In a phase Ib trial, the combination of a polymerase inhibitor, a protease inhibitor, and ribavirin demonstrated potent antiviral activity.
Although the new triple regimens are effective for the treatment of patients with chronic hepatitis C virus (HCV) infection, they have been linked to serious adverse events. Interferon — the backbone of all current therapies — is a major contributor to these effects. Now, researchers have conducted an industry-sponsored, phase Ib, international, open-label trial to evaluate the efficacy and safety of an interferon-free regimen.
Treatment-naive adults with HCV genotype 1 infection were randomized to receive 4 weeks of therapy with either 400 mg or 600 mg of BI 207127 (a nonnucleoside polymerase inhibitor, 3 times daily). Patients also received BI 201335 (a protease inhibitor, 120 mg once daily) and ribavirin (1000 mg or 1200 mg daily). The primary endpoint was virologic response (HCV RNA less then 25 IU/mL) at week 4.
Thirty-two patients received at least one dose of the assigned treatment; 31 patients completed 4 weeks of therapy. All patients demonstrated a rapid and steep decline in viral load during the first 2 days of treatment. Virologic response rates at days 15, 22, and 29 were 47%, 67%, and 73%, respectively, in the BI 207127 400-mg group and 82%, 100%, and 100% in the 600-mg group. In the 400-mg group, response rates were higher in patients with genotype 1a infections than in those with genotype 1b infections; in the 600-mg group, no subtype differences were seen. One patient in the 400-mg group experienced viral breakthrough at day 22. Adverse effects were mild and included rash, photosensitivity, and gastrointestinal disorders.
Comment: In this early-phase trial, potent antiviral activity was demonstrated by the combination of a polymerase inhibitor (particularly at the higher dose), a protease inhibitor, and ribavirin in patients with HCV genotype 1 infection. This study and the Inform-1 trial (JW Gastroenterol Nov 19 2010) offer hope for an interferon-free HCV treatment regimen. Ongoing later-phase trials of such regimens should provide more-detailed information on safety, resistance, and rates of sustained virologic response.
— Atif Zaman, MD, MPH
Published in Journal Watch Gastroenterology September 30, 2011
Citation(s): Zeuzem S et al. Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection. Gastroenterology 2011 Sep 16; [e-pub ahead of print]. (http://dx.doi.org/10.1053/j.gastro.2011.08.051)
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