Steven Flamm of Northwestern
Feinberg School of Medicine in Chicago and colleagues performed an integrated
analysis of efficacy and safety data from phase 2 and 3
clinical trials of glecaprevir/pibrentasvir for previously
untreated people with HCV genotype 3, either without cirrhosis or with
The analysis included seven studies in the
ENDURANCE, EXPEDITION, SURVEYOR and MAGELLAN programmes,
with a total of 571 participants. About 60% were men, around 90% were
white and the mean age was approximately 48 years for people without cirrhosis
and 56 years for those with cirrhosis. Almost all (99%) had HCV subtype 3a.
Among the people without cirrhosis, about 15% had
advanced (stage F3) fibrosis. Some of the trials included people with HIV, advanced
kidney disease (EXPEDITION-4) and
transplant recipients. Two-thirds of participants had a history of injection
drug use, 17% were on opiate substitution therapy and recent illicit drug use
was not excluded. About a quarter had NS5A resistance-associated variations at
Of the people without cirrhosis, 208 received once-daily
glecaprevir/pibrentasvir for 8 weeks and 294 were treated for
12 weeks. All of the 69 people with cirrhosis received the 12-week course. None
of the participants used ribavirin. The endpoint was sustained virological
response, or undetectable HCV RNA at 12 weeks post-treatment (SVR12).
In the pooled analysis, 95% of participants without
cirrhosis who were treated for 8 weeks and the same proportion of those treated
for 12 weeks achieved SVR12. After excluding people with non-virological
treatment failure in a modified analysis, cure rates rose to 98% and 99%,
respectively. There were five relapses in the 8-week group and four in the 12-week
group. The researchers concluded that for people without cirrhosis, there was no
additional benefit of extending treatment from 8 to 12 weeks.
Among people with cirrhosis treated for 12 weeks the
SVR12 rate was 97%, rising to 100% after excluding non-virological treatment
failures. There were no relapses.
People with stage F3 fibrosis had a slightly, but not significantly,
lower response rate using 8 compared to 12 weeks of therapy (94 vs 100%), a
difference not seen among those with absent to moderate (F0-F2) fibrosis.
Response rates did not differ significantly based on pre-treatment
HCV viral load, opioid substitution therapy use or recent illicit drug use. All African-American
patients were cured (a group that did not respond as well to interferon-based
Glecaprevir/pibrentasvir was generally safe and
well tolerated, with no drug-related serious adverse events and three treatment
discontinuations due to adverse events. The most common events reported by at
least 10% of individuals were headache (19-24%), fatigue (10-19%) and nausea
These findings, Dr Flamm said, support recent changes
HCV treatment guidelines that add Maviret as a recommended regimen for first-line treatment of people
with HCV genotype 3, without the need for baseline resistance testing or
addition of ribavirin. Despite the slightly lower response rate for people with
advanced fibrosis, he said he is confident that an 8-week regimen is adequate
for these people.