A two-drug pangenotypic regimen combining AbbVie's
glecaprevir and pibrentasvir demonstrated a high sustained response rate for
people with chronic hepatitis C who have severe kidney impairment, according to
results from the EXPEDITION-4 study presented at the 2016 AASLD Liver Meeting
last month in Boston.
Direct-acting antivirals used in interferon-free
regimens can now cure more than 90% of people with all hepatitis C virus (HCV)
genotypes, but there is still room for better options for the most difficult-to-treat people.
People with hepatitis C have an increased risk of
chronic kidney disease, experience more rapid kidney disease progression and
are more likely to require dialysis. People with serious kidney impairment may
be advised not to take certain medications and may be at greater risk for
- 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’.
Edward Gane of Auckland City Hospital in New Zealand
presented results from AbbVie's EXPEDITION-4 trial, which tested the
investigational glecaprevir/pibrentasvir regimen in
people with severe renal impairment.
Glecaprevir is an HCV NS3/4A protease
inhibitor and pibrentasvir is an NS5A inhibitor. Both drugs are pangenotypic,
or active against all HCV genotypes. Neither drug undergoes
significant excretion by the kidneys, and early studies showed no clinically
relevant increases in drug levels in people with kidney disease.
Other studies presented at The Liver
Meeting showed that glecaprevir/pibrentasvir cured 99% of people with hepatitis C with multiple genotypes
and most people with hard-to-treat genotype 3.
EXPEDITION-4 enrolled 104 people with hepatitis C with
stage 4 or 5 chronic kidney disease who had an estimated glomerular filtration
rate or eGFR – a method of estimating creatinine clearance – below 30 ml/min/1.73m2 (normal is over
90). Most (88%) had stage 5 kidney disease (eGFR 15-29 or dialysis) and 82%
were on dialysis.
About 80% were men and 25% were black (a group at
higher risk for kidney disease); the median age was 57 years (older age is also
a risk factor). About half had HCV genotype 1 (22% with 1a and 28% with 1b),
16% had genotype 2, 11% had genotype 3, 19% had genotype 4 and 1% had genotypes
5 and 6.
Participants could either be previously untreated for
hepatitis C (58%) or treatment-experienced using interferon- or
sofosbuvir-based regimens (40%). About one in five had compensated liver
cirrhosis. People with decompensated cirrhosis were excluded, as were those
with HIV/HCV co-infection.
All participants received glecaprevir/pibrentasvir
(300/120mg) once daily for 12 weeks. The primary study endpoint was
sustained virological response, or undetectable HCV RNA at 12 weeks after the
end of treatment (SVR12).
The overall SVR12 rate was 98% in an
intention-to-treat analysis, or 100% in a modified analysis of people who
completed treatment. One individual discontinued therapy early and one
was lost to follow-up, but there were no viral breakthroughs or relapses.
Treatment was generally safe and well tolerated. About
a quarter of individuals experienced serious adverse events, but none of these
were considered study drug-related. There were four treatment discontinuations
and one death due to serious adverse events, again not deemed study
drug-related. The most common adverse events were pruritus (20%), fatigue (14%)
and nausea (12%). Grade 3 or higher laboratory abnormalities were rare.
The researchers concluded that the results of
EXPEDITION-4 "demonstrate that a ribavirin-free glecaprevir/pibrentasvir
regimen achieves a high SVR12 rate in this population with severe renal
impairment and end-stage renal disease on haemodialysis."