Researchers from Corvas International Inc. reported Phase Iclinical trial results on Corsevin M, a potential anti-thromboticagent, on Tuesday at the 14th Congress of the InternationalSociety on Thrombosis and Hemostasis in New York.

The results of the dose-escalation trial in 18 patients indicatedthat Corsevin M, a monoclonal antibody against Factor VIIa, theblood enzyme that triggers the first step in the body's bloodclotting process, produced rapid, potent and reversible anti-coagulation at all three doses without bleeding problems orhuman anti-mouse antibody (HAMA) responses.

The patients, all of whom suffered from incurable malignancies,were otherwise stable in terms of their hematology and bloodcoagulation profiles, explained Howard Soule, Corvas' vicepresident of product development.

They received a single intravenous injection of drug, either 10,40 or 70 micrograms per kilogram. "At the high dose, there wastotal blockage of Factor VIIa and the levels returned to normalafter several hours," Soule told BioWorld. And "even in theabsence of total blockage of Factor VIIa there were no clinicallyrelevant adverse events such as bleeding," he added.

For Corvas (NASDAQ:CVAS), the completion of these Phase Itrials is the end of its involvement with Corsevin M per se."What the study does for Corvas is to tell us that Factor VIIa isstill a reasonable target for product development," Soule toldBioWorld. "It helps us justify the resources we're putting intothe development of small-molecule inhibitors of Factor VIIa.It's a very nice proof-of-principle."

Corvas of San Diego is using its Scafoldd drug discoverytechnology to develop inhibitors of factor VIIa (as well asFactor Xa, another enzyme involved in the blood coagulationcascade). "The inhibitors are based on a knowledge of thestructure of Factor VIIa, computer modeling of the Factor VIIamolecule and medicinal chemistry," Soule said.

Thus, while the Phase I trials are an end to exploring CorsevinM for Corvas, they are just the beginning for its marketingpartner Centocor Inc. (NASDAQ:CNTO), which now will take upthe clinical trial development of the product.

Centocor, which obtained a worldwide exclusive license to theproduct in November 1991, has already developed ahumanized version of the monoclonal for advanced trials, Soulesaid.

The Phase I trials have demonstrated that "for all the rightscientific reasons, Factor VIIa is a good target for anti-coagulation," explained Corvas' Soule. Moreover, "under thisdosing regimen, Corsevin M is clinically safe." And an antibodythat can neutralize Factor VIIa could be used to preventexcessive blood coagulation in diseases such as sepsis, in whichdisseminated intravascular coagulation can result in multipleorgan failure, hemorrhage and death.

-- Jennifer Van Brunt Senior Editor

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