By Mary Welch
Genentech Inc. submitted a biologics license application (BLA) for tenecteplase, seeking approval to market the drug for use in the treatment of heart attack patients.
"It's a great molecule and we believe clinicians will like using it when it becomes available," said David Stump, vice president of clinical research at Genentech. "It has a high level of safety and efficacy but also a convenience of usage. We believe it will be the standard of treatment for acute myocardial infarction."
The BLA is supported by a 17,000-patient Phase III trial conducted at 1,000 sites in 29 countries that pitted tenecteplase against Activase (alteplase, recombinant), which also is marketed by South San Francisco-based Genentech. The ASSENT II (Assessment of the Safety and Efficacy of a New Thrombolytic agent) trial was a randomized, double-blind, parallel-group study in patients with acute myocardial infarction, or heart attack.
Results, presented last March, showed the two drugs shared a mortality rate of 6.2 percent and had similar side effects, namely hemorrhaging. Patients taking tenecteplase (formerly TNK-tPA) had a 0.93 percent rate of intracranial bleeding, compared to 0.94 percent taking Activase. To date, some 21,000 patients worldwide were involved in tenecteplase clinical trials.
A single-bolus thrombolytic, tenecteplase has proved to be as effective and safe as Activase, the market-leading thrombolytic for the treatment of heart attacks. A bio- engineered plasminogen activator, tenecteplase is similar to Activase, which is a recombinant version of a naturally-occurring tissue plasminogen activator (t-PA), both of which dissolve blood clots causing heart attacks.
Tenecteplase has been specifically designed to have a prolonged half-life, increased specificity for fibrin (a key component in an intracoronary clots) and increased resistance to plasminogen activator inhibitor-1 (PAI-1) - a protein that can interfere with clot-dissolving effects of both naturally occurring and recombinant t-PA during a heart attack.
The difference - and possible sales advantage - is that tenecteplase is delivered via a quick shot vs. a 90-minute infusion for those taking Activase.
Jon Alsenas, managing director at ING Baring Furman Selz LLC in New York, said, "I think its absolutely necessary for Genentech to remain competitive in the thrombolytic market. The good news is this allows them to maintain market share, but long term it's getting clearer and clearer that thrombolytics are most effective in combination with platelet inhibitors."
Activase posted 1998 sales of $213 million. Stump said the company expects tenecteplase to assume a large percentage of those sales. "I'm sure some physicians will still use Activase because they are comfortable with it," he said. "But we expect tenecteplase will become the drug of preference. Activase is also indicated for acute pulmonary embolism as well as acute ischemic stroke."
Genentech may look into other indications for tenecteplase at a later time, he added.
European partner Boehringer Ingelheim GmbH, of Ingelheim, Germany will file for marketing approval there next month.
This is the second marketing license Genentech has applied for this summer. In June, it submitted a new drug application (NDA) for Nutropin Depot, a long-acting formulation of recombinant human growth hormone. Also that month, F. Hoffmann-La Roche Ltd., exercised its call option for the remaining 33 percent of Genentech's stock that it didn't own. The call price was $82.50. (See BioWorld Today, June 29, 1999, p. 4.; and June 4, 1999, p. 1.)
In July Genentech completed an initial public offering as Roche offered 20 million Genentech shares at $97 per share. (See BioWorld Today, July 21, 1999, p. 1.)
Genentech's stock (NYSE:DNA) closed Monday at $145, up $3.