By Karen Pihl-Carey
Staff Writer
In a collaboration to develop a more far-reaching therapy for heart attack patients, Cor Therapeutics Inc. and Schering-Plough Corp. will explore the use of their antiplatelet agent, Integrilin injection, in combination with Genentech Inc.'s single bolus fibrinolytic, TNKase (tenecteplase).
The study, called Integriti (Integrilin and tenecteplase in acute myocardial infarction), will compare Integrilin and different doses of TNKase against TNKase alone to see if blood flow improves through clogged arteries that supply oxygen to the heart.
The three companies announced the collaboration Tuesday at the 72nd Annual Scientific Sessions of the American Heart Association in Atlanta.
In a study conducted by the Thrombolysis in Myocardial Infarction (TIMI) research network, researchers found that normal coronary blood flow was restored in six out of every 10 patients treated with TNKase. "It is anticipated that significantly more patients may benefit from the dual effects of fibrinolysis with TNKase and inhibition of platelet aggregation with Integrilin," said TIMI director Eugene Braunwald.
The Integriti study will be done as a collaborative research effort between TIMI and Duke Clinical Research Institute, of Durham, N.C.
Studies showed that 90 minutes after therapy with TNKase began, half of patients treated experienced the restoration of normal blood flow. In the half that did not experience the restoration, researchers believe continued platelet aggregation resulted in rapid re-occlusion of the artery.
Integrilin, however, and other GP IIb/IIIa inhibitors seem to block platelet aggregation and total occlusion of the coronary arteries in patients with unstable angina. Preliminary trials of the inhibitors in combination with fibrinolytic therapy show an improvement in blood flow through clogged arteries, compared with fibrinolytic therapy alone.
Integrilin is currently indicated for patients with acute coronary syndrome, including those undergoing percutaneous coronary intervention. It is contraindicated in patients with a history of bleeding diathesis, severe hypertension, major surgery and stroke. Bleeding is Integrilin's most common complication. Schering-Plough, of Madison, N.J., and Cor, of South San Francisco, are worldwide partners for Integrilin.
TNKase is under regulatory review in the U.S. and Europe for approval to treat acute myocardial infarction. It is a bio-engineered plasminogen activator developed by South San Francisco-based Genentech. It is designed to prolong its half-life and increase specificity to fibrin, a key component to intracoronary clots. Its most severe side effect is intracranial hemorrhage and stroke.
Aside from the collaboration, Cor reported results from its Phase II Intro-Ami (Integrilin and reduced dose of thrombolytic in acute myocardial infarction) study.
The study showed that Integrilin combined with half-dose alteplase (tPA) restored blood flow through clogged arteries in 78 percent of patients. Studies of full-dose alteplase have reported a restoration of blood flow in 54 percent of heart attack patients. The trial involved 340 patients.
In other news from the conference:
The Overture Executive Committee, a panel of seven clinical experts and leaders in heart failure research, plan to study omapatrilat for the management of heart failure. Omapatrilat is a member of the vasopeptidase inhibitor class. It inhibits neutral endopeptidase and angiotensin-converting enzyme, which work in the cardiovascular system to control heart function and blood pressure. The Overture (omapatrilat vs. enalapril randomized trial of utility in reducing events) study will compare omapatrilat with a commonly used therapy in 4,420 patients at 659 sites worldwide. Omapatrilat was developed by Bristol-Myers Squibb Co., of New York.