Alfimeprase Has The Potential To Restore Catheter Function
Nuvelo announced results from the Phase 3 SONOMA-2 (Speedy Opening of Non-functional and Occluded catheters with Mini-dose Alfimeprase-2) trial (N=303), demonstrating that alfimeprase, the company's lead product candidate, actively restored catheter function and was well-tolerated in patients with catheter occlusion (CO). These data were presented yesterday in a poster session by Stephan Moll, M.D., associate professor at the University of North Carolina Medical School in Chapel Hill; Department of Medicine, Division of Hematology-Oncology, at the American Society of Hematology (ASH) 49th Annual Meeting, in Atlanta, GA. A webcast will be held Monday, December 10th at 4:30 p.m. ET to review these data.
"There is an unmet need for a safe and rapid thrombolytic," said Dr. Moll. "Afimeprase could offer a new treatment option for thrombotic-related disorders such as CO due to its potential ability to keep activity direct and localized."
Results from the SONOMA-2 trial show that alfimeprase restored catheter function in patients with occluded catheters within 15 minutes in 34.3 percent of patients in the alfimeprase group versus 21.6 percent in the placebo group (p=0.022). While alfimeprase restored catheter function in a greater number of subjects than placebo, it did not meet its primary endpoint by achieving a p-value of less than or equal to 0.00125 at 15 minutes. At 30 minutes post first or second infusion, catheter function was restored in 52.7 percent of patients treated with alfimeprase versus 30.4 percent in the placebo group (p=0.0002). Rates of adverse events (65.8 percent alfimeprase, 59.4 percent placebo), serious adverse events (15.5 percent alfimeprase, 16.8 percent placebo), and hemorrhagic adverse events (3.6 percent alfimeprase, 10.9 percent placebo) were comparable between treatment groups. No intracranial hemorrhages were observed. Cardiac-related events were reported at a higher rate in the alfimeprase group (6.7 percent) than the placebo group (2.0 percent), however analysis indicated that this was attributed to an imbalance in the distribution of subjects with heart disease at baseline.
"The SONOMA-2 trial results reinforce evidence that alfimeprase is an active and well-tolerated thrombolytic with the potential to quickly dissolve clots and rapidly restore catheter function," said Michael Levy, M.D., executive vice president of research and development for Nuvelo. "We are currently enrolling patients in the SONOMA-3 trial to evaluate whether a higher and more concentrated dose of alfimeprase will improve clot dissolution rates while maintaining the favorable risk benefit profile seen in SONOMA-2. We look forward to sharing top-line data from this trial in the first half of 2008."
Preclinical experiments have provided evidence of increased alfimeprase activity at higher concentrations. Nuvelo is currently enrolling patients in the SONOMA-3 trial. This open-label, single-arm trial evaluates the safety and efficacy of a single 10 milligram dose of alfimeprase with a concentration of 5 milligrams per milliliter in up to 100 patients with occluded central venous catheters.
SONOMA-2 Study Details
SONOMA-2 was a multi-center, multi-national, randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of alfimeprase in subjects with occluded catheters. Subjects were randomized in a 2:1 ratio to receive either 3.0 milligrams of alfimeprase or placebo. Study drug was delivered in a total volume of 2 milliliters. If catheter function was not restored within 30 minutes, a second dose of the same study drug was given and allowed to dwell for an additional 30 minutes. Re-establishment of catheter function was assessed by an attempt to withdraw 3 milliliters of blood and infuse 5 milliliters of saline. The primary efficacy endpoint was restoration of catheter function at 15 minutes post first infusion.