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
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.
So far, I do not consider the data proof of concept. Perhaps there will be statistical significance in reducing viral load in combination with interferon.
I'm not sure it's "a good thing" to reduce the ALT levels without a concommitant reduction in viral load.
We shall see. |
