Tuesday, Aug 26, 1997
South San Francisco, Calif. -- August 26, 1997 --Two new Phase II studies presented today at the European Society of Cardiology, demonstrated that TNK-tPA has comparable efficacy and safety properties to the current standard treatment for heart attacks, the 90-minute infusion of tissue plasminogen activator (tPA). TNK-tPA is a bioengineered drug designed to be administered as a single intravenous injection over five to ten seconds which dissolves clots that cause heart attacks without interfering with other clotting factors. The studies together represent the largest Phase II program for any clot-dissolving agent and provide a strong basis for a further study of TNK-tPA in a large international Phase III trial.
The two Phase II studies were conducted in parallel to evaluate the efficacy and safety of TNK-tPA at various doses in patients with heart attacks. The TIMI (Thrombolysis in Myocardial Infarction) 10B study evaluated the efficacy of TNK-tPA compared with tPA at restoring blood flow in coronary arteries at 90 minutes following the start of treatment. A total of 886 patients presenting within 12 hours of symptom onset at 76 hospitals in North America and Europe were randomized to receive intravenously either a single bolus of TNK-tPA or a 90-minute infusion of tPA. A similar number of arteries were opened by the single bolus of TNK-tPA as with the 90-minute tPA infusion. The 90-minute TIMI 3 flow rates were 63 percent with 40 mg of TNK-tPA as compared to 62.5 percent with tPA.
"The advantage of this `bolus thrombolytic' is that it simplifies treatment, which may help speed the time to treatment and thus save lives for heart attack patients," said Christopher Cannon, MD, Assistant Professor of Medicine at Harvard Medical School and a cardiologist at Brigham and Women's Hospital in Boston, USA. "It is also encouraging to note that, while the 90-minute coronary blood flow for TNK-tPA was similar to that for tPA , the 60 minute results tended to favor for TNK-tPA (54.7 percent for 40 mg of TNK-tPA versus 48.2 percent for tPA)," added Dr. Cannon.
The ASSENT I trial (Assessment of the Safety of a New Thrombolytic), evaluated the rates of intracranial hemorrhage (bleeding strokes) and mortality in patients treated with the same doses of TNK-tPA. A total of 3,325 patients presenting within 12 hours of symptom onset at 342 hospitals in 20 countries were randomized to receive one of several doses of TNK-tPA. The 30-day mortality of 40 mg of TNK-tPA was 5.9 percent. The incidence of intracranial hemorrhage with 40 mg of TNK-tPA was 0.75 percent.
"The ASSENT trial provides us with encouraging rates of intracranial hemorrhage and mortality at 30 days for TNK-tPA - similar to that for tPA. As we rapidly move into a Phase III trial, the Phase II data presented today gives us a very good understanding of the optimal dosing as well as the safety profiles of this new drug," said Dr. Frans Van de Werf from the University of Leuven, Belgium.
Another interesting observation in both trials was that using a lower dose of the blood-thinning medication, heparin, in conjunction with clot-dissolving medications, was associated with a lower rate of hemorrhagic strokes. Dr. Cannon noted that "our data suggest that lower doses of heparin are safer, and that physicians may consider using lower doses of heparin for their patients in conjunction with newer clot-dissolving agents."
The North American hospitals participating in both studies were coordinated at Brigham and Women's Hospital, under the chairmanship of Dr. Eugene Braunwald.
Hospitals outside North America were coordinated by Dr. Frans Van de Werf, at the University of Leuven, Belgium. TNK-tPA is a co-development effort between Genentech, Inc. and Boehringer Ingelheim GmbH.
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