WASHINGTON -- In the largest study of clot-busters everconducted, Genentech Inc.'s tissue plasminogen activator (t-PA), given in combination with heparin, statistically saved onemore heart attack patient per 100 than the much lessexpensive streptokinase.
"I think it's a wonderful day, mostly for heart attack patients,"David Stump, Genentech's senior director of clinical research,told BioWorld. "We have seen a definitive result which is goingto save as many as 2,000 (U.S.) lives per year."
Heart attack is the leading cause of death in the U.S.
"We have put to rest this battle of the thrombolytics," said EricTopol, chairman of the study and chairman of the Departmentof Cardiology at the Cleveland Clinic Health Sciences Center.
"Accelerated t-PA was significantly better (than streptokinase),with one life more saved per 100," Topol said. "If you openarteries more and faster, it will save more lives."
The two-year study, called the Global Utilization ofStreptokinase and t-PA for Occluded Coronary Arteries Trial(GUSTO), was the largest trial of confirmed myocardialinfarction ever conducted, and included 41,000 heart attackpatients -- 23,000 of them Americans -- in 1,100 sites in 15countries.
A variety of earlier studies had found no advantage for eitherdrug despite a compelling scientific rationale as to why t-PAshould be superior. Within 90 minutes, t-PA dissolves 50percent more clot than streptokinase, Stump told BioWorld.
In the earlier studies, patients had received t-PA over threehours, as approved by the FDA, while in the GUSTO study, thedose was administered in 30 minutes. This, Stump toldBioWorld, was responsible for t-PA's quick action comparedwith streptokinase.
"It had been our hypothesis for a long time that if you couldbring blood supply back to the muscle fast enough, you wouldreduce the magnitude of heart attack," said Topol. Angiographyof 2,400 of the patients demonstrated "improved heartpumping function right away, which is sustained throughoutthe week in the hospital, and which leads directly to reduced30-day mortality," he said.
The final score in the GUSTO study: 7.2 deaths per 100 amongpatients on streptokinase administered with subcutaneousheparin, 6.3 deaths on accelerated t-PA with intravenousheparin, 7 deaths with a combination of t-PA andstreptokinase, and 7.4 deaths with streptokinase withintravenously administered heparin.
The advantage of t-PA, trade named Activase, was bought at aslight cost of one extra disabling stroke per 1,000 overstreptokinase. The primary end point was 30-day mortality.
David Stone, an analyst with Cowen & Co., said the trial resultsare significant. "With the number of patients studied in thistrial," he said, "even a 1 percent decrease in mortality isclinically significant."
"Genentech is saying there are potentially 200,000 patientsavailable for t-PA therapy," said Brandon Fradd, an analystwith Montgomery Securities. "If you assume they penetratethat, it would dramatically expand sales," he said. "It's notillogical to think of sales of $200 to $400 million in the longterm. The $400 million could be reached if Genentech sells t-PAat $2,200 per dose to the full 200,000 patients. It shouldtranslate into earnings benefit."
Stock in the South San Francisco, Calif., company (NYSE:GNE)shot up $4.75 a share on Friday, closing at $37.50 in trading ofmore than 1 million shares.
Astra of Westborough, Mass., which markets streptokinase, saidin a statement that the results of the GUSTO trial are "not amandate" to change thrombolytic therapy from streptokinaseto t-PA. "Although the early data suggest small but statisticallysignificant differences between streptokinase and t-PA, closescrutiny and peer review are necessary before any reliableclinical conclusions may be drawn," Astra said.
"The differences observed between the agents used in GUSTOwere very small -- less that 1 percent for every end pointexamined," Astra said. "Whether such small differences haveclinical relevance in 'real world' settings remains open toquestion."
At more that $2,000 per patient, t-PA costs about 10 times asmuch as streptokinase. For each extra patient saved, the cost isabout $260,000, Jeremy Swan, professor of medicine at theUniversity of California, Los Angeles, and senior consultant tothe Cedars-Sinai Medical Center, told BioWorld.
But for each extra year of life, t-PA costs about $22,000, saidTopol, which is inexpensive compared with other widelyaccepted therapies. The use of different contrast agents incardiac catheterization costs $220,000 per extra year of life,and the cholesterol-lowering drug cholesterymine costs$180,000.
At Blue Cross and Blue Shield of Illinois, "we build it into thebenefit design if it was an approved therapy," Phil Lumpkin,director of health services, told BioWorld. "But right now, cost isnot even a question."
UCLA's Swan had high praise for the researchers, themethodology and t-PA's performance. However, he thinks theresults are not relevant outside of major medical centers.
t-PA is difficult to handle, and in tandem with heparin, evenmore so, Swan told BioWorld. In most instances, a pharmacisthas to supervise drug preparation. "Emergency room doctorsare uncomfortable with it; they all call cardiologists tosupervise them," Swan said. "That is not making the optimaluse of thrombolytics, because the sooner they give them thebetter."
-- David C. Holzman Washington Editor
(c) 1997 American Health Consultants. All rights reserved.