Lancet Study Reports Results of Combining RETAVASE and ReoPro in the Treatment of Heart Attack.

Business & Health/Medical Editors

MALVERN, Pa. & INDIANAPOLIS--(BW HealthWire)--June 14, 2001

Results of landmark GUSTO V trial provide promising information

regarding new treatment options in managing heart attack

Results of a large, international Phase III trial sponsored by Centocor, Inc. and Eli Lilly and Company (NYSE:LLY) were published in the June 16 issue of The Lancet. The study evaluated the combination of half the standard dose of the clot-dissolving fibrinolytic agent RETAVASE(R) (reteplase) and a standard dose of ReoPro(R) (abciximab), a drug that prevents the formation of blood clots, as a potential new treatment regimen for heart attack. In the trial, known as GUSTO V (Global Use of Strategies to Open Occluded Arteries in Acute Myocardial Infarction), the combination therapy arm reported reduced complications associated with heart attack, including the recurrence of heart attack and the need for urgent procedures to open coronary arteries.

"These findings about the combination of reteplase and abciximab may offer an important new option in the treatment of heart attack," said Eric J. Topol, chairman of the GUSTO V trial and of the Department of Cardiology at The Cleveland Clinic. "And importantly, the benefits of reduced second heart attack and lessened need for revascularizations represent a substantial advance in heart attack therapy."

The trial involved 16,588 patients suffering acute myocardial infarction, or heart attack. The primary endpoint was 30-day mortality, and the study was designed to evaluate if the combination treatment would be superior or not inferior to standard fibrinolytic therapy alone in regard to this primary endpoint. The 30-day mortality in the combined RETAVASE and ReoPro group was not inferior to the RETAVASE group (5.6 percent vs. 5.9 percent, respectively, p=0.43), thus comparable to conventional fibrinolytic monotherapy. The secondary endpoint of reinfarction was reduced with the combination, as was the need for urgent revascularization.

Patients treated with the combination of RETAVASE and ReoPro in the GUSTO V trial were 34 percent less likely to experience reinfarction (or the recurrence of heart attack) than patients treated with RETAVASE alone (2.3 percent vs. 3.5 percent, respectively, p value less than 0.0001). Other non-fatal complications, including recurrent ischemia and severe arrythmias, were reduced, which may provide stability to patients who receive the combination therapy. In addition, fewer patients given combination therapy required percutaneous coronary intervention (PCI), or angioplasty, procedures to open the artery in the first six hours after treatment, than in the RETAVASE alone group (5.6 percent vs. 8.6 percent, p value less than 0.0001).

The data also indicated that intracranial hemorrhage, an event that may result in death or permanent disability was low, at 0.6 percent in both treatment groups. Non-ICH bleeding, transfusion rates and thrombocytopenia were higher in the combination group, but procedure-related bleeding was similar in both groups during PCI.

About Heart Attack

According to the American Heart Association, an estimated 1.1 million Americans suffer heart attacks each year. Approximately 450,000 of these heart attacks are recurrent heart attacks.

Nearly all heart attacks are caused by a thrombus -- a blood clot that obstructs the flow of blood to the heart, thereby depriving it of oxygen and nutrients. Blood clots are composed of a protein called fibrin and disk-shaped blood elements known as platelets. While clot-busting, or thrombolytic, agents such as RETAVASE target only the fibrin component of clots, drugs known as glycoprotein IIb/IIIa inhibitors (e.g., ReoPro) target the platelet component of blood clots.

About RETAVASE

RETAVASE is a recombinant biologic cardiology care product administered for the treatment of acute myocardial infarction, or heart attack, to improve blood flow in the heart. When compared with older fibrinolytic agents, RETAVASE distinguishes itself by its ease of administration - a simple two-bolus injection given 30 minutes apart. RETAVASE also restored blood flow in significantly more patients, compared with t-PA, at 60 and 90 minutes after administration. However, the relationship between coronary artery patency and clinical efficacy has not been established. As with other clot-busters, the most common complication associated with the use of RETAVASE is bleeding.

About ReoPro

ReoPro, a unique multi-receptor inhibitor of glycoprotein (GP) IIb/IIIa, (alpha V beta 3) and MAC-1, reduces the ischemic complications associated with angioplasty and stenting. Giving patients ReoPro while they undergo procedures to open their arteries has been proven to reduce their risk of death or heart attack. ReoPro has demonstrated this benefit at 48 hours, 30 days, six months and one year. In addition, Phase III study results have demonstrated that using ReoPro in combination with stents reduces the risk of death by 57 percent one year after the procedure compared to stents alone.

ReoPro, derived from a monoclonal antibody, c7E3 Fab, takes a unique approach to preventing blood clots by targeting the GP IIb/IIIa receptors and binding to them, inhibiting platelet aggregation. ReoPro is currently indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing PCI and in patients with unstable angina not responding to conventional medical therapy when PCI is planned within 24 hours.

ReoPro has the potential to increase the risk of bleeding, particularly in the presence of anticoagulation, such as heparin or a clot-buster such as RETAVASE. The most common side effect of ReoPro is bleeding. Bleeding rates were reduced in the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable Refractory Angina) trial, and further reduced in the EPILOG (Evaluation in PTCA to Improve Long-Term Outcome with ReoPro GP IIb/IIIa Blockade) trial by use of modified dosing regimens and specific patient-management techniques. These modifications included the use of low-dose, weight-adjusted heparin and early sheath removal. In EPILOG, the incidence of major bleeding was not significantly different from that in patients receiving placebo.

About Eli Lilly Company and Centocor, Inc.

ReoPro is co-promoted in the United States by Eli Lilly and Company and Centocor, Inc. Eli Lilly and Company distributes the product worldwide, except in Japan, where Fujisawa Pharmaceutical Co., Ltd. will distribute it upon approval. The drug was developed by Centocor of Malvern, PA, and is manufactured by Centocor B.V. in Leiden, the Netherlands.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers -- through medicines and information -- for some of the world's most urgent medical needs. For more information on ReoPro, visit Lilly's ReoPro web site at www.ReoPro.com.

Centocor is a leading biopharmaceutical company that creates, acquires and markets cost-effective therapies that yield long-term benefits for patients and the healthcare community. Its products, developed primarily through monoclonal antibody technology, help physicians deliver innovative treatments to improve human health and restore patients' quality of life. Centocor is a wholly owned subsidiary of Johnson & Johnson, a worldwide leader of healthcare products. For more information, visit Centocor's web site at www.centocor.com.

Certain of the matters discussed herein with respect to clinical studies and Centocor's and Lilly's products may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are based on current expectations, estimates and projections about the industry, management beliefs and certain assumptions made by management. Investors are cautioned that matters subject to forward-looking statements involve risks and uncertainties, including economic, competitive, governmental, technological and other factors discussed in the two companies' respective filings with the Securities and Exchange Commission, which may affect the business and prospects of the two companies. More specifically, there can be no assurance that this product will achieve commercial success or that competing products will not preempt any market opportunity that might exist for the product.

ReoPro(R) is a registered trademark of Eli Lilly and Company.

RETAVASE(R) is a registered trademark of Centocor, Inc.