Hepatitis C patients treated with Merck’s investigative MK-5172, an oral NS3/4A protease inhibitor, combined with 24 or 48 weeks of peginterferon alfa 2b (Pegasys/ Roche) and ribavirin (Ribasphere/ Kadmon) have achieved a high rate of sustained viral response at 24 weeks (SVR24). Researchers reported at EASL/International Liver Conference interim data from a Phase 2 trial..
The investigators compared the treatment combination therapy to boceprevir (Victrelis/MERCK) among treatment-naïve, non-cirrhotic patients with genotype 1 HCV infection.
They enrolled 332 patients, who were randomized to MK-5172 at 100, 200, 400 or 800mg daily in combination with peginterferon alfa 2b and ribavirin, or to boceprevir plus peginterferon alfa 2b and ribavirin.
Of all subjects, 72.9% were IL-28B-cc (interleukin–28B CC genotype), 60.2% were HCV genotype 1a.
The researchers treated the MK-5172 subjects with MK-5172 and peginterferon alfa 2b- plus-ribavirin for 12 weeks, followed by an additional 12 or 36 weeks of peginterferon alfa 2b and ribavirin therapy, depending on week-4 HCV RNA.
During an early review of safety data, the investigators found ALT (alanine transaminase) elevations among patients in the 400and 800mg arms. They made a reassignment of the all 400mg and 800mg patients to 100mg.
Among evaluable-to-date reassigned 400mg patients, 91% (58/64) achieved SVR24. Among evaluable reassigned 800mg patients, 87% (52/60) have achieved SVR24.
Notably, 86% of 100mg plus peginterferon alfa 2b and ribavirin (55/64) evaluable patients, and 92% (61/66) of the 200mg plus peginterferon alfa 2b and ribavirin evaluable patients have achieved SVR24. And 54% (31/57) of the evaluable patients in the boceprevir plus peginterferon alfa 2b and ribavirin control arm have achieved SVR24.
For evaluable 100mg patients, bilirubin and transaminase increases were comparable to the control group. For a majority of original 400mg and 800mg subjects, transaminase levels became normal week 16.
Presenter Michael Manns, MD, Professor and Director of the Department of Gastroenterology, Hepatology and Endocrinology at the Hanover (Germany) Medical School, noted that SVR24 were comparable in patients with IL-28B CC and non-CC genotype. He added that SVR24 rates were numerically higher among subjects with genotype 1b compared to genotype 1a.
Phase 3 studies will evaluate MK-5172 at oral doses of 100mg only.
The study was supported by Merck.