Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection

Abstract

BACKGROUND & AIMS: The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis. METHODS: We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir. RESULTS: Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively.

Is an 8‐week regimen of glecaprevir/pibrentasvir sufficient for all hepatitis C virus infected patients in the real‐world experience?

“…It should be pointed out that the majority of publications concerning the 8-week GLE/PIB option in clinical trials has a pooled or meta-analysis nature, and some recent papers have repeated already published data. 17 It is also worth noting that although the GLE/PIB regimen has been available for 3 years, data on the efficacy and safety of the 8-week option in real world settings are still limited, with only a few conference reports and single papers having been published. Moreover, some of them also present summary analysis, not a single-country real-world experience.…”

Factors influencing the failure of interferon-free therapy for chronic hepatitis C: Data from the Polish EpiTer-2 cohort study

“…Interferon-free therapies with a short duration and the absence of significant adverse events (AEs) allow for a sustained virologic response (SVR) in over 90% of patients, both in randomized clinical trials[ 1 - 3 ] and in real-world settings[ 4 , 5 ]. Previous research has demonstrated that pangenotypic therapies significantly increase the effectiveness of treatment in patients infected with hepatitis C virus (HCV) genotype 3, which is considered more difficult to treat[ 6 - 9 ].…”

Japanese Man with HCV Genotype 4 Infection and Cirrhosis Who Was Successfully Treated by the Combination of Glecaprevir and Pibrentasvir

“…In general, the SVR rates in HCV GT4-infected patients treated with the combination of glecaprevir and pibrentasvir are reported to range from 95.5%-100% (Table 2) (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). In Japan, clinical trials of this combination treatment for HCV GT4 have not been performed.…”