An 8-week course of the combination of glecaprevir and
pibrentasvir (Maviret) is highly
effective in curing hepatitis C in people with compensated cirrhosis, across a
wide range of genotypes, Robert S. Brown of Weill Cornell Medical College
reported at the AASLD Liver Meeting in San Francisco this week.
Maviret is a highly
effective combination of an HCV protease inhibitor (glecaprevir) and an NS5A
inhibitor (pibrentasvir) that has been shown to cure hepatitis C in 98% of
people without cirrhosis after eight weeks of treatment. A previous study
showed that a 12-week course of the combination cured hepatitis C in 99% of
people with compensated cirrhosis. The EXPEDITION-8 study was designed to test
whether an 8-week treatment course was as effective in previously untreated
people with compensated cirrhosis as the rate of cure achieved in the previous
12-week study.
Reducing the duration of treatment to eight weeks saves
money and makes it easier for people to adhere to a course of treatment, so all
companies developing and marketing drugs for hepatitis C have been striving to
show that their products can deliver high rates of cure after eight weeks.
Glossary
- compensated cirrhosis
The earlier stage of
cirrhosis, during which the liver is damaged but still able to perform most of
its functions. See also ‘cirrhosis’ and ‘decompensated cirrhosis’.
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
- FibroScan
A non-invasive test, used instead of a biopsy, to measure the stiffness
or elasticity of the liver using an ultrasound probe.
The EXPEDITION-8 study is a non-randomised single-arm study
that recruited 270 previously untreated people with hepatitis C of all
genotypes apart from genotype 3. Participants were required to have compensated
cirrhosis, defined as a liver stiffness measurement greater than 0.75 or Fibroscan measurement less than 14.6
kPa or an APRI score of 2 or above, or biopsy-proven cirrhosis. People with
cirrhosis on the borderline of compensation and at higher risk of death
(Child-Pugh score above 6) were excluded, as were people with a history of
decompensated cirrhosis.
The study protocol was amended midway through the trial to
enrol 60 people with genotype 3 infection but results from this group of
participants were not included in the analysis presented at The Liver Meeting.
The study population was 60% male, 80% white and had a median
age of 60 years. The predominant genotypes were 1a and 1b, accounting for 83%
of the study population. Nine per cent had genotype 2 infection, 5% genotype 4
and 3% genotype 6. The study recruited one participant with genotype 5, which
is highly concentrated in South Africa and rarely found elsewhere in the world.
The median hepatitis C viral load (RNA) was 6.3 log10 IU/ml.
All participants received a glecaprevir and pibrentasvir
combination tablet once a day for eight weeks. Intent-to-treat analysis showed
that 98% of those who entered the study had a sustained virologic response 12
weeks after the completion of treatment; five people had missing HCV RNA
measurements 12 weeks after the completion of treatment but had undetectable
HCV RNA at the end of treatment. One participant discontinued treatment before
the end of the study. No participants experienced viral rebound after the
completion of treatment or viral breakthrough during treatment.
No drug-related serious adverse events were reported during
the study. The most frequent adverse events reported in the study were
headache, rash, nausea and pruritus (itching), each reported by less than 10%
of participants. No laboratory abnormalities were observed in any participant
during the study.
The investigators concluded that the study results support
the use of an 8-week regimen in all previously untreated people with
compensated cirrhosis.