People with genotype 3 hepatitis C are at higher risk of developing
advanced liver fibrosis and hepatocellular carcinoma than people
infected with other genotypes, and people with prior treatment
experience have fewer
interferon-free treatment options than those infected with other
genotypes.
Part 3 of the SURVEYOR-II study investigated the efficacy of
a 12 or 16-week regimen of glecaprevir and pibrentasvir in people with genotype
3 with prior treatment experience and/or cirrhosis. Treatment-experienced people
without cirrhosis (n = 44) were randomised 1:1 to receive a 12-week or 16-week
course of treatment. Previously untreated people with cirrhosis (n = 40) received
a 12-week course of treatment, while treatment-experienced people with
cirrhosis (n = 47) received a 16-week course of treatment.
Treatment-experienced people with exposure to direct-acting
antivirals other
than sofosbuvir were excluded from the study, as were people with HIV or
hepatitis B virus co-infection. People with a previous history of
hepatic decompensation were
excluded from the study.
In the non-cirrhotic study arms 64% of participants were
male, 77% and 91% were male in the 12- and 16-week arms, 35% and 41%
respectively had been exposed to sofosbuvir, 50% and 68% respectively had F0 or
F1 fibrosis, and 32% and 23% respectively had F3 fibrosis. A high proportion in
each arm (41% and 32% respectively) had a high viral load at baseline (> 6
million IU/ml).
In the cirrhotic study arms patient characteristics were
broadly similar. Sixty per cent of the previously untreated and 77% of the
treatment-experienced arms were male, 93% and 89% respectively were white, 10%
and 23% had a high viral load at baseline, and 53% of the treatment-experienced
group had previous exposure to sofosbuvir.
Intent-to-treat analysis showed that the regimen was highly
effective. In treatment-experienced people without cirrhosis the 16-week regimen
was more effective than the 12-week regimen, with 96% achieving SVR12 in the
16-week arm compared to 91% in the 12-week arm. In the cirrhotic arms 98% of
previously untreated and 96% of treatment-experienced participants achieved
SVR12.
Five virologic failures occurred in the study – four cases
of viral relapse and one viral breakthrough on treatment – all of them in
people with very high baseline viral loads (range 2.84 million – 18.9 million
IU/ml). All failures occurred in treatment-experienced people (2 with
cirrhosis).
Six serious adverse events were reported in the study
population but none were considered to be related to the study drugs. Fatigue
and headache were the most commonly reported adverse events (fatigue 13-34%
by study arm, headache 13-25% by study arm). Three Grade 3 liver enzyme and
one Grade 3 total bilirubin elevations were observed.
In conclusion, said David Wyles of Denver Medical Center
presenting the findings, G/P proved highly effective and well tolerated
in
perhaps the hardest-to-treat patient populations, treatment-experienced
people and people with cirrhosis with genotype 3 infection who until now
have had very
limited options for achieving a hepatitis C cure.