New data show a pediatric formulation of the direct-acting antiviral (DAAs) therapy glecaprevir/pibrentasvir (GLE/PIB) is highly effective and well-tolerated in pediatric patients with hepatitis C virus (HCV) infection.
The findings mark a milestone in the treatment of children with HCV infection, since the data suggest that the dramatic results DAAs have brought about in adults can also be realized in children as young as 3.
Corresponding author Maureen M. Jonas, MD, of Boston Children’s Hospital and Harvard Medical School, said she was pleased with the way the drug’s manufacturer, AbbVie, embraced the effort to make the therapy available to children, something that does not happen in every therapeutic area.
“Often, we have to wait many years for things to percolate down to children,” she told HCP Live. “But these companies across the board addressed the issue of pediatric (patients) relatively early in the process.”
The drugs have a good safety profile in adults, and Jonas said there was good reason to believe they would be successful in children, in part because an earlier phase of the study showed success in children ages 12 up to 18. About 13.2 million of the world’s estimated 71 million people with HCV infection are children between the ages of 1 and 15.
The challenge of the present phase, which focused on children between the ages of 3 and 12, was to find the right dose and also to find a formulation that children would take. In this case, the winning formulation turned out to be small film-coated granules of GLE and PIB.
The study enrolled 80 patients with chronic HCV infection, genotypes 1-6, with or without compensated cirrhosis. The children were split into three age-based cohorts and given weight-based doses for either 8, 12 or 16 weeks. The primary endpoints were sustained virologic response at 12 weeks (SVR12) and steady-state exposure.
Of the 80 patients in the study, 77 achieved SVR12. One patient on the initial dose ratio had relapsed within 4 weeks of the end of treatment and 2 non-responders discontinued the study.
In the end, the investigators found doses of 250 mg GLE and 100 mg PIB were efficacious for children weighing 30 up to 45 kg. A dose of 200 mg GLE plus 80 mg PIB worked for children from 20 up to 30 kg, and the smallest patients (those 12-20 kg) achieved results at a dose of 150 mg GLE plus 60 mg PIB. No serious drug-related adverse events were reported and pharmacokinetic exposures were comparable to those of adults.
The majority of children become infected with HCV as a result of vertical transmission. While a minority of patients (roughly one-quarter) will see their infection resolve on its own, most patients will develop long-term infections. The ability to successfully treat HCV when the patients are young could prevent potential long-term damage, the investigators wrote. Jonas said the therapy would also open up new possibilities for organ donation, since the organs of patients with HCV infection could be transplanted to patients in need and the recipients could then be treated with DAAs to cure the infection.
Perhaps the bigger question, Jonas said, is not so much whether the therapy will work in children, but rather whether it will be available to children. She noted that DAAs typically have a steep price tag. While patients in wealthier regions, such as the United States and Europe, might be able to easily access the therapies, that access is not guaranteed in many developing countries. She said the highest prevalence of the disease is in less-wealthy regions like Egypt, Asia, southeast Asia, and Africa.
“If we really want to eradicate it and decrease global prevalence we’ve got to get out there and not just the developing world,” she said.
The study, “Pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir in children with chronic hepatitis C virus: part 2 of the DORA study,” was published online in Hepatology.