rBPI21 is a recombinant 193 amino acid protein derived from human BPI, a naturally occurring 456 amino acid host defense molecule made in neutrophils. rBPI21 possesses multiple properties which include binding, clearing and neutralizing bacterial endotoxin, killing Gram-negative and Gram-positive bacteria, and enhancing bactericidal activity of a wide range of antibiotics. Neuprex ®, the intravenous formulation of rBPI21, has been evaluated in over 1700 patients to date in human volunteer studies and five Phase I/II indications, involving patients with meningococcemia, hemorrhagic trauma, complicated abdominal infections, partial liver resections and cystic fibrosis. The product has demonstrated an excellent safety profile and evidence of biological activity in every study completed to date. Thus far, two indications, meningococcemia and hemorrhagic trauma, have moved into Phase III trials.
References
1.
Horwitz AHExpression and characterization of cysteine-modified forms of an amino terminal fragment of bactericidal/ permeability-increasing protein. Protein Expr Purif1996; 8: 28.
2.
Elsbach P., Weiss J.Oxygen-independent antimicrobial systems of phagocytes. In: Inflammation: Basic Principles and Clinical Correlates. New York: Raven Press, 1992; 603—636.
3.
Ammons WS, Kung Ahc.Recombinant amino terminal fragment of bactericidal/permeability-increasing protein prevents hemodynamic responses to endotoxin. Circ Shock1993; 41: 176.
4.
Lin YL, Ammons WS, Leach WJ, Kung Ahc.Protective effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein on endotoxic shock in conscious rabbits. Shock1994; 2: 324.
5.
Lin YL, Leach WJ, Ammons WSSynergistic effects of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein and cefamandole in the treatment of rabbit Gram-negative sepsis. Antimicrob Agents Chemother1996; 40: 65.
6.
Lambert L., Wong P., Hoppe P., Scannon P.Recombinant bactericidal/permeability-increasing (rBPI) protein kills both Gram-positive and Gram-negative bacteria. Late Breaker Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy1994; 34: C6.
7.
Gazzano-Santoro H., Parent JB, Grinna L., Horwitz AH, Parsons T., Theofan G. et al. High-affinity binding of the bactericidal/permeability-increasing protein and a recombinant amino-terminal fragment to the lipid A region of lipopolysaccharide. Infect Immun1992; 60: 4754.
8.
Fink MPAnother negative clinical trial of a new agent for the treatment of sepsis: rethinking the process of developing adjuvant treatments for serious infections . Crit Care Med1995; 23:989.
9.
Bauer C., Reimer-Paxian R., Larsen R., Marzi I.Recombinant bactericidal/permeability-increasing protein (rBPI21) prevents shock-induced microcirculatory alterations in the liver. Crit Care Med1997; 25: 1283.
10.
von der Möhlen Mam, Kimmings AN, Wedel NI, Mevissen Mlmc, Jansen J., Friedmann N. et al. Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein. J Infect Dis1995; 172: 144.
11.
von der Möhlen Mam, van Deventer Sjh, Levi M., van den Ende B., Wedel NI, Nelson BJ et al. Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23). Blood1995; 85: 3437.
12.
de Winter RJ , van der Möhlen Mam, van Lieshout H., Wedel NI, Nelson BJ, Delemarre Bjm et al. Recombinant endotoxin-binding protein (rBPI23) attenuates endotoxin-induced circulatory changes in humans . J Inflamm1995; 45: 193.
13.
Kirsch EA, Barton P., Kitchen L., Giroir B.Pathophysiology, treatment and outcome of meningococcemia: a review and recent experience. Pediatr Infect Dis1996; 15: 967.
14.
Giroir B., Quint PA, Barton P., Kirsch EA, Kitchen L., Goldstein B. et al. Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in a children with severe meningococcal sepsis. Lancet1997; 360: 1439.
15.
Agarwal N., Murphy JG, Cyten CG, Stahl WMBlood transfusion increases the risk of infection after trauma. Arch Surg.1993; 128: 171—177.
16.
Duke BJ, Modlin GW, Schecter WP, Horn JKTransfusion significantly increases the risk for infection after splenic injury : Arch Surg1993; 128: 1125—1132.
17.
Yamashita M.Bactericidal/permeability-increasing protein ameliorates hypercoagulability after hemorrhagic shock. Thromb Res1997; 87: 323.
18.
Yao Y-M., Bahrami S., Leichtfried G., Redl H., Schlag G.Pathogenesis of hemorrhage-induced endotoxemia in rats: effects of recombinant bactericidal/permeability-increasing protein (rBPI21). Ann Surg1995; 221: 398.
19.
Smith JS, Scannon PJ, the BPI Trauma Study Group.Phase II trial of rBPI21 (recombinant bactericidal/permeability-increasing protein) in adults with hemorrhage due to trauma. Shock1997; 8: S16.
20.
Meijer C., Hack CE, Wedel NI, Thijs LG, Wiezar MJ, Wünsche R., et al. rBPI21 in the prevention of the inflammatory response after liver resection in patients: results of the low dose phase. 4th International Congress on the Immune Consequences of Trauma, Shock and Sepsis. 1997.
21.
Heseltine Pnr et al. Open-label, pilot Phase II trial of three dose levels of recombinant bactericidal/permeability-increasing protein (rBPI 21) administered by continuous intravenous infusion to patients with complicated intraabdominal infections. Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy1998; 38: 603.
