By Charles Craig
Texas Biotechnology Corp. said two Phase II studies of its heparin substitute, Novastan, support continued development of the drug as an adjunct to thrombolytics for treatment of acute heart attacks.
Novastan (argatroban) is a small molecule inhibitor of thrombin, an enzyme involved in blood clotting. Texas Biotechnology licensed U.S. and Canadian rights to the drug, which is derived from an amino acid called L-arginine, from Genentech Inc., of South San Francisco. Mitsubishi Chemical Corp., of Tokyo, markets Novastan in Japan for chronic arterial occlusions.
Joseph Welch, vice president of business development for Houston-based Texas Biotechnology, noted the most advanced clinical studies of Novastan evaluate the drug for patients allergic to heparin, which is the standard anticoagulant used in coronary procedures.
Novastan is in Phase III trials for angioplasty and coronary surgery patients who are at risk of developing heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia thrombosis syndrome (HITTS). Results are expected in the second quarter of 1997 and the company plans to file a new drug application with the FDA for Novastan in June.
In another clinical development program, Texas Biotechnology designed studies to evaluate Novastan as a more effective alternative to heparin for treating acute myocardial infarction. Phase II trials tested Novastan against heparin when used with TPA or streptokinase, two standard thrombolytics. Another Phase II trial evaluated Novastan with streptokinase versus streptokinase alone.
In the U.S., heparin routinely is used with TPA, but not with streptokinase. In Europe heparin is used with both thrombolytics.
Phase II data reported this week at the American College of Cardiology annual meeting, in Anaheim, Calif., showed Novastan outperformed heparin when both were used with TPA. In the 120-patient U.S. trial heart attack patients were randomized to receive either heparin or Novastan with TPA, which is sold by Genentech under the brand name Activase. Investigators reported Novastan improved arterial reperfusion 29 percent over heparin, which they added was a statistically significant finding.
A Phase II trial of Novastan with streptokinase against streptokinase alone was designed to test Novastan's safety and effectiveness in preventing cardiac complications 30 days following treatment. The composite endpoint included prevention of another heart attack, urgent angioplasty or coronary bypass, congestive heart failure and death.
The study, involving 900 patients, showed Novastan was safe and caused no major bleeding, but did not achieve statistical significance versus streptokinase and a placebo in preventing the composite of subsequent cardiac complications. However, investigators said Novastan demonstrated trends toward improvement of specific complications contained in the composite endpoint.
Texas Biotechnology is sharing data from its Phase II trials of Novastan with Synthelabo S.A., of Montrouge, France, which has rights to develop Novastan in Europe. Synthelabo is conducting Phase II studies of Novastan against heparin when used with TPA and streptokinase. Results from those trials have not been released.
Welch said Texas Biotechnology will evaluate data from its studies and the Synthelabo trials to determine how to structure Phase III tests and what thrombolytics to use in combination with Novastan.
Despite what Texas Biotechnology described as promising results from the Phase II studies, the company's stock (AMEX:TXB) dropped 21 percent Monday when the data were released. Texas Biotechnology closed Tuesday at $4.938, down $0.312. *