Washington Editor

After a difficult journey through the FDA's regulatory process, Corixa Corp. and partner GlaxoSmithKline plc Monday received approval for Bexxar, a radioimmunotherapy for the treatment of patients with non-Hodgkin's lymphoma.

Specifically, the FDA approved Bexxar (tositumomab and iodine-131 tositumomab) as a treatment for patients with CD20-positive, follicular, non-Hodgkin's lymphoma, with and without transformation, whose disease is refractory to Rituxan and has relapsed following chemotherapy.

"Bexxar offers patients a more benign toxicity profile and much longer duration of response," said Thomas Dietz, managing director with Pacific Growth Equities in San Francisco. "It is going to be positioned against high-dosed chemo, certainly against Zevalin. But right now Bexxar looks like it has a better safety profile and a better efficacy profile than Zevalin." (Zevalin is San Diego-based IDEC Pharmaceuticals Inc.'s treatment for non-Hodgkin's lymphoma, while Rituxan is South San Francisco-based Genentech Inc.'s product for the same disease.)

The launch is expected within 30 days, Steven Gillis, Corixa's chairman and CEO, told BioWorld Today. "Not many people get across the goal line - it's nice to do it," he said.

Regulatory approval triggers a milestone payment from GSK, said Gillis, who would not release the amount of the payment. In total, he said, GSK has invested about $100 million in Bexxar's development.

Both companies gained interest in Bexxar via buyouts or mergers. Corixa, of Seattle, got its hands on the product in 2000 when it took over San Francisco-based Coulter Pharmaceuticals Inc. in a stock swap. At the time of the deal, Coulter was partnered with SmithKline Beecham plc, which later merged with Glaxo. (See BioWorld Today, Oct. 17, 2000.)

GSK will be responsible for U.S. sales of Bexxar in its first 18 months on the market, while Corixa begins building its sales team, Gillis said. The companies have a 50-50 partnership.

Gillis wouldn't discuss specifics about the cost of Bexxar, simply saying the price would be comparable to similar products.

But, a research note released by Dietz said the Rituxan/chemotherapy refractory market opportunity for Bexxar is estimated at $500 million. Dietz believes Bexxar has the potential for use as a first-line therapy.

Corixa's printed material describes Bexxar as a dual-action therapy that pairs the tumor-targeting of a cytotoxic (cancer killing) monoclonal antibody (tositumomab) and the therapeutic potential of radiation (iodine-131) with patient-specific dosing. Combined, they form a radiolabeled monoclonal antibody that is able to bind to the target antigen CD20 found on NHL cells, thereby initiating an immune response against the cancer and delivering a dose of radiation directly to tumor cells.

Bexxar's efficacy was studied in a multicenter, single-arm study of 40 patients with follicular NHL whose disease had relapsed or had not responded to Rituxan.

"A certain percentage of patients didn't respond in the efficacy population that we presented to ODAC [Oncology Drugs Advisory Committee]," Gillis said. "One way to look at all the data is that if I get Bexxar, what is my chance of having a response that lasts for five years or more? That number was about one in four. If you actually were one of the patients who had a complete response, which means 100 percent elimination of tumor, what's the chance that that response is going to last five years or more? That was about a 60 percent chance."

Eighty-eight percent of patients in the study met the definition of being refractory to Rituxan. Sixty-three percent of those patients had a response to Bexxar, with a median duration of response of 25 months. Twenty-nine percent of patients had a complete response. The median duration of complete responses has not been reached after a median follow-up of 26 months, the company said in a prepared statement.

The most common adverse events were neutropenia, thrombocytopenia and anemia that can be prolonged and severe.

ODAC reviewed the application in December, agreeing unanimously that Bexxar proved beneficial in chemotherapy-refractory patients with low-grade and follicular NHL. In a separate vote, the panel agreed 10-3 that there was substantial evidence of clinical benefit in patients with rituximab-refractory follicular NHL. (See BioWorld Today, Dec. 18, 2002.)

Winning support from ODAC was quite a coup considering the hurdles Corixa had jumped to get to the panel. Corixa filed a dispute resolution in May 2002 against an FDA decision requiring additional studies before Bexxar could be approved. The company dropped the dispute months later when the agency returned the Bexxar biologics license application back to active status and agreed to call an ODAC panel. (See BioWorld Today, Dec. 4, 2000, and March 12, 2002.)

The agency issued conventional approval on the monoclonal antibody, meaning success in Phase IV studies comparing Bexxar and Zevalin, or Bexxar and Rituxan, is not necessary to remain on the market, Dietz told BioWorld Today.

Corixa's stock (NASDAQ:CRXA) closed Monday at $7.74, up 54 cents, or 7.5 percent.