BETHESDA, MD. _ An FDA advisory panel voted Thursday night torecommend approval of Centocor Inc.'s ReoPro as an adjunctivetherapy to prevent complications of angioplasty in high-risk patients.Only one member of the Cardiovascular and Renal Drugs AdvisoryCommittee dissented from the majority opinion.This preliminary regulatory triumph is not only good news forCentocor, a company that has remade itself in the last two years, butalso for the entire biotechnology sector, which is hungry for positiveand valid Phase III trial results. One more group stands to gain: the 10to 25 percent of the nation's approximately 400,000 angioplastypatients who are at high risk for post-procedure myocardial infarctionsand/or emergency interventions.The advisory panel determined that the benefits of therapy withReoPro, a statistically significant 35 percent reduction in complicationsseen in a 2,099-patient Phase III trial, outweighed the increased risk ofmajor bleeding episodes. The drug was tested as a adjunct to thecurrent clinical standard of care for patients _ a combination ofheparin and aspirin.The recommendation for approval sets Centocor squarely on the pathtoward FDA marketing approval. Indeed, FDA reviewers whopresented the agency's viewpoint to committee members appearedfavorably disposed toward the drug. They concluded that drug-relatedepisodes of major bleeding did not lead to the two worst outcomes:death or intracranial bleeding. The FDA has scheduled an inspection ofCentocor's ReoPro manufacturing facility in Leiden, The Netherlands,to take place at the end of June.Advisory committee members called upon Centocor to conduct furtherclinical studies to refine the heparin dosing regimen of patients whoreceive ReoPro and to improve the overall risk-to-benefit ratio.Centocor has already initiated pilot studies in preparation for anotherlarge-scale trial that will use "radically lower" doses of heparin inpatients who also receive ReoPro.Further trials will test the hypothesis that the undesirable bleeding sideeffect was a function of heparin dosage. The heparin dose used in thetrial was not weight-adjusted and one puzzling finding discussed atlength in the committee's deliberations was weight-related safety andefficacy discrepancies.For example, patients who weighed more experienced fewer bleedingepisodes and enjoyed greater benefit from ReoPro therapy. However,patients who weighed less were more likely to suffer bleeding episodesand less likely to benefit. The weight-efficacy interaction was quitecomplex and no one was able to adequately explain the finding.The Malvern, Pa. company's stock (NASDAQ:CNTO) closed at$11.88, up $1 per share _ well before the vote took place at 7:15 p.m.EST. The stock jump might have been due to the fact that printedquestions distributed by the FDA at the meeting seemed to focus onlabeling issues rather than core data issues, suggesting that the FDAwas inclined to license the drug. (For more background information onCentocor's ReoPro, see BioWorld Today, June 9, 1994, p. 1.) n
-- Lisa Piercey Washington Editor
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