www.hivandhepatitis.com

EASL 2016: Adolescents with Hepatitis C Achieve High Cure Rates with Sofosbuvir/Ledipasvir

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 2016 EASL International Liver Congress in Barcelona.

The advent of direct-acting antivirals (DAAs) used in interferon-free regimens has revolutionized 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 U.S. 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, pegylated interferon plus ribavirin remains the standard of care for this group.

Sanjay Bansal from 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 age 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 Bansal said 5 reported injection 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 1 patient had cirrhosis.

The first 10 participants in this open-label study underwent intensive pharmacokinetic monitoring for 10 days to see if the adult dosage of 400/90 mg in the fixed-dose sofosbuvir/ledipasvir coformulation is appropriate for people in this age group.

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).

Results

• The pharmacokinetic lead-in showed that administration of 1 tablet daily provided plasma exposures of sofosbuvir, GS-331007 (the primary metabolite of sofosbuvir), and ledipasvir comparable to those observed in adults.
• All but 3 participants -- or 97% -- achieved SVR12 in an intention-to-treat analysis.
• The remaining 3 were lost to follow, 2 of whom had undetectable HCV RNA 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 event profile was similar to that of adults, with the most common being headache (27%), fatigue (14%), diarrhea (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 favorable side-effect profile than the treatments currently licensed for teenagers," Bansal said in an EASL press release.

Bansal noted that research is currently ongoing to test sofosbuvir/ledipasvir in younger children, age 3-6 and 6-12, using smaller doses.

"It is very important to have treatment for this population," Heiner Wedemeyer from 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 emphasized the importance of treating children with hepatitis C before they begin engaging in behavior such as injection drug use or sex that could transmit the virus.

4/22/16

References

K Schwarz, KF Murray, P Rosenthal, S Bansal, et al. High rates of SVR12 in adolescents treated with the combination of ledipasvir/sofosbuvir. EASL International Liver Congress 2016. Barcelona, April 13-17, 2016. Abstract GS17.

Other Source

EASL. New study demonstrates efficacy of all-oral treatment regimens in adolescents with hepatitis C virus. Press release. April 16, 2016.