Clinical Trial With INTEGRILIN(R) (eptifibatide) Injection in Early Use Acute Coronary Syndrome Setting

Main Category: Public Health
Article Date: 02 Jun 2004 - 22:00 PDT

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Critical Trial to Evaluate Benefits of Early INTEGRILIN Use. Millennium Pharmaceuticals, Inc and Schering-Plough Corporation today announced the initiation of a multicenter phase IIIb clinical trial to evaluate the benefit of INTEGRILIN when administered early to high-risk patients experiencing non-ST-segment elevation acute coronary syndrome.

The trial, known as EARLY ACS (Early Glycoprotein IIb-IIIa Inhibition in Non-ST-segment Elevation Acute Coronary Syndrome: A Randomized, Placebo-Controlled Trial Evaluating the Clinical Benefits of Early Front-loaded Eptifibatide in the Treatment of Patients with Non-ST-segment Elevation Acute Coronary Syndrome) will evaluate the benefit of INTEGRILIN compared to placebo in reducing death and other major adverse cardiac events, including heart attack, within 96 hours and up to 30 days following randomization. EARLY ACS is designed to include 10,500 patients at 500 sites worldwide.

(Photo: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO )

"This trial is a high priority for Millennium because evidence suggests that early intervention with a glycoprotein (GP) IIb-IIIa inhibitor such as INTEGRILIN -- as currently recommended by the ACC/AHA Guidelines -- can significantly reduce the high incidence of heart attack and in-hospital mortality," said Nancy Simonian, M.D., senior vice president, clinical development at Millennium. "We believe that this trial will provide further clinical evidence to support findings from the CRUSADE quality improvement initiative which to date suggest that adherence to the guidelines in the early stages of an adverse cardiac event can help save patients' lives," she added.

The EARLY ACS trial will evaluate the effectiveness of INTEGRILIN(R) (eptifibatide) Injection in an early use setting, when emergency room patients are diagnosed as being at high-risk for a heart attack or death and are scheduled to be managed with an invasive strategy (such as diagnostic catheterization, stent implantation, or coronary artery bypass graft (CABG) surgery) no sooner than the next calendar day.

INTEGRILIN will be administered as a double bolus followed by infusion, and will be used in combination with other common antithrombotic therapies. This trial is designed to reflect current treatment guidelines and real world practice patterns and will also include a combination of biomarkers, including troponin levels, and other clinical features to characterize the benefits of INTEGRILIN in high-risk subgroups.

"With the EARLY ACS trial, we seek to provide data that give clinicians real-world contemporaneous guidance that benefits patients," said Eugene Braunwald, M.D., Distinguished Hersey Professor of Medicine at the Harvard Medical School, chairman of the Thrombolysis and Myocardial Infarction (TIMI) Study Group at Brigham and Women's Hospital and study principal investigator.

"We are excited to be starting this important, company-sponsored trial which is a critical component of our growth strategy for INTEGRILIN as we believe there is significant market opportunity based on data that demonstrates patient benefit in the early use setting," said Arthur Hiller, senior vice president, sales and marketing at Millennium. "We are committed to exploring the full potential of INTEGRILIN in early use through the EARLY ACS trial and in other settings through a comprehensive, ongoing clinical development program."

To be eligible for the EARLY ACS study, patients must be experiencing symptoms of cardiac ischemia at rest with episodes lasting at least 10 minutes within 24 hours of randomization and must have at least two of the following characteristics:

-- Electrocardiogram (ECG) changes of acute ischemia;

-- Elevated troponin;

-- Aged 60 or older; and

-- All patients must be able to be randomized within eight hours of presentation and scheduled to undergo invasive clinical management strategy no sooner than next calendar day.

The EARLY ACS trial will evaluate the benefit of INTEGRILIN in a setting that closely parallels contemporary patterns of care observed in CRUSADE, which shows an average delay of 24 hours prior to cardiac catheterization and low use of GP IIb-IIIa inhibitors upon diagnosis. Nearly 100,000 patients have been tracked in CRUSADE to characterize the medication and interventional norms in the United States.

INTEGRILIN is currently being evaluated in other studies to evaluate its effectiveness in various treatment settings both alone and in combination with novel and conventional agents, including:

-- REMOVE: A trial designed to evaluate the use of INTEGRILIN with or without heparin in low-risk patients undergoing percutaneous coronary intervention (PCI);

-- PROTECT: A three-arm trial designed to evaluate the use of INTEGRILIN plus heparin, INTEGRILIN plus enoxaparin, or bivalirudin alone in high-risk PCI patients;

-- TITAN: An open-label trial for ST-segment elevation acute myocardial infarction (STEMI) patients planned for primary angioplasty designed to compare the early use of INTEGRILIN versus INTEGRILIN given at time of angioplasty; and

-- EVENT: A patient registry designed to collect information on the use of bare metal or drug-eluting stents with and without use of a GP IIb- IIIa inhibitor.

About Non-ST-segment Elevation Acute Coronary Syndromes

Non-ST-segment elevation acute coronary syndromes includes unstable angina and non-ST-segment elevation acute myocardial infarction (NSTEMI). Unstable angina (UA) is a severe constricting pain in the coronary region of the chest occurring at rest as well as during exercise. UA is usually caused by the buildup of plaque (deposits of fat-like substances), a process called atherosclerosis.

The plaque can eventually burst, tear or rupture, creating a "snag" where a blood clot forms and blocks the artery, limiting the supply of oxygenated blood in the vessels leading to the heart muscle. Unstable angina is a warning sign that a heart attack may soon occur. NSTEMI is a term used to describe the most common form of heart attack.

In NSTEMI, small platelet- rich particles can detach from the clot and completely block smaller vessels, decreasing oxygen levels (for longer periods of time than with unstable angina, where blockage is less severe) and causing the death of small regions of the heart muscle.

About INTEGRILIN(R) (eptifibide) Injection

INTEGRILIN is indicated for the treatment of patients with acute coronary syndrome (unstable angina/non-ST-segment myocardial infarction), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI). It is also indicated in the United States for the treatment of patients at time of PCI, including in patients undergoing intracoronary stenting.

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 glycoprotein (GP) IIb-IIIa inhibitor; 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.

INTEGRILIN is co-promoted and co-developed by Millennium Pharmaceuticals, Inc. and Schering-Plough Corporation.

About Millennium

Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE(R) (bortezomib) for Injection, a novel cancer product, co-promotes INTEGRILIN(R) (eptifibide) Injection, a market-leading cardiovascular product, and has a robust clinical development pipeline of product candidates. The Company's research, development and commercialization activities are focused in three therapeutic areas: oncology, cardiovascular, and inflammation. By applying its knowledge of the human genome, its understanding of disease mechanisms, and its industrialized drug discovery platform, Millennium is seeking to develop breakthrough products.

About Schering-Plough

Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of physicians, patients and consumers served by its more than 30,000 people around the world.

Millennium Forward-Looking Statement

This press release contains "forward-looking statements," and other statements about our growth and future operating results, discovery and development of products, potential acquisitions, strategic alliances and intellectual property. Various important risks may cause the Company's actual results to differ materially from the results indicated by these forward-looking statements, including: adverse results in our drug discovery and clinical development programs; failure to obtain patent protection for our discoveries; commercial limitations imposed by patents owned or controlled by third parties; our dependence upon strategic alliance partners to develop and commercialize products and services based on our work; difficulties or delays in obtaining regulatory approvals to market products and services resulting from our development efforts; the commercial success of INTEGRILIN(R) (eptifibatide) Injection and VELCADE(R) (bortezomib) for Injection; and the requirement for substantial funding to conduct research and development and to expand commercialization activities. For a further list and description of the risks and uncertainties we face, see the reports we have filed with the Securities and Exchange Commission. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Schering-Plough Disclosure Notice

The information in this press release includes certain "forward-looking" information including the market potential for INTEGRILIN. Forward-looking statements relate to expectations or forecasts of future events. Many factors cause actual results to differ from Schering-Plough's forward-looking statements. The extent that INTEGRILIN will be prescribed will be determined by market forces and the market viability of any particular product is subject to substantial risks and uncertainties. In addition, the forward-looking statements may also be affected by general market and economic factors, product availability, current and future branded, generic or over-the-counter competition, federal and state regulations and legislation, the regulatory process for new products and indications, manufacturing issues, trade buying patterns, patent positions and the outcome of litigation and investigations. Schering-Plough does not assume the obligation to update any forward-looking statement. For further details and a discussion of other risks and uncertainties that may affect forward-looking statements, see the company's Securities and Exchange Commission filings, including the company's first quarter 2004 10-Q

Editor's Note: This release is available under the Companies' websites at http://www.millennium.com and http://www.schering-plough.com

SOURCE Millennium Pharmaceuticals, Inc.; Schering-Plough Corporation 06/01/2004

CONTACT: Kelly Lindenboom, media, +1-617-679-7405, or Cynthia Clayton, investor, +1-617-551-8607, both of Millennium; or Mary-Frances Faraji, media, +1-908-298-7109, or Alex Kelly, investor, or Janet Barth, investor, or Lisa W. DeBerardine, investor, +1-908-298-7436, all of Schering-Plough Corp.

Web site: http://www.millennium.com

http://www.schering-plough.com

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