Vertex Pharmaceuticals Reports Six-Month Results from Phase II Clinical Study of Merimepodib (VX-497) in HCV
-- Merimepodib Demonstrated Proof-of-Mechanism (Tolerability and Clinical
Activity) in Combination with Pegylated Interferon and Ribavirin --
CAMBRIDGE, Mass., Oct. 17 /CNW/ -- Vertex Pharmaceuticals
Incorporated (Nasdaq: VRTX) today reported encouraging results from a six-
month interim analysis of an ongoing Phase II clinical trial with its novel
drug merimepodib (VX-497) for the treatment of hepatitis C virus (HCV)
infection. This 31-patient study is designed to evaluate the safety,
tolerability and clinical activity of merimepodib administered in combination
with pegylated interferon (peg-IFN) and ribavirin in HCV patients who were
non-responsive to treatment with a previous course of interferon and
ribavirin. At six months, merimepodib met its primary endpoint of safety and
tolerability and was not associated with any serious adverse events. At six
months, merimepodib also met its secondary endpoint of clinical activity and
demonstrated a statistically significant antiviral response in combination
with pegylated interferon and ribavirin.
"In this six-month interim analysis, merimepodib was well tolerated and
showed a statistically significant dose-dependent antiviral effect, suggesting
that merimepodib may enhance the antiviral activity of pegylated interferon
and ribavirin," stated John J. Alam, M.D., Senior Vice President of Drug
Evaluation and Approval. "Based on the tolerability and clinical activity of
merimepodib observed in the interim analysis of this study, we believe proof-
of-mechanism for merimepodib in treatment-refractory patients has been
obtained. The complete analysis, which will include 12-month treatment and
six-month post-treatment data, will be used to guide the clinical path of
merimepodib going forward."
"Within the limitations of the size of this study, we are encouraged by
the tolerability and additive antiviral activity that merimepodib demonstrated
in patients who were non-responsive to previous combination therapy," stated
Dr. Patrick Marcellin, Professor of Medicine at University of Paris VII, and
the lead investigator for the study. "The main goal of HCV treatment is to
clear the virus from patients. The addition of merimepodib to a standard-of-
care regimen appears to increase the proportion of treatment-refractory
patients who show a viral response at six months, representing a clinically
important finding."
Study Design
The Phase II, double-blind, placebo-controlled, randomized study is
designed to evaluate the safety and tolerability of two dose regimens of
merimepodib in combination with peg-IFN and ribavirin in patients with HCV
genotype 1 who were non-responsive to interferon-alpha and ribavirin therapy.
The secondary objective of the study is to assess the pharmacokinetics and
clinical activity of merimepodib. The study is being conducted in Europe.
Patients enrolled in the study had previously received a minimum of 12 weeks
of IFN and ribavirin treatment without achieving undetectable viral RNA (vRNA)
at any time point. After the initial six months of the trial, patients had
the option to extend treatment for an additional six months. Collection of
12-month end-of-treatment data and six-month post-treatment sustained
virologic response data is continuing. Vertex anticipates that when the study
is complete, the full trial results will be presented at a medical conference.
Merimepodib is one of several drug candidates in Vertex's product
portfolio that the Company is developing independently in the areas of
infectious disease, autoimmune disease, inflammation and genetic disorders.
Based on results from ongoing studies, as well as an analysis of market
opportunity, Vertex expects to prioritize two drug candidates from this
portfolio for full development and commercialization in high-value markets
served by specialists. At the same time, Vertex will continue to pursue
strategic alliances to maximize the near-term and downstream commercial value
of certain research and clinical development programs. Vertex currently
retains all worldwide development and commercial rights for merimepodib.
About Merimepodib
Merimepodib is a small molecule, orally administered inhibitor of the
enzyme inosine monophosphate dehydrogenase (IMPDH). IMPDH inhibition leads to
a reduction in intracellular guanosine triphosphate (GTP), a molecule required
for DNA and RNA synthesis. Recent reports in the medical literature suggest
that IMPDH inhibitors such as merimepodib may enhance the antiviral activity
of ribavirin in vitro by depleting GTP and increasing the rate of
incorporation of ribavirin into viral RNA, rendering the virus
nonfunctional(1). These insights provide a mechanistic interpretation for the
antiviral activity observed clinically when merimepodib is added to ribavirin-
containing HCV therapies. IMPDH inhibition may therefore represent an
attractive strategy for increasing the sustained viral response rate in HCV
patients, the principal goal of treatment.
Previous Studies of Merimepodib
Merimepodib has been evaluated in two previous short-term studies in HCV
patients. Vertex previously reported data from a 28-day Phase II study to
evaluate the safety, tolerability and clinical activity of merimepodib
combined with interferon-alpha in treatment-naive HCV patients. The viral
load data from this study showed a trend toward enhanced antiviral activity in
patients treated with merimepodib combined with interferon as compared to
patients receiving interferon alone.
Vertex has also conducted a 28-day Phase II study of merimepodib
administered as a monotherapy to HCV patients who were non-responsive to prior
treatment with interferon-alpha. Results from this study showed that
merimepodib was well tolerated and appeared to reduce levels of serium alanine
aminotransferase (ALT), a marker of liver inflammation.
About HCV Infection
HCV infection is a serious disease that causes inflammation of the liver,
which may lead to fibrosis and cirrhosis, liver cancer, and ultimately, liver
failure. Chronic hepatitis C infection afflicts approximately 2.7 million
people in the U.S., many of whom are unaware of their infected status. HCV
may go undetected for up to 20 years following initial infection. Worldwide,
the disease strikes as many as 185 million people. Each year, 8,000 to 10,000
people in the U.S. die from complications of HCV. Current treatments have
been effective for only 40 to 60 percent of patients chronically infected with
genotype 1 HCV, the most difficult viral strain to treat and the most common
form in the U.S. Patients who are non-responsive to current HCV therapy have
limited treatment options, and clinical experience shows that only a very low
proportion of such patients achieve a sustained viral response with subsequent
treatment regimens.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company
committed to the discovery and development of breakthrough small molecule
drugs for serious diseases. The Company's strategy is to commercialize its
products both independently and in collaboration with major pharmaceutical
partners. Vertex's product pipeline is principally focused on viral diseases,
inflammation, autoimmune diseases and cancer. Vertex's first approved product
is the HIV protease inhibitor Agenerase(R) (amprenavir), which Vertex co-
promotes with GlaxoSmithKline.
Vertex Safe Harbor Statement
This press release may contain forward-looking statements, including
statements that i) that merimepodib may enhance the antiviral activity of
pegylated interferon and ribavirin; ii) that proof-of-mechanism has been
obtained based on interim data from Vertex's clinical study; and iii) that
Vertex will prioritize two drug candidates from its portfolio for independent
development and commercialization in high-value markets served by specialists.
While management makes its best efforts to be accurate in making forward-
looking statements, such statements are subject to risks and uncertainties
that could cause Vertex's actual results to vary materially. These risks and
uncertainties include, among other things, the risk that i) the six-month
interim analysis of the study may not be indicative of the 12-month analysis;
ii) data suggesting proof-of-mechanism may not be confirmed by 12-month data,
or the results of this small Phase II study of merimepodib may not be
indicative of the results that would be obtained in a larger trial; iii)
Vertex's drug development programs may not proceed as planned due to
partnership, technical or patient enrollment issues, and other risks listed
under Risk Factors in Vertex's form 10-K filed with the Securities and
Exchange Commission on March 31, 2003.
Agenerase(R) is a trademark of the GlaxoSmithKline group of companies.
Vertex's press releases are available at www.vrtx.com.
(1) Zhou, S. et al. (2003) The effect of ribavirin and IMPDH inhibitors on
hepatitis C virus subgenomic replicon RNA. Virology 310: 333-342.
Vertex Contacts:
Lynne H. Brum, Vice President, Corporate Development and Communications,
(617) 444-6614
Michael Partridge, Director, Corporate Communications, (617) 444-6108
Jaren Irene Madden, Media Relations Specialist, (617) 444-6750 |
