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.
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
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
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.
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.
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.
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.
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.