By Jim Shrine
The first significant trial of Centocor Inc.¿s ReoPro in stroke patients pointed to improved clinical function without increased intracranial bleeding, and will lead to further studies in that indication.
Centocor, of Malvern, Pa., plans to follow up the Phase IIa study with a Phase IIb study in acute ischemic stroke, before moving into a large-scale Phase III trial. Results of the Phase IIa study were presented over the weekend at the Eighth Annual European Stroke Meeting, in Venice, Italy.
Nearly all patients in the study were treated more than three hours after the onset of stroke. The standard treatment, t-PA, is indicated for treatment within three hours.
¿What was nice in this trial was we were able to look at patients who received ReoPro up to 24 hours [after the onset of stroke],¿ Centocor spokesman Christopher Allman said. ¿The opportunity to open up the treatment window is certainly important and encouraging, and something we want to look at further.¿
Approximately half the people in the 74-patient trial were treated more than 12 hours after the onset of stroke. They were treated with placebo or one of four doses of ReoPro. About 20 patients were in the placebo group.
A preliminary analysis showed 35 percent of ReoPro patients and 20 percent of placebo patients had minimal or no residual disability three months after treatment. Half of ReoPro patients versus 40 percent of placebo patients showed improved ability to perform daily activities. There also was a trend toward improved neurological functioning with ReoPro, according to the University of Iowa Hospital and Clinics, a trial site in Iowa City.
ReoPro (abciximab) is a monoclonal antibody anti-platelet drug that inhibits both the glycoprotein IIb/IIIa and alpha V beta 3 receptors. In the stroke indication, it may be useful in clearing plaque or other blockages in blood vessels in the brain.
The drug was approved in 1994, initially for use in high-risk angioplasty patients, and the label was broadened later to include all angioplasty procedures. Worldwide sales of ReoPro in 1998 were $365 million ($302 million in the U.S.). Centocor recorded sales of $206 million to partner Eli Lilly and Co., of Indianapolis.
Allman said it¿s premature at this early stage to speculate about what a stroke indication might mean for ReoPro sales, though he pointed out that five million people die each year from stroke and about 700,000 Americans suffer a first or recurrent stroke each year.
The protocol for the Phase IIb study in stroke has been written, Allman said, and is under review.
Meanwhile, enrollment began last fall in a 4,000-patient trial of ReoPro in acute coronary syndrome patients, most of whom present with unstable angina. Some data from that study are expected to be presented next year, Allman said. A sub-study is being conducted that combines ReoPro and Fragmin, a low molecular weight heparin product from Pharmacia and Upjohn, of Bridgewater, N.J. Fragmin is under review by the FDA as a treatment for unstable angina.
Separately, Centocor expects to begin this quarter a 16,000-patient study combining ReoPro and its clot-buster, Retavase, in acute myocardial infarction.
Centocor¿s stock (NASDAQ:CNTO) fell 62.5 cents per share Monday to close at 36.875.