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.

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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.


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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.

Reference

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