Almost all young children ages 3 to 6 years with
chronic hepatitis C achieved sustained virological response after 12 weeks of
treatment using sofosbuvir/ledipasvir oral granules, according to findings presented at the 2018 AASLD Liver Meeting in San Francisco.
The prevalence of hepatitis C virus (HCV) infection is
low among children in Europe and the US, though there is concern that the rate
may be rising in the US as more young women become infected as a consequence of
the burgeoning opioid epidemic. In some resource-limited countries such as Egypt, HCV among children is
much more common.
The advent of
direct-acting antiviral agents (DAAs) has revolutionised the treatment of
hepatitis C for adults. These include Gilead Science's HCV polymerase inhibitor
sofosbuvir (marketed alone as Sovaldi)
and NS5A inhibitor ledipasvir, which are co-formulated in a 400/90mg once-daily
Last year the
European Medicines Agency and the US Food and Drug Administration approved
sofosbuvir and the Harvoni co-formulation for adolescents and teens age 12 or
older, or weighing at least 35kg.
younger children, however, the standard of care remains pegylated interferon
plus ribavirin, which is less effective, poorly tolerated and
requires weekly injections for up to two years.
last year's EASL International Liver Congress, researchers reported that treatment with a half-strength tablet containing
200/45mg sofosbuvir/ledipasvir for 12 weeks cured 99% of children ages 6 to 11 years
with chronic hepatitis C.
Gilead went on to develop an oral granule
formulation for younger paediatric patients. The granules can be sprinkled on
the tongue or mixed with non-acidic foods such as ice cream or pudding. In a
pharmacokinetic study, children weighing 17kg or more received 200mg sofosbuvir
plus 45mg ledipasvir, while those weighing less received 150mg sofosbuvir plus
33.75mg ledipasvir. These doses produced drug exposure levels within the range
known to be effective for adults.
At The Liver Meeting, Dr Kathleen Schwarz
of Johns Hopkins Hospital in Baltimore presented results from a study of the
new formulation in 34 children in the UK, US and Australia. About 70% were
girls, about 80% were white and all were infected via mother-to-child
transmission. The mean age was 4 years and 29% weighed less than 17kg. All but
one had HCV genotype 1, with the remaining child having genotype 4. They were
all previously untreated and none had liver cirrhosis.
weeks of therapy plus 12 weeks of post-treatment follow-up, all but one child achieved
undetectable HCV RNA – a sustained virological response rate of 97%. The child
with genotype 4 was among those cured. There was one early discontinuation, but no cases of virological
treatment failure. All children
with resistance-associated viral mutations at baseline were cured.
was generally safe and well tolerated. There were no serious adverse events,
laboratory abnormalities or treatment discontinuations due to severe side-effects. One child stopped treatment after five days because of the taste of
the drugs. The most common adverse events were typical symptoms of childhood
illness such as vomiting, cough, fever, runny nose and strep throat infection.
these findings, the researchers concluded that the sofosbuvir/ledipasvir
granule formulation "represents a highly effective, well tolerated
treatment option" for children 3 to 6 years old with chronic HCV
said she expects that these results will lead to updating of HCV treatment
guidelines to recommend that all children
with hepatitis C age 3 and older should to be treated with direct-acting