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EASL 2017: Children with Hepatitis C Respond Well to Sofosbuvir/Ledipasvir

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Almost all children age 6 to 11 with hepatitis C 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 at the at the EASL International Liver Congress this week in Amsterdam.

In the U.S. and Europe 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 revolutionized the treatment of hepatitis C for adults, with sustained response rates above 90%.

Likewise, a study presented at last year's EASL meeting showed that treatment with sofosbuvir/ledipasvir was highly effective for adolescents with hepatitis C. This month the U.S. Food and Drug Administration approved the first DAA regimens for adolescents age 12 to 17 and weighing at least 35 kg/77 lb.

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

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

The study enrolled 90 children with chronic hepatitis C, usually acquired through mother-to-child transmission. About 60% were boys and 80% were white. Most had HCV genotype 1, but 2 each had genotypes 3 and 4. The liver disease status of most participants was unknown, but 2 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 U.K. 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, 1 treatment-experienced child with HCV genotype 1 and cirrhosis extended treatment to 24 weeks, and 2 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.

Results

  • Treatment was found to be highly effective.
  • All but 1 child treated with sofosbuvir/ribavirin for 12 weeks had undetectable HCV RNA at 12 weeks post treatment -- an SVR12 rate of 99%.
  • The remaining child on this regimen relapsed at 4 weeks post-treatment.
  • All 3 children treated for 24 weeks were cured.
  • Therapy was generally safe and well-tolerated.
  • There was 1 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 diarrhea, cough, and sore throat, which are common among children this age.
  • 1 child not taking ribavirin developed anemia.

Based on these findings, the sofosbuvir/ledipasvir 200/45 mg 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 age 3 up to 6 years.

Murray said that the 200/45 mg 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.

4/21/17

Sources

KF Murray, W Balistreri, S Bansal, 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. EASL International Liver Congress. Amsterdam, April 19-23, 2017. Abstract GS-010.

L Modin, A Arshad, B Wilkes, et al. Epidemiology of hepatitis C infection in children and young people in the UK
. EASL International Liver Congress. Amsterdam, April 19-23, 2017. Abstract LBP-525.

EASL. Investigational dose of oral interferon-free treatment can cure hepatitis C in children. Press release. April 21, 2017.

EASL. UK: Serious liver disease develops in one-third of young people with childhood acquired HCV. Press release. April 21, 2017.

Gilead Sciences. Gilead Announces Scientific Presentations Demonstrating Efficacy of Harvoni (Ledipasvir/Sofosbuvir) in Special Patient Populations With HCV Infection. Press release. April 21, 2017.