A well-written release......
Monday November 8, 4:01 pm Eastern Time
Company Press Release
SOURCE: Vertex Pharmaceuticals Incorporated
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 - news). 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 |
