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Vertex Reports Six-Month Results from Phase II Clinical Study of Merimepodib (VX-497) in HCV
  The following press release from Vertex Pharma was issued Oct 17, 2003:
-Merimepodib Demonstrated Proof-of-Mechanism (Tolerability and Clinical Activity) in Combination with Pegylated Interferon and Ribavirin-
Cambridge, MA, October 17, 2003 -- 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-naïve 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.
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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
(1) Zhou, S. et al. (2003) The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic replicon RNA. Virology 310: 333-342.
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