COR Therapeutics Inc. tried to cushion its fall Wednesday fromdisappointing Phase III trial data on Integrelin by focusing onpositive aspects of the study, but Wall Street investors and analystswere not sympathetic as the company's stock dropped 45 percent.(See BioWorld's Special News Bulletin, issued Wednesday.)

South San Francisco-based COR Therapeutics (NASDAQ:CORR)ended the day at $10.25 after plummeting $8.50 on more than 7.7million shares traded.

Preliminary data from the company's Impact II study involving morethan 4,000 angioplasty patients showed Integrelin, a platelet inhibitor,did not reach statistical significance compared with a placebo inpreventing a composite of adverse cardiac events (death, heart attacksand reclosure of arteries), which was the primary endpoint.

However, COR's president and CEO Vaughn Kailian said the anti-blood clotting drug was successful if the evaluation of data focusedonly on the nearly 3,900 patients treated with either the drug orplacebo.

About 3 percent of the 4,010 patients enrolled in the study wereexcluded from the treatment protocol after enrollment, but becausethe trials at 82 medical centers were conducted on an intent-to-treatbasis, all patients were included in the statistical analysis.

Despite COR's interpretation, Mark Simon, of Robertson Stephens &Co. in San Francisco, said there were some "perplexing aspects" tothe data that contributed to investor concerns. Chief among them, hesaid, was that the drug performed better at the lower of two doses.

"Why is the benefit better in a low dose than a high dose?" Simonasked. "There was no explanation for this."

Carl Jordan, of Mehta & Isaly in New York, suggested COR also hasto explain why some patients were excluded from treatment.

"It's accepted that the way to look at trials is on an intent-to-treatbasis," Jordan said.

Integrelin, a small molecule drug, is part of a class of compoundsaimed at inhibiting the IIb/IIIa receptor, which mediates plateletaggregation.

In April, COR signed a potential $120 million collaboration withSchering-Plough Corp., of Madison, N.J., on developing andmarketing Integrelin. Both companies said they will continue ongoingclinical studies of the drug for unstable angina and heart attacks.COR said it will not decide whether to file for FDA approval ofIntegrelin for angioplasty until it meets with the agency to assess theImpact II study.

Integrelin is viewed as a potential competitor for ReoPro, which wasdeveloped by Malvern, Pa.-based Centocor Inc. and approved lastDecember by the FDA. ReoPro, a monoclonal antibody, also targetsthe IIb/IIIa receptor.

Some analysts said Integrelin's downfall could boost ReoPro'smarket potential. Centocor's stock (NASDAQ: CNTO) gained $1.62Wednesday, closing at $15.37, a 12 percent jump.

But Simon said Wall Street's favorable response toward Centocormay not be indicative of the reaction in hospital operating roomswhere doctors have been cautious about using ReoPro, which isexpensive and causes bleeding.

He suggested Centocor and its ReoPro marketing partner,Indianapolis-based Eli Lilly and Co., could have benefited from morepositive Integrelin data because both drugs target the samemechanism of platelet inhibition.

"Now you have 82 more hospitals where the naysayers of ReoProhave more ammunition," he said.

In addition, other analysts noted, Integrelin demonstrated it causesless bleeding than ReoPro, indicating the former could have an edgeif it's approved by the FDA.

Another fallout from the disappointing Integrelin data was the abrupthalt of the upward stock movement in the biotechnology industryspurred by Monday's release of positive Phase III trials ofMyotrophin. The drug, made by West Chester, Pa.-based CephalonInc., is a treatment for Lou Gehrig's disease.

"This clearly disrupts the momentum," said Simon, referring to theIntegrelin trials.

The American Stock Exchange Biotech Index, which soared 15points to 96.16 on the strength of Cephalon's success, fell back 5.19points on COR's disappointment.

In releasing the preliminary data, COR said that when treated patientswere analyzed, there was a 22 percent reduction in adverse cardiacevents for angioplasty patients receiving the lower of two Integrelindoses and a 14 percent reduction for those who got the higher dose.By combining the two groups treated with the drug, the data showedan 18 percent reduction, which the company said was statisticallysignificant.

However, if all patients enrolled in the trial were included in theanalysis, the percentage reduction in adverse events associated withangioplasty dropped to 19 percent for the low dose group and 13percent for those receiving the high dose. Then by combining the twoIntegrelin groups, there was a 16 percent reduction in adverse events,which was not statistically significant when compared to the placebogroup. n

-- Charles Craig

(c) 1997 American Health Consultants. All rights reserved.