Integrilin -- eptifibatide -- Injection Significantly Improves Long-term Outcomes in Patients Undergoing Intracoronary Stenting.

Business Editors/Health & Medical Writers

SOUTH SAN FRANCISCO, Calif. & KENILWORTH, N.J.--(BW HealthWire)--

Jan. 8, 2001

COR and Schering-Plough Announce Positive 6-Month

Results From the ESPRIT Study

Today, COR Therapeutics, Inc. (Nasdaq:CORR) and Schering-Plough Corporation (NYSE:SGP) reported the 6-month results from the ESPRIT study with INTEGRILIN(R) (eptifibatide) Injection which demonstrated a significant reduction in the incidence of death or myocardial infarction (heart attack) over the 6 months following intracoronary stent implantation from 11.5% with placebo to 7.5% with INTEGRILIN (P=0.0015). This represents a highly significant 35% reduction in these adverse outcomes.

Analysis of the results also showed that INTEGRILIN significantly reduced the combined occurrence of death, myocardial infarction, or the need for repeat target vessel revascularization from 18.3% with placebo to 14.2% (P=0.0083). Myocardial infarction alone was significantly reduced by 33% (P=0.0047). Death alone was reduced by 43% from 1.4% with placebo to 0.8% with INTEGRILIN (P=0.19).

"These results clearly show that treating patients with eptifibatide during coronary stent angioplasty procedures provides a sustainable, long-term benefit," stated James E. Tcheng, MD, lead investigator for ESPRIT and Associate Professor of Medicine at Duke University Medical Center. "These findings, much awaited by the interventional cardiology community, corroborate the positive long-term effects previously reported with eptifibatide in the setting of non-ST-segment elevation acute coronary syndromes."

The ESPRIT (Enhanced Suppression of Platelet Receptor GP IIb-IIIa using INTEGRILIN Therapy) study was the first trial designed to assess the efficacy and safety of GP IIb-IIIa inhibitor therapy in patients undergoing non-urgent percutaneous coronary intervention (PCI) with the wide variety of intracoronary stents currently used in clinical practice. In ESPRIT, INTEGRILIN was dosed using an experimental regimen of a 180 mcg/kg bolus, immediately followed by a 2 mcg/kg/min infusion, then followed by a second 180 mcg/kg bolus ten minutes later. The infusion was continued until hospital discharge for up to 18 to 24 hours.

On February 4, 2000, an independent Data Safety Monitoring Committee (DSMC) stopped enrollment early in ESPRIT after an interim analysis of 1,758 patients revealed a highly statistically significant reduction in the incidence of death or heart attack at 48 hours with INTEGRILIN as compared to placebo. Analysis of the entire cohort of 2,064 patients enrolled in ESPRIT at the time of study termination documented that the primary endpoint of death, myocardial infarction, need for urgent target vessel revascularization, or need for thrombotic bail-out therapy at 48 hours was reduced with INTEGRILIN from 10.5% with placebo to 6.6% (P=0.0013). The incidence of death, myocardial infarction, or need for urgent target vessel revascularization at 30 days was reduced from 10.5% with placebo to 6.8% with INTEGRILIN (P=0.0034). Consistent with previous clinical trials of GP IIb-IIIa inhibitors, major bleeding, primarily at the site for PCI catheter placement, was increased from 0.4% to 1.3%.

Follow-up information was available for 98.5% of all patients at 6 months.

Nearly 600,000 percutaneous coronary interventions are performed in the United States each year to restore blood flow through occluded arteries that supply oxygen to heart muscle. More than 60% of all PCI procedures employ the use of intracoronary stents, metal mesh structures that hold the artery open after the procedure. Although PCI and intracoronary stenting are generally successful at restoring blood flow and preventing the collapse of the artery, the deployment of the stent into the artery wall can result in the clumping of blood cells called platelets and the development of an intracoronary thrombus or blood clot. Because the thrombus can obstruct blood flow through the artery and thus deprive the heart muscle of oxygen supply, myocardial infarction (heart attack) or death can occur. Some patients may require urgent repeat intervention to reopen the artery. The vast majority of these thrombotic complications take place shortly following the PCI procedure.

INTEGRILIN helps prevent reocclusion of the stented artery by blocking certain receptors, known as GP IIb-IIIa, on platelets that are responsible for thrombus development. The effects of INTEGRILIN are exerted at the time of the PCI procedure when the patient is at highest risk. Upon drug discontinuation, INTEGRILIN is eliminated from the circulation, thus helping to reduce potential bleeding complications.

INTEGRILIN(R) (eptifibatide) Injection

INTEGRILIN is currently indicated for the treatment of patients with 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. It is also indicated for the treatment of patients at time of PCI.

INTEGRILIN is contraindicated in patients with a history of bleeding diathesis, or evidence of abnormal bleeding within the previous 30 days; severe hypertension (systolic blood pressure greater than 200 mm Hg or diastolic blood pressure greater than 110 mm Hg) not adequately controlled on antihypertensive therapy; major surgery within the preceding six weeks; history of stroke within 30 days, or any history of hemorrhagic stroke; current or planned administration of another parenteral GP IIb-IIIa inhibitor; platelet count less than 100,000 per cubic millimeter; serum creatinine greater than or equal to 4.0 mg/dL (in patients with serum creatinine levels between 2.0 mg/dL and 4.0 mg/dL, a 135 mcg/kg bolus and 0.5 mcg/kg/min infusion should be administered); dependency on renal dialysis; or known hypersensitivity to any component of the product.

Bleeding is the most common complication encountered during INTEGRILIN therapy. The majority of excess major bleeding events were localized at the femoral artery access site. Oropharyngeal, genitourinary, gastrointestinal and retroperitoneal bleeding were also seen more commonly with INTEGRILIN compared to placebo.

COR Therapeutics, Inc. and Schering-Plough Corporation are worldwide partners for INTEGRILIN. Both companies market and sell the drug in the United States. Schering-Plough markets INTEGRILIN in Europe. COR has the right to co-promote INTEGRILIN in Europe at a later date.

COR Therapeutics, Inc.

COR Therapeutics, Inc. is dedicated to the discovery, development and commercialization of novel pharmaceutical products for the treatment and prevention of severe cardiovascular diseases. COR has complementary research and development programs that seek to address critical needs in severe cardiovascular care, including unstable angina, acute myocardial infarction, deep vein thrombosis, and restenosis.

In addition to the historical information contained herein, this press release contains forward-looking statements that involve risks and uncertainties. Actual results may differ materially from the anticipated results discussed in such forward-looking statements, due to factors such as results of clinical trials with INTEGRILIN and other factors discussed in the Company's SEC reports, including, but not limited to, the Company's Report on Form 10-Q for the quarter ended September 30, 2000, and Report on Form 10-K for the year ended December 31, 1999. Forward-looking statements are based on current expectations and the Company does not intend to update such information to reflect later events or developments.

Schering-Plough Corporation

Schering-Plough Corporation, of Kenilworth, N.J., is a research-based company engaged in the discovery, development, manufacturing and marketing of pharmaceutical products worldwide. Schering Laboratories is the U.S. prescription pharmaceutical marketing arm of Schering-Plough.