Reports of Durable, Objective Responses
Analysis of data on 582 patients with relapsed, refractory low-grade or transformed low-grade NHL who received Bexxar in clinical trials from 1990-2000, by John Leonard, M.D., clinical director, Center for Lymphoma and Myeloma, Weill Medical College of Cornell University, New York, and his colleagues, showed that Bexxar produced an overall response (defined as a reduction of at least 50 percent in overall tumor burden) in 57 percent of patients, half of whom remained in remission for 14.3 months or more [ASH Abstract #2527]. Furthermore, 28 percent of all patients showed a complete response (total elimination of disease confirmed by clinical or radiological evaluation) to Bexxar therapy, half of whom remained in remission for 4.8 years or longer. The average follow-up was 1.3 years with a maximum of 8.5 years.
"These results provide further evidence that Bexxar produces durable responses in patients with either low-grade or transformed low-grade NHL," said Dr. Leonard.
Novel First-Line Triple Modality Therapy
To evaluate a new approach to previously untreated NHL, investigators treated 35 patients in a clinical trial of "triple modality" therapy, the combination of chemotherapy (fludarabine), radiation (Iodine-131) and a monoclonal antibody (tositumomab) [ASH Abstract #3505]. All patients (100 percent) in the trial exhibited an investigator-assessed response to the treatment, with 77 percent achieving a complete response. After a median of 23 months of follow-up, more than half of the patients were showing no signs of disease progression.
"We are encouraged by the results of this study and the apparent utility of this triple modality approach using fludarabine and Bexxar radioimmunotherapy," said Dr. Leonard. "Combination regimens have been successful in many cancers and offer new strategies for patients with lymphoma." The triple modality regimen consisted of three cycles of fludarabine followed by Bexxar, administered six to eight weeks later, for patients with previously untreated low-grade NHL. Ninety-seven percent of the participants were classified as stage III (widespread disease to both sides of the diaphragm), or stage IV (spread outside of the lymph system to one or more organs and the bone marrow). The patient population ranged in age from 25 to 82. The hematologic side effects of the triple modality therapy were principally decreases in white blood cell counts that responded to supportive care. Three patients were hospitalized for neutropenic fever (one after fludarabine and two after fludarabine and Bexxar).
"This novel approach produces a high response rate in initial therapy for low-grade non-Hodgkin's lymphoma," concluded Dr. Leonard. "We have also found that by using fludarabine to debulk or reduce a patient's tumor burden, including tumor in the bone marrow, we can expand the number of patients who can benefit from Bexxar therapy."
Triple modality therapy, combining various chemotherapies with Bexxar, is being investigated for the treatment of other types of non-Hodgkin's lymphoma. Results from one such study, a Phase II clinical trial of CHOP, a standard combination chemotherapy regimen, followed by Bexxar, for treatment of newly diagnosed follicular NHL, were also reported at ASH by researchers affiliated with the Southwestern Oncology Group (SWOG) [ASH Abstract #3504]. In this study, 80 percent of the 71 patients evaluated following the sequential therapy had achieved an objective remission, either having a complete response (52 percent) or a partial response (28 percent). Grade 4 toxicities were reported in 38 percent of the 88 evaluable patients who had received CHOP. Thirteen percent of 60 presently evaluable patients who went on to receive Bexxar experienced additional Grade 4 toxicity. In 17 patients (24 percent), the addition of Bexxar to CHOP improved the overall best response, either from a partial to a complete response (15 patients or 21 percent) or from an unconfirmed to a confirmed complete response (2 patients or 3 percent). The investigators reported that "the addition of I-131-tositumomab [Bexxar] radioimmunotherapy to 6 cycles of CHOP chemotherapy is feasible, well-tolerated and efficacious."
Importance of Radiation Component of Bexxar Therapy Demonstrated
Investigators also presented data that clearly demonstrated the clinical utility of the radioactive component in Bexxar [ASH Abstract #3503]. This study, a randomized, open label, multicenter clinical trial of 78 patients treated at nine sites investigated the safety and efficacy of treatment with either Bexxar or its unlabeled antibody component, tositumomab. Seventeen percent of patients enrolled in this trial presented with transformed disease, a particularly difficult prognostic factor with respect to survival and response. Independently assessed confirmed overall responses were observed in 55 percent of the patients treated with Bexxar and 17 percent of patients treated with two doses of tositumomab. Confirmed complete responses were achieved in 33 percent of patients treated with Bexxar compared to 8 percent of patients treated with tositumomab. The median duration of confirmed responses for patients treated with Bexxar has not been reached, whereas half of the patients treated with unlabeled tositumomab had relapsed after 18 months. The study allowed patients who did not respond or who relapsed after unlabeled tositumomab to crossover to receive Bexxar. Of the 19 patients who did so, 68 percent had a confirmed response and 42 percent had a confirmed completed response.
"We have demonstrated that radiolabeling with I-131 provides significant therapeutic benefits over an unlabeled anti CD-20 antibody," said Mark S. Kaminski, M.D., professor of internal medicine and co-director of the leukemia/lymphoma bone marrow transplant program at the University of Michigan Cancer Center.
Hematologic toxicity was observed in a greater number of Bexxar patients than tositumomab patients. "In our assessment, the greater therapeutic activity of Bexxar outweighed the lower toxicity observed for the unlabeled antibody," said Dr. Kaminski.
Overall Bexxar Hematological Toxicity Reported
Dr. Kaminski also presented an analysis of hematologic toxicity following treatment with Bexxar based on data from 677 previously treated patients with relapsed or refractory low-grade NHL and 76 previously untreated patients [ASH Abstract #1433]. He and his colleagues found that Grade 4 neutropenia, anemia, and thrombocytopenia occurred in 16 percent, 2 percent, and 3 percent of patients respectively, with serious infections reported in 5 percent and Grade 3 or 4 bleeding events in only 1 percent. Twenty-three percent of these previously treated patients required some form of supportive care (such as growth factors or transfusions) for hematologic side effects. Hematologic toxicity was less frequent in previously untreated patients. No patients in this cohort exhibited hematologic toxicity that required treatment with either growth factors or transfusions. The researchers concluded that the hematologic side effects in patients who received Bexxar were manageable and reversible, and the use of supportive care was uncommon.
"Furthermore, because Bexxar therapy is administered as a single course of treatment, it avoids the repeated and cumulative treatment related toxicity that may result from successive cycles of standard chemotherapy," said Dr. Kaminski.
Non-Hodgkin's Lymphoma
Non-Hodgkin's lymphoma is a form of cancer that affects the blood, bone marrow and lymphatic tissues. NHL currently is the sixth leading cause of death among cancers in the United States and has the second fastest growing mortality rate. According to statistics from the National Cancer Institute (NCI), approximately 300,000 people are afflicted with NHL in the United States alone. Of that total, the NCI estimates that approximately 140,000 people have low-grade NHL or transformed low-grade NHL, an aggressive, difficult to treat, and particularly deadly form of the disease. Typically, the response rates and duration of response for NHL patients decline with each subsequent course of chemotherapy. Bexxar therapy combines the targeting ability of a monoclonal antibody and the therapeutic potential of radiation, with patient-specific dosing. The radiolabeled monoclonal antibody attaches to the target molecule CD20 found on NHL cells, thereby mediating an immune response and delivering a dose of Iodine-131 radiation to tumor cells. Bexxar is the only investigational NHL therapy that is precisely dosed based on individual drug clearance rates, resulting from such factors as tumor size and metabolism. Patient-specific dosing allows for a predictable level of therapeutic radiation to be delivered to each patient and may enhance the tolerability of the treatment.
About Corixa
Corixa (Nasdaq: CRXA) is a developer of immunotherapeutics with a commitment to treating and preventing autoimmune diseases, cancer and infectious diseases by understanding and directing the immune system. Corixa is focused on immunotherapeutic products and has a broad technology platform enabling both fully integrated vaccine design and the use of its separate, proprietary product components on a stand-alone basis. Corixa currently has 16 programs in clinical development and 22 programs in preclinical development, including its most advanced product candidate, Bexxar therapy, a monoclonal antibody conjugated to a radioisotope. The company partners with numerous developers and marketers of pharmaceuticals, targeting products that are Powered by Corixa™ technology with the goal of making its potential products available to patients around the world. Corixa was founded in 1994 and is headquartered in Seattle, Washington, with additional operations in Hamilton, Montana and South San Francisco, California. For more information, please visit Corixa's Website at www.corixa.com or call the company's investor relations information line at 1.877.4CORIXA or 1.877.426.7492.
About GlaxoSmithKline
GlaxoSmithKline (NYSE: GSK)-- one of the world's leading research-based pharmaceutical and healthcare companies-- is committed to improving the quality of human life by enabling people to do more, feel better and live longer.
GlaxoSmithKline is committed to the research, development, manufacturing and marketing of therapeutic and supportive care products for hematology and oncology patients. Currently, GlaxoSmithKline Oncology markets Zofran® (ondansetron HCl), Hycamtin® (topotecan hydrochloride), Navelbine® (vinorelbine tartrate) Injection, Argatroban Injection, Alkeran® (melphalan), Leukeran® (chlorambucil), Compazine® (prochlorperazine), Purinethol® (mercaptopurine), Myleran® (busulfan), and Thioguanine. GlaxoSmithKline Oncology has novel agents in late-stage development, including a radioimmunotherapy Bexxar. For company information, visit GlaxoSmithKline on the World Wide Web at www.gsk.com.
Corixa Forward-Looking Statement
Except for the historical information presented, certain matters discussed in this press release are forward-looking statements. Forward-looking statements are based on the opinions and estimates of management at the time the statements are made. They are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Factors that could affect Corixa's actual results include, but are not limited to, failure of the FDA to approve Bexxar for commercial sale and the "Factors Affecting Our Operating Results, Our Business and Our Stock Price," described in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2001, copies of which are available from our investor relations department. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release.
GlaxoSmithKline Forward-Looking Statement Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the Company cautions investors that any forward-looking statements or projections made by the Company, including those made in this Announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under Risk Factors in the Operating and Financial Review and Prospects in the Company's Annual Report on Form 20-F for 2000, filed with the US Securities and Exchange Commission.
Research Presented at ASH