Initial Results of a Randomized Phase II Study Suggest That Rituxan Maintenance Therapy Prolongs Remission in Indolent NHL.

Business Editors/Health/Medical Writers

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SAN DIEGO--(BUSINESS WIRE)--Dec. 8, 2003

Genentech, Inc. (NYSE:DNA) and Biogen Idec, Inc. (Nasdaq:BIIB) today announced initial results from a randomized Phase II study showing that patients with indolent non-Hodgkin's lymphoma (NHL) who received Rituxan(R) (Rituximab) maintenance therapy experienced 31 months of progression-free survival (PFS) as compared to eight months PFS for those patients who were retreated with Rituxan at the time of disease progression. The study also demonstrated that duration of Rituxan benefit, the primary endpoint of the study, can be prolonged by either maintenance therapy (31 months) or retreatment (27 months). The duration of Rituxan benefit was measured from the date of documented remission to the date that treatment other than Rituxan was necessary. Indolent lymphoma is a slow-growing, incurable disease in which the average patient survives between six and 10 years, following numerous periods of remission and relapse.

Results from this multi-center, randomized Phase II study of 114 patients were presented at the American Society of Hematology (ASH) 45th Annual Meeting by John Hainsworth, M.D., of Sarah Cannon Cancer Center and Tennessee Oncology. The study was designed to compare the efficacy of Rituxan maintenance therapy to retreatment with Rituxan at the time of disease progression. In this study, maintenance therapy was defined as treatment with Rituxan every six months for two years with the objective of keeping lymphoma from returning or progressing. Retreatment was defined as waiting until the disease progressed prior to administering another course of Rituxan.

Overall response rates (ORR) were 52 percent (23/44) for patients treated with Rituxan maintenance therapy and 35 percent (16/46) for those in the retreatment arm. Complete response (CR) rates for patients in the maintenance arm were 27 percent (12/44) while only 4 percent (2/46) remained in continuous complete remission in the retreatment arm.

"The goal of treating patients with indolent lymphomas is to keep them disease-free and treatment-free for as long as possible. We are encouraged by these data, which indicate that patients whose response was maintained with Rituxan and those who were retreated numerous times with Rituxan were able to survive almost three years without undergoing chemotherapy," said Gwen Fyfe, M.D., Genentech's vice president of Clinical Hematology/Oncology. "These data are particularly encouraging, as they come just a few weeks after we learned that a Phase III study (ECOG 1496) of Rituxan maintenance therapy stopped randomization to the observation arm of the study after meeting its pre-specified primary endpoint early. We will look to these studies and others to further our understanding of Rituxan's use in indolent NHL."

All patients received induction treatment with Rituxan (375 mg/m2 weekly x4). Ninety of the 114 patients had an objective response or stable disease and were randomized to receive Rituxan maintenance therapy (375 mg/m2 weekly for four weeks at six-month intervals for a total of four courses) or retreatment with a standard four-week course of Rituxan at the time of disease progression.

"This study provides important preliminary information on Rituxan's potential to prolong the time until a patient would need a more toxic therapy," said Dr. Hainsworth. "The larger number of patients in continuous remission with the maintenance approach may prove to be an advantage in terms of optimal palliative treatment. Further studies are necessary to better address these issues."

There were no differences in side effects between the two arms of the study.

ECOG 1496 Phase III Study

Recently, Genentech, Biogen Idec and Roche announced that the Eastern Cooperative Oncology Group (ECOG) stopped further randomization of patients into the observation arm of its study of Rituxan maintenance therapy in patients with previously untreated indolent NHL when it met its pre-specified primary efficacy endpoint early. During a pre-planned interim analysis of the study data conducted by an independent ECOG Data Monitoring Committee (DMC), the data showed a statistically significant improvement in time to treatment failure (TTF) for patients who received Rituxan maintenance therapy. At the time the study was stopped, 322 patients who responded or had stable disease following induction cyclophosphamide, vincristine and prednisone (CVP) chemotherapy had been randomized to receive either Rituxan maintenance therapy or no further treatment. Data from this study are expected to be presented at an upcoming medical meeting in 2004.

About Rituxan

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. Rituxan is referred to as MabThera outside the United States. More than 300,000 patients have been treated with Rituxan worldwide.

Genentech and Biogen 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 by Roche and Zenyaku Kogyo Co. Ltd.

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.

About Genentech

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 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 www.biogenidec.com.

For full prescribing information, including Boxed Warnings, please call 650-225-5873. For more information on Rituxan, visit www.rituxan.com.