By Frances Bishopp
Centocor Inc. filed two supplements to its product license application with the FDA for ReoPro use in all patients undergoing angioplasty and for use in stabilizing patients who are eligible for angioplasty and have unstable angina that doesn't respond to conventional therapy.
ReoPro, a monoclonal antibody that inhibits platelet aggregation, is currently available in the U.S. and Europe for prevention of blood clots following angioplasty in patients who are at high risk of artery reclosure.
The supplements to the PLA are supported by results of the company's Phase III Epilog and Capture trials, as well as by a three-year follow-up of patients from the Phase III Epic study, which was the basis of the original submission for approval of ReoPro. The drug was cleared for marketing in both Europe and the U.S. in 1994.
The Epilog trial was designed to study use of ReoPro in a broad population of angioplasty patients, regardless of risk, Bruce Carroll, manager of government affairs and public relations at Centocor, told BioWorld Today. In the primary 30-day intention-to-treat analysis, ReoPro with a low-dose heparin regimen reduced the number of deaths, myocardial infarctions or urgent interventions by 56 percent. A maintained benefit was shown at six months with a 43 percent reduction in adverse events.
The Capture trial was designed to determine if ReoPro would reduce ischemic complications and stabilize unstable angina patients who were slated to undergo angioplasty, Carroll said. In this trial, which was different from both the Epic and Epilog trials, ReoPro was started up to 24 hours prior to the operation and continued until one hour after completion of the procedure.
Results demonstrated that in the 30-day intent-to-treat analysis, ReoPro reduced deaths, myocardial infarctions or urgent interventions by 29 percent. A reduction in heart attacks was seen both pre- and post-angioplasty.
In the original Epic trial, Carroll said, the most common side effect was bleeding. The recently concluded Epilog trial, however, demonstrated that bleeding events can be reduced by making adjustments in the dosing of ReoPro and heparin, as well as by improved catheter and catheter-site management.
Carroll said Centocor, of Malvern, Pa., is a few weeks away from applying for the same indications in Europe.
In December 1995, the Epilog and Capture trials were stopped at the recommendation of independent Safety and Efficacy Monitoring Committees after data from the first 1,500 participants demonstrated the drug successfully achieved the study's primary endpoints of preventing death and heart attacks within 30 days of the procedures.
Carroll said sales of ReoPro its first year were $24 million and last year's sales were approximately $150 million.
David Crossen, an analyst with Montgomery Securities, of San Francisco, said the filing was done on schedule and incorporates all the Epilog and Capture data, which broadens the population of patients. "ReoPro has fully incorporated the data that was part of the submission," Crossen said, "and its growth is very rapid and reflects that data. The label expansion will occur by year end, but it won't be pivotal because I think ReoPro will grow no matter what."
"The more important issue is that ReoPro will be addressing progressively larger markets, mainly stroke and the heart attack market," Crossen said. "We have the company at profitability for 1997. I ultimately have ReoPro sales by 2000 at about $1.2 billion."
Analyst Tim Wilson, of UBS Securities Equity Research, of New York, said he expects ReoPro sales to reach $266 million in 1997, $490 million in 1998 and $649 million in 1999. Wilson said he expects a straightforward FDA review and full approval within 12 months.
ReoPro prevents blood clots by targeting the glycoprotein (GP) IIb/IIIa receptor on the surface of platelets. Derived from an antibody that seeks out and selectively binds to these receptors, ReoPro prevents the binding of fibrinogen, thereby blocking platelet aggregation and inhibiting clot formation.
While ReoPro binds selectively to the receptor sites primarily involved in platelet aggregation, this process does not interrupt platelet adhesion to the blood vessel wall. This means that ReoPro is less likely to interfere with the formation of a protective layer of platelets over the site of a blood vessel injury.
ReoPro was developed by Centocor and is manufactured by Centocor B.V. in Leiden, the Netherlands. Eli Lilly & Co., of Indianapolis, markets, sells and distributes the product worldwide, except in Japan, where Fujisawa Pharmaceuticals, of Tokyo, has the marketing rights.
ReoPro is Centocor's flagship therapeutic product. The company's stock (NASDAQ:CNTO) Wednesday gained $2.00, closing at $39.25. *