Boehringer Mannheim Pharmaceuticals Corp. plans to conduct PhaseIII studies of its clot buster, reteplase (rPA), in a pivotal head-to-headcompetition with Genentech Inc.'s alteplase (tPA) for treating heartattacks.

The 12-month trials, dubbed GUSTO III, are scheduled to begin thissummer at 500 centers in the U.S. and Europe and will involve10,000 and 12,000 patients, respectively.

Boehringer Mannheim Pharmaceuticals, of Gaithersburg, Md., hasdecided to launch the studies, in part, after Phase II trials, which itcalled Rapid 2, showed that rPA opened blocked arteries faster thantPA.

The primary aim of the new GUSTO (Global Utilization Strategy forThrombolysis of Occluded Arteries) study will be to assess the effectof reteplase, or recombinant plasminogen activator, on mortality.

Genentech's tPA, or tissue plasminogen activator, is sold under thebrand name Activase and is considered the gold standard amongthrombolytic agents. Activase accounts for 70 percent of sales in theU.S. among blood clot dissolvers. Germany-based BoerhingerIngleheim GmbH markets tPA in Europe.

Genentech spokesman, Jim Weiss, said the South San Francisco-based company is not directly involved in the GUSTO III studies.

Despite the apparent early stage success of reteplase, analysts saidGenentech's market position is not threatened in the near term.

"This product [reteplase] is a long way from being approved and along way from demonstrating superiority to tPA," said BarbaraHoffman, an independent biotechnology analyst in Denver. "We'llhave to wait several years to find out."

Genentech's stock (NYSE:GNE) closed Monday at $48.87, down 12cents.

Boerhringer Mannheim, a subsidiary of London-based Corange Ltd.,announced their plans for GUSTO III Monday in New Orleans at anAmerica College of Cardiology conference. The company alsopresented data from the Rapid 2 trials and another study, calledINJECT, comparing reteplase with streptokinase, which is marketedby Astra AB and Kabi Pharmacia AB of Sweden.

The Rapid 2 trials involved 324 patients. Investigators reported thereteplase opened arteries more completely than Genentech's Activaseat 60 minutes and 90 minutes after the start of therapy.

However, in the INJECT trials involving 6,000 patients, reteplase didnot perform any better than streptokinase in comparisons involvingmortality. A spokesman for Boerhinger Mannheim said the studiesshowed reteplase was "at least as effective" as streptokinase and thatreteplase "still had a tendency to open arteries faster."

It was data from the first GUSTO trials, involving 41,000 patientsand completed in 1993, that established Activase as the standardthrombolytic therapy. Those studies showed Genentech's tPA had a 1percent survival advantage over streptokinase.

Hoffman said the thrombolytic field has been competitive from thestart and will continue to be a heated battleground.

Weiss said Genentech has a second generation tPA product in clinicaldevelopment. Phase I studies of the drug, called TNK, have revealedit opens arteries faster and has fewer adverse side effects than tPA.

GUSTO trials are coordinated by Eric Topol, chairman of theDepartment of cardiology and professor of medicine at the ClevelandClinic Foundation, and Robert Califf, professor of medicine at DukeUniversity Medical Center in Durham, N.C.The ongoing GUSTO II trials are designed to test anticoagulants assubstitutes for heparin. n

-- Charles Craig

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

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