Genentech Inc. last week renewed its defense of Activase t-PAin the wake of formal publication of the year-old ISIS-3 studyof clot dissolvers and new publication of data showing elevatedoccurrences of stroke associated with the drug.

The results of ISIS-3, a 40,000-patient comparison that showedno advantage of high-priced t-PA over cheaper clot dissolvers,were published last week in The Lancet.

An accompanying editorial stated, "The clearest message toemerge from this massive enterprise is that ... no thrombolyticregimen performed better, in terms of 35-day survival, thanthe simple and cheap" combination of aspirin andstreptokinase. Activase costs $2,200, about 10 times the cost ofstreptokinase.

The study compared a form of t-PA made by BurroughsWellcome Co. with streptokinase and APSAC, a clot dissolverbased on streptokinase. Wellcome's drug is no longer produced.Activase is prescribed to half of U.S. heart-attack patientstreated with a thrombolytic, streptokinase to 36 percent, andAPSAC to 11 percent, according to Genentech market researchconducted in January.

Genentech spokesman Jim Weiss said Activase's market shareshould not change with publication of the study, the results ofwhich were reported at a cardiology conference a year ago andwere covered widely by the press. The South San Francisco,Calif., company is pinning its hopes on the GUSTO internationaltrial of Activase and streptokinase, which should end in 1993.

Genentech maintains that the use of subcutaneous heparin inISIS-3, which differs from U.S. practice, had an important effecton the results. The company argues that the intravenousadministration of heparin in the GUSTO trial will provide amore relevant measure of the anti-coagulant's effects whencombined with clot dissolvers.

Based on nine clinical trials, the company also said the pooledrate for intracranial bleeding with its t-PA was five-tenths of apercent. The ISIS-3 rate was seven-tenths of a percent.

Genentech on Thursday also said that its data base of morethan 17,000 Activase patients shows a stroke rate "well below"the 7 per 1,000 rate reported by ISIS-3.

However, The Lancet this week also published a letter in whichSwiss researchers reported a stroke rate of 3 percent withGenentech's agent. "Our findings are worrying because theoverall incidence of intracranial hemorrhage is five timeshigher than that seen in the larger" randomized clinical studies,the researchers wrote.033092ISIS-3

-- Roberta Friedman, Ph.D. Special to BioWorld

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