BI and Genentech to evaluate heart attack treatment

Boehringer Ingelheim and Genentech plan to test the single-bolus thrombolytic TNKase/Metalyse (Tenecteplase) in combination with percutaneous coronary intervention (PCI, also known as primary angioplasty) as a potential treatment regimen for acute myocardial infarction (AMI).

The 4,000-patient trial, ASSENT 4 PCI (Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial Infarction) has two arms: half the patients enrolled will receive a drug regimen consisting of a full-dose, single bolus of TNKase/Metalyse plus unfractionated heparin followed by immediate PCI. The other 50% of patients will receive immediate PCI alone.

The study will be carried out at approximately 350 enrolling sites internationally. Its purpose is to investigate whether patients who arrive at the catheterisation laboratory with a fully or partially opened artery as a result of lytic therapy have better outcomes than those who do not receive the lytic regimen before PCI. The primary endpoint of ASSENT 4 PCI is a composite of death or cardiogenic shock or congestive heart failure within 90 days.

'Until now, clinicians treating heart attack patients have tended to choose either a thrombolytic agent or PCI,' observed Prof Frans Van de Werf, University Hospital Gasthuisberg, Leuven, Belgium, and chairman of the ASSENT 4 PCI trial. 'However, the two therapeutic modalities may prove to be complementary. It is our goal to determine whether patients who undergo PCI with an artery that is already opened [via thrombolysis] can be discharged from the hospital with a smaller infarct and better left ventricular function and a more favorable clinical outcome,'

When a blood clot in an artery nearly or completely stops blood flow to the heart, cells in the heart muscle begin to die so the sooner patients receive treatment, the sooner blood flow can be restored, often saving a life or significantly decreasing irreversible damage to the muscle.

ASSENT 4 PCI will enroll patients for whom PCI is the planned therapeutic option but only where patients expected arrival to the catheterisation lab is longer than 60mins and less than 3 hours, either because the hospital is not capable of immediately mobilising the PCI team and gaining access to the catheterisation lab, or because patient transfer is required in order to provide PCI. The ASSENT 4 PCI trial is expected to enroll the first patient within the next month.

Tenecteplase is the only thrombolytic that can be administered over five seconds in a single dose, offering physicians the fastest administration of a thrombolytic to date in the treatment of heart attack. It works by stimulating the body's own clot-dissolving mechanism by activating plasminogen, a naturally occurring substance secreted by endothelial cells in response to injury to the artery walls that contributes to clot formation. When Tenecteplase activates plasminogen, it converts into plasmin, which breaks down the fibrin mesh that binds the clot together. The clot is then dissolved, restoring blood flow to the heart.

Genentech markets Tenecteplase (TNKase) in the United States. Boehringer Ingelheim markets Tenecteplase worldwide, with the exception of the US, Canada, and Japan, under the trade name Metalyse.