By Lisa Seachrist
WASHINGTON — COR Therapeutics Inc.'s stock soared 79 percent in response to news the FDA had issued an approvable letter for the company's anti-clotting agent, Integrilin, for the treatment of patients with acute coronary syndromes and as an adjunct to coronary angioplasty and atherectomy.
COR's stock (NASDQ:CORR) jumped $9.844 to close at $22.312 Thursday. The surge was in stark contrast to the 53 percent dive the company's stock took after a Jan. 29 advisory panel offered the company only lukewarm support for the drug.
The FDA essentially ignored the committee's recommendation in providing the company a broad indication, which includes patients with acute coronary syndromes (unstable angina and non-Q-wave myocardial infarction) as well as those undergoing percutaneous transluminal coronary angioplasty (PTCA) and atherectomy.
"It's been quite a long journey for us," said Vaughn Kailian, president and CEO of South San Francisco-based COR. "It certainly hasn't been a paved superhighway. This is one of those days when you are glad you stuck with it."
The FDA's letter informed the company Integrilin may be approved following satisfactory completion of product labeling and response to outstanding questions.
Integrilin, an inhibitor of platelet aggregation, is a synthetic peptide derived from the venom of the Southeastern pygmy rattlesnake. The drug specifically blocks the GPIIb-GPIIIa receptor, which binds fibrinogen and mediates platelet aggregation — the first step in clotting. Integrilin has a very rapid onset and a short duration.
Should the drug be approved, it will join Malvern, Pa.-based Centocor Inc.'s GPIIb-GPIIIa inhibitor, ReoPro, which is already on the market, albeit with narrower indications. ReoPro is approved for patients undergoing percutaneous coronary interventions (PCI) including angioplasty, atherectomy and stent placement, but is indicated only in unstable angina patients targeted for PCI. ReoPro is a monoclonal antibody.
FDA's 'Illogical' Advisory Panel A Major Hurdle
The Cardiovascular and Renal Drugs Advisory Committee has been a major hurdle in Integrilin's road to market. The panel rejected the drug twice, noting that in 1997, a single Phase III trial of Integrilin didn't provide sufficient evidence to recommend the drug for approval as an adjunct to angioplasty.
In January, the panel decided a second Phase III trial of the drug in nearly 11,000 patients with unstable angina and non-Q wave myocardial infarction supported the angioplasty trial and suggested the FDA approve the drug only as an adjunct to angioplasty at a dosage that the company considered suboptimal.
"I have been calling that panel the Cardiovascular Illogical Committee," said Matthew Geller an analyst with CIBC Oppenheimer, in New York. "Their decision made no sense; it was such a big, successful study. If FDA had followed their recommendation, the agency would have discouraged companies from doing big trials."
Instead, the agency offered the label that the company requested in its new drug application (NDA). The FDA suggested the company use a dosage of 180 micrograms per kilogram bolus plus a 2 microgram per kilogram per minute infusion of Integrilin for patients with acute coronary syndromes, and a dosage of 135 micrograms per kilogram bolus plus a 0.5 microgram per kilogram per minute infusion when used and an adjunct to PTCA. The dosages were the ones used in the two studies.
"The FDA completely rejected the advice of the panel in issuing this letter," said Mark Simon, managing director with BancAmerica Robertson Stephens, of New York. "My suspicion is that the FDA listened to the principal investigators and physicians who ran the study. They are really the best judges of whether or not the drug works."
Simon and Geller noted that even though ReoPro is on the market, Integrilin has an indication that will allow it to be used on any patient who comes in with acute coronary syndrome. As a result, when a patient presents in the emergency room with unstable angina, they will receive Integrilin. Only patients who clearly must have an angioplasty are likely to receive ReoPro.
"Plus, ReoPro is a very expensive drug," Geller said. "The cardiologists I have talked to say that if Integrilin is priced well, they are going to use it."
In addition to ReoPro and Integrilin, Merck & Co. Inc., of Whitehouse Station, N.J., is going to present data on Aggrastat, its GPIIb-GPIIIa inhibitor, to the Cardiovascular and Renal Drugs Advisory Committee next week. Simon observed the market for these types of drugs is estimated to be $3 billion worldwide. "There is plenty of room for all three competitors to succeed," he said.
Kailian noted the company expects to have approval and the drug on market by the third quarter of this year. COR's marketing partner for Integrilin worldwide is Schering-Plough Corp., of Madison, N.J. *