Two direct-acting antivirals against hepatitis C virus (HCV) currently in development improved virologic responses among patients with HCV when administered alone or in combination with pegylated interferon-alpha-2a (pegIFN-alpha-2a) and ribavirin, phase-2 trial results indicate.

BMS-650032, a NS3 protease inhibitor, and BMS-790052 a NS5A replication complex inhibitor (Bristol Myers Squibb), may offer alternative treatment options for as many as 60% of patients with HCV genotype 1 that do not respond to standard therapy with pegIFN-alpha-2a and ribavirin alone.

“Quadruple therapy can result in a high rate of cure in this difficult to treat population,” study investigator Anna Lok, MD, a professor of medicine at the University of Michigan in Ann Arbor, said at the 46th Annual International Liver Conference in Berlin, Germany.

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She and colleagues from several U.S. sites enrolled 21 previously unresponsive HCV patients — 19 of whom had interleukin 28B, a gene associated with treatment failure — in a phase-2a trial to explore the drugs’ safety and efficacy compared with standard therapy.

Patients were randomly assigned to receive either BMS-790052 60 mg once a day and BMS-650032 600 mg twice daily, alone (n=11), or with pegIFN-alpha and ribavirin (n=10) for 24 days.

Data indicated that some patients had a favorable response to BMS-790052 and BMS-650032 alone, with four of the 11 patients achieving a sustained virologic response at 12 weeks post treatment, raising the possibility that some patients with HCV may “be cured without interferon or ribavirin.”

When BMS-790052 and BMS-650032 were added to standard dual therapy, responses improved even more, with 100% achieving a sustained virologic response at 12 weeks.

Diarrhea was the most common adverse event (71.4%), but no serious side effects were reported and no patients discontinued therapy due to an adverse event.

“While it’s expected that the first direct-acting antivirals and triple therapy will be approved for use later this year, quadruple therapy appears to have a more profound effect on virological responses, with less of a resistance problem,” secretary general for the European Association for the Study of the Liver, Heiner Wedemeyer, MD, said in a press release.

Lok and colleagues are currently enrolling more patients in a phase-2b study to validate the study findings.


Lok A. #1356. Presented at: 46th Annual International Liver Conference; March 30- April 3, 2011; Berlin, Germany.