SAN DIEGO, CA -- December 10, 2004 -- Nuvelo, Inc. (Nasdaq: NUVO) announced that data from a Phase 2 clinical trial showed that its lead product candidate, alfimeprase, has the potential to restore function in patient's with occluded central venous access devices (CVADs). These data were presented at The American Society of Hematology (ASH) 46th Annual Meeting and Exposition.
"This study showed that alfimeprase has the potential to restore function in occluded CVADs and to be a well tolerated therapy for use in catheter occlusion," said Steven R. Deitcher, M.D., vice president of medical affairs for Nuvelo and former principal investigator (PI) for the trial. Dr. Deitcher was also the PI for one of the Cathflo®Activase® catheter occlusion trials. "We are encouraged by these results and will work rapidly to initiate a Phase 3 clinical development program in this second potential indication."
Phase 2 Study Design and Results
This Phase 2 randomized, double-blind, active-controlled, dose-ranging study compared the safety and activity of three doses of alfimeprase (0.3 mg; 1.0 mg; and 3.0 mg) against the approved dose of Cathflo®Activase® (2.0 mg). Fifty-five patients were treated to reestablish patency to their occluded CVADs. Catheter patency was assessed at 5, 15, 30, and 120 minutes after each dose. If patency was not achieved after the first dose of either alfimeprase or Cathflo®Activase®, patients received a second dose. Adverse events including bleeding events were assessed for a 30-day period after exposure to study drug.
The alfimeprase 3.0 mg dose produced cumulative patency rates of 50% at 15 minutes after the first dose, 60% at 120 minutes after the first dose, and 80% at 120 minutes after the second dose. This is compared to Cathflo®Activase® (2.0 mg) which produced patency rates of 0% at 15 minutes after the first dose, 46% at 120 minutes after the first dose, and 62% at 120 minutes after the second dose. No major hemorrhagic events were reported in any treated patients and only one patient had a catheter-related infection.
Results from this Phase 2 study support further evaluation of alfimeprase in fixed doses ranging from 1.0 mg to 3.0 mg for the treatment of occluded CVADs.
"Alfimeprase is the cornerstone of a growing cardiovascular franchise at Nuvelo. The catheter occlusion data presented at ASH reflects the expanded potential opportunity we have with this versatile and unique agent," said Ted W. Love, M.D., president and CEO of Nuvelo. "We look forward to discussing the next clinical development steps for alfimeprase in catheter occlusion, particularly the potential for a Phase 3 program. We expect to meet with the Food and Drug Administration for an end of Phase 2 meeting in the first half of next year."
About Alfimeprase
Alfimeprase is an enzyme produced by recombinant DNA technology. It is a thrombolytic agent or blood clot dissolver that is intended to directly degrade fibrin when delivered through a catheter at the site of a blood clot. Thrombolytics currently on the market such as Abbokinase® or Activase® are plasminogen activators which rely on the plasminogen system to degrade fibrin. The activity of plasminogen activators is impacted by the amount of plasminogen found in the blood clot and may require prolonged infusions. Alfimeprase directly degrades fibrin, producing a rapid dissolution of blood clots. In addition, alfimeprase possesses a unique mechanism of action. Preliminary testing suggests that its lytic activity is localized to the site of delivery. Alfimeprase is inhibited within seconds of moving away from the clot and into the general circulation by alpha-2 macroglobulin, a naturally occurring protein in our blood. This clearance mechanism helps focus the thrombolytic activity to the site of delivery and in preclinical and clinical testing, appears to minimize bleeding side effects.
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 access devices (CVADs). Each year approximately five million CVADs are placed in patients in the United States, of which as many as 25% become occluded. Catheter occlusion is a major complication affecting CVADs and can impair the ability to infuse fluid through, or withdraw fluid from the catheter. When a catheter becomes occluded, the ultimate goal is to restore patency (i.e., flow) in a timely and cost-effective manner with minimal risk to the patient. In many cases, restoring flow is preferred over replacement of the catheter for several reasons. These include: limited interruption of therapy, reduced risk of trauma to the patient, reduced risk of complications and decreased cost. In the case of thrombolytic 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 CVADs.
Additional Alfimeprase Programs
Nuvelo plans to begin a Phase 3 (NAPA-2) trial of alfimeprase for the potential treatment of patients with acute peripheral arterial occlusion (PAO) in the first quarter of 2005. For more information on NAPA-2 or alfimeprase, go to www.nuvelo.com.
SOURCE: Nuvelo, Inc.
