ACS accounts for more than one million hospitalizations annually in the United States. It occurs when an atherosclerotic plaque ruptures in a coronary artery, triggering the coagulation cascade, which results in the formation of a blood clot. The clot blocks the flow of blood to the heart muscle depriving it of oxygen (ischemia), which can result in unstable angina or heart attack.
"Treatment with rNAPc2 resulted in a reduction in ischemia without an increase in clinically significant bleeding. This outcome appears to be mediated by rNAPc2's inhibition of coagulation initiation, thereby preventing blood clot formation," said Dr. Giugliano. "This novel mechanism is of interest since currently approved drugs, such as heparin, do not target the proximal stages of the coagulation process. These proof-of-concept data warrant larger-scale evaluation to determine if rNAPc2 improves clinical outcomes in NSTE-ACS patients."
ANTHEM/TIMI 32 Study Details and Results
The ANTHEM (Anticoagulation with rNAPc2 To Help Eliminate MACE)/TIMI 32 trial consisted of a Phase 2a dose escalation safety trial and a Phase 2 heparin replacement trial. The Phase 2a dose escalation trial investigated the safety of rNAPc2 in combination with other antithrombotics in 203 patients with NSTE-ACS. Safety results from this trial were presented at the 2005 American Heart Association Scientific Sessions and demonstrated that rNAPc2 has an acceptable safety profile and is well tolerated in doses up to 10 mcg/kg in patients being treated for NSTE-ACS.
The Phase 2 heparin replacement study was an open-label study evaluating the efficacy and safety of rNAPc2 in combination with half-dose or no unfractionated heparin. The goal of the study was to assess the potential of rNAPc2 by reducing the dose of, and ultimately replacing, unfractionated heparin in patients being treated for NSTE-ACS. Fifty-two patients at 24 centers across the United States and Canada were enrolled into two cohorts of 26 each. One cohort received 10 mcg/kg rNAPc2 and a half-dose regimen of heparin, and the second cohort received 10 mcg/kg rNAPc2 and no heparin. The primary endpoint was the rate of major plus minor bleeding. rNAPc2 did not increase major/minor bleeding (3.7 vs. 2.5%, p=NS) despite prolonging the time to clot formation in a dose related fashion, as determined by the internationalized normalized ratio (INR). Four cases of procedure-related thrombosis occurred among the no heparin treatment arm, and none occurred in the half-dose heparin arm.
All patients in the ANTHEM/TIMI 32 study had 3-lead Holters for central assessment for recurrent ischemia, measurement of prothrombin time and F1+2 concentration, and clinical follow-up for up to six months. Data presented at the World Congress of Cardiology demonstrate that rNAPc2 at doses of 7.5 and 10 mcg/kg (higher-dose) were associated with greater than 50% reduction in the incidence and duration of ischemia as measured by continuous ECG monitoring. These same doses suppressed prothrombin fragment F1+2 levels compared to placebo (p<0.01). Hemorrhage rates were 2.5%, 2.9%, and 4.5% for placebo, low- dose, and higher-dose rNAPc2 respectively (p = 0.77).
"Based on these Phase 2 data, rNAPc2 may offer the potential to favorably treat NSTE-ACS patients in conjunction with a reduced dose of heparin or no heparin at all," said Steven R. Deitcher, M.D., vice president and chief medical scientist at Nuvelo.
Webcast Call Information
Nuvelo will hold a conference call today at 4:30 p.m. Eastern Time to discuss this presentation. To participate in the conference call, please dial 866-713-8567 for domestic callers and 617-597-5326 for international callers and reference conference passcode, 21826949. A telephone replay of the conference call will be available through Tuesday, September 12, 2006. To access the replay, please dial 888-286-8010 for domestic callers and 617-801-6888 for international callers and reference conference passcode, 96057794.
This call is also being webcast by Thomson/CCBN and can be accessed at Nuvelo's website at www.nuvelo.com or by visiting Thomson/CCBN's StreetEvents Network. Individual investors can listen to the call at www.earnings.com, Thomson's individual investor portal, powered by StreetEvents. Institutional investors can access the call via Thomson StreetEvents (www.streetevents.com), a password-protected event management site.
About rNAPc2
A novel anticoagulant, rNAPc2 is a recombinant protein fashioned after one originally isolated from the saliva of the dog hookworm. The anticoagulant effect of rNAPc2 results from its ability to block the factor VIIa/tissue factor protease complex, which is responsible for the initiation of the process leading to blood clot formation. Unlike heparin, thrombin inhibitors and other agents that exert their effects at later stages of the blood coagulation cascade, rNAPc2 shows the potential to block the first step in the cascade, inhibiting the coagulation cascade before it starts.
About Nuvelo
Nuvelo, Inc. is dedicated to improving the lives of patients through the discovery, development and commercialization of novel drugs for acute cardiovascular and cancer therapy. Nuvelo's development pipeline includes three acute cardiovascular programs: alfimeprase, a direct-acting thrombolytic in Phase 3 clinical trials for the treatment of thrombotic- related disorders; rNAPc2, an anticoagulant that inhibits the factor VIIa and tissue factor protease complex that recently completed Phase 2 clinical development in acute coronary syndromes; and preclinical candidate NU172, a direct thrombin inhibitor for use as a short-acting anticoagulant during medical procedures. Nuvelo is also advancing an emerging oncology pipeline, which includes NU206 for the potential treatment of chemotherapy/radiation therapy-induced mucositis, as well as rNAPc2 for potential use as a cancer therapy. In addition, Nuvelo expects to leverage its expertise in secreted proteins and cancer antibody discovery to further expand its pipeline and create additional partnering and licensing opportunities.
Information about Nuvelo is available at our website at www.nuvelo.com or by phoning 650-517-8000.
This press release contains "forward-looking statements" regarding the timing and progress of Nuvelo's clinical programs and the potential improvement or benefit that current and future clinical trial programs may demonstrate which statements are hereby identified as "forward-looking statements" for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Such statements are based on our management's current expectations and involve risks and uncertainties. Actual results and performance could differ materially from those projected in the forward- looking statements as a result of many factors, including, without limitation, uncertainties relating to drug discovery; clinical development processes; enrollment rates for patients in our clinical trials; changes in relationships with strategic partners and dependence upon strategic partners for the performance of critical activities under collaborative agreements; the impact of competitive products and technological changes; uncertainties relating to patent protection and uncertainties relating to our ability to obtain funding. These and other factors are identified and described in more detail in Nuvelo filings with the SEC, including without limitation Nuvelo's Quarterly Report on Form 10-Q for the quarter ended June 30, 2006 and subsequent filings. We disclaim any intent or obligation to update these forward-looking statements.
Source: Nuvelo, Inc.
