By Matthew Willett
Corvas International Inc. reported positive results from a Phase II clinical trial of the injectable anticoagulant rNAPc2 for prevention of deep vein thrombosis (DVT) and related complications.
The trial enrolled patients undergoing total knee replacement surgery and showed rNAPc2 - a small protein originally discovered in blood-feeding hookworms and now produced as a recombinant protein for clinical use - reduced the risk of DVT by 50 percent versus standard-of- care treatment using low-molecular-weight heparin (LMWH).
Vice President of Research and rNAPc2 innovator George Vlasuk said the results support advancing the program into Phase III trials.
"It's highly encouraging," he said. "We're putting together the Phase III program right now, and we're planning to move into Phase III testing in the second half of 2001. It'll be a randomized, double-blind study comparing the compound to low-molecular-weight heparin in orthopedic surgery patients."
The Phase II trial was a 292-patient open-label, dose-ranging study that found safety of the drug comparable to LMWH treatment. Safety was evaluated using incidence of major and minor bleeding.
Incidence of DVT - the study's primary efficacy endpoint, measured by unilateral venography - was compared to historical data for LMWH treatment in patients in the study population.
Three Phase I trials preceded the Phase II clinical trial, and the compound is currently under evaluation in a Phase IIa trial initiated in 1999 with patients undergoing elective percutaneous transluminal coronary angioplasty.
Corvas initiated the Phase II trial reported on this week in 1998. The San Diego-based company is also developing therapies for acute myocardial infarction, unstable angina and pulmonary embolism, as well as oncology therapeutics, stroke, malaria and hepatitis C treatment.
Corvas' anticoagulant works by inhibiting the serine protease Factor VIIa, which, in binding to Tissue Factor, catalyzes the formation of Factor Xa, the formative agent for thrombin.
A similar compound, rNAP5, inhibits Factor Xa directly. and the company has conducted preclinical development in preparation for Phase I testing for similar indications.
Venous thrombosis is the third leading cause of cardiovascular morbidity and mortality, and is closely associated with pulmonary embolism, the often-fatal transport of a blood clot to the lungs.
Standard-of-care treatment for post-surgical prophylaxis of DVT demonstrated a 40 to 50 percent reduction in DVT versus no prophylaxis.
The company estimates the global market for LMWHs and other anticoagulants at more than $2 billion annually.
Corvas plans to present details of the study at the 42nd American Society of Hematology Annual Meeting in San Francisco Dec. 1-5.