Monday, Dec 9, 2002
Philadelphia -- December 9, 2002 --Genentech (NYSE: DNA) and IDEC Pharmaceuticals Corporation (Nasdaq: IDPH) today announced results from an investigational, randomized, multi-center study of extended Rituxan® (MabThera®/Rituximab) therapy in patients with indolent non-Hodgkin’s lymphoma (NHL). The study results demonstrated that extended single-agent Rituxan therapy (eight Rituxan doses over a nine month period) reduced the risk of disease progression or relapse by 55 percent for responding patients and nearly doubled event-free survival for chemotherapy-naïve (front-line) indolent NHL patients. The study was presented at the 44th Annual American Society of Hematology (ASH) meeting.
“As demonstrated by the nearly 200 abstracts related to Rituxan at ASH, significant data continue to emerge highlighting Rituxan’s important potential role in the treatment of patients with non-Hodgkin’s lymphoma,” said Gwen Fyfe, M.D., Genentech’s Vice President, Oncology, Medical Affairs. “For previously-untreated patients with indolent NHL, the potential ability of additional doses of Rituxan to extend disease-and treatment-free survival by as much as 17 months is especially noteworthy.”
Extended Therapy with Single Agent Rituxan [Abstract #604, Dec. 9 at 3:30pm]
Professor Michele Ghielmini from the Swiss Group for Clinical Cancer Research (SAKK) discussed data from the extended therapy single agent Rituxan study in an oral presentation.
The study enrolled 202 patients of which 185 patients were eligible for evaluation. At the time of study entry, 57 patients had received no prior therapy and 128 patients had received some form of prior chemotherapy for their NHL. All patients received an induction course of Rituxan (375mg/m2 weekly for 4 weeks). The overall response rate to induction therapy was 67 percent (38/57 patients) for chemotherapy-naïve patients and 46 percent (59/128) for those with relapsed disease.
At week 12, 80 percent (151/185) of patients achieved either a complete response (CR), a partial response (PR) or stable disease from the initial course of Rituxan therapy. These patients were then randomized to receive either extended therapy with Rituxan (N=73) (one dose 375mg/m2 at months 3,5,7,9 for a total of four additional doses) or were observed and did not receive further Rituxan treatment (n=78). (A CR is defined by disappearance of all signs of cancer and a PR is defined as a decrease in tumor size of more than 50 percent).
After a median of 35 months follow-up, the primary endpoint of event-free survival was a median of 23 months in patients who received extended Rituxan therapy compared to 12 months for patients who did not receive extended therapy and were observed. The difference in event-free survival was greater in chemotherapy-naïve patients than previously-treated patients. Event-free survival for the chemotherapy-naïve patients receiving extended Rituxan therapy was 36 months compared to 19 months for patients who were observed. For responding patients at week 12, 56 percent of patients in the observation arm and 80 percent of patients who received extended Rituxan therapy were in remission one year after initiation of the study. (Event-free survival is defined as ongoing survival without events including disease progression or relapse, death or initiation of new alternative treatment).
According to the authors, there was no clinically significant increase in adverse events or infections for patients receiving extended Rituxan therapy compared to the observation control arm. Adverse events in this study were similar to those seen in the pivotal trial of Rituxan (see Rituxan safety information below).
Larger, randomized, Phase III studies of extended or maintenance Rituxan therapy are currently being conducted by the U.S. Cooperative Cancer Study Groups. These clinical trials are evaluating the safety and efficacy of additional Rituxan therapy (four doses every six months for two years) following completion of standard induction therapy in both patients with indolent and aggressive NHL.
Long-Term Follow-Up of Rituxan plus Chemotherapy in Aggressive NHL [Abstract #1396, Dec. 7 at 6:00pm]
A poster presentation, Julie Vose, M.D., of the University of Nebraska, Omaha, NE, presented five-year follow-up data from a Phase II study of Rituxan plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy in aggressive front-line NHL. Patients received six cycles of both Rituxan (375 mg/m2) and CHOP.
The initial analysis reported a 97 percent (32/33) overall response rate, with 61 percent (20/33) of patients experiencing a complete response and 36 percent (12/33) having a partial response to therapy. At 26 months median follow-up, 91 percent (30/33) were alive and 88 percent (29/33) were free of disease progression.
With more than five years of follow-up (62+ months), patients continue to do well with 88 percent (29/33) alive and 81 percent (27/33) of patients free from disease progression.
“This study adds to the growing body of investigational data evaluating Rituxan with CHOP chemotherapy in previously-untreated patients demonstrating the potential ability to provide durable long-term remissions in both aggressive and indolent NHL,” continued Dr. Fyfe. “Of importance to responding patients in the Phase II study, the extended remission was achieved without any observed long-term adverse events.”
Adverse events of Rituxan plus CHOP were similar to those observed with CHOP chemotherapy alone. Hematologic toxicity included Grade III and IV neutropenia. Neutropenic fever and dehydration were the most common causes of hospitalization. No long-term adverse events were reported for the Rituxan/CHOP combination.
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 and are 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 therapeutic 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 is indicated as a single-agent treatment for relapsed or refractory low-grade or follicular, CD20 positive, B-cell NHL. MabThera, in combination with CHOP chemotherapy, received European approval to treat aggressive NHL in March 2002. More than 300,000 patients have been treated with Rituxan worldwide.
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 by Roche and Zenyaku Kogyo Co. Ltd.
About Non-Hodgkin's Lymphoma
There are more than 250,000 people in the United States and a total of almost 1.5 million people around the world with NHL. Approximately 50 percent have indolent 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.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Fifteen of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes ten 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.
Roche is the world leader in oncology. Its portfolio includes three drugs with survival benefit: MabThera® (Rituximab), Xeloda® (capecitabine) and Herceptin® (Trastuzumab). It also includes NeoRecormon® (epoetin beta), Roferon®-A (interferon alfa-2a), Neupogen® (filgrastim) and Kytril® (granisetron HCl). Roche Oncology has four research sites (two in the U.S., Germany and Japan) and four HQ development sites (two in the U.S., UK and Switzerland).
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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