麻豆传媒

AMSTERDAM -- Treatment with a half-strength tablet of sofosbuvir/ledipasvir (Harvoni) for 12 weeks cured 99% of children, ages 6 to 11 years, with chronic hepatitis C, researchers reported here.

All but one child treated with sofosbuvir/ledipasvir (200 mg/45 mg) for 12 weeks achieved sustained virological response, or undetectable HCV RNA, 12 weeks after finishing treatment. A single child relapsed at 4 weeks post-treatment. All three patients treated for 24 weeks were cured, according to , of Seattle Children's Hospital, and colleagues.

The combination was safe and well tolerated -- a major improvement for pediatric patients for whom interferon-based therapy remains the standard of care, she said at the International Liver Congress, the annual meeting of the European Association for the Study of the Liver (EASL).

Sofosbuvir is a HCV NS5A inhibitor and ledipasvir is a NS5A inhibitor. They are coformulated into a single once-daily 400 mg/90 mg tablet for adults.

"This study showed that some of these children have a surprisingly large amount of liver disease at a young age, and we need to treat those children before they run into trouble," Graham Foster, MD, from Queen Mary University of London told 麻豆传媒.

The prevalence of hepatitis C virus (HCV) infection in children is up to 0.4% in the U.S. and Europe, and as high as 6% in some resource limited countries such as Egypt, according to Murray.

"Direct-acting antivirals have transformed [HCV] treatment, and really changed the paradigm for adult treatment, but we have more limited options in children," she told reporters at an EASL press conference.

Cure rates for adults treated with interferon-free direct-acting antiviral (DAA) regimens exceed 90%. Similarly, a study presented at last year's EASL meeting showed that sofosbuvir/ledipasvir was highly effective for adolescents with HCV.

Earlier this month, the FDA approved sofosbuvir (Sovaldi) and sofosbuvir/ledipasvir coformulation for adolescents, ages 12 to 17. These are the first DAAs to get the nod for this age group, but to date no interferon-free treatment has been available for younger children.

Murray's group evaluated the safety and efficacy of sofosbuvir/ledipasvir for children, ages 6 to 11 years.

The ongoing study enrolled 90 children with chronic HCV, generally acquired through mother-to-child transmission, in the U.S., U.K., Australia, and New Zealand. They mostly had HCV genotype 1, but two each had genotypes 3 and 4. The liver disease status of many participants was unknown, but two children had cirrhosis despite their young age.

Most children were treated with sofosbuvir/ledipasvir alone for 12 weeks. One treatment-experienced child with HCV genotype 1 and cirrhosis was treated for 24 weeks, and two children with genotype 3 were treated longer and added ribavirin.

The first 12 children to enroll were included in a pharmacokinetic substudy to confirm dosing with the new coformulation. It showed that drug exposure levels were comparable to those seen in adults treated with Harvoni in clinical trials, according to Murray.

There was one serious adverse event not related to the study medication and no one stopped treatment early due to adverse events, Murray said. A number of patients experienced adverse events such as headaches, fever, vomiting or diarrhea, cough, and sore throat, but Murray noted that these are all common among children of that age group.

The sofosbuvir/ledipasvir half-strength coformulation "represents a highly effective and well-tolerated treatment option for children 6 to 11 years old with chronic HCV infection," Murray concluded.

Drugmaker Gilead Sciences is also testing sofosbuvir/ledipasvir in an ongoing study that is recruiting kids, ages 3 to 6 year, with HCV Murray told 麻豆传媒. She said that the half-strength tablet is not much smaller than Harvoni for adults, but younger children will take the drugs in a granule formulation.

Foster, who was not involved in the study, stressed the importance of effective HCV treatment for children of all ages.

"I think if you had a young child with hepatitis C, you'd want to get rid of it," he told 麻豆传媒. "It ostracizes them, it takes them out of play time, and it just makes life more difficult for them. It's actually very difficult to transmit hepatitis C on a playground, but there's a stigma."

"This study is a breakthrough for the management of children aged six 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," said Frank Tacke, MD, PhD, of the University Hospital Aachen in Germany, and an EASL governing board member.

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