GLFD Guilford Pharmaceuticals (MM)

AGGRASTAT(R) Strategy Trial Data Presented At American Heart Association Annual Meeting Guilford's Phase III Development Plan Progresses; Enrollment in AGGRASTAT(R) Phase III TENACITY Trial Begins BALTIMORE, Nov. 12 /PRNewswire-FirstCall/ -- Guilford Pharmaceuticals Inc. (NASDAQ:GLFD) today announced the presentation of data from the STRATEGY trial of AGGRASTAT(R) Injection (tirofiban hydrochloride) at the 2004 Scientific Sessions of the American Heart Association Annual Meeting in New Orleans. The study found that a combination of AGGRASTAT(R) and a drug- eluting stent (DES; Sirolimus eluting stent) resulted in a significantly lower rate of death, MI, stroke, and binary restenosis at six months, while also providing a similar cost of care when compared to abciximab used in combination with a bare metal stent. Marco Valgimigli, M.D., Chair of Cardiology, University of Ferrara, and principal investigator for the STRATEGY trial, commented, "The use of GP IIb- IIIa inhibitor therapy has been the standard of care for patients undergoing coronary stent procedures. However, increasing costs have prevented the adoption of approaches such as DES that have been shown to reduce the incidence of binary restenosis and target vessel revascularization. A new, cost-saving strategy for using DES with a GP IIb-IIIa inhibitor will help us improve outcomes in the cath lab without increasing costs for the health care system." "Today's data add to a growing body of evidence regarding the use of AGGRASTAT(R) both in and outside the cardiac cath lab," commented Craig R. Smith, M.D., President and Chief Executive Officer of Guilford. "Including the results from STRATEGY, eight trials involving more than a thousand patients have now been completed using the new single high-dose bolus AGGRASTAT(R) regimen in various clinical settings." Dr. Smith continued, "Our Phase III clinical development program will employ a single high-dose bolus regimen of AGGRASTAT(R) followed by a maintenance infusion in two separate Phase III trials in over 10,000 patients, comparing AGGRASTAT(R) to current standard of care or placebo. The first trial to begin, TENACITY, which has recently started patient enrollment, will evaluate whether the 30-day efficacy of a single high-dose bolus regimen of AGGRASTAT(R) retains at least 50% of the treatment benefit of abciximab in patients undergoing PCI with coronary stent placement. In addition, TENACITY will, for the first time, evaluate the 30-day safety and efficacy of bivalirudin (Angiomax(R)) versus heparin with a single high-dose bolus regimen of tirofiban or abciximab." Guilford plans to conduct a superiority trial outside the United States. The trial will be a multi-center, double-blind, placebo-controlled trial evaluating the 30-day efficacy of the single high-dose bolus regimen of AGGRASTAT(R) compared to placebo in high-risk patients undergoing PCI with coronary stent placement. The trial is expected to enroll approximately 2000 patients in 100 centers. All patients will receive background treatment including heparin, aspirin and clopidogrel (Plavix(R)), if not contraindicated. The results of this trial are expected to provide a basis for seeking FDA approval to expand the present indication of AGGRASTAT(R) to include a new dosing regimen for treatment with AGGRASTAT(R) in the cardiac cath laboratory at the time of PCI. STRATEGY Trial: High-Dose BoluS TiRofibAn and Sirolimus Eluting STEnt versus Abiciximab and Bare Metal Stent in Acute MYocardial Infarction (STRATEGY) Study The six-month study included 175 patients with myocardial infarction who had persistent ST segment elevation on their electrocardiogram (STEMI) who were randomized to receive either the single high-dose bolus (SHDB) tirofiban regimen (N=87; bolus of 25 mcg/Kg/3-min, followed by an infusion of 0.15 mcg/Kg/min for 18-24 h) plus DES, or abciximab (N=88; standard regimen) and bare metal stent (BMS). At six months, clinical and angiographic follow-up was conducted in 144 patients. The primary end-point, a composite of death, myocardial infarction (MI), stroke and binary restenosis rate, occurred in 23% of patients receiving SHDB tirofiban-DES and 48% of patients receiving abciximab-BMS (p=0.003). There was also a statistically significant reduction of 6-month MACE for patients treated with single high-dose bolus tirofiban-DES (15%) compared to those treated with abciximab-BMS (23%), p=0.04. There was a trend towards reduction in all bleeding events for patients treated with SHDB tirofiban-DES compared to abciximab-BMS (16 patients vs. 9 patients, P=0.3). Moreover, there was a significant reduction in thrombocytopenia in patients treated with SHDB tirofiban-DES versus abciximab-BMS (9 patients versus 1 patients, p=0.03). Follow-up for these patients is ongoing. About GP IIb/IIIa Antagonists Platelets are blood cells that provide an early defense from the potential complications of vascular injury. When a blood vessel is damaged, platelets adhere to the site and promote blood clot formation. Clot formation prevents bleeding and recruits other cells to help heal the damage. While usually a beneficial process, these effects can be harmful when a clot forms on a ruptured lipid plaque within the coronary vasculature. GP IIb/IIIa antagonists block the ability of platelets to aggregate, inhibiting clot formation and reducing the potential for cardiac ischemia. Over the last 8-10 years, several large-scale, placebo-controlled clinical trials have established the efficacy of intravenous GP IIb/IIIa inhibitors for patients with acute coronary syndrome who are medically managed or go to the cath lab. Important Information About AGGRASTAT(R) Injection AGGRASTAT(R) was approved by the Food and Drug Administration (FDA) on May 14, 1998. AGGRASTAT(R), in combination with heparin, and aspirin, if not contraindicated, is indicated for the treatment of ACS including patients who are to be managed medically and those undergoing PTCA or atherectomy. In this setting, AGGRASTAT(R) has been shown to decrease the rate of a combined endpoint of death, new myocardial infarction or refractory ischemia/repeat cardiac procedure. In most patients, AGGRASTAT(R) should be administered intravenously, at an initial rate of 0.4 mcg/kg/min for 30 minutes and then continued at 0.1 mcg/kg/min. For complete information, please refer to the product's prescribing information. AGGRASTAT(R) (tirofiban hydrochloride) is contraindicated in patients with known hypersensitivity to any component of the product; active internal bleeding or a history of bleeding diathesis within the previous 30 days; or a history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm. Other contraindications to AGGRASTAT(R) include: a history of thrombocytopenia following prior exposure to AGGRASTAT(R); history of stroke within 30 days or any history of hemorrhagic stroke; major surgical procedure or severe physical trauma within the previous month; or history, symptoms, or findings suggestive of aortic dissection. AGGRASTAT(R) is also contraindicated in patients with: severe hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg); concomitant use of another parenteral GP IIb/IIIa inhibitor; or acute pericarditis. Bleeding is the most common complication encountered during therapy with AGGRASTAT(R). Administration of AGGRASTAT(R) is associated with an increase in bleeding events classified as both major and minor bleeding events, by criteria developed by the Thrombolysis in Myocardial Infarction Study group (TIMI). Most major bleeding associated with AGGRASTAT(R) occurs at the arterial access site for cardiac catheterization. Fatal bleedings have been reported. AGGRASTAT(R) should be used with caution in patients with platelet count