Biotech Values

[DewDiligence]

NUVO beings pivotal trial in acute PAO

[Unlike earlier trials, in which Alfimeprase merely had to show an improvement in clot-lysing time relative to tPA, this phase-3 trial has as its primary endpoint the reduction of the need for open surgery. Even though the control arm in this trial is a placebo, I think the surgical endpoint will be a tough one to hit. A second phase-3 trial in PAO will start later with an undisclosed design that will likely include DNA’s tPA as a comparator.]

http://biz.yahoo.com/prnews/050418/sfm061.html?.v=5

>>
Nuvelo Begins Phase 3 Trial of Alfimeprase for Acute Peripheral Arterial Occlusion, or 'Leg Attack' NAPA-2 trial to Evaluate Avoidance of Open Vascular Surgery Within 30 Days of Treatment

SUNNYVALE, Calif., April 18 /PRNewswire-FirstCall/ -- Nuvelo Inc., (Nasdaq: NUVO - News) today announced that it has begun patient enrollment in a Phase 3 trial of its lead product candidate, alfimeprase, for the treatment of acute peripheral arterial occlusion (PAO), or "leg attack."

This Phase 3 trial, also known as NAPA-2 (Novel Arterial Perfusion with Alfimeprase-2), is a randomized, double-blind study comparing 0.3 mg/kg of alfimeprase versus placebo in approximately 300 patients. The trial will be conducted in over 100 centers worldwide. The study's primary endpoint is avoidance of open vascular surgery within 30 days of treatment. Open vascular surgery includes procedures such as surgical embolectomy and peripheral arterial bypass graft surgery as well as amputation, but does not include catheter-based procedures such as percutaneous angioplasty or stenting. A variety of secondary endpoints are also being evaluated, including safety endpoints such as the incidence of bleeding, as well as pharmacoeconomic endpoints, such as length of hospital and intensive care unit (ICU) stay.

"I'm excited to be part of the next step in evaluating this promising new therapy for a patient population that would very much benefit from a new and improved treatment option," said Dr. Sean Lyden, assistant professor at the Cleveland Clinic and the first physician to treat a patient in our Phase 3 program. "Current treatments can be time consuming and cause significant side effects, particularly bleeding. In clinical trials to date, alfimeprase has shown potential as an easily administered, rapid acting clot dissolver with a favorable safety profile and attractive dosing schedule."

Previously announced results from the NAPA-1 trial, a Phase 2 multi-center, multi-national, open-label, dose-escalation study, revealed that alfimeprase can restore arterial blood flow within four hours of initiation of dosing, demonstrated a favorable safety profile with minimal bleeding complications and resulted in a minority of patients requiring open vascular surgery within 30 days of treatment.

Because there are no FDA approved thrombolytic therapies available to treat acute PAO, off-label use of plasminogen activators are often used in this indication. As noted in published studies, plasminogen activators may require a prolonged infusion averaging 24 to 36 hours in patients with leg attack, and carry the risk of significant bleeding complications.

"Nuvelo is committed to delivering cardiovascular products that are safe, effective and easy to administer in order to advance the care of patients suffering from medical problems caused by a thrombus or blood clot," said Dr. Steven R. Deitcher, vice president of medical affairs for Nuvelo. "We are encouraged by alfimeprase's potential to offer physicians treating PAO patients an important, new and improved therapeutic alternative."

"The initiation of this trial is a significant milestone for Nuvelo and is evidence of our progress in advancing our acute cardiovascular franchise," stated Dr. Ted W. Love, president and chief executive officer of Nuvelo. "It has been only three years since we acquired alfimeprase and began our first human clinical study. It is exciting to see this promising drug move into late-stage clinical trials."

About Leg Attack

Acute peripheral arterial occlusion (PAO), or "leg attack," is the blocking of arterial blood flow to the lower limbs by a clot. Affecting more than 100,000 people in the United States per year, it is the result of underlying peripheral arterial disease, in which chronic fatty plaque buildup restricts blood flow and is complicated by the formation of an acute clot. If blood flow is not restored quickly, leg attack can lead to permanent nerve and muscle damage, gangrene, and in the most severe cases, amputation and death.

About Alfimeprase

Alfimeprase is an enzyme produced by recombinant DNA technology. It is a thrombolytic agent 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 according to published studies, may require prolonged infusions averaging 24 to 36 hours when dissolving very large clots such as those found in patients with acute PAO. In addition, studies have shown that plasminogen activators cause major bleeding in 5-16% of patients and intracerebral hemorrhage (ICH) in 1-2% of patients.

In contrast, alfimeprase possesses a unique mechanism of action. It directly degrades fibrin, producing a rapid dissolution of blood clots. In clinical studies, alfimeprase has been shown to have the ability to degrade large arterial clots within four hours of initiation of dosing. In addition, preliminary testing suggests that its lytic activity is localized to the site of delivery because within seconds of moving away from the clot and into the general circulation it is inhibited 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 clinical testing, appears to minimize bleeding side effects.

Additional Clinical Trials

The NAPA-2 study is the first of two overlapping Phase 3 trials evaluating alfimeprase for the treatment of acute PAO. The Phase 3 acute PAO program is expected to include up to 700 patients between the two trials. The second Phase 3 trial is expected to begin in the second half of 2005.

Alfimeprase is also under evaluation for a second target indication, central venous catheter occlusion, which affects over one million patients each year in the U.S. alone. Catheter occlusion occurs when a clot forms within an in-dwelling catheter, hindering the inward or outward flow of solutions or blood. 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. A recently completed Phase 2 study demonstrated the ability of alfimeprase to lyse clots in occluded catheters in as early as five minutes. A Phase 3 program in catheter occlusion is expected to begin in the second half of 2005.
<<