For the second time in a week Centocor Inc. has halted alarge-scale Phase III trial of ReoPro based on positivefindings from an interim analysis of the anti-bloodclotting drug's ability to prevent adverse cardiac events inangioplasty patients.
The study stopped Wednesday, Centocor officials said,demonstrated ReoPro not only reduced death and heartattack rates in refractory unstable angina patients within30 days of angioplasty, but also prevented those cardiaccomplications 24 hours prior to the procedures.
The pre-angioplasty findings, officials said, indicateReoPro, an anti-platelet monoclonal antibody, worked instabilizing the patients, alleviating the need foremergency interventions.
The interim data from the European study, calledCAPTURE, showed ReoPro reduced by more than 50percent the rate of death and heart attacks prior to andfollowing angioplasty.
Officials at Centocor, of Malvern, Pa., said details of theplacebo-controlled trials, held at 75 European sites, willbe released next year at a scientific conference.
ReoPro's president and CEO, David Holveck, said theCAPTURE studies show ReoPro is an effectivepretreatment drug for seriously ill coronary patients.
"It's a major milestone," Holveck said. "It gives us anexpansion of how the drug can be used."
The trials, expected to enroll 1,400 patients, were haltedafter an interim analysis of the first 1,050. The decisionwas made by an independent Safety and EfficacyMonitoring Committee (SEMC), which said thepreliminary findings showed efficacy exceeding apredetermined stopping point.
The data also revealed bleeding rates, considered anadverse side effect of ReoPro, were essentially the samein both the treatment and placebo groups. It was thesecond Phase III trial in which the results counteredworries about bleeding.
The drug was approved by the FDA in December 1994for use with high risk angioplasty, but sales by marketingpartner Eli Lilly and Co., of Indianapolis, have beenslower than expected because of bleeding concerns andthe drug's high price, $1,350 per treatment.
Last week a 4,800-patient Phase III trial in the U.S. andEurope, called EPILOG, also was stopped early after apositive interim analysis revealed a 70 percent reductionin death and heart attack rates within 30 days ofangioplasty for patients receiving ReoPro. (See BioWorldToday, Dec. 18, 1995, p. 1.)
That data, analysts said, indicated a likely expansion ofReoPro's use for all angioplasty patients, who numbermore than 700,000 per year in the U.S. and Europe. Thedrug's current label limits use to patients at high risk ofartery reclosure. Those patients account for about 10percent to 30 percent of the total.
Release of the positive EPILOG interim findings Dec. 14,1995, sent Centocor's stock (NASDAQ:CNTO) soaringthe next day 68 percent to $24.
Trading in Centocor was halted Wednesday afternoon inresponse to news about the CAPTURE trial. The stockwas at $25.
In the EPILOG studies patients were divided into threegroups; those receiving a placebo with heparin and therest who were given ReoPro with either low-dose orstandard-dose heparin. Patients received a dose of ReoProduring the angioplasty and a 12-hour infusion followingthe procedure.
EPILOG stands for evaluation in PTCA (percutaneoustransluminal catheter angioplasty) to improve long-termoutcome with ReoPro GP IIb/IIIa blockade. ReoProtargets the IIb/IIIa receptor to inhibit platelet aggregation.
Unstable angina patients in the CAPTURE study weredivided into two groups, one receiving a placebo with theconventional therapy (heparin, aspirin and nitroglycerin)and the other getting ReoPro in combination with thestandard drugs. Patients received treatment with ReoPro24 hours preceding the angioplasty and for one hourfollowing it.
CAPTURE refers to chimeric anti-platelet monoclonalantibody therapy in unstable angina refractory to standardtreatment. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.