BETHESDA, MD. _ The FDA's Cardiovascular and Renal DrugsAdvisory Committee voted unanimously on Friday afternoon torecommend that an accelerated dosing regimen of Genentech Inc.'s t-PA is safe and effective for the treatment of heart attacks and should beincorporated into the product's labeling.The committee's action, especially if it is followed by swift FDAapproval, could help clear the clouds of controversy that have swirledaround competing clot-buster drugs t-PA and streptokinase (alsoknown as thrombolytics). Analysts said on Friday that formal FDAapproval could allow the South San Francisco company to gain an evenlarger share of the thrombolytic market than its current 70 percent.Genentech's stock (NASDAQ:GNE) closed the day at $49.25, up $1.50per share on the news."Today's recommendations are an important step toward improvingheart attack survival rates in this country," said Genentech's presidentand CEO, G. Kirk Raab. "As many as 1,700 additional lives might besaved by increased use of Activase t-PA. We hope formal FDAapproval of the committee's recommendations will soon follow."The advisory committee voted 10 to 0 to recommend that the FDAapprove a rapid infusion of the drug over 90 minutes in addition to itscurrent approved dosing regimen of infusion over three hours. Therapid infusion regimen was tested in a 41,021-patient study called theGlobal Utilization of Streptokinase and t-PA for Occluded Arteries(GUSTO) trial.GUSTO randomized patients at 1,081 hospitals in 15 countries toreceive four different thrombolytic regimens: streptokinase plusintravenous heparin, streptokinase plus subcutaneous heparin,accelerated dose t-PA, or a combination of streptokinase and t-PA. At30 days post-treatment, patients who received an accelerated dose of t-PA had a 1 percent lower mortality rate than those who receivedstreptokinase. The 1 percent absolute difference in mortality representsa 14.6 percent risk reduction that was statistically significant (p =0.001).The benefits of t-PA in the GUSTO trial did not come without risks.The drug increases the incidence of both fatal and non-fatal strokes inpatients. But advisory committee members said the risks wereoutweighed by the drug's benefits. Certain characteristics, such asadvanced age, location of heart attack (inferior region of the heart vs.anterior), and high blood pressure, appeared to dispose patients tohigher risk for strokes. However, the committee recommended againstlabeling t-PA in such a way as would formally exclude those patientsfrom treatment with the accelerated regimen.In addition, the accelerated regimen appeared to lose its efficacyadvantage over other regimens when patients were treated more thansix hours from the onset of heart attack symptoms, such as chest pain.Committee members voted six to three to recommend that the FDAinclude information on the new label about the age, time-to-treatmentand infarction location issues regarding t-PA's use.Genentech spent $55 million on GUSTO in a gamble to determinewhether t-PA or streptokinase was best for treating heart attackpatients. Critics have focused on the cost differential between the twodrugs: t-PA at $2,200 per dose and streptokinase at $200 per dose.However, drug prices are not subject to FDA review.One unique aspect of t-PA's labeling is that it will compare the drug'sperformance to that of its most direct competitor, establishing a newprecedent. For example, t-PA's label will now include GUSTO data onmortality rates and incidences of stroke for both t-PA andstreptokinase. Most drugs' labels measure efficacy against a placebo,not another drug. But FDA reviewer Robert Temple predicted onFriday that increasing numbers of drug trials will involve comparisonsbetween competing drugs as manufacturers scramble to prove the cost-effectiveness of their products. n
-- Lisa Piercey Washington Editor
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