By Mary Welch
Coulter Pharmaceutical Inc. reported positive results from a Phase III investigational trial of Bexxar in non-Hodgkin's lymphoma patients who no longer responded to chemotherapy.
Patients given Bexxar, a monoclonal antibody conjugated to iodine 131, achieved longer durations of remission when given the drug, as compared to their most recent chemotherapy treatment.
"Typically, patients do worse with each subsequent [chemotherapy] treatment," said Sylvia Wheeler, director of investor relations for Palo Alto, Calif.-based Coulter. "In other words, if they achieved remission duration of six months with their first round of chemotherapy, they tend to respond for maybe three to four months with the second round. So, to actually provide patients with longer durations of remission compared to their last chemotherapy suggests a reversal of the natural history of the disease."
Coulter has applied to the FDA for fast-track designation and intends to submit a biologics license application for Bexxar by year's end. The company will disclose detailed trial results in December at the American Society of Hematology meeting in Miami.
The primary endpoint in the 60-person trial was duration of response. Secondary endpoint was the overall response rate. "When you're talking about non-Hodgkin's lymphoma, it hard to talk about your typical endpoints," Wheeler said.
Bexxar, an anti-CD20 antibody, attaches to a protein found only on the surface of B cells, including non-Hodgkin's B cells and some normal B cells, in order to provide a greater concentration of therapeutic radiation to tumor cells.
In the intravenous antibody approach, a treatment to determine proper dosage is given, and about a week later, a therapeutic dose is administered. Conventional chemotherapy treatments are given repeatedly over several months. If approved, Bexxar would be the first radioimmunotherapy approved in the U.S. for cancer.
"We know how radiation can be effective, and by combining monoclonal antibodies with the power of radiation, it seems like we've got a great combination," Wheeler said.
Patients in the Phase III trial had received on average four previous regimens of chemotherapy, including salvage treatments, which are especially toxic. The 60 patients were refractory to chemotherapy, having either no response to prior chemotherapy or disease progression within six months following their last chemotherapy treatments.
Of that number, 32 experienced a longer duration of response to Bexxar as compared to chemotherapy, while only nine had a shorter response duration with Bexxar than chemotherapy. Nineteen patients had equivalent duration of response to both treatments.
"We prefer to focus on the patients who are doing better," Wheeler said, adding that the 19 who showed equivalent duration of response to Bexxar and chemotherapy "typically would have had less duration response with chemotherapy. So, again, that actually is an improvement of what they could have expected."
The secondary endpoint, overall response rate, was also significantly greater for Bexxar, with 67 percent of the patients responding to it compared to 28 percent responding to prior chemotherapy.
Among the side effects was a decrease in blood counts, which was reversible and generally self-limiting. A minority of these heavily pre-treated patients required support by blood cell transfusion or growth factor. A mild flu-like symptom was also observed in some.
The company intends to announce a partner to share marketing responsibilities of Bexxar, assuming approval, in the fourth quarter of 1998. In early August, the company raised $60 million in a public offering of 2.4 million shares for $25 per share. Later that month, the company grossed an additional $6.1 million, as underwriters of the public offering exercised an overallotment option of 245,000 shares at $25 per share. Underwriters were BT Alex. Brown Inc., of Baltimore; Hambrecht & Quist LLC, of San Francisco; Pacific Growth Equities Inc., of San Francisco; and Piper Jaffray Inc., of Minneapolis. (See BioWorld Today, Aug. 3, 1998, p. 1, and Aug. 28, 1998, p. 2.)
Coulter's stock (NASDAQ:CLTR) closed Wednesday at $24.625, down $2.50. *