By Debbie Strickland

In a Phase III trial involving 10,948 patients, COR Therapeutics Inc.'s injectable anticoagulant, Integrilin, significantly reduced the occurrence of death or heart attack in patients with unstable angina and non-Q-wave myocardial infarction (MI).

Integrilin, an inhibitor of platelet aggregation, is a synthetic peptide derived from the venom of Southeastern pygmy rattlesnakes. Integrilin specifically blocks the gylcoprotein (GP) IIb-IIIa receptor, which mediates platelet aggregation by binding fibrinogen.

The Phase III trial data lifted COR's shares (NASDAQ:CORR) to $12.938, a gain of $1.375, or 11.9 percent.

"We believe, based on the size of the trial, the clean primary endpoint and clear statistical significance on an intent-to-treat analysis, that the drug has an extremely high chance of being approved in the United States and abroad," wrote analyst Matt Geller, of Oppenheimer & Co. Inc., in New York.

According to Geller's report, the "potential market . . . for this class of drugs" is $3.1 billion in the U.S. COR's revenues could hit $315 million in five years, the analyst calculated "very conservatively."

The drug may eventually compete for market share with FDA-approved ReoPro, developed by Malvern, Pa.-based Centocor Inc. and marketed by Eli Lilly & Co., of Indianapolis. ReoPro, a monoclonal antibody, also targets the GP IIb/IIIa receptor.

COR, of South San Francisco, is planning to file an amended new drug application this year for the indications of unstable angina and non-Q-wave MI. Schering-Plough Corp., of Madison, N.J., has marketing rights worldwide.

"If we file in the fourth quarter and we get approval by the end of the second quarter [of 1998], we could hit the market as early as the third quarter [of 1998]," said Vaughn Kailian, COR's president and CEO.

The company earlier this year sought FDA approval of Integrilin on the basis of the IMPACT II angioplasty trial, but the agency's Cardiovascular and Renal Drugs Advisory Committee advised that although the data indicated Integrilin had activity, the results were not sufficiently compelling to forego the FDA's customary requirement of two positive clinical trials prior to the approval of a new drug. COR received a letter in March indicating the drug was not approvable without additional trial data.

According to COR, the new Phase III trial, dubbed PURSUIT, is the largest ever conducted for unstable angina and non-Q-wave MI. More than 700 sites in 28 countries participated, including more than 280 hospitals in the U.S. Researchers presented initial results Monday at the 19th Congress of the European Society of Cardiology, in Stockholm.

"The PURSUIT results demonstrate that this class of agents improves clinical outcomes in the treatment of unstable angina," said Robert Califf, professor of medicine at the Durham, N.C., Duke University Medical Center and director of the Duke Clinical Research Institute, which coordinated the trial in conjunction with The Cleveland Clinic and Cardialysis, in Rotterdam, The Netherlands.

"This result combined with other recently reported trials provides strong evidence that GP IIb-IIIa inhibitors should be standard therapy for this condition."

The primary efficacy endpoint in the Phase III trial was prevention of death or myocardial infarction within 30 days following treatment. Integrilin produced a statistically significant reduction in the incidence of death or MI from 15.7 percent to 14.2 percent within 30 days. An absolute reduction of 1.5 percentage points in the rate of death or MI was demonstrated at 96 hours and at seven days, and this reduction was maintained to 30 days.

In addition, Integrilin treatment reduced significantly the combined incidence of death or major MI (as measured by cardiac enzyme levels) from 8.5 percent to 7.3 percent and reduced the incidence of Q-wave myocardial infarction from 1.7 percent to 1.1 percent, each within 30 days.

The reduction in death or MI was most pronounced in the U.S., Canada and Western Europe, where more than 8,500 patients were enrolled. In these countries, the incidence of death or MI fell from 14.9 percent to 12.7 percent. In the other regions of the study there was not a significant drug effect in the incidence of death or MI.

The favorable safety profile of Integrilin was consistent with earlier trials. In particular, there was no significant increase in the incidence of stroke or thrombocytopenia — a potentially serious condition of platelet depletion. The incidence of major bleeding in the placebo group was 9.1 percent, vs. 10.6 percent in the Integrilin group.

A major finding of the trial was the higher than expected incidence of death and MI in the patient population. In the U.S., more than 1 million patients are hospitalized each year with urgent chest pain diagnosed as unstable angina or non-Q-wave myocardial infarction. Until now, it was estimated one in nine patients died or experienced heart attacks over the 30-day period following an episode of unstable angina or non-Q-wave myocardial infarction. The PURSUIT study suggests the disease carries even greater morbidity, with an estimated one in six patients experiencing death or MI within 30 days of their presenting episode.

COR and Schering-Plough are worldwide partners for Integrilin under terms of a 1995 agreement that paid COR $20 million up front, with another $100 million in milestones. COR, in addition to having three-quarters of development costs covered by Schering-Plough, has the right to copromote the product in the U.S. and Canada. After receiving royalties for a period of time in Europe, COR would gain the right to copromote there also.

As of June 30, COR had cash, cash equivalents and short-term investments of $38.52 million. The company's second-quarter net loss was $8.96 million. *