Faldaprevir effective across patient sub-groups with several baseline characteristics associated with treatment outcomes

The experimental hepatitis C virus (HCV) protease inhibitor is efficacious across a range of subgroups, according to research presented to the recent Liver Meeting 2013, the 64th annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC. Primary results showing the safety and efficacy of faldaprevir were presented to the International Liver Congress (EASL 2013) in April.

In the latest study, investigators pooled results from this research. Results consistently showed that the addition of faldaprevir improved treatment outcomes across sub-groups, and that white and Asian people were more likely to achieve a sustained virological response than individuals of African American or black ethnicity. Several well-established baseline characteristics were also associated with treatment outcomes.

Faldaprevir is an experimental oral HCV protease inhibitor. Its safety and efficacy has been examined in three phase III clinical trials, two of which involved treatment with faldaprevir or placebo in combination with pegylated interferon and ribavirin. The STARTVerso1 study recruited people in Europe and Japan and the study population in the STARTVerso2 study was drawn from the United States, Korea and Taiwan.

All study participants were treatment naive (had not taken treatment before) and had HCV genotype-1. Both studies had the same design. Participants were randomised into three arms: placebo plus pegylated interferon and ribavirin for 24 weeks; faldaprevir 120mg once daily plus pegylated interferon and ribavirin for 12 or 24 weeks; or faldaprevir 240mg once daily plus pegylated interferon and ribavirin for twelve weeks. People randomised to the faldaprevir arms who achieved an early virological response stopped all therapy at week 24. The primary endpoint of the studies was a sustained virologic response twelve weeks after the completion of therapy.

Investigators wished to see how faldaprevir performed across patient sub-groups and which baseline characteristics were associated with treatment outcomes. They therefore pooled the results of these two studies.

The characteristics of the participants were similar in both studies. Approximately 20% of participants were from Asia with 40% each from Europe and North America. Approximately three-quarter (71%) were white, 20% were Asian and 7% were black. The mean age was 49 years.

Just under half (47%) of participants had HCV genotype-1a infection and between 36 and 41% of individuals had the IL28B CC gene variant. Cirrhosis was present in approximately 10% of patients and the mean HCV RNA was 6.4 log₁₀ copies iu/ml.

A sustained virologic response was achieved by 50% of people in the placebo arm and by 72 and 73% of people treated with the 120mg and 240mg doses of faldaprevir, respectively (p < 0.001).

In Europe, 77% of people taking faldaprevir achieved a sustained virologic response, as did 88% of the participants in Asia. However, outcomes were poorer in north America, with only 60 to 63% of people treated with the two faldaprevir doses having a successful outcome. The investigators noted that there was a higher rate of treatment discontinuation in north America for reasons other than the failure of therapy. They believe this was related to the management of side-effects.

Several baseline characteristics were also associated with increased chances of achieving a sustained virolgic response. These included baseline HCV RNA (p < 0.001), IL28B CC gene variant compared to CT or TT (p < 0.001), infection with HCV genotype 1b compared to genotype 1a (p = 0.0023), younger age (p = 0.0027), white or Asian ethnicity compared to black ethnicity (p = 0.0.123) and the absence of cirrhosis (p = 0.0002).

The investigators therefore conclude that faldaprevir with pegylated interferon and ribavirin is effective for the treatment of HCV genotype-1 infection across a range of patient sub-groups.