Initial Phase III clinical trial results on Centocor Inc.'s heartdrug, CentoRx, are promising enough that the Malvern, Pa.,company intends to file a product license application (PLA)with the FDA this year.

Researchers associated with the multicenter, 2,100-patientPhase III trial reported Tuesday at the American College ofCardiology Meeting in Anaheim, Calif., that CentoRx can reduceby nearly 40 percent the occurrence of heart attack and theneed for emergency repeat angioplasty in patients withcoronary artery disease at high risk for complications followingballoon angioplasty.

CentoRx, or 7E3, is a monoclonal antibody designed to bind tosurface receptors on blood platelets, thus preventing theaggregation and clotting that can lead to blood vessel closure.

All 2,099 individuals in the EPIC trial (Evaluation of IIb/IIIaPlatelet Receptor Antagonist 7E3 in Preventing IschemicComplications) were treated with aspirin and the blood-thinnerheparin, a standard protocol that has been shown to reduceclotting problems, said Eric Topol, chairman of the departmentof cardiology at the Cleveland Clinic Foundation and a directorof the study.

One-third of the patients received a bolus injection of 7E3 of0.25 milligrams per kilogram body weight, plus 10 microgramsper minute infusion for the next 12 hours, Topol told BioWorld.A second third of the patients received the bolus only, and theremaining third received a placebo.

The bolus plus infusion effectively reduced by 36 percent theincidence of major ischemic complications (8.3 percent vs. 12.8percent), including heart attack and the need for an urgentrepeat angioplasty. The fact that the bolus injection alonereduced that incidence by less -- about 11.5 percent vs. 12.8percent -- indicated to the researchers that inhibition ofplatelet aggregation must be sustained to achieve a markedclinical effect.

Still, "These are highly significant results," Topol told BioWorld.If the drug were available today, he added, about 25,000 to40,000 patients would be well-suited for treatment.

There's still some fine-tuning to be done, though. For one,patients in this study suffered from excessive bleeding,although this was related to the puncture site where thecatheter was inserted per se and in no way life-threatening, Topol said. Possible ways to reduce the bleedingwould be to lower the doses of heparin or to give iron insteadof transfusions, he commented.

CentoRx is a humanized monoclonal antibody fragment specificfor the platelet receptor GPIIb/IIIa. But it's not the onlycompound being developed to attack or neutralize thesereceptors. Telios Pharmaceuticals (NASDAQ:TLIO) of San Diego,for instance, is developing a synthetic peptide drug, TP-9201,that blocks the IIb/IIIa receptors on platelets.

In animal models of heart attack and thrombosis, thecompound was able to prevent blood clotting withoutincreasing bleeding time, according to results presented byTelios' scientific collaborators last November at the AmericanHeart Association Meeting.

And Cor Therapeutics (NASDAQ:CORR) of South San Francisco,Calif., is developing a peptide it terms Integrelin that acts as arapidly reversible blocker of GPIIb/IIIa. Cor initiated Phase IIclinical trials last October in patients undergoing coronaryangioplasty.

Eli Lilly and Co. acquired the rights to CentoRx last July as partof its $100 million capital infusion into Centocor(NASDAQ:CNTO). Half of that money went to fund the renewedPhase III clinical trials of Centoxin or HA-1A, the company'smonoclonal antibody product for treating septic shock. Centocorhalted those trials in January and abandoned any furtherefforts at resuscitation (see accompanying story). The Lilly-Centocor agreement stipulated that if HA-1A was not approvedin the U.S. by the end of this year, Lilly would receive therights to CentoRx at no additional cost.

Centocor's stock closed Tuesday at $7.50 a share, up 25 cents.

-- Jennifer Van Brunt Senior Editor

(c) 1997 American Health Consultants. All rights reserved.

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