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New HCV Protease Inhibitor Effective Against Hepatitis C

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NEW YORK (Reuters Health) May 15 - A new, oral HCV protease inhibitor, SCH
503034, is well tolerated and may be effective against hepatitis C (HCV)
genotype 1 that is refractory to interferon treatment, according to a report
in the April issue of Gastroenterology.

SCH 503034 is a specific inhibitor of NS3 protease, which plays an essential
role in the replication of HCV, the authors explain.

Dr. Christoph Sarrazin from Saarland University Hospital, Hamburg, Germany
and associates evaluated the safety and tolerability of SCH 503034, alone
and in combination with pegylated interferon-alpha-2b (IFN), in 26 patients
with chronic HCV infection that had not responded to treatment with IFN with
or without ribavirin.

Both as monotherapy and in combination with IFN, SCH 503034 was generally
well tolerated, the authors report.

One week of treatment with SCH 503034 alone resulted in a mean maximal
reduction in HCV RNA of 1.08 log10 at 200 mg 3 times daily, and 1.61 log10
at 400 mg 3 times daily, the investigators say.

Combination therapy with SCH 503034 and IFN resulted in greater decreases in
HCV RNA than with IFN alone, the researchers note. The best results (a mean
decrease in HCV RNA of 2.68 log10 after 2 weeks) were seen with the
combination of SCH 503034 400 mg 3 times daily and IFN.

"Evaluation of virologic response during monotherapy and combination therapy
suggests that combination SCH 503034 plus IFN was associated with anti-HCV
activity in these patients who had previously not responded to IFN with or
without ribavirin," the authors report.

"Phase II clinical trials with HCV genotype 1 nonresponders are underway to
determine the optimum dosing and exposure levels for this potentially
important therapeutic regimen," the researchers add.

"Novel oral antiviral approaches are exciting and fashionable," writes Dr.
Jean-Michel Pawlotsky from Hopital Henri Mondor, Creteil, France in a
related editorial. "The spectacular antiviral efficacy of some of these
drugs should not, however, be allowed to mask the specific new problems they
raise."

"Although adjunction of an oral HCV inhibitor may give interesting results,
other options are already available for the treatment of chronic hepatitis
C, including optimization of the current pegylated IFN-alpha-ribavirin
combination," the editorial concludes. "All these options should be
explored, as they may benefit patients in the near future."

Gastroenterology 2007;132:1270-1278,1611-1615