GLFD Guilford Pharmaceuticals (MM)

Guilford Pharmaceuticals Announces Publication of Data Analysis From TACTICS-TIMI 18 Trial in Circulation Early Treatment with AGGRASTAT(R) Results in Lower Rates of Death, Heart Attack or Rehospitalization in High-Risk Patients with ACS BALTIMORE, March 2 /PRNewswire-FirstCall/ -- Guilford Pharmaceuticals Inc. announced today the publication of new data in the journal, Circulation, demonstrating that the addition of AGGRASTAT(R) Injection, along with aspirin, heparin and coronary stenting, coupled with an aggressive, early intervention treatment strategy for acute coronary syndrome (ACS) was associated with a statistically significant decrease in the rate of death, myocardial infarction (heart attack) or rehospitalization for patients with ACS(p < 0.0001), compared to early intervention alone. The article, entitled, Implications of Upstream Glycoprotein IIb/IIIa Inhibition and Coronary Artery Stenting in the Invasive Management of Unstable Angina/Non-ST- Elevation Myocardial Infarction, compares data from two previously published trials, TIMI IIIB and TACTICS-TIMI 18. Marc S. Sabatine, MD, MPH, Cardiovascular Division, Brigham and Women's Hospital, commented, "In the past decade, we have seen a continued evolution in the early care of patients presenting with ischemic heart disease. By comparing results of TACTICS-TIMI 18 with the earlier TIMI IIIB trial, we were able to identify and underscore the impact and importance of these new therapies, particularly GP IIb/IIIa inhibition." Chris Cannon, M.D., Cardiovascular Division, Brigham and Women's Hospital, stated, "These data provide additional compelling evidence that upstream utilization of AGGRASTAT(R) effectively reduces the incidence of major adverse cardiac events in patients with ACS. Approximately two-thirds of intermediate to high-risk ACS patients currently do not receive treatment with a GP IIb/IIIa inhibitor upstream, despite ACC/AHA guidelines recommending the use of GP IIb/IIIa inhibitors as part of an early invasive approach. These new data should encourage early / upstream use of GP IIb/IIIa's in the ACS patient population." AGGRASTAT(R), a glycoprotein GP IIb/IIIa receptor antagonist, in combination with heparin, is indicated for the treatment of acute coronary syndrome (ACS) including patients who are to be medically managed and those undergoing percutaneous transluminal coronary angioplasty or atherectomy. AGGRASTAT(R) may also be used to treat patients prior to undergoing angioplasty, a procedure to openblockages in arteries supplying blood to the heart. In January 2004, Guilford announced that it had completed the expansion of its hospital salesforce and had launched marketing efforts for AGGRASTAT(R) Injection (tirofiban hydrochloride) in the United States. Guilford acquired U.S. marketing rights to AGGRASTAT(R) from Merck and Co., Inc. in October 2003. AGGRASTAT(R) is currently available in 82 countries worldwide and is marketed by Merck in all countries outside the United States and its territories. "These are extremely important new data, which underscore the importance of treating ACS patients with a IIb / IIIa early, in this case AGGRASTAT(R) along with aspirin and heparin," commented Michael Kelly, Vice President of Commercial Operations at Guilford. "The comparison of the results of TACTICS- TIMI 18 with the TIMI IIIB trial, in which no IIb / IIIa was given, demonstrate that patients in the TACTICS-TIMI 18 trial had a significantly lower rate of death, myocardial infarction, or rehospitalization when compared to ACS patients in TIMI IIIB." TACTICS-TIMI 18 Trial Study Design The six-month multicenter study included 2,220 patients who received heparin, (bolus dose of 5,000U, followed by an infusion of 1,000U/hr), aspirin (325mg/daily, unless contraindicated) and AGGRASTAT(R) Injection (intravenous loading infusion of 0.4 mcg/kg) followed by a 48- to 108-hour infusion (0.1 mcg/kg). The drugs were administered immediately upon diagnosis. Patients were randomized within 24 hoursof the last episode of chest pain to either an early invasive or early conservative treatment strategy. For patients in the early invasive arm (n = 1114), cardiac catheterization (usually angioplasty) was performed within 4 to 48 hours after randomization and revascularization as appropriate (usually PCI with stent implantation). Patients in the early conservative arm (n = 1106) were treated medically and did not undergo cardiac catheterization unless they experienced one or more pre-specified clinical criteria for medical therapy failure. The primary endpoint of the study was a composite of death, MI or rehospitalization measured at 30 days and 6 months. 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. Important Information About AGGRASTAT(R) 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. 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