Adolescents with hepatitis C achieve high cure rates with sofosbuvir/ledipasvir

Liz Highleyman
Published:
25 April 2016
Sanjay Bansal presenting at ILC 2016. Photo by Liz Highleyman, hivandhepatitis.com

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.

Reference

Schwarz K et al (Bansal S presenting). High rates of SVR12 in adolescents treated with the combination of ledipasvir/sofosbuvir. International Liver Congress, Barcelona, abstract GS17, 2016.