Healthcare Industry News: NAPA-2
News Release - February 27, 2006
Nuvelo and Bayer HealthCare Begin SONOMA-3, Second Phase 3 Trial of Alfimeprase in Patients With Central Venous Catheter OcclusionSAN CARLOS, Calif. and LEVERKUSEN, Germany, Feb. 27 (HSMN NewsFeed) -- Nuvelo Inc. (Nasdaq: NUVO ) and Bayer HealthCare (BHC) today announced that they have begun patient enrollment in a second pivotal Phase 3 clinical trial of lead product candidate, alfimeprase, for the treatment of central venous catheter occlusion (CO).
The Phase 3 trial, known as SONOMA-3 (Speedy Opening of Non-functional and Occluded catheters with Mini-dose Alfimeprase-3), is the second of two overlapping, multi-national trials in the Phase 3 alfimeprase program for CO. This open-label, single-arm trial will evaluate the safety and efficacy of 3 mg of alfimeprase in 800 patients with occluded central venous catheters.
"We believe that alfimeprase has the potential to quickly dissolve clots and rapidly restore the ability to infuse critical therapy such as chemotherapy or antibiotics through once occluded catheters," said Steven R. Deitcher, M.D., vice president of medical sciences for Nuvelo and former principal investigator of the Phase 2 trial. "We look forward to completing the first trial in this program, SONOMA-2, later this year and expect the Phase 3 trial results to confirm the ability of alfimeprase to restore function to occluded catheters in 15 minutes or less, as demonstrated in our Phase 2 trial."
Previously announced results from a Phase 2 multi-center, randomized, double-blind study in 55 patients with occluded central venous catheters demonstrated that alfimeprase restored flow to 40 percent and 50 percent of occluded catheters 5 and 15 minutes after the first dose, respectively. By comparison, Cathflo®Activase® (alteplase) did not restore flow at either time point. Alfimeprase also restored flow to 60 percent of occluded catheters at 120 minutes after the first dose and to 80 percent of occluded catheters at 120 minutes after the second dose compared with 46 percent at 120 minutes after the first dose and 62 percent at 120 minutes after the second dose with Cathflo®Activase®.
About Catheter Occlusion
Delivery of chemotherapy, nutritional support, antibiotics and blood products, as well as the frequent withdrawal of blood samples for laboratory testing, are often facilitated via central venous catheters. Approximately 5 million catheters are placed in patients in the United States each year, with as many as 25 percent becoming occluded. When a catheter becomes occluded, the goal is to restore flow in a prompt and cost-effective manner with minimal risk to the patient. As these catheters are primarily inserted in patients receiving life-saving medications such as chemotherapy, it is critical to restore flow through the catheter as soon as possible. In the case of thrombotic occlusions, treatment with thrombolytic drugs represents a less-invasive and more cost-effective alternative to replacement. Currently, Cathflo®Activase® is approved in the United States for restoring function to central venous catheters.
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 Clinical Trials
The first study in the ongoing Phase 3 clinical program in CO, SONOMA-2, began in September 2005 and is expected to complete enrollment in the second half of this year. This randomized, double-blind study is comparing the efficacy of 3 mg 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.
Alfimeprase is also being studied in an ongoing Phase 3 program known as the NAPA (Novel Arterial Perfusion with Alfimeprase) program, for the treatment of acute peripheral arterial occlusion (PAO), or "leg attack." The program consists of two overlapping, randomized, double-blind, multi-national trials comparing 0.3 mg/kg of alfimeprase with placebo in a total of 600 patients. 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, including safety endpoints such as the incidence of bleeding, and pharmacoeconomic endpoints such as length of hospital and intensive care unit (ICU) stay. In January 2006, Nuvelo received fast track designation from the U.S. Food and Drug Administration (FDA) for the NAPA program. Fast track designation is reserved for new drugs that demonstrate the potential to address an unmet medical need and are intended for the treatment of a serious or life-threatening condition. The first trial in this program, NAPA-2, is expected to complete enrollment in the second half of this year. The second trial, NAPA-3, is expected to begin in early 2006 and is being conducted under a special protocol assessment from the FDA.
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 a Phase 2 trial of alfimeprase for the treatment of deep venous thrombosis 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, has received a $50 million up front payment and is eligible to receive an additional $335 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.
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 syndrome 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, 2004 and subsequent filings. We disclaim any intent or obligation to update these forward-looking statements.
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