This article first appeared on our sister site, HCPLive.
An 8-week course of glecaprevir/pibrentasvir (G/P) treatment was a safe and effective treatment for adults and adolescents with previously untreated acute hepatitis C virus (HCV) infection, according to a study presented at The Liver Meeting 2023 from the American Association for the Study of Liver Diseases. Therapy demonstrated a virologic response at posttreatment week 12 (SVR12) rate, which was superior to the prior efficacy threshold.
While the trial did not achieve the protocol-specified number of patients in the principal safety stratum (PSS) to analyze liver safety, no new safety signals were observed in patients with acute HCV compared with the chronic HCV population.
“There are currently no direct-acting antivirals (DAAs) approved to treat acute HCV infection, leading to delays in treatment, increased loss to follow up and onward HCV transmission,” wrote lead investigator Stanislas Pol, MD, PhD, professor of Hepatology and Gastroenterology at the Université Paris Sorbonne, Paris, France. “This gap in the standard of care affects vulnerable populations, such as people who inject drugs (PWID).
What You Should Know
The 8-week course of G/P treatment was found to be safe and effective in adults and adolescents with previously untreated acute HCV infection.
While the trial did not achieve the protocol-specified number of patients for the principal safety stratum (PSS), there were no new safety signals observed in patients with acute HCV compared to the chronic HCV population.
The study highlighted the current gap in standard care for acute HCV infection, emphasizing the lack of approved direct-acting antivirals (DAAs) for this population.
The retrospective, noninterventional, single-arm patient chart review study evaluated the efficacy and safety of an 8-week G/P intervention in patients with acute HCV infection across 7 countries. Data was obtained 6 months prior to the first G/P dose though 24 weeks post-treatment. Eligible patients had an acute HCV infection, were aged ≥12 years, had no history of liver or kidney transplant or liver decompensation, and were naïve to HCV treatment for their current infection. Information was evaluated at baseline and during treatment.
The primary efficacy endpoint was SVR12 in the modified full analysis set (mFAS), excluding nonvirologic failures, which was compared to an efficacy threshold, defined as 92.6% by previous G/P SVR12 rates from chronic HCV trials. Other efficacy endpoints included on-treatment virologic failure (OTVF), and relapse and reinfection in the FAS. Safety endpoints were adverse events (AEs) and alanine aminotransferase (ALT). Efficacy was assessed using HCV ribonucleic acid (RNA) data.
In total, 202 patients were included in the FAS assessment, of which most (85.1%) were male, 88.6% were White, 98.6% were noncirrhotic, 68.5% did not have a prior HCV infection, 51.3% had HIV coinfection, and 54.1% were HCV genotype 1.
Superiority to the efficacy threshold was reported in the mFAS population (99.3%; 95% confidence interval [CI] [96.3 – 99.9]), with 1 subject experiencing relapse posttreatment. The SVR12 rate was lower in the FAS when compared with the historic comparative group, mostly due to missing SVR12 data in the FAs. No AE was associated with treatment discontinuation and no AEs of hepatic decompensation of failure were reported. Regarding AEs, 2 patients experienced serious AEs; however, they were not associated with G/P treatment. No participants experienced on-treatment ALT elevations of grade ≥2 which worsened from baseline. All incidences were comparable with the chronic HCV comparator cohort.
During the treatment period, all patients with an ALT grade ≥2 at baseline improved to grade 0/1 according to the PSS (n =42/42) and FAS (n = 53/53). Among the 6 patients with a total bilirubin grade ≥2 at baseline, 5 improved to grade 0/1. The 1 patient with a grade 4 at baseline improved to grade 2 during the trial.
Investigators noted the insufficient patient enrollment to evaluate safety and the retrospective real-world study with inadequate follow-up data limited the results of the study.
“These data support further clinical investigation of the 8-week G/P regimen in acute HCV, to enable shortening of the care cascade and reducing onward HCV transmission, and helping to achieve HCV elimination,” investigators concluded.
Reference
Pol S, Thompson A, Collins M, Venier E, et al. Effectiveness and Safety of 8-Week Glecaprevir/Pibrentasvir for the Treatment of Patients With Acute Hepatitis C: A Single-Arm Retrospective Study. Paper Presented at: AASLD The Liver Meeting, November 10-14, 2023. Accessed November 22, 2023.
