By Jim Shrine
Bone-marrow transplant patients taking the Abgenix Inc. mouse antibody ABX-CBL in a Phase II trial showed positive responses in graft vs. host disease (GVHD).
The Fremont, Calif., company expects to meet with the FDA on Feb. 16 to discuss the results and the design of a Phase III trial in GVHD, an often-fatal complication that follows bone marrow transplants.
"We're encouraged by the results, and are making further investment in the product," said Kurt Leutzinger, vice president and chief financial officer at Abgenix. "We expect to begin a Phase III trial by mid-year, and we are investing in commercial scale-up of the material."
The Phase II study included 27 patients, 23 of whom were evaluated for efficacy, which was defined as a 2-point reduction on the 4-point International Bone Marrow Transplant Registry (IBMTR) GVHD Severity Scale. In general, patients in grades 3 and 4 have become resistant to steroid treatment, and have a one-year survival rate of only 15 percent. Lowering their grades to the 1 or 2 range allows them to use steroid treatment to suppress the grafted immune cells.
Eight patients in the study received a very low dose of ABX-CBL - .01 milligram per kilogram of body weight - and essentially were used as controls. Two of them (25 percent) had improvements of two grades or more. In the three higher doses - of .1, .2 and .3 milligrams per kilogram of body weight - 11 of 15 patients (73 percent) improved by two grades or more in GVHD.
"Our endpoint was strictly improvement in grade," Leutzinger said, adding that the FDA set that as the criterion needed for this indication.
The treatment appeared to be safe and well-tolerated, Abgenix said, other than temporary muscle pain experienced after infusions.
ABX-CBL, the company's lead product, was licensed from the Los Angeles-based CV Cancer Center, which was set up by Ron Billings. He discovered the CBL antigen, which is overexpressed on activated immune cells, and developed antibodies to it.
Results from earlier studies of the product were published in the Sept. 23, 1995, issue of The Lancet. Data from Abgenix's Phase II trial will be presented the first week in March at the IBMTR meeting in Keystone, Colo.
Abgenix has used its XenoMouse technology to develop fully human antibodies to the CBL antigen. They are not needed in GVHD, however, since no human anti-mouse antibody response is mounted. The antibodies are being developed for autoimmune diseases such as rheumatoid arthritis, psoriasis and lupus. Using the mouse antibody, for which data already was compiled, allowed Abgenix to begin trials at the Phase II level.
Last week was a busy one at Abgenix. The company released its year-end results - which showed a net loss of $16.8 million on revenues of $3.8 million - and filed for a public offering of 3 million shares. It also signed a six-year, potentially $120 million deal that provides Genentech Inc., of South San Francisco, access to the XenoMouse technology. That technology uses a strain of genetically engineered mice to make entirely human antibodies. (See BioWorld Today, Jan. 28, 1999, p. 1.)
Abgenix's stock (NASDAQ:ABGX) closed Thursday at $17.125, up $0.375.