatal outcome, have been reported in patients treated with Rituxan. These severe reactions typically occur during the first infusion. The most severe manifestations and sequelae include hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation and cardiogenic shock. Patients who develop clinically significant infusion reactions should have their Rituxan infusion discontinued and receive medical treatment. Acute renal failure requiring dialysis with instances of fatal outcome has been reported in the setting of tumor lysis syndrome following treatment with Rituxan. Severe mucocutaneous skin reactions, some with fatal outcome, have been reported in association with Rituxan treatment. Patients experiencing a severe mucocutaneous reaction should not receive any further infusions and seek prompt medical evaluation. Abdominal pain, bowel obstruction and perforation, in some cases leading to death, were observed in patients receiving Rituxan in combination with chemotherapy for DLBCL. Other serious or potentially life-threatening adverse reactions that have been reported following Rituxan therapy include Hepatitis B reactivation with fulminant hepatitis, other viral infections, hypersensitivity reactions, and cardiac arrhythmias.

About Rituxan

Rituxan is a therapeutic antibody that targets and selectively depletes CD20-positive B-cells without targeting stem cells or existing plasma cells. Rituxan is also being studied in other hematologic malignancies as well as autoimmune diseases, including rheumatoid arthritis, lupus, multiple sclerosis and ANCA-associated vasculitis.

Rituxan, discovered by Biogen Idec, received 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 was approved in the European Union under the trade name MabThera(R) in June 1998 and based on the results of the GELA trial, was approved by the European Agency for the Evaluation of Medicinal Products (EMEA) for aggressive NHL in combination with CHOP chemotherapy. 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 by Chugai and Zenyaku Kogyo Co. Ltd. Rituxan is the top-selling oncology therapeutic in the United States.

Source: Genentech, Inc.

Posted: February 2006


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