A trial of clot busters for treating peripheral arterial occlusion(PAO), or blood clots in the limbs, has been halted, GenentechInc. announced Friday.

The company was seeking to develop broader applications forits tissue plasminogen activator (t-PA).

In January 1992, Genentech initiated a Phase III clinical trialthat compared thrombolytic therapy -- either Genentech's t-PAor Abbott Laboratories' urokinase -- with surgery alone fortreating PAO. That trial, termed the STILE (surgery andthrombolysis for ischemia of the lower extremity) study andled by Robert Graor at the Cleveland Clinic Foundation, has nowbeen discontinued.

Genentech (NYSE:GNE) said Friday that technical failures in thethrombolytic arm of the study rendered the therapy notevaluable. Apparently "there were difficulties placing thecatheter delivering the drug into the clot," said Barry Sherman,Genentech's vice president and chief medical officer.

"If the thrombolytic agent can't be delivered directly to theclot, you can't really tell whether the thrombolytic is effectivein dissolving the clot," Sherman added.

Apparently, at least anecdotal evidence has shown that thethrombolytic therapy should work. "Although it's not indicated,physicians have used urokinase for this indication for a longtime," Jim Weiss, Genentech's manager of corporatecommunications, told BioWorld.

But a preliminary analysis of the available data on the 300patients in this study indicated that surgery alone was betterthan either thrombolytic in satisfying the primary efficacy endpoint criteria, which included mortality, major amputation orrecurrent ischemia, explained Weiss.

Once the data have been analyzed, Genentech of South SanFrancisco, Calif., will consider whether to conduct additionaltrials in the broad PAO patient population, which altogetherconsists of about 120,000 people in the U.S. annually.

Meanwhile, the company is already planning to run two PhaseIII clinical trials on PAO patient subpopulations this fall. Thosetrials, which will probably begin in the third quarter, will testthe efficacy of t-PA in treating patients at high risk ofrequiring a limb amputation and patients whose clots are onlya few hours old (rather than chronic).

-- Jennifer Van Brunt Senior Editor

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