By Mary Welch

A Phase III/IV study of Integrilin (eptifibatide) injection in patients undergoing coronary intervention with stenting was halted after an interim analysis showed a reduction of almost 50 percent in death or heart attacks, the principle endpoints.

"The independent data safety monitoring committee notified us that the interim results were so highly statistically significant that they were recommending halting the trial," said Vaughn Kailian, president and CEO of South San Francisco-based COR Therapeutics Inc, which is developing the drug along with Madison, N.J.-based Schering-Plough Corp. "We had already treated about 2,100 people and about 1,758 of them reached the endpoint within 48 hours. Slightly less than that reached the endpoints after 30 days."

The study was designed to treat 2,400 patients.

The results showed that the combined incidence of death or myocardial infarction (MI) - or heart attack - with Integrilin compared to placebo over 30 days following a stenting procedure was statistically significant (p=0.0011). In addition, a significant reduction was seen in as early as 48 hours (p=0.0017).

There also was no difference in the incidence of severe bleeding between Integrilin and placebo, the committee concluded. There was, however, a modest increase in the incidence of moderate bleeding with Integrilin.

"We'll now gather our data and prepare for an FDA filing around the third quarter of this year," Kailian said. "It's our belief that this should be the standard of care for patients undergoing intracoronary stenting."

The study, called Enhanced Suppression of Platelet Receptor GP IIb-IIIa (ESPRIT), was designed to judge the efficacy and safety of Integrilin in patients undergoing non-urgent percutaneous coronary intervention with the wide variety of intracoronary stents currently in use.

In ESPRIT, Integrilin was dosed as a 180 micrograms per kilogram (ug/kg) bolus, immediately followed by a 2 ug/kg/min infusions, then followed by a second 180 ug/kg bolus 10 minutes later. The infusion was continued until hospital discharge for up to 18 to 24 hours later.

The primary endpoint was the combined incidence of death, MI, urgent repeat intervention, or need for bail-out GP IIb-IIIa inhibitor therapy at 48 hours.

The secondary endpoints included the composite endpoint, as well as the composite of death, MI, or urgent repeat revascularization, at 12 hours, 24 hours, seven days and 30 days.

Integrilin is a synthetic peptide derived from the venom of the Southeastern pygmy rattlesnake. The drug specifically blocks the GP IIb-IIIa receptor, which binds fibrinogen and mediates platelet aggregation. Integrilin has a very rapid onset and a short duration. Last year it posted sales of $63.7 million.

The FDA approved the anti-clotting agent in 1998 for acute coronary syndrome (unstable angina and non-Q-wave myocardial infarction), including patients who are to be managed medically and those undergoing percutaneous coronary intervention, which comprises balloon angioplasty, atherectomy and stent replacement. It is also indicated for the treatment of patients undergoing percutaneous coronary interventions. (See BioWorld Today, May 20, 1998, p. 1.)

Integrilin is currently in Phase II trials for heart attack patients, with Phase III trials expected to start by the end of this year or early next year.

"This drug has had a steady upward climb," Kailian said, "But it didn't start very high."

COR Therapeutics' stock (NASDAQ:CORR) closed Friday at $40.50, up $14.937, or 58 percent.