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Supplemental Biologics License Application for Tositumomab Regimen Filed
Corixa has requested approval for BEXXAR's expanded use in treatment of patients with relapsed or refractory low grade, follicular, or transformed CD20 positive non-Hodgkin's lymphoma, whose disease has relapsed following chemotherapy. The BEXXAR therapeutic regimen is currently indicated for the treatment of patients with CD20 positive, follicular, non-Hodgkin's lymphoma, with and without transformation, whose disease is refractory to the antibody treatment Rituximab and has relapsed following chemotherapy.
In January 2004, Corixa and the FDA reached mutual agreement regarding the contents of the supplemental BLA submission as required by the Agency for review.
Determination of the effectiveness of the BEXXAR therapeutic regimen in patients with relapsed or refractory non-Hodgkin's lymphoma will be based on duration of response. The request for expanded use is based on a multicenter, single-arm, open-label study of 60 chemotherapy refractory patients. Patients enrolled had not responded to prior therapy or had responded with a duration of response of less than or equal to six months. The median number of prior chemotherapy regimens was four, ranging from two to 13. The primary endpoint for this study was a comparison of the number of patients with a longer duration of response (greater than 30 days) following the BEXXAR therapeutic regimen to the number of patients with a longer duration of response following their last qualifying chemotherapy regimen. The results were confirmed by an independent panel.
Twenty-six patients had a longer duration of response following the BEXXAR therapeutic regimen while only five had a longer duration of response following their last qualifying chemotherapy regimen (p less than 0.001). Secondary endpoints included response rate and duration of response.
"We are pleased to submit this supplemental BLA in support of BEXXAR's expanded use in chemotherapy relapsed and refractory NHL patients," said Steven Gillis, Ph.D., chairman and chief executive officer of Corixa. "We look forward to the agency's review of this filing."
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 pre-determined amount of radiation to each patient.
The BEXXAR therapeutic regimen has been studied for over 13 years. In a multi-center, single-arm, clinical trial in patients who had received an average of four prior chemotherapies and who had Rituximab-refractory disease (N=35), 63 percent (22 of 35) responded to BEXXAR. The median duration of response was 25 months. The results of this study were supported by demonstration of durable objective responses in four single-arm studies enrolling 190 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. Determination of clinical benefit of the BEXXAR therapeutic regimen was based on evidence of durable responses without evidence of an effect on survival.
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.
BEXXAR may not be for everyone. Patients who are pregnant or allergic to any components of the regimen should not receive BEXXAR. Treatment with BEXXAR resulted in very low blood counts in the majority of patients, which could be serious, for an extended period of time (about a month). Infections occurred in almost half the patients, bleeding in one of eight patients, and treatment with supportive care in about one of four patients. Allergic reactions, including anaphylaxis, which may be severe, have occurred in patients receiving BEXXAR. Other less severe reactions during or following the infusion have included fever, chills, sweating, nausea, low blood pressure, shortness of breath and trouble 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. Thirty-two cases (3.2 percent) of myelodysplastic syndrome (a type of pre-leukemia) and/or leukemia and 52 cases of secondary tumors were reported in 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 is co-marketed in the United States by Corixa Corporation and GlaxoSmithKline. Additional information about the BEXXAR therapeutic regimen, including complete prescribing information, may be obtained by calling 1-877-4BEXXAR or visiting www.BEXXAR.com.
Source: Corixa Corporation