When Centocor Inc.'s ReoPro abciximab was first approved for use in patients undergoing percutaneous coronary intervention in December 1994, it was the only GPIIb/IIIa platelet inhibitor on the market. Six years later, it has two competitors. And while ReoPro still retains the lead in total dollar sales, Cor Therapeutics Inc. now claims the lead in the number of prescriptions ordered, estimating that its Integrilin eptifibatide holds a 45% market share.

The change is largely due to an expansion of the available patient population into indications for which ReoPro has not been approved, lower pricing by the competitors, and in the case of Integrilin, improvements in physician confidence following alteration of recommended dosing schedules.

Thus it is not enough to be first to market with a novel treatment. Because many products in development for cardiovascular, immunological, metabolic, and neurological diseases will be approved based on their ability to alleviate symptoms and slow disease progression rather than actual cure rates, post-marketing competition can significantly affect sales. In the GPIIb/IIIa inhibitor market, in which the three products offer widely variable clinical trial results depending on the specific product dose and indication, other influences on physician decisions are driving product sales.

GPIIb/IIIa inhibitors are approved for use in patients with unstable angina, acute coronary syndrome, and patients undergoing emergency or elective percutaneous coronary intervention (PCI), which includes angioplasty or stenting.

ReoPro is approved only for patients undergoing elective or emergency PCI. Integrilin received approval for both patients with acute coronary syndrome (ACS) or unstable angina and PCI in May 1998. At the same time, Merck & Co. Inc.'s Aggrastat tirofiban was approved for patients with ACS or unstable angina, and emergency PCI; however, Aggrastat is not approved for elective PCI (see "Marketed GPIIb/IIIa inhibitors," A2).

Use of GPIIb/IIIa inhibitors thus has gradually been moving to manage cardiovascular events prior to their use in the catheterization lab. "We are trying to expand the upstream use of GPIIb/IIIa inhibitors," David Lee, staff physician of cardiovascular medicine at Stanford University, told BioCentury.

Guidelines from the American College of Cardiology (ACC) on the treatment of patients with unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI) recommend the use of GPIIb/IIIa inhibitors in patients with ST segment shifts and positive cardiac markers. But there is no consensus on the choice of product. That is probably because trial results have been difficult to compare (see Triaging Patients, A5).

Making the choice

Most interventional cardiologists agree that the marketed GPIIb/IIIa inhibitors have significantly improved treatment for patients undergoing angioplasty or stenting. "We love these drugs - it's sexy to use them," said Lee.