Vertex Reports VX-497 Phase II Clinical Data for Hepatitis C
Virus Infection - Drug Appears to Reduce Liver Inflammation;
Company Announces Extension of HCV Monotherapy Trial
DALLAS, Nov. 8 /PRNewswire/ -- An investigational new drug,
VX-497, appears to reduce liver inflammation in patients with
hepatitis C virus (HCV) infection, according to results presented
here today at the annual meeting of the American Association for
the Study of Liver Diseases. VX-497 is an inhibitor of inosine
monophosphate dehydrogenase (IMPDH) being developed by Vertex
Pharmaceuticals Incorporated (Nasdaq: VRTX). Preliminary Phase II
data for VX-497 indicate that the drug was well-tolerated and
resulted in reduced levels of serum alanine aminotransferase (ALT),
a marker of liver inflammation, in HCV patients treated for 28
days. HCV is a chronic viral disease that can result in
inflammation of the liver, leading to cirrhosis, liver failure, and
liver cancer. Vertex is now beginning a three-month treatment
extension study to further explore the safety and pharmacokinetics
of VX-497 as monotherapy in patients with HCV.
"VX-497 is a promising new IMPDH inhibitor. In our first study
of VX-497 in hepatitis C patients who failed prior interferon
therapy, results indicate that VX-497 was well-tolerated by
patients in all dose groups," said Dr. Teresa Wright, Associate
Professor in the University of California at San Francisco's
Division of Gastroenterology and a principal investigator for the
study. "Although this trial was not designed as an efficacy study,
we were pleased to see statistically significant decreases in
patients' ALT levels, particularly since patients were dosed for a
relatively short period. We are encouraged by both the tolerability
and the ALT effects we are seeing. We look forward to the
continuation of the study, which will allow us to learn more about
the safety and preliminary activity of VX-497 over a longer
duration of treatment."
The Phase II clinical trial reported today was a randomized,
double-blind, placebo-controlled dose-escalation study designed to
measure the tolerability, safety, pharmacokinetics and preliminary
activity of VX-497 as a single agent in HCV-infected adult patients
unresponsive to prior treatment with interferon alpha, a standard
HCV therapy. The trial enrolled 30 patients, who were treated with
VX-497 at doses of 100, 200 or 400 mg, or placebo, three times a
day for 28 days. Ten patients were enrolled in each dose group.
These preliminary results indicate that VX-497 was
well-tolerated by hepatitis C patients at all three doses studied
in this 28-day trial. No patients discontinued treatment. The most
common treatment-related adverse events were mild/moderate diarrhea
and mild nausea. The study also made a preliminary assessment of
VX-497's effect in reducing levels of serum ALT and HCV viral RNA
in plasma. In the 200 mg dose group, patients had a mean 25%
reduction in serum ALT levels compared to baseline ALT values upon
study entry, a statistically significant change (p value = 0.01).
In the 400 mg dose group, patients had a mean 21% reduction in
serum ALT levels compared to baseline ALT values upon study entry,
a statistically significant change (p value = 0.04). The similarity
in ALT reduction levels in the 200 and 400 mg dose groups is
consistent with the observation of similar blood levels of VX- 497
in both groups. Patients receiving 100 mg of VX-497 had no
significant changes in ALT levels, compared to baseline. Patients
receiving placebo also had no significant changes in ALT levels,
compared to baseline. No consistent change in HCV serum RNA level
was observed in patients receiving 100, 200, or 400 mg of VX-497
over the duration of this 28-day study.
The initial results from Vertex's Phase II study of VX-497 for
treatment of HCV infection will allow the Company to move forward
on two clinical development paths for VX-497. Vertex will shortly
initiate an extension of this Phase II monotherapy study, treating
this continuing group of patients who were unresponsive to prior
treatment with interferon-alpha for an additional three months. The
Company also plans to begin a study of VX-497 combined with
interferon-alpha in treatment-naive patients next year.
"The good tolerability profile of VX-497 and its effect on liver
inflammation encourage us to conduct studies to assess the
antiviral activity of VX-497 in less refractory patient populations
and in combination with interferon-alpha. Further studies of VX-497
in hepatitis C patients, both as monotherapy and in combination
with interferon-alpha, if successful, will allow Vertex to develop
a commercial and regulatory approval path for VX-497. Vertex is
committed to the discovery and development of new antiviral drugs
that may bring innovative therapies to patients with few treatment
options," commented Dr. John Alam, Vice President of Clinical
Development at Vertex.
Hepatitis C virus infection is recognized as a major threat to
public health. Approximately 4 million people in the United States
are infected with the hepatitis C virus, although many are
currently undiagnosed. According to the Centers for Disease Control
(CDC), hospitalization and death rates due to HCV are projected to
triple from current levels over the next 10-15 years.
In vitro studies presented at the meeting continue to support
the profile of VX-497 as a potent antiviral compound with a broad
spectrum of activity. Vertex scientists presented data from
laboratory studies which suggest VX-497 has greater potency than
that of ribavirin against a variety of DNA and RNA viruses such as
hepatitis B virus, respiratory syncytial virus, and bovine viral
diarrhea virus (BVDV). BVDV, like HCV, is a flavivirus, and the two
viruses are closely related in genome organization. Ribavirin is
marketed in the United States in an aerosol form for treatment of
respiratory syncytial virus infections in children and as an oral
agent, in combination with interferon-alpha, for the treatment of
HCV infection. Data presented from an in vitro study comparing the
antiviral effect of VX-497 in combination with interferon-alpha to
that of ribavirin in combination with interferon-alpha showed the
VX-497/interferon-alpha combination was more potent against the
encephalomyocarditis virus. Both findings suggest that VX-497 may
have broad- spectrum antiviral activity, both on its own and in
combination with interferon-alpha.
VX-497 is a potent inhibitor of inosine monophosphate
dehydrogenase (IMPDH), a cellular enzyme that is essential for
production of guanine nucleotides, the building blocks of RNA and
DNA. Blocking IMPDH may be an effective strategy for blocking the
proliferation (growth) of certain cell types, such as lymphocytes,
and the replication of viruses, because both lymphocytes and
viruses depend on nucleotide synthesis for replication.
Vertex Pharmaceuticals Incorporated discovers, develops and
markets small molecule drugs that address major unmet medical
needs. The Company has nine drug candidates in clinical development
to treat viral diseases, inflammation, cancer, autoimmune diseases
and neurological disorders. Vertex has created its pipeline using a
proprietary approach, information-based drug design, that
integrates multiple technologies in biology, chemistry and
biophysics aimed at increasing the speed and success rate of drug
discovery. Vertex's first approved product is Agenerase(TM)
(amprenavir), an HIV protease inhibitor, which Vertex co-promotes
with Glaxo Wellcome.
There can be no assurance that clinical trials will continue,
that initial clinical trial results will be predictive of any
future results, that compounds currently undergoing clinical
testing will be the subject of filings for regulatory approval,
that compounds will receive marketing approval from the U.S. Food
and Drug Administration or equivalent regulatory authorities, or
that drugs, if any, which receive such approval will be marketed
successfully. Investors are also directed to consider other risks
and uncertainties discussed in Vertex documents filed with the
Securities and Exchange Commission.
SOURCE: Vertex Pharmaceuticals Incorporated
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