By Karen Pihl-Carey

Abgenix Inc. is taking its steroid-resistant graft-vs.-host disease (GVHD) product, ABX-CBL, into a Phase III trial, based on positive Phase II data.

The Fremont, Calif., company also is seeking a corporate partner to develop and commercialize the product. It plans to start the Phase III trial on its own, but hopes to have a partner in place before the trial is completed.

"What's interesting is Abgenix's business is so strong right now that they decided to partner it after the Phase III starts," said Jay Silverman, senior analyst with BancBoston Robertson Stephens Inc. in New York. "They'll probably get good terms from a partner because they already have a lot of data and they're in Phase III."

The company's stock (NASDAQ:ABGX) rose 10.8 percent Wednesday to close at $88.50, up $8.625.

Data from the 59-patient Phase II trial were presented at the annual meeting of the American Society of Hematology in New Orleans earlier this week. In the trial, conducted at the Seattle-based Fred Hutchinson Cancer Research Center, patients who received higher doses of the drug had more than twice the 180-day survival rate of patients receiving the lowest dose. Patients receiving the higher dose displayed a 50 percent survival rate, compared with a 22 percent rate for patients in the lowest dose.

"The data was good, and more importantly, it was received incredibly well," said Eric Ende, a senior analyst with Lehman Brothers Inc. in New York. In contrast, Ende said, negative results of anti-thymocyte globulin (ATG) for GVHD were presented shortly after the ABX-CBL presentation.

In the Phase III trial, Abgenix will compare ABX-CBL to ATG, "which at this past conference has been shown not to work," Ende told BioWorld Today. "Therefore, they have a pretty good shot of hitting their endpoint in the comparison to ATG."

The multi-center, controlled trial will enroll 92 patients and will take 18 months to two years to complete. The primary endpoint is survival.

"Survival is a tough endpoint, but it's an endpoint that will show if this drug works or if it doesn't," Silverman said.

Kurt Leutzinger, vice president and chief financial officer of Abgenix, said the company will press the FDA for registration on the basis of the trial.

"We think that considering this is a serious, life-threatening disorder with no treatments, we think we would have a strong case for making this the last trial," he said, "but we need to demonstrate the data."

Leutzinger also said the company will continue the Phase III on its own if necessary, but that a "number of parties" have shown interest in partnering with Abgenix. "Our strategy has always been to partner things, even if we have the capital, because we don't want to gamble the company on a single product," he told BioWorld Today.

About half of patients receiving transplants of stem cells contract GVHD when the transplanted cells attack the patient's tissues. Such transplants, or grafts, are used to treat patients with leukemia, certain other cancers and immune system disorders. When a patient's own bone marrow cells and immune system are suppressed by radiation or chemotherapy and cannot mount a sufficient immune response, a transplant is intended to restore normal circulating blood cells and immune cells. GVHD forms when a portion of the graft recognizes the host's own cells as foreign and attacks the cells.

About half of GVHD patients fail to respond to current steroid and other drug treatments, such as ATG, a horse polyclonal antibody mixture.

ABX-CBL is a monoclonal antibody that binds to the protein CD147, which is upregulated on certain activated immune cells. It works when it attaches to the CD147 antigen, then signals other immune cells to destroy the tagged cell. Earlier this year, the drug showed positive results in a separate Phase II trial in GVHD patients. (See BioWorld Today, Feb. 5, 1999, p. 1.)

Abgenix also has two other products in clinical trials. ABX-IL8 is in Phase I for rheumatoid arthritis and recently completed a Phase I/II trial in psoriasis. The company expects to start several Phase II trials in psoriasis in the first half of 2000. And ABX-EGF is in a Phase I for cancer.

In the preclinical phase, the company has a fully human version of ABX-CBL, "which could address larger markets than CBL can, such as rheumatoid arthritis, the autoimmune diseases," Leutzinger said. That product is called ABX-RB2.

Last week, the company signed its largest XenoMouse collaboration to date, with Human Genome Sciences Inc., of Rockville, Md. The XenoMouse technology uses a strain of genetically engineered mice that, once immunized with an antigen, make entirely human antibodies that cause no immunogenic response in humans. (See BioWorld Today, Dec. 2, 1999, p. 1.)