Corixa Corporation and GlaxoSmithKline announced that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) agreed that studies of the investigational radioimmunotherapy Bexxar (tositumomab and iodine I 131 tositumomab) provided substantial evidence of clinical benefit in both rituximab-refractory patients and in chemotherapy-refractory, low-grade and follicular non-Hodgkin's lymphoma (NHL), with or without transformation. The panel voted 10-3 in support of the efficacy of Bexxar therapy in rituximab-refractory patients and unanimously supported its clinical utility in chemotherapy-relapsed and refractory, low-grade NHL, with or without transformation. Bexxar therapy is being co-developed in the United States by Corixa and GlaxoSmithKline.
The FDA is not bound by the Committee's action, but often takes its recommendations into consideration when determining marketing approval of a new product. The new Prescription Drug User Fee Act (PDUFA) goal date for the FDA to complete its review of all materials regarding Bexxar therapy is May 2, 2003.
"We are very pleased to have the endorsement of ODAC on the clinical benefit demonstrated by Bexxar therapy in our clinical trials," said Steven Gillis, chairman and chief executive officer of Corixa Corporation. "These positive panel votes validate many years of hard work by dedicated researchers and move us closer to being able to provide an important treatment option for physicians and their patients with low-grade non-Hodgkin's lymphoma."
"The compelling testimony provided by several patients who have battled NHL highlights the need for new treatment alternatives," said Kevin Lokay, vice president of Oncology at GlaxoSmithKline. "We look forward to continuing to work with Corixa and the FDA to complete the regulatory process and make Bexxar therapy available to appropriate patients as soon as possible."
"Clinical trial results with Bexxar therapy demonstrate that patients with relapsed or refractory low-grade NHL, even those who have been heavily pretreated, can achieve durable complete responses," explained Richard I. Fisher, director, James P. Wilmot Cancer Center, University of Rochester. "A therapy that can produce complete remissions that last more than a year, and in some cases as long as 8 years, after a single treatment would be a significant addition to our arsenal against the most aggressive forms of NHL."
The committee reached its conclusions following presentations from Corixa and the FDA regarding the safety and efficacy of Bexxar therapy from a number of clinical trials, including studies that examined the effects of Bexxar therapy on duration of clinical response in multiple relapsed, chemotherapy-refractory patients. Data were also presented from a randomized clinical trial comparing the efficacy of Bexxar vs. the non-radiolabeled antibody present in the product. In addition, data were presented from a study of Bexxar safety and efficacy in rituximab-failure patients. Bexxar therapy resulted in a high level of durable responses across multiple clinical studies.
According to research presented to the Committee in the public meeting, 30 percent of the 250 patients evaluated in 5 clinical trials had a durable response to Bexxar therapy with a time to progression of a year or more. These patients had a median time to disease progression of approximately 5 years, with some patients showing no signs of disease progression at up to 8 years.
The panel voted unanimously that the overall response rates and durations of responses observed across the 5 clinical trials conducted with BEXXAR therapy, in light of the toxicity profile observed, were likely to predict clinical benefit in patients with chemotherapy-refractory, low-grade and follicular NHL, with or without transformation. The majority of panel members (10 to 3) agreed that the results from a trial in Rituxan-refractory patients, plus data from other clinical trials, constituted substantial evidence of clinical benefit. The panel also made recommendations to the FDA about the designs of post-approval clinical trials already agreed to by Corixa.