Tuesday, May 15, 2001
-- Updated Data from Front-line and Maintenance Study of Rituxan Also Presented --
SAN FRANCISCO, Calif., -- May 15, 2001 -- Genentech, Inc. (NYSE: DNA) and IDEC Pharmaceuticals Corporation (Nasdaq: IDEC) today announced positive preliminary results from two ongoing studies presented at the 37th annual meeting of the American Society of Clinical Oncology (ASCO). The first is a Phase II clinical trial investigating the use of Rituxan® (Rituximab) and the chemotherapeutic agent fludarabine in previously-untreated patients with chronic lymphocytic leukemia (CLL). The second study is evaluating Rituxan alone as front-line and maintenance therapy for patients with low-grade non-Hodgkin's Lymphoma (NHL) or small lymphocytic leukemia (SLL) -- a type of lymphoma closely related to CLL.
Rituxan with Fludarabine in Previously-Untreated CLL Patients (Abstract# 1116)
Conducted by the Cancer and Leukemia Group B (CALGB), a National Cancer Institute (NCI) sponsored U.S. cancer cooperative group, the study found that two different dosing schedules of Rituxan and fludarabine each produced high overall and complete response rates. John C. Byrd, M.D., of Ohio State University, presented the results during an oral presentation.
"While preliminary, these results build upon the growing body of data that Rituxan may play an important role in the treatment of CLL, especially when used early in the course of the disease with chemotherapy," said Gwen Fyfe, M.D., Genentech's senior director of Oncology, Medical Affairs. "In this Phase II study we saw a 90 percent overall response rate and 47 percent complete response rate in the study arm that received fludarabine concurrently with Rituxan."
Bruce Cheson, M.D., head of the Medicine section, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis of the National Cancer Institute commented, "The encouraging data from this clinical trial will form the basis of one arm of a planned Phase III randomized study in newly diagnosed CLL patients. It will be conducted by CALGB to determine the best initial therapy for CLL patients."
In the CALGB Phase II study presented, 104 previously-untreated patients with CLL were randomized to receive one of two dosing regimens of Rituxan and fludarabine. Patients in the concurrent arm received fludarabine 25 mg/m2 on days one to five repeated monthly for six cycles. During cycle one, Rituxan was administered on day one and four and for the remaining five cycles Rituxan was given on day one of each cycle. Patients in the sequential arm received the same fludarabine dosing regimen, and two months after completing fludarabine therapy these patients received four weekly doses of Rituxan.
Based on an intent-to-treat analysis of the 104 enrolled patients, the overall response rate in the concurrent arm was 90 percent (46 patients), with 47 percent (24 patients) achieving a complete response and 43 percent (22 patients) achieving a partial response. The activity of Rituxan and fludarabine was similar in the sequential arm of the trial with an overall response of 77 percent (41 patients). Twenty-eight percent (15 patients) achieved a complete response and 49 percent (26 patients) achieved a partial response.
"The most encouraging aspect of this data is the complete response rate achieved of nearly 50 percent that is significantly better than the historical complete response rate with fludarabine alone in previously-untreated CLL patients," said Dr. Fyfe.
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).
Updated Data from Front-line NHL Single Agent Rituxan Study (Abstract #1175)
In a poster presentation by John Hainsworth, M.D., of The Sarah Cannon Medical Center, 62 previously-untreated patients with low-grade Non-Hodgkin's lymphoma (NHL) and small lymphocytic leukemia (SLL) were enrolled in a multi-center community-based clinical trial to determine the safety and effectiveness of single agent Rituxan as a front-line therapy with maintenance therapy for responding patients. Thirty-eight NHL and 24 SLL patients were enrolled in the trial and received single agent Rituxan (375 mg/m2) once weekly for four weeks, i.e. one course of therapy. Patients who responded to the first course of Rituxan therapy or had stable disease were then scheduled to receive one additional maintenance course of Rituxan therapy every six months for two years.
The study reports that at week six, 28 out of 60 evaluable patients (47 percent) had an objective response (reduction in tumor by more than 50 percent) with seven percent (four patients) achieving complete responses to single agent Rituxan. Twenty-nine patients (48 percent) had stable or minor response. At a minimum of 15 months follow-up, the objective response rate increased to 65 percent with a complete response rate of 27 percent for patients receiving maintenance courses of Rituxan.
One- and two-year progression-free survival reached 69 percent and 67 percent, respectively. Response rates and progression-free survival times are similar in patients with low-grade NHL and SLL.
"The updated results from this study suggest that Rituxan may be a highly active therapy when given as an initial therapy to patients with either NHL or SLL," said Gwen Fyfe, M.D., Genentech's senior director of Oncology, Medical Affairs. "We are most encouraged by our findings that suggest patients may benefit from additional courses of Rituxan that can lead to increased response rates and conversion of partial responses to complete responses without any significant increase in toxicity and delay the time until patients have to receive their first course of chemotherapy."
Overall adverse events observed with repeat courses were less frequent than those observed with the initial course of Rituxan. Only two patients (three percent) had reversible grade 3/4 infusion-related adverse events. No additional toxicity occurred with maintenance courses of Rituxan. To date, patients in the study receiving more than one course of Rituxan did not demonstrate an immune response to the therapy -- human anti-chimeric antibody (HACA) -- or any evidence of impaired bone marrow function (myelosuppression).
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, adult 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 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 novel approach to treating low-grade (indolent) or slow-growing NHL. It 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 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.
About CLL, NHL and SLL
CLL is one of four major types of leukemia and the second most common form of the disease, primarily affecting middle-aged and elderly adults. An estimated 8,100 people have the disease in the United States with 5,100 deaths annually. A cancer of mature B-cells called lymphocytes, CLL is manifested by progressive accumulation of cells in blood, bone marrow and lymphatic tissue.
There are more than 250,000 people in the United States with B-cell NHL. Approximately 50 percent have low-grade or follicular lymphoma, while the other half are patients with aggressive NHL. SLL, a form of B-cell NHL that is similar to CLL, accounts for approximately five percent of NHL cases in adults. 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.
Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Fourteen of the currently approved biotechnology products stem from Genentech science. Genentech markets nine biotechnology products directly in the United States. The company has headquarters in South San Francisco, Calif. 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, Calif., and is traded on the NASDAQ National Market System under the stock symbol, IDPH.
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