A new combination of direct-acting antivirals developed by
AbbVie is highly effective in curing hepatitis C in people with genotype 3
infection and cirrhosis, results of two phase II studies
presented at last week’s International Liver Congress showed.
Almost 30% of worldwide hepatitis
C infections are estimated to be genotype 3, with a particular concentration in
the Indian sub-continent and among populations of Indian origin living
elsewhere. Genotype 3 is also widespread in the Russian Federation,
Scandinavia, Thailand, Brazil and Australia. Genotype 3 hepatitis C virus (HCV)
is more difficult to cure than other genotypes of HCV, requiring a
longer course of treatment with most regimens. The most effective available
regimens for treatment of genotype 3 have cured between 78 and 88% of people
treated.
AbbVie is developing the
combination of ABT-493 and ABT-530 as a pan-genotypic regimen for hepatitis C
treatment.
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’.
ABT-493 is an HCV NS3/4A protease inhibitor active against
all genotypes of hepatitis C. ABT-530 is an NS5A inhibitor also active against
all genotypes of HCV. Both agents are active against common variants that
confer resistance to first-generation agents of their classes. ABT-493 is more
potent against genotype 3 than other HCV protease inhibitors, including
products being developed by Merck (grazoprevir) and Gilead (GS-9451), and
ABT-530 has demonstrated higher potency than most other NS5A inhibitors across
all genotypes.
Dr Paul Kwo of the University of Indiana presented results
from the SURVEYOR-II study in people with compensated cirrhosis (Child-Pugh A
cirrhosis).
SURVEYOR-II enrolled 48 previously untreated people with
genotype 3 infection and randomised them to receive either ABT-493 (300mg) and
ABT-530 (120mg) dosed once daily, or the same regimen with once-daily ribavirin
(800mg), for 12 weeks.
The study excluded treatment-experienced people, those with
a previous history of liver decompensation and people with HIV and
HCV co-infection.
The two study arms were evenly matched in most respects,
although men predominated in the ribavirin arm (75 vs 52% in the
ribavirin-sparing arm) and a higher proportion of the ribavirin-sparing arm had
a Child-Pugh score above 6 (21 vs 13%). Median HCV RNA was 6.4 log10
IU/ml.
The primary endpoint of the study was sustained virologic
response. Twelve weeks after the completion of treatment all participants had sustained
virologic response (SVR12), regardless of baseline resistance profiles (18 participants
had viral variants associated with resistance in either the NS3 or NS4A
regions, and 4 participants had viral variants associated with resistance in
both regions).
Two serious adverse events occurred in the ribavirin arm
(anaemia possibly related to ribavirin, and a delusional disorder possibly
related to study drugs on the same day as amphetamine and alcohol use). Mild
adverse events including headache, fatigue, nausea and dizziness occurred more
frequently in the ribavirin arm.
Paul Kwo also presented results of a small study of an 8-week
treatment course of the same regimen in people with genotype 3 infection
without cirrhosis. A previous dose-ranging study had observed a high cure rate
after 12 weeks of treatment in both treatment-experienced and previously
untreated patients; this study was designed to test whether an 8-week course of
treatment could deliver a similar cure rate (>95%) in patients without cirrhosis.
The study assigned 29 previously untreated patients to receive
an 8-week course of treatment with ABT-493 (300mg) and ABT-530 (120mg) dosed
once daily. The study excluded treatment-experienced people or those with
HIV and HCV co-infection.
Fifty-two per cent of participants were male, 90% were white and the median
HCV RNA was 6.5 log10 IU/ml.
The primary endpoint of the study was sustained virologic
response. Twelve weeks after the completion of treatment 28 out of 29
participants had achieved SVR12 (97%). One participant
withdrew at week 6 due to intolerance of blood draws but had an undetectable
HCV RNA at this time.
No serious adverse events occurred during the study and the
most common adverse events were headache, fatigue, nausea and diarrhoea. One participant
experienced a grade 2 bilirubin elevation (>1.5-3 x ULN).