By Mary Welch
Genentech Inc. reported that results from a 17,000-patient Phase III trial showed its single-bolus thrombolytic, tenecteplase (formerly TNK-tPA), proved to be as effective and safe as Activase, the market-leading thrombolytic for the treatment of heart attacks.
¿We are really, really happy about the results,¿ said Susan Hellmann, Genentech¿s chief medical officer. ¿We did what we set out to do, which is develop a new-generation thrombolytic that was as good as Activase, which is the gold standard.¿
The advantage of tenecteplase lies in ease of administration ¿ a quick shot vs. a 90-minute infusion for those taking Activase.
The trial, conducted at 1,000 sites in 29 countries, pitted tenecteplase against Activase (Alteplase, recombinant), which is also marketed by South San Francisco-based Genentech. The trial was designed as a randomized, double-blind, parallel-group study in patients with acute myocardial infarction, or heart attack.
The results, given at the scientific session of the American College of Cardiology in New Orleans, showed that both Activase and tenecteplase had mortality rates of 6.2 percent. In addition, side effects, particularly intracranial hemorrhaging, were similar. Patients taking tenecteplase had a 0.93 percent rate of intracranial bleeding, compared to 0.94 percent taking Activase.
¿We looked at the bleeding rates of Activase, and really all the thrombolytic drugs, and tried to reduce the incidence of bleeding,¿ Hellmann said. ¿It¿s really exciting to engineer a molecule to do something, and it does it.¿
The results of the ASSENT 2 trial (Assessment of the Safety and Efficacy of a New Thrombolytic agent) will be submitted as part of a biological license application (BLA) to the FDA. They also will be submitted in Europe by Boehringer Ingelheim GmbH, of Ingelheim, Germany. Both filings are planned for the third quarter of this year. Boehringer Ingelheim is the co-sponsor of the ASSENT 2 study and Genentech¿s international marketing partner for Alteplase and developmental collaborator for tenecteplase. Final results will be presented during the European Society of Cardiology meeting this August in Barcelona, Spain.
¿We¿re done,¿ Hellmann declared. ¿We¿re ready to file this with the FDA as soon as possible and launch this drug. There are no outstanding issues, no safety or dose questions. It¿s a great position to be in.¿
In Phase II trials, tenecteplase, a bioengineered version of Activase, dissolved the clots that caused heart attacks as well as Activase, but required only a single intravenous injection as compared to the 90-minute infusion of Activase to clear a blocked coronary artery. To date, tenecteplase has been studied in clinical trials involved more than 21,000 patients worldwide. (See BioWorld Today, Aug. 27, 1997, p. 1.)
Activase is a recombinant version of naturally occurring tissue plasminogen activator (t-PA). However, tenecteplase has been specifically designed to prolong its half-life, increase specificity for fibrin (a key component of intracoronary clots) and increase resistance to plasminogen activator inhibitor-1 (PAI-1), a protein that can interfere with the clot-dissolving effects of both naturally occurring and recombinant t-PA during a heart attack.
Activase sales were $213 million in 1998 (down from $269.7 million in 1997) but it still is the market leader among thrombolytic agents. More than 1 million heart attack patients have been given the drug since its launch in 1987.
Genentech¿s stock (NYSE:GEN) closed Tuesday at $81.437, down 6.25 cents. n