GLFD Guilford Pharmaceuticals (MM)

Guilford Pharmaceuticals Announces Plans to Initiate Two Major Clinical Trials Evaluating AGGRASTAT(R) Injection in Percutaneous Coronary Intervention BALTIMORE, Aug. 12 /PRNewswire-FirstCall/ -- Guilford Pharmaceuticals Inc. (NASDAQ:GLFD) today announced plans to launch two major trials for AGGRASTAT(R) Injection (tirofiban hydrochloride), that are designed to determine the optimal therapeutic regimen for patients at the time of percutaneous coronary intervention (PCI). Guilford plans to conduct the first trial outside the United States as 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 2,000 patients in 100 centers. According to present plans, 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 catheterization laboratory at the time of PCI. Guilford will be meeting with the FDA to discuss the details of its design and its appropriateness for securing an expanded label. Under the current trial design, investigators will employ a single high- dose bolus of 25 mcg/kg followed by a 0.15 mcg/kg/min tirofiban infusion. This dosing regimen has been utilized in 520 patients enrolled in 6 clinical trials, including the ADVANCE trial, recently published in the Journal of the American College of Cardiology. Results from this trial demonstrated 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. 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 arm, and one patient in each treatment arm had mild thrombocytopenia. "We know the current labeled dosing regimen of AGGRASTAT(R) provides therapeutic value when administered early, prior to acute coronary syndrome patients getting to the cath lab," explains David Moliterno, M.D. and principal investigator in the TENACITY trial. "We believe this single high- dose bolus administered at the time of PCI will increase AGGRASTAT(R)'s therapeutic value and versatility while preserving safety." The second study, TENACITY ("Tirofiban Novel Dosing vs. Abciximab with Evaluation of Clopidogrel and Inhibition of Thrombin Study") will be a multi- center, double blind, randomized comparison of AGGRASTAT(R) and ReoPro(R) (abciximab) that is expected to enroll at least 8,000 patients in approximately 200 centers across the United States. The Cleveland Clinic Cardiovascular Coordinating Center (C5) and Duke Clinical Research Institute (DCRI) will coordinate the trial. The primary objective is to determine whether the 30-day efficacy of a single high-dose bolus regimen of AGGRASTAT(R) is non-inferior to 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 tirofiban or abciximab. If successful, TENACITY is expected to advance medical practice in the field of interventional cardiology by defining the role of AGGRASTAT(R) in combination with other anti-platelet and anti- thrombotic agents in this patient population. "TENACITY will be a head-to-head comparison of AGGRASTAT(R) against what most interventional cardiologists perceive as the 'gold standard' GP IIb/IIIa inhibitor for use at the time of PCI," explains trial chairman, Eric Topol, M.D. He continues, "The novel design of TENACITY will help clarify how GP IIb/IIIa inhibitors can be optimally used with other anti-platelet and anti- thrombotic agents. In many ways, it is the trial the interventional cardiology community has been waiting to conduct." Craig R. Smith, M.D., Guilford's President and CEO commented, "We are investing in these trials because we are fully committed to providing physicians with the information they need to optimize patient care. Approved labeling in this market would create a significant opportunity for AGGRASTAT(R) since the majority of the $550 million GP IIb/IIIa U.S. market is within 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