Nuvelo Announces Positive Phase 1b Proof-of-Concept Data With Anticoagulant NU172
- Phase 2 development to begin in late 2008 or in early 2009 -
SAN CARLOS, Calif., Aug. 14, 2008 /PRNewswire-FirstCall/ -- Nuvelo, Inc. (Nasdaq: NUVO) today announced positive results from the Phase 1b proof-of-concept trial of NU172, demonstrating that the direct thrombin inhibitor rapidly produced and maintained anticoagulation with a rapid return toward baseline after the infusion ended with a favorable safety profile.
"NU172 has the potential to address many of the limitations of currently available anticoagulants given the profile we have seen to date in preclinical and Phase 1 testing, including its ability to produce rapid and predictable onset and offset of anticoagulation without the need for an antidote, its potential ability to work in stagnant blood, its predominately non-renal clearance, and the option to stop and restart anticoagulation as needed during or after surgery," said A. Michael Lincoff, M.D., vice chairman of the department of cardiovascular medicine and an interventional cardiologist at the Cleveland Clinic. "Because of these characteristics, NU172 could potentially offer an improved approach to anticoagulation for procedures such as coronary artery bypass graft (CABG) surgery, kidney dialysis, and percutaneous coronary intervention (PCI)."
The single-center, Phase 1b trial examined the safety, tolerability and pharmacokinetics of intravenous bolus plus infusion dosing of NU172, in 24 healthy male volunteers. Volunteers were given a 2 mg/kg bolus dose followed by escalating infusion doses of NU172 for four hours. In all four cohorts, NU172 produced dose-dependent increases in anticoagulation, measured by activated clotting time (ACT), prothrombin time (PT) and activated partial thromboplastin time (aPTT). The highest infusion dose rate tested, 6.0 mg/kg/hr, resulted in an average ACT per subject ranging from 373 to 414 seconds and an increase of approximately three times baseline. Average PT values per subject ranged from 56 to 92 seconds and had an increase of approximately five times baseline. Average aPTT values per subject ranged from 130 to 178 seconds and had an increase of approximately five times baseline. All measurements were maintained stably throughout the four-hour infusion. Once the infusion ended, the ACT and other coagulation parameters showed a rapid return toward baseline, consistent with the short plasma half-life of NU172 observed in the Phase 1a trial. In addition, NU172 was well-tolerated with no serious adverse events.
"In this study, we were able to identify a dose that meets or exceeds the level of anticoagulation needed for the indications we plan to evaluate, including CABG surgery," said Dr. Ted W. Love, chairman and chief executive officer of Nuvelo. "In addition to supporting our previous proof-of-concept data, the Phase 1b study shows that anticoagulation with NU172 can be maintained for four hours, which is longer than a typical CABG procedure. We are on track to launch a Phase 2 study evaluating NU172 in the fourth quarter of 2008 or the first quarter of 2009."
Approximately 450,000 CABG procedures, 50 million dialysis procedures, and 1.2 million PCIs are performed annually in the U.S. During these procedures, anticoagulants are given to prevent blood clotting. In CABG procedures and often in dialysis, the anticoagulation effect of heparin must be reversed with protamine once the procedure has been completed.
About Aptamers and NU172
Aptamers are chemically synthesized single-stranded nucleic acids that form well-defined three-dimensional shapes, allowing them to bind target molecules in a manner that is conceptually similar to antibodies. Characteristics of aptamers include high specificity and affinity, and the ability to target protein-protein interactions.
NU172 is an aptamer designed to directly inhibit thrombin's ability to stimulate blood clot formation in the setting of medical procedures where human blood is exposed to foreign materials. Specifically, NU172 is being studied for use as a potential short-acting anticoagulant during procedures such as coronary artery bypass graft surgery, kidney dialysis and percutaneous coronary interventions. Data from the Phase 1 trial and preclinical studies suggest that NU172 has the potential to produce rapid and predictable onset and offset of anticoagulation, work in stagnant blood, avoid thrombocytopenia, and has the potential for non-renal clearance.
About Nuvelo and Archemix's Joint Collaborative Effort
In August 2006, Nuvelo expanded its collaboration with Archemix to develop and commercialize aptamers that have a short-acting anticoagulant effect. Under the agreement, Archemix is responsible for discovery of short-acting aptamers for use in medical procedures, and Nuvelo leads development and worldwide commercialization of these aptamers.
Nuvelo, Inc. is dedicated to improving the lives of patients through the discovery, development and commercialization of novel drugs for acute cardiovascular disease, cancer and other debilitating medical conditions. Nuvelo's development pipeline includes NU172, a direct thrombin inhibitor which has completed Phase 1 development for use as a potential short-acting anticoagulant during medical or surgical procedures; and NU206, a Wnt pathway modulator in Phase 1 development for the potential treatment of chemotherapy/radiation therapy-induced mucositis and inflammatory bowel disease. In addition, Nuvelo is pursuing research programs in leukemia and lymphoma therapeutic antibodies and Wnt signaling pathway therapeutics to further expand its pipeline and create additional partnering and licensing opportunities.
This press release contains "forward-looking statements," which include statements regarding the timing, progress and anticipated completion of Nuvelo's clinical stage and research programs, and the potential benefits that patients may experience from the use of our clinical stage compounds, 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 and the regulatory approval process; 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; and the impact of competitive products and technological changes. These and other factors are identified and described in more detail in Nuvelo's filings with the SEC, including without limitation Nuvelo's quarterly report on Form 10-Q for the quarter ended June 30, 2008 and subsequent filings. We disclaim any intent or obligation to update these forward-looking statements.
Posted: August 2008