Nuvelo has announced the publication of Phase 2 clinical trial results in the July 1st issue of the Journal of Clinical Oncology (JCO), demonstrating that alfimeprase can quickly restore function to occluded central venous access devices (CVADs). The Phase 2 randomised, double-blind, controlled, dose-ranging study compared the safety and activity of three fixed doses of alfimeprase (0.3mg, 1mg and 3mg) against the approved dose of CathfloActivase (alteplase).
Alfimeprase is an enzyme produced by recombinant DNA technology that rapidly dissolves blood clots through a unique mechanism of action, it directly degrades fibrin, a protein that provides the scaffolding for blood clots. In clinical studies, this direct mechanism of action has been shown to provide rapid clot dissolution with a well-tolerated safety profile. Alfimeprase’s thrombolytic activity is localized to the site of delivery because it is rapidly inactivated by alpha-2 macroglobulin, a naturally occurring protein in the blood, as it moves away from the site of delivery and into the general blood circulation. This clearance mechanism focuses the thrombolytic activity to the site of the clot and, in clinical testing, appears to minimize bleeding side effects.
In the study, 55 patients were treated to re-establish patency to their occluded CVADs. The results demonstrated that at the highest dose of 3mg, alfimeprase produced cumulative patency rates of 40% at five minutes, 50% at 15 minutes and 60% at 30 and 120 minutes after the first dose, as well as 80% at 120 minutes after the second dose. By comparison, CathfloActivase produced patency rates of 0% at five and 15 minutes, 23% at 30 minutes and 46% at 120 minutes after the first dose, as well as 62% at 120 minutes after the second dose.
“Restoration of CVAD function within minutes is important because it may facilitate timely delivery of prescribed therapies or enable early identification of CVAD obstructions that require prompt catheter replacement,” said Dr Steven R Deitcher, vice president, medical sciences for Nuvelo and former principal investigator for the trial. “The ability to rapidly restore catheter function also may reduce patient anxiety related to missed or delayed treatment and improve treatment center efficiency.”
Nuvelo’s ongoing Phase 3 clinical program evaluating alfimeprase in catheter occlusion (CO) consists of two overlapping, multi-national trials. The first trial, SONOMA-2 (Speedy Opening of Non-functional and Occluded Catheters with Mini-Dose Alfimeprase), is expected to complete enrolment in the second half of this year. This randomised, double-blind trial is comparing the efficacy of 3mg of alfimeprase with placebo in 300 patients with occluded central venous catheters. Two-thirds of the participants are receiving alfimeprase and the remainder are receiving placebo. The primary endpoint is restoration of catheter function within 15 minutes. The second trial, SONOMA-3, began enrolling patients in February 2006 and is an open-label, single-arm trial that is evaluating the efficacy and safety of alfimeprase in restoring catheter function in 800 patients.
Alfimeprase is also being studied in two pivotal Phase 3 clinical trials, NAPA-2 and NAPA-3, for the treatment of acute peripheral arterial occlusion (PAO). Both trials are randomised, double-blind studies comparing 0.3mg/kg of alfimeprase with placebo in a total of 600 patients between the two studies. The primary endpoint in both trials is avoidance of open vascular surgery within 30 days of treatment. A variety of secondary endpoints are also being evaluated in the two trials, including safety endpoints, such as the incidence of bleeding, and pharmacoeconomic endpoints, such as length of hospital and intensive care unit stay.
In addition, Nuvelo plans to initiate a Phase 2 trial of alfimeprase for the treatment of ischemic stroke in the second half of 2006 and an additional Phase 2 trial of alfimeprase for the treatment of deep venous thrombosis in 2007.
Based on these promising Phase 2 results, we have initiated two overlapping, multi-national Phase 3 trials evaluating the 3mg dose of alfimeprase in catheter occlusion. “We anticipate data from the first of these trials, the SONOMA-2 trial, in the second half of this year, and hope to confirm the ability of alfimeprase to restore function to occluded catheters in 15 minutes or less,” said Dr Ted W Love, chairman and CEO of Nuvelo.
