Vertex Reports VX-497 Phase II Clinical Data for HCV


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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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