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FDA Approves Expanded Indication for the Bexxar Therapeutic Regimen

GlaxoSmithKline today announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental Biologics License Application (sBLA) for expanded use of the BEXXAR® Therapeutic Regimen (Tositumomab and Iodine I 131 Tositumomab).

The BEXXAR Therapeutic Regimen is now indicated for the treatment of patients with CD 20 antigen expressing relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin's lymphoma, including patients with Rituximab-refractory non-Hodgkin's lymphoma. The original indication specified that patients have disease that was refractory to Rituximab and had relapsed following chemotherapy. Determination of the effectiveness of the BEXXAR Therapeutic Regimen was based on overall response rates in patients whose disease is refractory to chemotherapy alone or to chemotherapy and Rituximab. The effects of the BEXXAR Therapeutic Regimen on survival are not known. The BEXXAR Therapeutic Regimen is not indicated for the initial treatment of patients with CD20 positive non-Hodgkin's lymphoma. The BEXXAR Therapeutic Regimen is intended as a single course of treatment. The safety of multiple courses of the BEXXAR Therapeutic Regimen, or combination of this regimen with other forms of irradiation or chemotherapy, has not been evaluated.

The sBLA was filed on July 1, 2004, and it was granted priority review status. The expanded indication will make BEXXAR an earlier option for patients with relapsed low-grade or follicular non-Hodgkin's lymphoma.

"We are pleased that the FDA has moved so quickly to make BEXXAR available to a larger group of patients," said Kevin Lokay, vice president of Oncology and Acute Care at GlaxoSmithKline. "This expanded indication establishes BEXXAR as an important alternative for initial treatment of relapsed disease. We've worked with cancer treatment centers across the country to ensure that the BEXXAR Therapeutic Regimen is widely available. Now clinicians will be able to offer the potential benefits of BEXXAR earlier in the treatment course for their patients with non-Hodgkin's lymphoma, and not have to wait for their disease to become refractory."

The sBLA was based on a multicenter, single-arm, open-label study of 60 chemotherapy refractory patients. The median age of study participants was 60 (range 38-82), the median time from diagnosis to protocol entry was 53 months (range 9-334), and the median number of prior chemotherapy regimens was 4 (range 2-13). Fifty-three patients had not responded to prior therapy and 7 patients had responded with a duration of response of less than 6 months. As determined by an independent panel that reviewed patient records and radiologic studies, the overall response rate for BEXXAR in this study was 47 percent (95% C.I. {95% confidence interval} = 34 to 60 percent), with a median duration of response of 12 months (range 2 to 47; 95% C.I. = 7 to 47) and the complete response rate was 20 percent (95% C.I. = 11 to 32 percent), with the median duration of response of 47 months (range 9 to 47; 95% C.I. = 47 to Not Reached) after a median follow-up of 30 months.

About the BEXXAR Therapeutic Regimen
BEXXAR pairs the targeting ability of a monoclonal antibody (Tositumomab) and the therapeutic potential of radiation (Iodine-131). Combined, these agents form a radiolabeled monoclonal antibody regimen that is able to bind to the target antigen CD20 found on B cells, including normal cells and those that become cancerous in non-Hodgkin's lymphoma, thereby delivering the dose of radiation. BEXXAR, which is given in four visits over one to two weeks, is specifically dosed based on an individual's drug clearance rate, allowing the delivery of a predetermined amount of radiation to each patient.

The BEXXAR Therapeutic Regimen has been studied for more than 13 years. It was originally approved based on a multicenter, single-arm, clinical trial in 40 patients who had received a median of four prior chemotherapies and whose disease had not responded to or had progressed after at least 4 doses of Rituximab. In this study, 68 percent (95% C.I. = 51 to 81 percent) responded to BEXXAR. The median duration of response was 16 months (range 1 to 38; 95% C.I. = 10 to Not Reached).

The results of these two studies were supported by demonstration of durable objective responses in three single-arm studies enrolling 130 patients evaluable for efficacy with Rituximab-naive, follicular non-Hodgkin's lymphoma, with or without transformation, who had relapsed following or were refractory to chemotherapy.

BEXXAR is not for everyone. Patients who are pregnant or allergic to any components of the regimen should not receive BEXXAR. Serious hypersensitivity reactions, including some with fatal outcome, have been observed with the BEXXAR Therapeutic Regimen. Treatment with BEXXAR resulted in very severe decreases in blood counts (platelets, white blood cells, and red blood cells) in the majority of patients, which could be life-threatening, for an extended period of time (about a month). In up to 7 of 100 patients, these decreases persisted for more than 90 days. Infections occurred in almost half the patients, bleeding in one of eight patients, and treatment with supportive care in about one of four patients. Other less severe reactions during or following the infusion have included fever, chills, sweating, nausea, low blood pressure, shortness of breath and difficulty breathing. Patients may also experience weakness, fever, nausea, increased cough, infection, pain, chills, rash or headache. There is a risk of hypothyroidism following the administration of BEXXAR. Administration of BEXXAR resulted in the development of antibodies to the mouse antibody (called HAMA). Certain cancer therapies including BEXXAR have been associated with the development of a second type of blood cancer and solid tumors. At a median follow-up of 29 months, forty-four cases of myelodysplastic syndrome (a type of pre-leukemia) and/or leukemia and 65 cases of secondary tumors in 54 patients were reported among the 995 patients enrolled in BEXXAR studies. After being treated with BEXXAR, less than five percent of patients suffered hair loss or developed severe nausea, vomiting or mucositis (sores in the mouth or gastrointestinal tract). Healthcare providers must be specifically trained to administer BEXXAR.

BEXXAR was developed by Corixa Corporation and introduced under a collaboration agreement with GSK. On December 31, 2004, GSK assumed full worldwide rights and responsibilities for manufacturing, clinical development and commercialization of the BEXXAR Therapeutic Regimen from Corixa Corporation.

Additional information about the BEXXAR Therapeutic Regimen, including complete prescribing information, may be obtained by calling (877) 423-9927 (4BEXXAR) or visiting http://www.bexxar.com/.

Source: GlaxoSmithKline

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