GLFD Guilford Pharmaceuticals (MM)

New Clinical Trials Evaluate High-Dose AGGRASTAT(R) in High-Risk Patients BALTIMORE, July 29 /PRNewswire-FirstCall/ -- Guilford Pharmaceuticals, Inc. (NASDAQ:GLFD) today announced the publication of two new clinical trials of AGGRASTAT(R) that evaluated the safety and efficacy of high-dose AGGRASTAT(R) Injection (tirofiban hydrochloride) in patients undergoing primary coronary angioplasty for ST segment elevation myocardial infarction (STEMI) and high-risk coronary angioplasty. These trials used a new dosing regimen of AGGRASTAT(R) (25 mcg/kg bolus over 3 minutes followed by infusion at 0.15 mcg/kg/min for 18 hours) and compared this regimen to abciximab (ReoPro(R)) or placebo. AGGRASTAT(R), in combination with heparin and aspirin, is indicated for the treatment of acute coronary syndrome (ACS) including patients who are to be managed medically and those undergoing PTCA or atherectomy. Results from the first trial known as ADVANCE, published in the Journal of the American College of Cardiology(1) yielded a significantly reduced primary composite end point (death, nonfatal MI, urgent TVR, and bailout GP IIb/IIIa inhibitor therapy during follow-up) with heparin plus tirofiban over heparin plus placebo [20% vs. 35%, respectively (hazard ratio 0.51, 95% confidence interval 0.29 to 0.88; p = 0.01)]. This double-blind, placebo-controlled, randomized trial included 202 high-risk patients undergoing percutaneous coronary intervention (PCI).(2) In this trial, 98% of patients underwent stenting. Any stent type approved by a regulatory agency could be implanted. All patients were pretreated with aspirin (160 to 325 mg orally) and thienopyridine (ticlopidine 500 mg as a loading dose and then 250 mg twice daily or clopidogrel 300 mg orally as a loading dose and then 75mg/day at least 48 or 6 hours before the procedure). Investigators conclude that high-dose bolus tirofiban plus heparin was safe and effective in this study. Minor bleeding was observed in both the tirofiban and placebo arms; the difference between the two was not statistically significant (p=0.19). There was no severe thrombocytopenia in either treatment, and one patient in each treatment arm had mild thrombocytopenia. "These data suggest that high-dose tirofiban can reduce the frequency of major adverse cardiovascular events in high-risk patients undergoing PCI," says Matthew Meldorf, M.D., Senior Director, Medical Affairs of Guilford Pharmaceuticals. "We are encouraged by these data and are evaluating our options for pursuing additional large-scale trials to confirm these results." Findings from a randomized study of 100 patients, published in the American Journal of Cardiology(3) suggest high-dose bolus tirofiban may be as effective as abciximab for 30-day recovery of left ventricular function (as the primary endpoint) in patients undergoing primary coronary angioplasty for STEMI [mean baseline LV ejection fraction - 47 plus or minus 7%, increased to 55 plus or minus 9% similarly in both groups (p = 0.001)]. In the trial, 97% of patients underwent stenting. Thrombolysis In Myocardial Infarction (TIMI) grade flow (a secondary endpoint) was 0 in approximately 80% of patients prior to the procedure. After the procedure, final TIMI 3 grade flow was achieved in 88% of tirofiban patients vs. 86% of abciximab patients, respectively (p = 1.0). Investigators conclude that abciximab and tirofiban affected both initial angiographic outcomes and 30-day recovery of LV function following primary coronary angioplasty. With no major bleeding or severe thrombocytopenia and no need for red blood cell transfusions, researchers say the study provides important information about the safety of high-dose bolus tirofiban. More abciximab-treated patients than tirofiban-treated patients [8% vs. 4%, respectively] experienced minor bleeding, but this difference was not significant (p=0.71). The 30-day incidence of major adverse cardiovascular events was also greater, but not significantly so, in the abciximab group when compared to the tirofiban group [6% vs. 4% (p = 0.74)]. Eric Topol, M.D. of the Cleveland Clinic Heart Center explains, "This study provides further support for doing a repeat large-scale trial testing tirofiban versus abciximab, since so much data now suggest the bolus dose we used (for tirofiban) in TARGET was inappropriately low." In the Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial (TARGET) trial, tirofiban was given at 10 mcg/kg bolus followed by a 0.15 mcg/kg/min infusion for 18 to 24 hours. 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