AVI BioPharma Presents Initial Results on Hepatitis C Virus Clinical Trial at
the International Conference on Antiviral Research Annual Meeting
PORTLAND, Ore.--(BUSINESS WIRE)--May 10, 2006 - AVI BioPharma, Inc.
(Nasdaq:AVII) will present initial data from the second phase of its multicenter
study in patients with chronic active hepatitis C virus (HCV) infection at the
prestigious International Conference on Antiviral Research (ICAR) annual meeting
today. AVI's presentation titled "AVI-4065, An Antisense Approach to Active HCV
Infection: Preclinical and Clinical Evaluation" will be presented by Patrick L.
Iversen, Ph.D., AVI's senior vice president of research and development. See
www.georgetown.edu/research/arc/ISAR for details.
The second phase of the trial has been designed to assess the safety,
tolerability, pharmacokinetics (PK) and viral and clinical response to treatment
with AVI's proprietary NEUGENE(R) antisense compound, AVI-4065, among HCV
patients.
AVI-4065 exhibited favorable safety and tolerability profiles in all patients
treated thus far, with no serious drug-related adverse events or tolerability
issues observed during treatment or follow-up. Based on the relatively long
elimination half-life of AVI-4065 and its mechanism of action, an irreversible
binding to the viral genome preventing viral protein synthesis, a slow, steady
liver loading with test drug was expected in patients with high levels of viral
target in the liver. This correspondingly predicts a slow, steady decrease in
viral load over the drug-loading period.
The PK analysis in patients treated thus far was consistent with this
prediction; there was a significant decrease in the concentration of drug in the
plasma (Cmax) in HCV patients compared with the normal subjects in the initial
phase of the trial. This was consistent with an increased elimination of drug
found in the urine, most likely bound to the virus in the HCV-infected patients.
In addition, there was a significant correlation between viral titer at day one
and the extent of reduction in Cmax, further supporting this mechanism of
elimination. These observations demonstrate a significant and direct
pharmacodynamic response to HCV infection.
Viral responses have been assessed in only a few patients out to the 28th day of
the study. During the 14 days of treatment, three of five patients evaluated had
an initial decrease in viral load, whereas two of five exhibited little initial
change in viral titer. The mean viral titers of all patients tested thus far
showed a slight decrease (0.30 log reduction) both during and after treatment,
with no rebound effect observed out to 28 days. These are very preliminary
results in a small number of patients, and active enrollment and evaluation is
ongoing, with formal results expected around the end of the year.
"Based on the PK and mechanism-of-action of our drug, we expected a slow, steady
accumulation of drug in the liver with a corresponding decrease in viral load,"
said Dr. Iversen. "The maximal tissue concentration of drug would be reached in
three to five half-lives, or approximately 33 to 55 days. This indicates that an
extension of treatment duration is required to reach maximum drug concentration
and reduction of viral load in the liver. These preliminary results are
consistent with that and very encouraging for ongoing drug development.
Extending the treatment period would be expected to further reduce viral load in
responding patients and may ultimately decrease viral load in those patients who
are not early responders."
"We are pleased to have shown early signs of an anti-HCV response in our first
human study," said Denis R. Burger, Ph.D., chief executive officer of AVI.
"Because our drug has a significant therapeutic window, we have several options
for modifying the therapeutic regimen to enhance the results. Our options
include increasing the duration of treatment, increasing the dose, enhancing the
delivery, fine-tuning the target, enhancing target affinity, and exploring
combinations of antisense agents, or combinations of antisense agents with other
drugs. We firmly believe that, after seeing initial trends, we can develop an
optimal, viable drug therapy for HCV."
The first phase of this study was completed in March 2006 and evaluated 31
healthy volunteers who received 14 consecutive days of treatment with AVI-4065
at three dosage levels. In the second phase of this clinical trial, patients
with HCV are stratified into two cohorts, one composed of patients who have not
received previous treatment and the other composed of patients who failed
conventional interferon and ribavarin treatment. In addition to efficacy as
measured by HCV virological responses to treatment with AVI-4065, the study will
continue to assess the safety, tolerability and pharmacokinetics of the
compound. Patients will also be monitored for four months following treatment to
assess the duration of the virological response to AVI-4065, and sequencing of
the viral genome will be performed to assess potential resistance.
HCV is a single-stranded RNA virus. Because HCV and other single-stranded RNA
viruses have relatively simple genetic structures, they are attractive targets
for AVI's NEUGENE antisense, which is designed to target conserved portions of
the viral genetic code that are not likely to mutate over time.
About Hepatitis C Infection
Chronic HCV infection causes an inflammation of the liver that can result in the
development of cirrhosis, liver cancer or liver failure. According to the World
Health Organization, approximately 170 million people worldwide are chronically
infected with HCV. It is the most common chronic blood-borne infection in the
developed world and the leading cause of liver transplants in the U.S. The
Centers for Disease Control estimates that approximately 3.9 million Americans
have been infected with HCV, of whom 2.7 million are chronically infected.
The Hepatitis Foundation International estimates that between 8,000 and 10,000
people die annually in the U.S. from HCV-related cirrhosis or liver cancer. The
current treatment for HCV, 24 to 48 weeks of therapy with pegylated interferon
alpha and ribavirin, is successful in less than half of the patients infected
with genotype 1 HCV, the most common form of the virus in the U.S. Furthermore,
this treatment has numerous side effects, some of them severe, which make it
difficult for nearly half of initially treated patients to tolerate the
recommended dosages and duration of treatment.
About AVI BioPharma
AVI BioPharma develops therapeutic products for the treatment of
life-threatening diseases using third-generation NEUGENE antisense drugs. AVI's
lead NEUGENE antisense compound is designed to target cell proliferation
disorders, including cardiovascular restenosis, cancer and polycystic kidney
disease. In addition to targeting specific genes in the body, AVI's antiviral
program uses NEUGENE antisense compounds to combat disease by targeting
single-stranded RNA viruses, including West Nile virus, hepatitis C virus,
dengue virus, Ebola virus and influenza A virus. AVI has introduced a
NEUGENE-based exon-skipping technology called ESPRIT therapy. More information
about AVI is available on the company's Web site at http://www.avibio.com.
"Safe Harbor" Statement under the Private Securities Litigation Reform Act of
1995: The statements that are not historical facts contained in this release are
forward-looking statements that involve risks and uncertainties, including, but
not limited to, the results of research and development efforts, the results of
preclinical and clinical testing, the effect of regulation by the FDA and other
agencies, the impact of competitive products, product development,
commercialization and technological difficulties, and other risks detailed in
the company's Securities and Exchange Commission filings.
Contact AVI BioPharma, Inc. Michael Hubbard, 503-227-0554 hubbard@... or
Lippert/Heilshorn & Associates Inc. Investor Contact Jody Cain, 310-691-7100
jcain@... or Waggener Edstrom Worldwide Bioscience and Healthcare Practice
Jenny Moede, 503-443-7000 jmoede@...
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