Nuvelo Announces Publication of Alfimeprase Phase 1 Clinical Trial Results
August 08 2005 - 7:30AM
PR Newswire (US)
SUNNYVALE, Calif., Aug. 8 /PRNewswire-FirstCall/ -- Nuvelo Inc.,
(NASDAQ: NUVO) today announced the publication of clinical data
from the Phase 1 trial of its lead product candidate, alfimeprase,
in the August issue of the Journal of Vascular and Interventional
Radiology. The study of patients with chronic peripheral arterial
occlusion (PAO) showed that alfimeprase was generally
well-tolerated with no bleeding complications. "Plasminogen
activators, which are currently used to treat acute PAO, can take
several hours to days to work and can cause significant side
effects, including bleeding and intracerebral hemorrhage," said
Kenneth Ouriel, M.D., Chairman of the Division of Surgery at The
Cleveland Clinic and a lead investigator for Nuvelo's alfimeprase
PAO trials. "A drug with the ability to localize its lytic activity
to the target blood clot within a notably decreased treatment time
would represent a significant advance in treatment for this very
sick patient population." The Phase 1 multicenter, open-label,
dose-escalating study evaluated the safety and pharmacokinetic
profile of alfimeprase in patients with chronic lower extremity
PAO. Each of the study's 20 patients was given one of five
escalating doses of intra-arterial alfimeprase (0.025, 0.05, 0.1,
0.3 and 0.5 mg/kg). Results showed that no drug-related serious
adverse events were observed. Plasminogen and fibrinogen levels
remained unchanged, further evidence that alfimeprase acts
directly, independent of the plasminogen-plasmin system. There was
a dose-dependent consumption of alpha-2 macroglobulin, the protein
that rapidly inactivates alfimeprase once it enters the systemic
circulation. Alpha-2 macroglobulin levels returned to baseline
within 14 days of receiving drug. In addition, no anti-alfimeprase
antibodies were detected within 3 months after drug exposure. Since
this Phase 1 study was conducted in chronic PAO patients,
thrombolytic efficacy was not an objective of the study, however,
lysis of blood clots and restoration of blood flow were observed in
40% of cases. "The safety findings in this Phase 1 trial have since
been confirmed in a Phase 2 study, and our Phase 3 program is now
underway to evaluate the efficacy of alfimeprase in patients with
acute PAO," said Michael D. Levy, M.D., senior vice president,
research and development for Nuvelo. "Clinical trials to date have
demonstrated that alfimeprase is well tolerated and has shown
potential as a rapid-acting clot dissolver with a favorable safety
profile and attractive dosing schedule." About Acute PAO 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 then
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. Because there is no FDA approved thrombolytic therapy
available to treat acute PAO, plasminogen activators are often used
off-label in this indication. About Alfimeprase Alfimeprase, an
enzyme produced by recombinant DNA technology, is a thrombolytic or
blood clot dissolver that possesses a unique mechanism of action.
It has the ability to directly degrade fibrin, producing a rapid
dissolution of blood clots. In clinical studies, alfimeprase has
been shown to degrade large arterial clots within four hours of
initiation of dosing as well as the ability to restore function to
occluded catheters in as early as five minutes. Thrombolytics
currently on the market such as Activase(R) 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, preliminary testing suggests that
alfimeprase's 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. In
contrast, studies have shown that plasminogen activators can cause
major bleeding in 5-16% of patients and intracerebral hemorrhage
(ICH) in 1-2% of patients. Alfimeprase in Clinical Trials A Phase 3
trial of alfimeprase for the treatment of acute PAO is currently
ongoing. This randomized, double-blind study is comparing 0.3 mg/kg
of alfimeprase versus placebo in 300 patients at more than 100
centers worldwide. It 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. A separate Phase 3 clinical
program for alfimeprase in catheter occlusion is expected to begin
enrollment in the second half of 2005. This program will include
two overlapping, multi-national trials. The first trial 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. The second
trial will be 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. About Nuvelo
Nuvelo, Inc. is engaged in the discovery, development and
commercialization of life improving therapeutics for the treatment
of human disease. Nuvelo's clinical pipeline includes three product
candidates, alfimeprase, a direct acting thrombolytic for the
treatment of acute peripheral arterial occlusion (PAO) and catheter
occlusion; rNAPc2, an anticoagulant that inhibits factor
VIIa/tissue factor; and ARC183, a direct thrombin inhibitor that is
being developed for use in acute anticoagulant applications. Nuvelo
recently identified NU206 as a preclinical development candidate
from its proprietary research programs and expects to leverage
expertise in secreted proteins and antibody discovery to expand its
pipeline and create partnering and licensing opportunities.
Information about Nuvelo is available at our website at
http://www.nuvelo.com/ or by phoning 408-215-4000. This press
release contains "forward-looking statements" regarding potential
use of alfimeprase as a treatment for PAO and catheter occlusion
and timing and progress of Nuvelo's clinical stage and internal
research programs, 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. DATASOURCE: Nuvelo Inc. CONTACT: Nicole
Estrin, Associate Director of Corporate Communications & IR of
Nuvelo Inc., +1-408-215-4572, or ; or Carolyn Bumgardner Wang of
WeissComm Partners, Inc., +1-415-946-1065, or , for Nuvelo Inc. Web
site: http://www.nuvelo.com/
Copyright