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.
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.