By Karen Pihl-Carey

About eight months after the FDA asked for a modified biologics license application (BLA) for Bexxar, SmithKline Beecham plc (SKB) returned to Coulter Pharmaceutical Inc. all development and commercialization rights to the product outside the U.S.

Philadelphia-based SKB, however, intends to continue contributing to the U.S. development and potential commercialization of the product. Bexxar is a treatment for relapsed or refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphoma.

While Coulter viewed the news as positive because it gives the South San Francisco-based company the opportunity for full profits rather than royalties on Bexxar sold outside the U.S., the investment community responded negatively. Coulter's stock (NASDAQ:CLTR) fell 16 percent, or $3.43, on Tuesday, to close at $17.562.

"We're actually quite excited about it," said Michael Bigham, Coulter's CEO and president. "I know it's a dicey market out there. People don't always react the way you want them to. But we're very excited."

Bigham said SKB's interest in the smaller European market may have changed with SKB's proposed merger with London-based Glaxo Wellcome plc.

"With the merger between SmithKline and Glaxo creating the world's largest pharmaceutical company, I think SmithKline reassessed the market opportunity in Europe and engaged in conversations with us, asking whether we'd like to do it ourselves there," Bigham told BioWorld Today.

Coulter decided to reacquire the rights, which will give the company full profits from a European market, as opposed to a small royalty, Bigham said. The reacquisition will be effective on June 30. Coulter plans to directly market Bexxar in Europe upon approval to specialized centers. It may seek partners in specific countries. A regulatory filing in Europe is expected about a year after the resubmission of a BLA in the U.S. The review period in Europe then could take another 12 to 18 months.

"It's really a long-term strategic investment for us to establish profitability in Europe with a drug we believe in," Bigham said.

Coulter and SKB also expanded their collaboration in the U.S. in which Coulter's sales force will assist SKB's sales and marketing team with the promotion of SKB's oncology drugs, Hycamtin (topotecan hydrochloride) and Kytril (granisetron hydrochloride), for a period of time prior to the commercial launch of Bexxar. SKB intends to compensate Coulter in its promotion of the two SKB products.

Last summer, Coulter and SKB filed a BLA for Bexxar. The companies were expecting approval by the end of 1999, and analysts expected sales to be in the $400 million range within three to five years. (See BioWorld Today, July 1, 1999, p. 1.)

But in late August, the FDA requested that the companies modify the BLA. The FDA wanted an easier database access, the clarification of a computer glitch and a reorganization of the analysis. It did not request any additional data. (See BioWorld Today, Aug. 31, 1999, p. 1.)

"We are still working diligently toward resolving the issues the FDA raised last summer, and we are making very good progress," Bigham said. He would not estimate when the BLA will be resubmitted.

Coulter and SKB entered into a $132 million deal in December 1998. SKB paid $41.5 million up front and extended a $15 million line of credit to Coulter. The deal specified that the companies would equally share profits in the U.S., with Coulter receiving royalties from sales elsewhere. SKB held exclusive marketing and distribution rights throughout the world except the U.S. and Japan. (See BioWorld Today, Dec. 7, 1998, p. 1.)

Under the original agreement, SKB was covering slightly higher portions of the development costs at clinical sites outside the U.S., but the two companies now will split those costs evenly. And while SKB covered the costs for trials solely for European purposes, Coulter now assumes 100 percent of those costs.

Bexxar is an antibody specific to the CD20 antigen on B cells conjugated to radioactive iodine-131. It attaches to a protein found only on the surface of B cells, including non-Hodgkin's lymphoma B cells.

Non-Hodgkin's lymphoma is a form of cancer that affects the blood and lymphatic tissues. It is the sixth leading cause of death among cancers in the U.S. and has the second fastest growing mortality rate. About 300,000 people in the U.S. suffer from the disease.