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Genentech (DNA) Release: Initial Data Released From Phase III ECOG 4494 Study Of Rituxan As Front-Line And Maintenance Therapy In Aggressive Non-Hodgkin's Lymphoma; Early Drug Data Fails To Show Survival When Given As Maintenance Therapy



10/19/2005 5:10:15 PM

SAN DIEGO & SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Nov. 4, 2003-- INITIAL DATA RELEASED FROM PHASE III ECOG 4494 STUDY OF RITUXAN AS FRONT-LINE AND MAINTENANCE THERAPY IN AGGRESSIVE NON-HODGKIN'S LYMPHOMA

Rituxan Plus CHOP Induction Therapy Significantly Prolonged Time to Treatment Failure in Newly-Diagnosed Patients

Additional Phase III Studies Also to be Presented at the American

Society of Hematology (ASH) Meeting in December

Genentech (NYSE:DNA - News) and IDEC Pharmaceuticals Inc. (NYSE:IDPH - News) today announced that an abstract which contains initial data from a Phase III study (E4494) conducted by the Eastern Cooperative Oncology Group (ECOG) of Rituxan® (rituximab) in patients with newly-diagnosed diffuse large B-cell lymphoma was released by the American Society of Hematology (ASH) and is available on its web site (www.hematology.org).

The study was designed with two distinct randomizations: the first, called the induction phase, randomized patients to receive either six-to-eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone or CHOP in combination with four-to-five doses of Rituxan. Patients who responded to Rituxan plus CHOP or CHOP alone in the induction phase were then randomized for a second time 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) -- the authors reported that patients who received Rituxan plus CHOP chemotherapy demonstrated a significant prolongation in TTF, as compared to patients receiving CHOP alone.

The addition of Rituxan to CHOP did not influence the overall response rate (ORR) in the induction phase. Complete and partial response information was not included in the abstract. Additionally, the authors concluded that - at this time - no statistically significant differences in overall survival (OS) were observed.

With regard to the primary endpoint for the maintenance phase of the study, patients treated with maintenance Rituxan for up to an additional two years had a significant prolongation in TTF, compared to patients who did not receive further treatment. This advantage appeared limited to patients who received CHOP alone during the induction phase of the study.

The abstract did not include safety information from the E4494 study. Updated results are scheduled for presentation in a plenary session at this year's ASH meeting on Sunday, December 7, 2003.

"While we are encouraged by the preliminary data on time to treatment failure in both the induction and maintenance arms of the study, we believe that the maintenance information is currently immature and require more clinical events in patients to be available for analysis to further understand the results," said Susan Desmond-Hellmann, M.D., MPH, Genentech's executive vice president, Development and Product Operations, and chief medical officer.

About the Phase III Study

Patients enrolled in the E4494 study had Stage I-IV diffuse large B-cell lymphoma, or primary mediastinal B-cell lymphoma. Patients were required to be at least 60 years old with measurable disease, no prior therapy and a performance status (PS) of 0-3.

Approximately 632 patients were randomly assigned to one of two treatment groups:

Arm A received CHOP plus Rituxan every 21 days for six-to-eight cycles. Two doses of Rituxan were given before the first cycle of CHOP and prior to cycles three and five. For patients who received eight cycles of CHOP chemotherapy, an additional dose of Rituxan was given prior to cycle seven. Arm B received CHOP every 21 days for six-to-eight cycles. Patients with complete or partial responses were then randomized to one of two groups:

Maintenance arm 1 received maintenance doses of Rituxan for four consecutive weeks every six months for two years beginning three weeks after their last CHOP chemotherapy dose. Maintenance arm 2 served as the observation group as patients did not receive Rituxan maintenance therapy and were observed. Additional Rituxan Studies to be Presented at ASH

In addition to the ECOG 4494 study, initial results from a randomized Phase III study evaluating Rituxan in combination with cyclophosphophamide, vincristine, and prednisolone (CVP) chemotherapy compared to CVP alone as a front-line therapy in patients with indolent lymphoma will be presented. The study met its primary endpoint of prolonging time to treatment failure in patients receiving Rituxan/CVP as compared to patients receiving CVP alone. Dr. Robert Marcus of Addenbrookes Hospital, Cambridge is scheduled to discuss these data at ASH in an oral presentation on Sunday, December 7, 2003.

Numerous other studies will be presented at ASH providing new and updated data on Rituxan in various disease settings, including:

Initial results from a randomized, Phase III study conducted by the German Low Grade Lymphoma Group Study (GSLG) in patients with follicular and mantle cell lymphoma; Eight-year follow-up data on a Phase II study of Rituxan and CHOP in patients with indolent lymphoma; Initial results from a randomized, Phase II study evaluating maintenance and retreatment with Rituxan in patients with indolent NHL; and Data from a retrospective study investigating the use of Rituxan in addition to fludarabine in previously-untreated chronic lymphocytic leukemia (CLL). 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 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, referred to as MabThera outside the United States, in combination with CHOP chemotherapy, received European approval to treat aggressive NHL in March 2002. More than 300,000 patients have been treated with Rituxan worldwide.

Genentech and 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.

About ECOG

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.

Webcast

Genentech will be offering a live webcast of a discussion of the ECOG 4494 study. The webcast will begin at 2:00 p.m. Pacific Time on November 4, 2003. The live webcast can be accessed by going to Genentech's website at http://www.gene.com and will be archived and available for replay until 5:00pm Pacific Time on November 11, 2003.

An audio replay of the webcast will be available beginning at 5:00 p.m. Pacific Time on November 4, 2003 and ending at 5:00 p.m. Pacific Time on November 11, 2003. Access numbers for this replay are: 1-800-642-1687 (U.S./Canada) and 1-706-645-9291 (international); passcode number is 3865023.

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 press releases and additional information about the company, please visit http://www.gene.com

About IDEC

IDEC Pharmaceuticals Corporation is a leader in the discovery, development, and commercialization of targeted immunotherapies for the treatment of cancer and autoimmune diseases. IDEC discovered and developed the first commercially available radioimmunotherapy product (Zevalin(TM)) approved in the United States, which is used to treat certain non-Hodgkin's lymphomas. IDEC also discovered, and with co-promotion partner Genentech, Inc., developed the first monoclonal antibody product (Rituxan) approved in the United States for the treatment of cancer. Rituxan is approved in over 70 countries worldwide and is also used to treat various types of non-Hodgkin's lymphomas. IDEC is a San Diego based, integrated biopharmaceutical company with multiple products in clinical stage development and strategic alliances in a variety of research platforms.

For full prescribing information, including Boxed Warnings, please call 650-225-8681. For more information on Rituxan, visit www.rituxan.com.

Contact: GNE Neil Cohen, 650-225-8681 (Media) Kathee Littrell, 650-225-1034 (Investor) or IDEC Vince Reardon, 858-431-8801

Source: Genentech


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