Eight weeks of treatment with glecaprevir/pibrentasvir was well tolerated in patients who were treatment-naive with chronic hepatitis C virus (HCV) genotypes (GT) 1 to 6 and compensated cirrhosis and led to high sustained virologic response (SVR) rates that were similar to those seen with the 12-week treatment regimen, according to a study published in the Journal of Hepatology.
A single-arm, multicenter, phase 3b trial of 8 weeks of once-daily glecaprevir/pibrentasvir in patients who were treatment-naive with chronic HCV GT 1 to 6 with compensated cirrhosis was conducted (A Study of Glecaprevir [GLE]/Pibrentasvir [PIB] in Treatment-Naive Adults With Chronic Hepatitis C Virus Genotype 1-6 Infection and Compensated Cirrhosis [EXPEDITION-8]; ClinicalTrials.gov Identifier: NCT03089944). Primary efficacy end points were SVR12 rates (defined as HCV ribonucleic acid [RNA] < lower limit of quantification [LLoQ] 12 weeks after last dose) in participants with HCV GT 1, 2, 4, 5, or 6 in the per-protocol (PP) and the intention-to-treat (ITT) populations. The ITT population was defined as all participants receiving at least 1 dose of glecaprevir/pibrentasvir, and the PP population was defined as the ITT population, excluding participants who discontinued treatment before week 8, experienced virological breakthrough, or had missing SVR12 data.
Secondary efficacy end points were rates of SVR12 in participants with HCV genotype 1 to 6 in the PP and ITT populations, the percentage of participants with HCV genotype 3 in the PP and ITT populations achieving SVR12, and the percentage of participants in the ITT population across genotypes with on-treatment virological failure and posttreatment relapse. On-treatment virological failure was defined as an increase above nadir in 2 consecutive HCV RNA measurements >1 log10 IU/mL during treatment or 2 consecutive HCV RNA measurements ≥100 IU/mL after HCV RNA had fallen to <LLoQ during treatment. Posttreatment relapse was defined as 2 consecutive HCV RNA measurements ≥LLoQ between end of treatment and 12 weeks after the last glecaprevir/pibrentasvir dose in participants who had completed treatment with HCV RNA <LLoQ at the last treatment visit and had at least 1 posttreatment HCV RNA measurement. Among 343 participants who received at least 1 glecaprevir/pibrentasvir dose, 342 completed treatment.
Among participants with HCV GT 1, 2, 4, 5, or 6, the SVR12 rate was 100% in the PP population (274/274; 95% CI, 98.6-100) and 98.2% in the ITT population (275/280; 95% CI, 96.7-99.8). Among participants with HCV GT 3, the SVR12 rate was 98.4% in the PP population (60/61; 95% CI, 91.3-99.7) and 95.2% in the ITT population (60/63; 95% CI, 86.9-98.4). All primary and key secondary efficacy objectives were met, with the 95% CI lower bound for each SVR12 rate exceeding the corresponding predefined efficacy threshold (94% for the PP population and 93% for the ITT population). No participant experienced on-treatment virological failure, and 1 participant (genotype 3a) experienced relapse at week 4 posttreatment. Overall, 46% (158) of participants experienced treatment-emergent adverse events, 100 of whom (63%) had a maximum severity of grade 1, with the most common being fatigue (9%), headache (8%), pruritus (8%), and nausea (6%). Among the 6 (2%) participants experiencing serious adverse events, no events were considered to be treatment related.
Although the trial was limited by a relatively low number of participants with HCV GT 5 or 6, study investigators conclude, “In treatment-naive patients with chronic HCV genotype 1–6 infection and compensated cirrhosis … the once-daily, oral, fixed-dose combination of glecaprevir/pibrentasvir for 8 weeks was well tolerated and achieved very high SVR12 rates, comparable to those demonstrated with a 12-week treatment duration. Based on the results of this study, glecaprevir/pibrentasvir for 8 weeks is now approved for the treatment of treatment-naïve patients with compensated cirrhosis. Shortening treatment duration in this population may support efforts to simplify the HCV care pathway, furthering the progress towards HCV elimination.”
Disclosure: This clinical trial was supported by AbbVie. Please see the original reference for a full list of authors’ disclosures.
Brown RS Jr, Buti M, Rodrigues L, et al. Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: the EXPEDITION-8 trial [published online November 2, 2019]. J Hepatol. doi: 10.1016/j.jhep.2019.10.020