Glecaprevir/pibrentasvir shows favourable efficacy signals for paediatric HCV

Findings from the ongoing POLAC project demonstrate that treatment with the pangenotypic regimen comprising glecaprevir/pibrentasvir (GLE/PIB) for 8 weeks is highly effective against chronic hepatitis C virus (HCV) infection in children and adolescents. This regimen also showed a good safety profile.

In the intention-to-treat (ITT) population, all but one patient achieved sustained virologic response at 12 weeks after treatment, translating to a 97.5-percent efficacy rate. In the per-protocol cohort, a 100-percent rate was achieved, noted Dr Anna Dobrzeniecka from the Regional Hospital of Infectious Diseases, Warsaw, Poland, during her presentation at ESPID 2024.

This treatment effect was observed regardless of the participants’ age, sex, baseline BMI, HCV genotype, and extent of liver fibrosis, Dobrzeniecka added.

Of note, most of the participants already had undetectable HCV RNA after 4 weeks of GLE/PIB treatment. [ESPID 2024, abstract PS002]

“[Moreover,] we observed significant decreases in aminotransferase levels during subsequent visits, which corresponded to liver function improvement,” Dobrzeniecka explained.

Over 40 percent of participants reported experiencing adverse events (AEs). Of the AEs, 24 were deemed probably or possibly related to GLE/PIB treatment. The most frequently reported AEs were abdominal pain and headache (9.8 percent each), followed by pruritus, somnolence, and fatigue (7.3 percent each). “All of these were mild and manageable,” said Dobrzeniecka. Other AEs reported were diarrhoea, nausea, rash, calf cramps, and taste disorder.

Most paediatric cases undiagnosed

“HCV remains a significant global health problem,” Dobrzeniecka said. Over 3 million children are living with HCV worldwide, and most of the cases remain undiagnosed. [JHEP Rep 2021;doi:10.1016/j.jhepr.2021.100227; Lancet Gastroenterol Hepatol 2020;5:374-392]

Although direct-acting antivirals provide a chance for HCV eradication, Dobrzeniecka underlined that the main concern is the opportunity for treatment in paediatric populations. “[There is a] notable lack of recommendations for HCV testing in children.”

In this open-label study, the ITT cohort comprised children and adolescents aged 5–18 years with chronic HCV (n=41; median age 8 years, 54 percent girls). They were split into two groups based on age and weight. Those aged >12 years or who weighed >45 kg (n=13) were given a fixed dose of GLE/PIB 300/120 mg tablets. Younger participants (<12 years; n=28) were given the GLE/PIB granule formulation, which was adjusted according to patients’ weight. Participants were to undergo treatment for 8 weeks.

Ninety-five percent of participants acquired their HCV infection vertically. The majority of participants were infected with HCV genotype 1 (n=25 [61 percent]), 11 had HCV genotype 3, while four had HCV genotype 4. One patient had both HCV genotypes 3 and 4.

Two participants presented with significant fibrosis, two had steatosis (one S2 [moderate] and one S3 [severe]), but importantly, none had cirrhosis.

“Our study confirms that 8 week-therapy with GLE/PIB in children with chronic hepatitis C is highly effective and has a good safety profile,” Dobrzeniecka said. She called for further evaluations to ascertain the long-term effect of GLE/PIB treatment.