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BERKELEY, CA -- November 11, 1997 -- New research by XOMA Corporation (Nasdaq: XOMA) suggests that measuring lipopolysaccharide-binding protein (LBP) levels in blood may be useful in diagnosing and determining the prognosis of patients with severe gram-negative bacterial infections, including sepsis, as well as infectious complications of traumatic injury and surgery.
Today, findings from multiple clinical studies using XOMA's patented methods for measuring levels of LBP, a biochemical marker of exposure to gram-negative bacteria and bacterial endotoxins, will be summarized at the Sixth Vienna Shock Forum by Stephen F. Carroll, PhD, XOMA's vice president of preclinical research.
"There is a clear need for a test that differentiates gram-negative infectious complications from other inflammatory states with similar clinical symptoms," Dr. Carroll said. "XOMA's LBP assay could form the basis of such a test. Among other uses, this tool could help determine which patients would benefit from treatment with drugs such as our Neuprex(tm) product."
Dr. Carroll described XOMA findings from studies of LBP levels in plasma samples from healthy adults and from over 700 patients suffering from 20 different septic, inflammatory and non-inflammatory diseases. Significant elevations in LBP levels were identified in patients with presumed gram-negative sepsis, meningococcemia, complicated abdominal infections, and inflammatory bowel disease. This suggests that elevation of LBP in humans is a specific response to exposure to bacteria and their endotoxins.
These results prompted XOMA investigators to monitor plasma LBP levels in patients enrolled in studies of the anti-infective properties of Neuprex(tm) (rBPI-21). Data now available from meningococcemia and partial hepatectomy patients showed increased levels of LBP in both populations. Magnitude, kinetics and duration of LBP levels correlated well with clinical outcome. LBP data from XOMA's hemorrhage due to trauma study also supported the hypothesis that trauma patients suffering hemorrhage are exposed to bacteria and endotoxins translocated from their intestines that can cause infectious complications. Dr. Carroll concluded that collectively these studies demonstrate that elevated or increasing levels of LBP are diagnostic and prognostic of poor patient outcome in a variety of disease states.
Bacterial endotoxins, molecules called lipopolysaccharides (LPS), are an integral part of the cell walls of gram-negative bacteria. These molecules, on or released from the bacteria, can trigger an overwhelming systemic inflammatory response that can lead to severe complications in infected patients, including sepsis, respiratory distress, circulatory shock, organ failure, and death. LBP binds to endotoxin and is a key participant in this inflammatory response to infection.
XOMA has licensed its LBP technology to Biosite Diagnostics, San Diego, California (Nasdaq: BSTE), and SRL, Inc., Tokyo, Japan, who are using the technology to develop commercial tests which could aid in accurate diagnosis and prognosis of severe infections and their complications. To date XOMA has received one patent (U.S. Patent Number 5,484,705, issued January 16, 1996) and a Notice of Allowance for another, which cover diagnostic and prognostic methods for quantitating levels of LBP in humans. In addition, XOMA has acquired from Johnson & Johnson an exclusive sublicense to fundamental LBP-related technology discovered at The Scripps Research Institute in San Diego.
BPI (bactericidal/permeability-increasing protein), a human host-defense protein found in neutrophils, is a member of the same lipid-binding molecule family as LBP. Two earlier XOMA patents protect methods for measuring BPI in patients. BPI kills gram-negative bacteria and binds to LPS, but unlike LBP, it interrupts the inflammatory cascade. BPI was discovered in 1978 by Peter Elsbach, MD, professor of medicine, and Jerrold Weiss, PhD, professor of microbiology, at New York University School of Medicine. XOMA has collaborated with NYU since 1991 to extend and apply BPI-related research to commercial development of pharmaceuticals. XOMA's first BPI-derived drug, Neuprex(tm), is a injectable formulation of a modified recombinant fragment (rBPI-21) of BPI.
XOMA Corporation is a biopharmaceutical company developing products to treat infections, infectious complications, and immunological disorders. The company is focused on accelerated development of products derived from BPI. In addition to clinical studies in meningococcemia and trauma patients, XOMA is testing Neuprex(tm) to treat antibiotic-resistant lung infections in cystic fibrosis patients and is concluding a study in patients undergoing major liver surgery. Other BPI-derived products in development include I-PREX(tm), a topical ophthalmic formulation of rBPI-21, and Mycoprex(tm), an antifungal peptide. |
