AbbVie’s paritaprevir-based ‘3D’ regimen taken
for just 8 weeks without ribavirin led to sustained virological response in 98%
of easier-to-treat patients with hepatitis C virus (HCV) genotype 1b who did
not have cirrhosis, according to findings from the GARNET study, presented last
week at the EASL special conference New Perspectives in Hepatitis C Virus Infection – The
Roadmap for Cure in Paris.
Direct-acting antiviral therapy
has revolutionised treatment for hepatitis C, but researchers continue to look
for shorter-duration regimens that would be more convenient and less costly.
The 3D regimen (marketed as Viekirax/Exviera in
Europe and Viekira Pak or Viekira XR in the US) consists of the
HCV protease inhibitor paritaprevir boosted with ritonavir, the NS5A inhibitor
ombitasvir and the NS5B polymerase inhibitor dasabuvir. The approved indication
in the EU and US is 12 weeks of the 3D combination alone for people with HCV genotype
1b with or without liver cirrhosis, 12 weeks of 3D plus ribavirin for people
with harder-to-treat genotype 1a without cirrhosis and 24 weeks of 3D plus
ribavirin for people with genotype 1a and compensated cirrhosis.
- 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’.
HCV genotype 1b is the most common type in
Europe and Asia, and the second most common in the US. As previously reported in 2014, the phase 3 PEARL-III
trial showed that the 3D regimen taken alone for 12 weeks cured 99% of
previously untreated people with genotype 1b without cirrhosis, while 3D plus
ribavirin cured 99.5%.
Based on these excellent results, Tania Welzel of J.W. Goethe University in Frankfurt, Germany,
and colleagues conducted the GARNET study to evaluate whether a shorter 8-week
regimen of 3D without ribavirin would work as well for this easy-to-treat
The phase 3 GARNET trial enrolled 166 people
with chronic hepatitis C with no prior treatment experience at 20 sites. More
than half (57%) were women, almost all were white and the median age was 53
years. Almost all (98%) had HCV genotype 1b, as per the entry criteria, but three
people with other genotypes were included (1a, 1d and 6). The median baseline
HCV viral load was 6 log10 IU/ml; 93% had <6,000,000 IU/ml and
42% had <800,000 IU/ml. Most had absent to moderate liver fibrosis (stage
F0-F2), but 9% had advanced fibrosis (stage F3); none had cirrhosis, as
specified in the entry criteria. People with HIV or hepatitis B co-infection
All participants in this open-label, single-arm
study received the paritaprevir/ritonavir/ombitasvir coformulation (150/100/25mg)
once daily plus dasabuvir (250mg) twice daily for 8 weeks.
The primary endpoint was sustained virological
response, or continued undetectable HCV RNA (<15 IU/ml) at 12 weeks after
completing treatment (SVR12).
The SVR12 rate was 98% in an intent-to-treat
analysis that included all participants who received at least one dose of
treatment. The cure rate rose to 99% in a modified analysis that excluded
individuals with HCV genotypes other than 1b and a participant who discontinued
Three participants experienced virological
failure. Two people with genotype 1b and stage F3 fibrosis relapsed after
treatment, and the sole participant with genotype 6 did not achieve viral suppression.
Cure rates were similar for men and women,
people over age 65 and obese participants. People with baseline HCV RNA >800,000
IU/ml did equally well, but the SVR12 rate fell to 92% for those with
>6,000,000. The SVR rate was 99% for people with F0-F2 fibrosis, but dropped
to 87% for those with stage F3.
All 66 participants with either only NS5A or only
NS5B resistance-associated viral polymorphisms at baseline were cured, as were
17 of 18 (94%) who had both NS5A and NS5B resistance.
Treatment was generally safe and well-tolerated.
One person discontinued treatment due to elevated bilirubin, but still went on
to achieve SVR12. There were two serious adverse events (fainting and
gastroenteritis), both deemed unrelated to the study drugs. The most common
adverse events were headache (21%) and fatigue (17%).
“The 98% SVR rate demonstrated that
treatment-naive genotype 1b patients without cirrhosis can be effectively
treated with 3D for 8 weeks,” the researchers concluded. “Both genotype 1B
patients who experienced virologic failure had F3 fibrosis at baseline.”
Based on these findings, the newly released EASL hepatitis C treatment recommendations now say that previously untreated people with genotype 1b and without
cirrhosis can be treated with the 3D regimen for either 8 or 12 weeks.