Monday, Dec 10, 2001
Orlando, Fla. -- December 10, 2001 --Genentech, Inc. (NYSE: DNA), IDEC Pharmaceuticals Corporation (Nasdaq: IDPH) and Roche today announced that data from two studies evaluating the combination of the monoclonal antibody Rituxan®/MabThera® (Rituximab) with standard CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy indicated initial positive survival results in patients with aggressive and indolent (low grade) non-Hodgkin's lymphoma (NHL). The results were presented today at the annual meeting of the American Society of Hematology (ASH).
At a median of 24 months follow-up, the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Phase III study demonstrated a 23 percent relative increase in overall survival in patients with aggressive NHL treated with Rituxan and CHOP as compared to CHOP alone. In a Phase II indolent NHL study with Rituxan and CHOP, 100 percent (40/40 patients) of patients enrolled in the study responded to the combination therapy and 60 percent (21/35) of these patients have been in remission for at least four and up to seven years.
"The use of front-line Rituxan with chemotherapy in patients with NHL is producing significant results," said Susan D. Hellmann, M.D., M.P.H., executive vice president, Development and Product Operations, and chief medical officer. "The data from both studies suggests a survival benefit and the potentially synergistic effect of combining Rituxan, a targeted antibody, with standard chemotherapy. We are most encouraged with the data showing the addition of Rituxan appeared to improve upon standard CHOP chemotherapy in aggressive NHL and the majority of patients with indolent NHL that were treated with Rituxan and CHOP are free of disease five years after undergoing their initial treatment."
Rituxan Safety Profile
The majority of patient 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.
GELA Phase III Trial Update – Aggressive NHL in the Elderly (Abstract #3025)
In this Phase III study, 399 previously-untreated patients (60 years or older) with aggressive NHL were randomized to receive either standard CHOP chemotherapy alone (every three weeks for eight cycles) or Rituxan (375 mg/m2) plus CHOP. Rituxan was administered on day one of each cycle for the combination patients.
A significant improvement was seen in 24 month event-free survival from 37 percent in the CHOP alone arm to 57 percent in the Rituxan/CHOP arm -- a relative increase of 53 percent. Event-free survival was defined as ongoing survival without events including disease progression or relapse, death or initiation of new alternative treatment.
At a median follow-up of 24 months, overall survival was increased from 57 percent in the CHOP alone arm to 70 percent in the Rituxan/CHOP arm, a relative increase of 23 percent. At 18-months, complete response rate (disappearance of all detectable signs of cancer) increased from 64 percent in the CHOP alone arm to 77 percent in the Rituxan/CHOP arm, a relative increase of 20 percent.
"This is the first new drug combination in more than 20 years to show an improvement in overall survival for patients with aggressive NHL, a rapidly fatal form of the disease," said Bertrand Coiffier, professor and head, Department of Hematology, Hospices Civils de Lyon, France and principal investigator.
Approximately 10 percent of patients in the Rituxan/CHOP arm experienced Grade 3/4 infusion-related events. 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. As has been seen in prior studies with Rituxan, these events were generally limited to the first infusion of Rituxan and were reversible. Beyond these first infusion events, the addition of Rituxan to CHOP chemotherapy did not appear to cause a clinically significant increase in adverse events to those seen with CHOP chemotherapy alone.
In October 2001, the European Committee for Proprietary Medicinal Products (CPMP) recommended approval in the European Union (EU) of Rituxan (MabThera) and CHOP for the treatment of aggressive NHL.
Rituxan in Combination with CHOP for Indolent NHL (Abstract #2519)
Results from follow-up of the first single arm Phase II clinical trial of Rituxan and CHOP, initiated in 1994, demonstrate positive response rates and prolonged progression free survival in patients with indolent NHL. The study found that the Rituxan/CHOP combination therapy achieved an overall response rate of 100 percent with 63 percent (25/40) of patients achieving complete responses (defined as disappearance of all detectable signs of cancer) and 37 percent (15/40) of patients achieving partial responses (defined as decrease in tumor size greater than 50 percent).
Median duration of response thus far is more than 5.3 years, with progression-free survival still not reached after more than 5.1 years. Sixty-percent (21/35) of patients enrolled in the trial still are in remission after 3.9 years and up to 7.1 years.
"The prolonged progression-free survival shown in this study is noteworthy, and provides important long-term efficacy and safety data for the Rituxan/CHOP combination," said Myron Czuczman, M.D., associate professor of medicine, Roswell Park Cancer Institute, Buffalo, NY and principal investigator of the study. "These results suggest that Rituxan may help sensitize cancer cells to chemotherapy, resulting in improved patient benefit without adding any significant toxicity."
Forty patients (21 males, 19 females) with low-grade or follicular NHL entered the study. CHOP was administered at standard doses during three weeks for six cycles along with six infusions of Rituxan. Two doses of Rituxan were given both at the beginning and end of therapy, as well as single doses before the third and fifth cycles of CHOP.
The addition of Rituxan to CHOP chemotherapy did not cause a clinically significant increase in adverse events compared to those seen with CHOP alone. Adverse events were mostly Grade 1 or 2. Seventeen percent of all events were Grade 3 or 4 and consisted primarily of hematologic or infectious toxicities that were believed to be associated with CHOP chemotherapy.
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 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.
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. 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.
About Genentech, IDEC and Roche
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.
Roche, 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 patient's well-being and quality of life.
Roche's oncology franchise includes three products with survival benefit: Xeloda (colorectal cancer, breast cancer), Herceptin (breast cancer), MabThera (non-Hodgkin's lymphoma).
For full prescribing information please call (650) 225-8681.
For more information, please visit http://www.rituxan.com.
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