Monday, Dec 10, 2001
Orlando, Fla. -- December 10, 2001 --Genentech, Inc. (NYSE: DNA) and IDEC Pharmaceuticals Corporation (Nasdaq: IDEC) today announced the results of three studies presented at the annual meeting of the American Society of Hematology (ASH) that examine the role of Rituxan® (Rituximab) alone and in combination with chemotherapy in the early treatment of newly-diagnosed patients with chronic lymphocytic leukemia (CLL).
"The studies examining the combination of Rituxan with chemotherapy – treatments with complementary mechanisms of action – showed initial positive results in clinical trials as a way to attack B-cell cancer in newly diagnosed patients," commented Gwen Fyfe, M.D., Genentech's senior director of Oncology, Medical Affairs. "We also are encouraged that in an investigational study, patients who received maintenance doses of Rituxan continued to respond throughout the course of their treatment."
Rituxan and Fludarabine Combination Therapy in CLL (Abstract #3212)
In a randomized Phase II study conducted by the Cancer and Leukemia Group B (CALGB), a total of 104 previously-untreated patients with CLL were enrolled to compare the effect of four infusions of Rituxan given at the same time as fludarabine (concurrent) or two months following initial treatment with fludarabine (sequential).
Ninety percent (46/51) of patients in the concurrent arm responded, with 47 percent (24/51 patients) and 43 percent (22/51 patients) achieving complete (defined as disappearance of all detectable signs of cancer) and partial responses (defined as decrease in tumor size greater than 50 percent), respectively. In the sequential arm, the overall response rate was 77 percent (41/53), with 28 percent (15/53 patients) achieving a complete response and 49 percent (26/53 patients) a partial response.
In the concurrent arm, 29 percent of patients developed Grade 3/4 infusion toxicity during the first infusion of Rituxan, as compared to six percent of patients in the sequential arm. Infusion reactions with the second treatment in both arms were uncommon. Adverse events specific to concurrent therapy included neutropenia (29 percent Grade 3; 48 percent Grade 4), thrombocytopenia (14 percent Grade 3; 6 percent Grade 4) and infection (18 percent Grade 3). Adverse events for fludarabine in the sequential arm were neutropenia (11 percent Grade 3; 30 percent Grade 4), thrombocytopenia (8 percent Grade 3; 4 percent Grade 4) and infection (19 percent Grade 3; 2 percent Grade 4).
Rituxan and Fludarabine/Cyclophosphamide Combination Therapy (Abstract #3210)
A Phase II study conducted at the University of Texas M.D. Anderson Cancer Center was designed to evaluate the safety and effectiveness of Rituxan and fludarabine/cyclophosphamide as frontline combination CLL treatment. A total of 79 patients received six cycles of fludarabine (25 mg/m2), cyclophosphamide (250 mg/m2) and Rituxan (375 mg/m2 for first cycle; 500 mg/m2 all subsequent cycles). Treatment was given over three days and repeated every four weeks for the six cycles.
Sixty-six percent (52/79) of patients achieved a complete response (defined as disappearance of all detectable signs of cancer), 15 percent (12/79 patients) achieved a partial response (decrease in tumor size greater than 50 percent) and 14 percent (11/79 patients) a nodular partial response (residual lymphoid nodules in bone marrow).
"Taken together, the preliminary data from these two investigational studies show that Rituxan used front-line in combination with chemotherapy appears to potentially increase complete responses in CLL," said Dr. Fyfe. "We are most excited by the fact that in addition to CLL, all of the data presented at ASH demonstrated positive preliminary results when Rituxan was used in combination with chemotherapy for various forms of lymphoma."
Treatment was well tolerated with 76 percent of patients completing six cycles and only 2.5 percent of patients completing less than three treatment cycles. Fever and chills were experienced by nearly half of the patients with the first Rituxan infusion. Eighteen percent of patients experienced hypotension, 18 percent nausea and 10 percent dyspnea.
Neutropenia (Grade 4) was observed in 20 percent of all cycles administered, with patients experiencing Grade 3 or 4 thrombocytopenia in four percent of all cycles. In three percent of all cycles, patients experienced major infections (one percent sepsis; two percent pneumonia). Patients experienced minor infections in 14 percent of all cycles.
Single Agent Rituxan Given Every Six Months (Abstract #1530)
Researchers explored the effectiveness of front-line single agent and maintenance treatment with Rituxan in CLL and small lymphocytic lymphoma (SLL), a relatively rare form of B-cell non-Hodgkin's lymphoma.
Sixty-eight previously-untreated patients with CLL or SLL were treated with single-agent Rituxan for four weeks (375 mg/m2 weekly). All patients were re-evaluated for response two weeks after completing Rituxan therapy. Patients with objective responses (decrease in tumor size greater than 50 percent) or stable disease (cancer that is neither decreasing nor increasing in extent or severity) continued maintenance courses of Rituxan (using a standard four-week schedule) every six months for a maximum of four courses.
At the time of first re-evaluation, 33 of 66 evaluable patients (50 percent) achieved an objective response to Rituxan, and 32 additional patients (48 percent) had stable disease. Twenty-seven (41 percent) patients are continuing to receive maintenance courses of Rituxan, so the final response rate cannot yet be determined. However, four additional patients receiving maintenance Rituxan have already responded, for a current response rate of 56 percent. In the first group of 24 patients treated (all with SLL), median progression-free survival was 31 months.
"While preliminary, these results show that Rituxan is active as a front-line therapy for CLL and SLL," said John D. Hainsworth, M.D., director of clinical research, The Sarah Cannon Cancer Center, Nashville, TN.
Adverse effects seen in this trial were limited to Rituxan-related infusion reactions. 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. Only two patients experienced reversible Grade 3 or 4 toxicity, one of which was nausea and the other fatigue.
Rituxan is a monoclonal 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 received FDA approval in November 1997 for the treatment of relapsed or refractory low-grade or follicular, CD20 positive, B-cell NHL. It also was approved in the European Union (EU) under the trade name MabThera? in June 1998. 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 with 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 which is 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.
About Genentech and IDEC
Genentech, Inc., is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Fifteen of the currently approved products of biotechnology are based on or stem from Genentech science. Genentech markets ten 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.
IDEC Pharmaceuticals focuses on the commercialization and development of targeted therapies for the treatment of cancer and autoimmune diseases. IDEC's antibody products act chiefly through immune system mechanisms, exerting their effect by binding to specific, readily targeted immune cells in the patient's blood or lymphatic systems. IDEC is headquartered in San Diego, California, and is traded on the NASDAQ National Market System under the stock symbol, IDPH.
For full prescribing information please call (650) 225-8681.
For more information, please visit http://www.rituxan.com.
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