All adolescent patients available for follow-up after treatment with Harvoni for chronic hepatitis C genotype 1 achieved sustained virologic response at 12 weeks with no serious adverse events, further supporting its approval in this population.
“Treatment of pediatric patients has been controversial as the current standard of care, pegylated interferon and weight-based ribavirin, is associated with significant side effects, including growth impairment, and poor tolerability,” William F. Balistreri, MD, from the Cincinnati Children’s Hospital Medical Center, and colleagues wrote. “Similar to what has been observed in adults, treatment with ledipasvir-sofosbuvir was well tolerated in adolescents.”
From November 2014 to October 2015, researchers evaluated the safety and efficacy of Harvoni (ledipasvir/sofosbuvir, Gilead Sciences) in 100 patients aged 12 years to 17 years with chronic HCV genotype 1a (81%) or 1b (19%) in a phase 2 trial. Most patients were treatment-naive (80%), white (90%) and female (63%).
Ninety-eight patients achieved SVR at week 12 (95% CI, 93-100). Two patients were lost to follow-up. The rate of SVR was 98% (95% CI, 91-100) among treatment-naive patients. All patients who were treatment-experienced achieved SVR (95% CI, 83-100).
The most common adverse events included headache (27%), diarrhea (14%) and fatigue (13%), all of which were of mild or moderate intensity. The researchers observed no serious adverse events and no patient discontinued due to adverse events.
During a pharmacokinetic analysis, the plasma exposures of sofosbuvir, ledipasvir and GS-331007 in the adolescent patients were within the predefined pharmacokinetic equivalence boundaries of 50% to 200% compared with adults from the phase 2 and 3 studies of Harvoni.
Five patients had NS5A resistance-associated substitutions (RAS) and 5 had NS5B RAS, all of whom were treatment naive and achieved SVR.
“Many children with chronic HCV have deferred treatment until these newer options receive approval for pediatric use, putting them at risk for disease progression,” Balistreri and colleagues concluded. “Successful treatment of children with HCV could have several public health benefits, including reductions in the rates of disease progression and transmission. Data from adults indicate that successful treatment with ledipasvir-sofosbuvir leads to improvements in quality of life.”
As of April, 2017, Harvoni received approval for the treatment of pediatric patients 12 years and older or at least 77 lb with HCV genotypes 1, 4, 5 or 6 without cirrhosis or with mild cirrhosis. – by Talitha Bennett
Disclosure: Balistreri reports he received grants from Gilead. Please see the full study for the other researchers’ relevant financial disclosures.