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
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.