A monoclonal antibody that neutralizes blood-clotting FactorVIIa effectively prevents excessive blood coagulation, such asoccurs in sepsis.
The preclinical trial results on Corvas International Inc.'s(NASDAQ:CVAS) Factor VIIa inhibitor Corsevin M werepresented Wednesday by researcher Bart Biemond of theAcademic Medical Center in Amsterdam, the Netherlands, atthe 65th Annual American Heart Association Meeting in NewOrleans.
Factor VIIa is the blood enzyme that triggers the first step inthe body's clot-forming processes. Thus, for treating endotoxin-induced septic shock, an anti-Factor VIIa antibody mayprevent disseminated intravascular coagulation (DIC), aninappropriate clotting in blood vessels that can result inmultiple organ failure, hemorrhage and death.
The results reported in New Orleans came from an animalmodel of endotoxemia. The researchers injected chimpanzeeswith low doses of endotoxin to "recapitulate the process ofcoagulation that occurs in septic shock," Howard Soule, vicepresident of product development for Corvas of San Diego, toldBioWorld.
The researchers measured the anti-Factor VIIa antibody'sability to inhibit coagulation by its ease in blocking "coagulationmarkers," which include prothrombin fragment 1+2, thethrombin-anti-thrombin complex, and fibrinopeptide A, Souleexplained.
"All three markers were significantly elevated in untreatedanimals, but remained at baseline levels in animals treatedwith the monoclonal product," Soule said.
The murine antibody is currently in Phase I trials in humans,where "immunogenicity (human anti-mouse antibodyresponse) doesn't appear to be a problem," according to Soule.Moreover, "the product has already been chimerized, and PhaseIIs will be using a chimeric antibody."
Centocor (NASDAQ:CNTO) is Corvas' marketing partner forCorsevin M, having acquired a worldwide exclusive license tothe product in November 1991. "They're going to take this afterwe complete Phase I," Soule said.
Soule explained that the anti-endotoxin antibody products,such as Centocor's Centoxin, "don't solve the whole problem" intreating septic shock. Treatment is likely to require additionaltherapeutic strategies, such as Corvas' Corsevin M. "Our drugwill probably be co-administered with other agents," Soulesaid.
-- Jennifer Van Brunt Senior Editor
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