Monday, Dec 10, 2001
Orlando, Fla. -- December 10, 2001 --Genentech, Inc. (NYSE: DNA) and IDEC Pharmaceuticals Corporation (Nasdaq: IDEC) today announced positive preliminary results from two investigational studies examining the role of Rituxan® (Rituximab) in the treatment of immune thrombocytopenic purpura (ITP), an autoimmune disorder characterized by bruising and abnormal bleeding. The results were presented at the annual meeting of the American Society of Hematology (ASH).
ITP affects approximately 100,000 people in the United States and is associated with the production of antibodies that destroy blood platelets responsible for normal blood clotting. It is estimated that between 25 and 30 percent of patients develop chronic ITP, a disease that becomes refractory to several available treatments and often necessitates a splenectomy (removal of spleen). The ten-year mortality rate for these patients ranges from 10 to 20 percent.
"There is a significant unmet medical need for patients who have refractory ITP since there is no therapy with proven high success rates and few side effects, nor one that does not require major surgery," said Gwen Fyfe, M.D., Genentech's senior director of Oncology, Medical Affairs. "Part of our ongoing clinical trial effort is to explore the use of Rituxan in autoimmune diseases like ITP where B-cells may play a role."
Standard Course of Rituxan Study for Relapsed ITP (Abstract #2180)
The purpose of this trial was to examine the safety and efficacy of Rituxan in patients with ITP who had platelet counts of less than 30,000/µL and were refractory to at least one previous treatment. Each patient received the standard course of therapy -- 375 mg/m2 of Rituxan weekly for four weeks. Response was defined as a platelet increase of greater than 20,000/µL from base line in order to achieve a platelet count greater than 30,000/µL for more than one month duration, within 12 weeks of the first Rituxan infusion. A "good" response was defined as a platelet count greater than 50,000/µL on two counts one week apart and a complete response was considered a platelet count greater than 150,000/µL on two counts one week apart. Twenty-one out of 23 patients are evaluable after more than nine weeks since the first infusion.
To date, 47 percent (10/21) of evaluable patients have responded to treatment with 38 percent (8/21) achieving a complete response and nine percent (2/21) achieving a good response. Only one patient has relapsed and was successfully retreated. Four additional patients (19 percent) experienced an improvement in their platelet counts, resulting in a reduction of other therapies.
"The aim of treatment of ITP is to maintain a safe platelet count to halt bleeding with minimal adverse events," said Dr. Fyfe. "As we gain a better understanding about the immunologic abnormalities associated with the disorder, we are learning that B-cell depletion associated with Rituxan may provide a research opportunity worth exploring."
As has been seen in prior studies of Rituxan in malignant disorders, adverse events to therapy were associated with the first 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. Eight patients experienced reversible reactions following the first infusion that were characterized as red face, hives, itching and throat discomfort.
Dose Escalation Trial of Rituxan for Steroid Refractory ITP (Abstract #2179)
The safety and efficacy of Rituxan was tested in 26 patients with ITP who failed corticosteroid therapy and had blood platelet counts less than 75,000/mL. Eighteen patients had failed at least two prior therapies and 13 had undergone a prior splenectomy.
Patients were enrolled into one of three dose escalation treatment arms: Group One received a 50 mg/m2 dose of Rituxan on day one and 150 mg/m2 on days eight and 15; Group Two received 150 mg/m2 dose of Rituxan on day one and 375 mg/m2 on days eight, 15 and 22; Group Three received 375 mg/m2 of Rituxan on days one, eight, 15 and 22. Complete response was defined as a blood platelet count greater than 150,000/mL, while a partial response was a blood platelet count greater than 100,000/mL.
No responses were seen in Group One, which received the lowest dose of Rituxan. Of the 23 patients in Group Two and Three, four patients (17 percent) achieved a complete response and four patients (17 percent) a partial response, translating into an overall response rate of approximately 35 percent. Of the 12 patients who had undergone a splenectomy, three patients (25 percent) achieved a complete response and three patients (25 percent) a partial response, translating to a 50 percent overall response rate. Duration of response ranges from three to more than 24 months. To date, only one of the responding patients has relapsed, nine months following Rituxan therapy.
Overall, Rituxan was well-tolerated in the study, with most patients experiencing mild infusion reactions. No increase in infection was seen in these patients.
About Immune Thrombocytopenic Purpura (ITP)
ITP may be caused by reactions to drugs, infection, pregnancy or other autoimmune disorders such as lupus. Signs and symptoms of ITP include easy bruising, abnormal bleeding and skin hemorrhage. About half of all cases are classified as "idiopathic" meaning the cause is unknown.
Drugs that alter the immune system's attack on the platelets, such as prednisone or intravenous infusions of immune globulin often are used as well as surgical removal of the spleen in an attempt to increase the number of platelets and improve blood clotting. In more severe cases where these standard treatments have not shown benefit, various chemotherapy drugs, such as vincristine and cyclophosphamide, are used.
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 non-Hodgkin's lymphoma (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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