Sofosbuvir/ledipasvir (Harvoni) was well tolerated and led to sustained virological
response in 97% of adolescents (age 12-17) with chronic hepatitis C, with high
cure rates regardless of prior treatment experience or presence of liver
cirrhosis, according to a report presented at the International Liver Congress last week in Barcelona.
The advent of direct-acting
antivirals (DAAs) used in interferon-free regimens has revolutionised hepatitis
C treatment, but there is little data on their use in children and adolescents.
It is estimated that up to 0.4% of children in the US and Europe, and up to 6%
in resource-limited countries such as Egypt, are living with hepatitis C. With
no DAA regimens specifically approved for them, interferon-based therapy
remains the standard of care for this group.
Sanjay Bansal of Kings College Hospital in London
presented findings from a study evaluating the safety, efficacy and
pharmacokinetics of the sofosbuvir/ledipasvir single-tablet regimen for
patients aged 12 to 17 with genotype 1 hepatitis C virus (HCV) infection.
The trial enrolled 100 participants. Nearly two-thirds
were female, 90% were white and the average age was 15 years. Most (84%) were
infected via mother-to-child or vertical transmission, though Dr Bansal said five
reported injecting drug use. A majority (81%) had harder-to-treat genotype 1a,
the mean baseline HCV RNA level was 6.0 log, 20% were treatment-experienced and
just one patient had cirrhosis.
The first ten participants in this open-label study
underwent intensive pharmacokinetic monitoring for ten days to see if the adult
dosage of 400/90mg in the fixed-dose sofosbuvir/ledipasvir co-formulation is
appropriate for adolescents.
After determining that it was, all participants
received this dose of sofosbuvir/ledipasvir once daily for 12 weeks. The
primary endpoint was sustained virological response, or continued undetectable
HCV viral load at 12 weeks after completing treatment (SVR12).
The pharmacokinetic lead-in showed that administration
of one daily tablet provided plasma exposures of sofosbuvir, GS-331007 (the primary
metabolite of sofosbuvir) and ledipasvir comparable to those observed in
adults.
All but three participants – or 97% – achieved SVR12
in an intention-to-treat analysis. The remaining three were lost to follow-up, two
of whom had undetectable HCV viral load at the end of treatment. All
treatment-experienced participants and the single patient with cirrhosis
achieved SVR12.
Treatment was generally safe and well tolerated, with
no serious adverse events or early discontinuations due to adverse events. The
adverse events profile was similar to that of adults, with the most common
being headache (27%), fatigue (14%), diarrhoea (13%) and nausea (12%).
Based on these findings, the investigators
concluded: "[Sofosbuvir/ledipasvir] represents an important treatment
option for adolescent patients with chronic HCV infection."
"These data in HCV-infected adolescents confirm that this drug
combination is effective in a younger population and has a more favourable
side-effect profile than the treatments currently licensed for teenagers,"
Dr Bansal said in an EASL press release.
Dr Bansal noted that research is currently ongoing to
test sofosbuvir/ledipasvir in younger children, aged 3 to 6 and 6 to 12, using smaller
doses.
"It is very important to have treatment for this population,"
Heiner Wedemeyer of Hannover Medical School stressed at an EASL press briefing.
He said sending children with hepatitis C to kindergarten is a
"disaster" and parents often feel they have to hide the child's status.
Another commenter emphasised the importance of treating children with
hepatitis C before they begin engaging in behaviour such as injecting drug use
or sex that could transmit the virus.