Children with hepatitis C respond well to sofosbuvir/ledipasvir

Liz Highleyman
Published:
22 April 2017
Karen Murray at the International Liver Congress 2017. Photo by Liz Highleyman, hivandhepatitis.com

Almost all children with hepatitis C, aged 6 to 11 years, who were treated with a half-strength tablet of sofosbuvir/ledipasvir were cured, which is important as some of them had advanced liver damage even at that young age, according to a presentation on Friday at the International Liver Congress in Amsterdam.

In Europe and the US, the prevalence of hepatitis C virus (HCV) infection among children is estimated at up to 0.4%. In some resource-limited countries such as Egypt, however, it can be as high as 6%.

The advent of direct-acting antiviral agents (DAAs) used in interferon-free regimens has revolutionised the treatment of hepatitis C for adults. This month the US Food and Drug Administration (FDA) approved the first DAA regimens for adolescents aged 12 to 17 and weighing at least 35kg.

But DAAs have generally not been studied and are not approved for younger children, leaving pegylated interferon plus ribavirin as the standard of care, which is less effective, often poorly tolerated and requires weekly injections for 12 to 24 months.

Karen Murray of Seattle Children’s Hospital and colleagues evaluated the safety and efficacy of sofosbuvir/ledipasvir for children aged 6 to 11. The study was conducted at more than 30 sites in the UK, US, Australia and New Zealand.

Gilead Science's sofosbuvir (marketed as Sovaldi) is an HCV NS5A inhibitor and ledipasvir is an NS5A inhibitor. They are coformulated in a single once-daily 400/90mg tablet for adults (Harvoni). For this study, researchers developed a half-strength coformulation containing 200mg sofosbuvir and 45mg ledipasvir.

The study enrolled 90 children with chronic hepatitis C, mostly acquired through mother-to-child transmission. About 60% were boys and 80% were white. Most had HCV genotype 1, but two each had genotypes 3 and 4. The liver disease status of most participants was unknown, but two were known to have cirrhosis despite their young age.

A related study presented at the conference found that more than a third of young people in the UK who acquired HCV as children developed serious liver disease, with 5% progressing to liver cancer and 4% needing a liver transplant.

Most participants in this open-label study were treated with sofosbuvir/ledipasvir alone for 12 weeks. However, one treatment-experienced child with HCV genotype 1 and cirrhosis extended treatment to 24 weeks, and two children with genotype 3 added ribavirin and were treated for 24 weeks.

The first 12 children took part in a pharmacokinetic study to confirm dosing with the new coformulation, which showed that drug exposure levels were comparable to those seen in adults treated with Harvoni in clinical trials.

Treatment was found to be highly effective. All but one child treated with sofosbuvir/ribavirin for 12 weeks had undetectable HCV RNA at 12 weeks post treatment – an SVR12 rate (sustained virological response) of 99%. One child relapsed at 4 weeks post-treatment. All three children treated for 24 weeks were cured.

Therapy was generally safe and well tolerated. There was one serious adverse event not considered related to the study medication and no early discontinuations due to adverse events. Around 15% of participants reported adverse events including headache, fever, abdominal pain, vomiting and diarrhoea, cough and sore throat, which Murray noted are common among children this age. One child not taking ribavirin developed anaemia.

Based on these findings, the sofosbuvir/ledipasvir 200/45mg coformulation "represents a highly effective, well tolerated treatment option for children 6 to 11 years old with chronic HCV infection," Murray and colleagues concluded.

An ongoing study is looking at sofosbuvir/ledipasvir for children aged 3 up to 6 years.

Murray said that the 200/45mg sofosbuvir/ledipasvir tablet is not much smaller than the Harvoni tablet for adults. Younger children will get the drugs in a granule formulation that allows for more precise dose adjustment.

"This study is a breakthrough for the management of children aged 6 to 11 years old with hepatitis C, demonstrating that the new DAA regimen is highly efficacious and, more importantly, safe in this group of HCV-infected children," Frank Tacke of University Hospital Aachen in Germany said in an EASL press release.

Reference

Murray KF et al. Ledipasvir/sofosbuvir ± ribavirin for 12 or 24 weeks is safe and effective in children 6–11 years old with chronic hepatitis C infection. International Liver Congress, abstract PS-101, 2017.

Modin L et al. Epidemiology of hepatitis C infection in children and young people in the UK. International Liver Congress, Amsterdam, abstract LBP-525, 2017.