SAN CARLOS, Calif. and LEVERKUSEN, Germany, April 10 /PRNewswire-FirstCall/ -- Nuvelo Inc. and Bayer HealthCare (BHC) today announced that they have begun patient enrollment in a second pivotal Phase 3 clinical trial of alfimeprase for the treatment of acute peripheral arterial occlusion (PAO), or “leg attack.” This Phase 3 trial, known as NAPA-3 (Novel Arterial Perfusion with Alfimeprase-3), recently received a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA).
NAPA-3 is the second of two overlapping multi-national trials in the Phase 3 alfimeprase program for acute PAO. Both trials are randomized, double-blind studies comparing 0.3 mg/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. Open vascular surgery includes procedures such as surgical embolectomy, peripheral arterial bypass graft surgery and amputation, but does not include catheter-based procedures such as percutaneous angioplasty or stenting. 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 (ICU) stay.
“We recently announced that we have received fast track designation from the FDA for the NAPA program and that we expect to complete enrollment in the first trial in this program, NAPA-2, in the second half of this year,” said Michael D. Levy, M.D., senior vice president of research and development for Nuvelo. “Now that we have initiated NAPA-3 and have plans to initiate additional trials in stroke and deep venous thrombosis (DVT), we are well on our way to bringing this potentially transformational therapy to the millions of patients suffering from clot related disorders.”
Previously announced results from the NAPA-1 trial, a Phase 2 dose- escalation study, demonstrated that alfimeprase can restore arterial blood flow within four hours of initiation of dosing, has a favorable safety profile with minimal bleeding complications, and resulted in a majority of patients avoiding open vascular surgery within 30 days of treatment.
About Leg Attack
Acute PAO, or “leg attack,” occurs when a blood clot blocks arterial blood flow to a lower limb. Affecting more than 100,000 people in the United States each year, acute PAO is the result of underlying peripheral arterial disease, in which chronic fatty plaque buildup restricts blood flow and is then complicated by the formation of an acute clot. If blood flow is not restored, leg attack can lead to permanent nerve and muscle damage, gangrene and, in the most severe cases, amputation and death.
Currently, because there are no FDA-approved thrombolytic therapies available to treat acute PAO, off-label use of plasminogen activators often occurs. As noted in published studies, plasminogen activators may require a prolonged infusion averaging 24 to 36 hours in patients with acute PAO, carry the risk of significant bleeding complications and typically require admission to the ICU for the duration of the infusion.
About Alfimeprase
Alfimeprase is an enzyme produced by recombinant DNA technology that rapidly resolves blood clots through a unique mechanism of action; it directly degrades fibrin, a protein that provides the scaffolding for blood clots. In clinical studies to date, alfimeprase has been shown to have the ability to resolve peripheral arterial (e.g. leg) clots within four hours of initiation of dosing and to clear occluded catheters in 15 minutes or less. In addition, its lytic activity is localized to the site of delivery due to its rapid inhibition by alpha-2 macroglobulin, a naturally occurring protein in the blood, as soon as it moves away from the clot and into the general circulation. This clearance mechanism helps focus the thrombolytic activity to the site of delivery and, in clinical testing, appears to minimize bleeding side effects.
Additional Alfimeprase Clinical Trials
In addition to acute PAO, alfimeprase is being studied in an ongoing Phase 3 clinical program known as the SONOMA (Speedy Opening of Non-functional and Occluded catheters with Mini-dose Alfimeprase) program, for the treatment of catheter occlusion. The program consists of two overlapping, multi-national trials. The first trial, SONOMA-2 is an efficacy study comparing 3 mg of alfimeprase versus placebo in 300 patients with occluded central venous catheters, evaluating restoration of function to the catheters at 15 minutes. SONOMA-2 is expected to complete enrollment in the second half of 2006. The second trial, SONOMA-3, is an open label, single-arm trial evaluating alfimeprase alone in 800 patients. This study’s primary endpoint is safety; however efficacy will also be evaluated. SONOMA-3 began enrollment in February 2006.
In addition, Nuvelo recently announced 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 DVT in 2007.
About the Collaboration
In January 2006, a global collaboration was formed between Nuvelo and BHC for the development and commercialization of alfimeprase. Under the terms of the agreement, BHC will commercialize alfimeprase in all territories outside the United States and will pay Nuvelo tiered royalties ranging from 15 to 37.5 percent. Nuvelo retains commercialization rights in the United States and is eligible to receive up to $385 million in milestone payments from BHC. In addition, BHC will be responsible for 40 percent of the costs for global development programs and Nuvelo will be responsible for 60 percent of the costs and will remain the lead for the design and conduct of the global development programs.
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 focused on 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 is currently in Phase 2 clinical development for acute coronary syndromes and a thrombin inhibiting aptamer for anticoagulation during medical procedures. Nuvelo is also progressing 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 alfimeprase clinical programs, the potential improvement or benefit that current and future clinical trial programs may demonstrate, the potential for regulatory approval for alfimeprase, and the numbers of patients who may be eligible for treatment by alfimeprase, 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 recent annual report on Form 10-K for the year ended December 31, 2005 and subsequent filings. We disclaim any intent or obligation to update these forward-looking statements.
Nuvelo, Inc.
CONTACT: Nicole Estrin, Associate Director of Corporate Communications &IR of Nuvelo, +1-650-517-8472, or nestrin@nuvelo.com; or Carolyn BumgardnerWang of WeissComm Partners, Inc., +1-415-225-5050, orcarolyn@weisscommpartners.com, for Nuvelo, Inc.; or Christina Sehnert,Global Corporate Communications of Bayer HealthCare, +49-214-30-66102
Web site: http://www.nuvelo.com/
