Monday, Dec 4, 2000
South San Francisco, Calif. -- December 4, 2000 --Roche, Genentech, Inc. (NYSE: DNA) and IDEC Pharmaceuticals Corporation (Nasdaq: IDPH) today announced interim results from an investigational Phase III study evaluating the use of Rituximab (MabThera®/Rituxan®) in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy in previously-untreated patients with aggressive non-Hodgkin's lymphoma (NHL).
"While use of CHOP chemotherapy alone has been shown to have a cure rate of 30 to 40 percent in aggressive NHL, we have been actively investigating novel ways to improve these results," said Bertrand Coiffier, professor and head, Department of Hematology, Hospices Civils de Lyon, France, and principal investigator. "These interim results, observed when adding the monoclonal antibody Rituximab to standard CHOP chemotherapy, are very important because this is the first new drug combination in 20 years to suggest an improvement in overall survival in this patient population."
GELA Phase III Study Results
The Phase III study, conducted by the Groupe d'Etude des Lymphomes de l'Adulte (GELA), a large cancer cooperative group of 130 institutions throughout Belgium, France and Switzerland, was presented at the plenary scientific lecture of the 42nd annual meeting of the American Society of Hematology (ASH).
In this Phase III study, 400 previously-untreated patients (60 years or older) with aggressive NHL were randomized to receive standard CHOP chemotherapy alone (every three weeks for eight cycles) or Rituximab (375 mg/m2) plus CHOP. Rituximab was administered on day one of each cycle.
Interim analysis of 328 patients demonstrated a significant improvement in one year event-free survival from 49 percent (78/159 patients) in the CHOP alone arm to 68 percent (115/169 patients) in the combination Rituximab/CHOP arm, a relative increase of 39 percent. Event-free survival is defined as ongoing survival without events including disease progression or relapse, death, or initiation of new alternative treatment.
Secondary endpoints demonstrated a significant increase in overall survival at one year from 68 percent (108/159 patients) in the CHOP alone arm to 83 percent (140/169 patients) in the Rituximab/CHOP combination arm, a relative increase of 22 percent. Complete response rate increased from 60 percent (95/159 patients) in the CHOP alone arm to 76 percent (128/169 patients) in the Rituximab/CHOP arm, a relative increase of 27 percent.
Approximately 10 percent of patients in the Rituximab/CHOP arm experienced Grade 3/4 infusion-related events. As has been seen in prior studies with Rituximab, these events were generally limited to the first infusion of Rituximab and were reversible. Beyond these first infusion events, the addition of Rituximab to CHOP chemotherapy did not appear to cause a clinically significant increase in adverse events to those seen with CHOP chemotherapy alone.
Rituximab Side Effects
The majority of patients experience infusion-related symptoms with their first Rituximab 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 Rituximab 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 Rituximab infusion discontinued and receive medical treatment.
U.S.-Based Phase III Studies
A multi-center, randomized Phase III trial being conducted by the Cooperative Cancer Study Groups (InterGroup) in the U.S., led by the Eastern Cooperative Oncology Group, ECOG, will continue to enroll patients. With 502 patients enrolled to date, the InterGroup trial is near completion of patient enrollment. It is important that this study is completed to verify and extend the interim analysis findings of the GELA in a U.S.-based setting and to address an additional important treatment question of whether using maintenance Rituximab after primary treatment with either CHOP or Rituximab plus CHOP can safely extend patient benefit. Additionally, Genentech and IDEC have temporarily suspended enrollment to a company-sponsored Phase III trial called S.E.A.R.Ch., that is in a very early stage of recruitment and similar in design to the GELA trial.
About Aggressive NHL
Approximately 4.5 million people worldwide are living with various forms of lymphoma, and it is estimated that 300,000 people die each year. In terms of incidence and death, NHL is the second fastest growing cancer in the United States and the third fastest growing in the rest of the world.
Lymphomas generally are classified into two equal groups: one half are indolent (low-grade) lymphomas while the remaining are aggressive (intermediate/high-grade). Intermediate/high-grade lymphomas spread rapidly, and left untreated, can be fatal within six months to two years. Patients who are diagnosed and treated in early stages of aggressive disease are more likely to experience a complete remission of several years in duration and are less likely to have late recurrences. In contrast, while low-grade lymphomas progress slowly and patients may live an average of six to seven years, standard treatments cannot cure the disease.
Rituximab is a novel approach to treating low-grade (indolent) or slow-growing NHL. It is a monoclonal antibody that works by binding 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-cells progenitors) in bone marrow lack the CD20 antigen, allowing healthy B cells to regenerate after treatment and return to normal levels within several months. Approximately 85 percent of all NHL cases are B-cell lymphomas.
Rituximab (RituxanC) initially received FDA approval in November 1997 for the treatment of relapsed or refractory low-grade or follicular, CD20 positive, B-cell NHL. It was also approved in the European Union under the trade name MabTheraC in June 1998. Genentech and IDEC have marketing rights to Rituxan in the U.S. and Zenyaku Kogyo Co. Ltd. will market the drug together with Roche in Japan. Roche has marketing rights to MabThera worldwide, excluding the U.S.
F. Hoffmann-LaRoche, headquartered in Basel, Switzerland, is one of the world's leading research-oriented healthcare groups in the fields of pharmaceuticals, diagnostics and vitamins. Roche's innovative products and services address needs for the prevention, diagnosis and treatment of diseases, thus enhancing people's well-being and quality of life. Roche has approximately 63,900 employees and sells its products in over 170 countries. The Roche Group posted sales of 20.3 billion Swiss francs in the first nine months of 2000. In the first half of 2000, the company is net income amounted to three billion Swiss francs. It invested 1.9 billion CHF in research and development.
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, 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.
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