Wednesday, Nov 20, 2002
Chicago -- November 20, 2002 --Genentech (NYSE: DNA) today announced that results from the ASSENT 3 PLUS trial demonstrate pre-hospital administration of the single-bolus thrombolytic (clot-dissolving) agent TNKase™ (Tenecteplase) to patients suffering from acute myocardial infarction (AMI, or heart attack) to be technically feasible and faster than in-hospital treatment. The results were reported today at the annual scientific sessions of the American Heart Association. Administration of clot-dissolving agents in the pre-hospital setting (home or ambulance) were shown to accelerate the treatment of heart attack patients by an average of more than 40 minutes.
The 1,639-patient, international, multicenter, randomized, open-label ASSENT 3 PLUS clinical trial was a satellite study of the larger hospital-based ASSENT 3 trial. The trial was carried out at centers in North America and Europe to evaluate the clinical impact of pre-hospital administration of clot-dissolving therapy. Patients presenting within 6 hours of AMI symptom onset
were randomized to receive one of two treatment regimens: full-dose TNKase + enoxaparin, a low molecular weight heparin, or full-dose TNKase +
unfractionated heparin (UFH). Ambulance response time to patients’ telephone calls was a mean of 16 minutes, and therapy was administered in the ambulance, or in the patient’s home, rather than waiting until arrival at the hospital.
“In this trial, we have been able to treat nearly half of all patients within two hours,” stated Prof. Lars Wallentin, Uppsala University, Uppsala, Sweden, and principal investigator of the ASSENT 3 PLUS study. “However, there is still a problem as to how long the patient takes to telephone the emergency services – more than one hour in half of the patients.” He noted that time from symptom onset to treatment, which has remained at 3 or more hours for decades, was cut to a mean of 2 hours 20 minutes in the ASSENT 3 PLUS trial.
ASSENT 3 PLUS was a descriptive study with two main, pre-specified composite endpoints: a composite efficacy endpoint to evaluate efficacy outcomes, and an “efficacy plus safety” composite endpoint to evaluate efficacy improvements when safety adverse events were added to the analysis. The pre-specified efficacy composite endpoint was measured as a composite of: reduction of 30-day mortality, reinfarction or refractory ischemia. The “efficacy plus safety” composite endpoint combined the above-stated efficacy endpoint with reduction of safety adverse events including intracranial hemorrhage (ICH) or major bleeding complications (other than ICH).
There were no statistically significant differences for either endpoint between TNKase + UFH (n=821) and TNKase + enoxaparin (n=818) (17.36% vs. 14.20% for the efficacy endpoint; 20.29% vs. 18.26% for the efficacy plus safety endpoint for TNKase + UFH and TNKase + enoxaparin, respectively).
Overall 30-day mortality for the TNKase + UFH arm was 5.99%; stratified by time to treatment it was 4.8% at 0-2 hours, 5.8% at 2-4 hours and 10.7% at 4-
6 hours. Overall 30-day mortality for the TNKase + enoxaparin arm was 7.47%; stratified by time to treatment it was 6.03% at 0-2 hours, 8.4% at 2-4 hours and 11.54% at 4-6 hours.
The frequency of the other individual components of the co-primary composite endpoints are as follows: reinfarction 5.85% vs. 3.55%; refractory ischemia 6.46% vs. 4.40%; ICH 0.97% vs. 2.20%, major bleeds 2.80% vs. 4.04% for TNKase + UFH and TNKase + enoxaparin respectively. While there were fewer episodes of reinfarction and refractory ischemia in patients receiving TNKase + enoxaparin, there were also more bleeding events.
To enable pre-hospital administration of thrombolytic therapy, ambulances were equipped with 12-lead electrocardiogram (ECG) machines that deliver a detailed picture of the heart’s activity. Ambulance emergency medical teams were able to transmit the ECG information to the hospital emergency department over mobile phone technology. Physicians at the hospital were then able to make an assessment of the ECG, diagnose acute myocardial infarction and if appropriate, give authorization to the ambulance team to administer a clot dissolving treatment.
ASSENT 3 PLUS was jointly sponsored by TNKase global marketing partner Boehringer Ingelheim and Aventis Pharma AG. maker of Lovenox® (enoxaparin). Boehringer Ingelheim markets TNKase as Metalyse® in Europe and abroad.
TNKase™ (Tenecteplase), is a single-bolus thrombolytic agent, that has been approved by the U.S. Food and Drug Administration for the treatment of acute myocardial infarction (AMI). TNKase is the first "clot-dissolver" that can be administered over five seconds in a single dose, offering physicians the fastest administration of a thrombolytic to date in the treatment of heart attack.
TNKase is a bioengineered variant of Activase® (Alteplase, recombinant), which is a recombinant DNA-derived version of naturally occurring tissue plasminogen activator (t-PA). It is constructed with amino acid substitutions at three sites (the letters T, N and K represent the three regions changed from the natural t-PA protein).
About Heart Attack
According to the World Health Organization, cardiovascular diseases account for 12 million deaths in the world each year. Currently, heart attack is a leading killer of men and women in developed countries. This year, as many as 1.1 million people in the United States will have a coronary attack (includes heart attack and fatal coronary disease), and 4 million people throughout Europe will die of cardiovascular disease.
In heart attack treatment, it is said that “time is muscle,” meaning the longer the heart is starved for blood during a heart attack, the more severe and long-lasting the damage will be, and the greater likelihood of death. Much attention has been focused on reducing delays in treatment – both through patient education and by optimizing the management of emergency care services, such as by incorporating the use of clot-dissolving drugs en route to the hospital.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Fifteen of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes ten biotechnology products directly in the United States. The company has headquarters in South San Francisco, California, and is traded on the New York Stock Exchange under the symbol DNA.
For TNKase and Activase full prescribing information in the U.S., please contact the company web site at www.gene.com.