By Randall Osborne
On the heels of positive interim results in a Phase III trial of Neuprex for a rare but deadly infection that strikes children, Xoma Corp. has launched another Phase III trial of the product, this one for infectious complications from hemorrhaging brought on by trauma.
Neuprex, derived from a human host defense protein that kills bacteria, also is being investigated for applications in cystic fibrosis, liver surgery and eye infections, and as an adjuvant to antibiotics in intra-abdominal infections.
The trauma trial, to be conducted at more than 40 sites, will enroll 1,650 patients who receive at least two units of blood as a result of blunt or penetrating trauma, said Peter Davis, chief financial officer of Berkeley, Calif.-based Xoma. Davis oversees the Neuprex program.
The primary endpoint will be a reduction in the percentage of patients who experience severe pulmonary complications such as pneumonia and acute respiratory distress syndrome.
"We think this is the clearest, cleanest endpoint, the best shot at getting approval," Davis said. An earlier double-blind, placebo-controlled trauma study used 401 patients and helped sharpen the current trial's focus.
Neuprex is derived from bactericidal/permeability-increasing protein (BPI), which is found in white blood cells. The drug works by punching holes in the outer shell of bacteria and killing them. It also enhances antibiotics, and binds and neutralizes endotoxin, a poisonous molecule produced in the cell walls of gram-negative bacteria. Endotoxin can trigger serious inflammatory complications in infected patients.
"A number of diseases can give you these complications, and we're picking them off one at a time," Davis said.
Xoma also is testing Neuprex in a Phase I study for the pulmonary bacterial exacerbations of cystic fibrosis. In vitro analysis has demonstrated that Neuprex, used alone and with antibiotics, killed the bacteria isolated from sputum samples of 40 cystic fibrosis patients.
The company is exploring applications of Neuprex for partial hepatectomy, which is the surgical removal of part of the liver. A planned 72-patient double-blind Phase II study is under way in the Netherlands. Patient accrual is going slowly, Davis said, and the study may use only 40 patients.
Neuprex also is being tested in a topical form, called I-Prex, designed for eye infections. The drug inhibits neovascularization, the new growth of blood vessels, which is a frequent complication of eye infections and corneal transplants. Xoma is seeking a corporate partner to further develop I-Prex.
Xoma is talking with ophthalmic companies about I-Prex, but Davis said Neuprex is on the front burner. "[I-Prex] is probably a $50 million product," he said. "We're shooting for something bigger than that with Neuprex."
As an adjuvant to antibiotics in intra-abdominal infections, Neuprex was tested in a Phase I/II pilot study of 21 patients. Data from that trial is being analyzed, Davis said.
An interim analysis of data from the Phase III trial of Neuprex for meningococcemia, the childhood infection, found no safety concerns. That trial is expected to finish by mid-1998. The blood-borne infection, caused by the same bug responsible for meningitis, can cause death in 12 to 24 hours. (See BioWorld Today, Sept. 25, 1997, p. 1.)
Xoma abandoned its search for a drug for gram-negative sepsis earlier this year, but "in a way, we're treating it" — very bad cases of it — with Neuprex in the meningococcemia trial, Davis said. "Sepsis is a syndrome, a secondary complication from a host of things," he added, and the youngsters in the meningococcemia trial show "rip-roaring sepsis," with endotoxins 10 to 20 times higher than those in the typical sepsis patient. (See BioWorld Today, April 28, 1997, p. 1.)
"Ironically, they could be viewed as a subset of sepsis patients," Davis said.
Xoma's stock (NASDAQ:XOMA) closed Wednesday at $7.687, down $0.25. *