A new pangenotypic direct-acting antiviral combination
developed by AbbVie is highly effective in curing hepatitis C in people with
cirrhosis, achieving a 99 per cent cure rate after 12 weeks of treatment with
minimal side effects, Xavier Forns reported on behalf of the EXPEDITION-1 study
investigators at the International Liver Congress in Amsterdam on Thursday.
The results come from a suite of phase III studies testing
AbbVie’s second generation direct-acting antiviral combination.
AbbVie’s second generation direct-acting antiviral
combination consists of a protease inhibitor and an NS5A inhibitor. Glecaprevir
is an HCV NS3/4A protease inhibitor active against all genotypes of hepatitis
C. Pibrentasvir is an NS5A inhibitor also active against all genotypes of
hepatitis C virus (HCV).
A direct-acting antiviral combination that doesn’t require
the addition of ribavirin for any genotype would be a big advantage, especially
for people with cirrhosis who tolerate ribavirin less well.
The Expedition-1 study tested the fixed-dose combination of glecaprevir
and pibrentasvir in 146 people with genotypes 1, 2, 4, 5 or 6 hepatitis C and
compensated cirrhosis. The study recruited previously untreated people and
those who had received any combination of pegylated interferon, ribavirin or
sofosbuvir. The study excluded people coinfected with HIV or hepatitis B.
Results of phase III studies in people without cirrhosis
at the AASLD Liver Meeting in Boston in November 2016. Those studies showed
cure rates of at least 98%.
The majority of people recruited to the study had genotype 1
infection (59.6%). Of the remainder, 23.3% had genotype 2 infection, 11%
genotype 4, 1.4% genotype 5 and 4.8% genotype 6.
Sixty two per cent of participants were male, with a median
age of 60 years, and 82% were white. Participants had Child-Pugh A stage
cirrhosis and 91% had a Child Pugh score of 5, indicating that they were still
at an earlier stage of cirrhosis.
Three-quarters had no previous treatment experience. Only 11
of 146 study participants had previous experienced of sofosbuvir and one had
been exposed to a protease inhibitor or an NS5A inhibitor. Nevertheless, 40%
had baseline polymorphisms (naturally occurring mutations) in the NS5A region
of the virus indicating potentially reduced sensitivity to NS5A inhibitors.
Treatment was just as effective in people with cirrhosis as
in those without cirrhosis recruited to previously reported studies. 99.3% of
participants were cured; 155 of 156 participants. One participant experienced a
post-treatment viral relapse eight weeks after completing treatment.
Adverse events related to the study medication were mild in
most cases (65%), most frequently headache (14%), fatigue (19%) and itching
(10%), and there were no grade 3 or 4 ALT (liver enzyme) elevations.