NUVELO INITIATES TRIAL OF RECOMBINANT ANTICOAGULANT

Nuvelo has begun enrolling patients in a Phase II trial of recombinant nematode anticoagulant protein c2 (rNAPc2) for the treatment of metastatic colorectal carcinoma, the second leading cause of cancer-related death in the United States, according to the company.

The primary objectives of the multicenter, two-stage trial are to determine the safety and efficacy of twice-weekly, subcutaneous rNAPc2 for the second-line treatment of metastatic colorectal carcinoma in combination with 5-fluorouracil (5-FU)-based chemotherapy regimens.

The first stage will evaluate the safety and activity of rNAPc2 in a three-tier dose escalation format (2.5, 5 and 10 micrograms/kg). The second stage will randomize patients to doses determined safe during the first stage by an independent data monitoring committee and placebo in conjunction with standard chemotherapy regimens. Nuvelo plans to enroll up to 100 patients in the study.

RNAPc2 is a recombinant protein fashioned after one originally isolated from the saliva of the dog hookworm. The factor VIIa/tissue factor protease complex has been shown to play a role in the cellular signaling of both metastasis and angiogenesis in a variety of cancers. In addition, rNAPc2 is an anticoagulant that results from its ability to block the factor VIIa/tissue factor protease complex, which is responsible for the initiation of blood clot formation.

Results from a Phase II dose-escalation safety trial of rNAPc2 in more than 200 patients with non-ST-segment elevation acute coronary syndromes demonstrated that rNAPc2 had an acceptable safety profile and was well tolerated in doses up to 10 micrograms/kg. The results showed that treatment with rNAPc2, in addition to standard antithrombotic therapies, resulted in a dose-related inhibition of thrombin generation without an increase in clinically significant bleeding. In addition, rNAPc2 suppressed F1+2 and prolonged the prothrombin time, both in a dose-related fashion.