FDA Approves Harvoni and Sovaldi for Adolescents with Hepatitis C


The U.S. Food and Drug Administration (FDA) on April 7 approved the first direct-acting antivirals for the treatment of chronic hepatitis C virus (HCV) infection in adolescents age 12 to 17 years. Sofosbuvir/ledipasvir (Harvoni) is now indicated for adolescents with HCV genotypes 1, 4, 5, or 6, while sofosbuvir (Sovaldi) plus ribavirin is approved for those with genotypes 2 or 3.

"These approvals will help change the landscape for HCV treatment by addressing an unmet need in children and adolescents," Edward Cox, MD, director of the FDA's Office of Antimicrobial Products, said in an FDA press release

New medications are typically first tested and approved for adults, with pediatric approval following some time later. While hepatitis C is not common among children and adolescents compared to older age groups, experts estimate that 23,000 to 46,000 have HCV, mostly attributable to mother-to-child transmission. Until now these young people have had no approved options other than interferon-based therapy, which is poorly tolerated and less effective than the new direct-acting antivirals.

Gilead Science's HCV polymerase inhibitor sofosbuvir was one of the first direct-acting antivirals that could be used without interferon, approved for adults in December 2013. The all-in-1 combination pill Harvoni, containing sofosbuvir and the HCV NS5A inhibitor ledipasvir, was approved in December 2014 for genotypes 1, 4, 5, and 6; ledipasvir does not work against genotypes 2 or 3. The new pangenotypic combination pill Epclusa (sofosbuvir/velpatasvir) pill, which works against all types of HCV, was approved in June 2016.

Both supplemental approvals cover pediatric patients age 12 to 17 years (after which the adult approval kicks in) and weighing at least 77 pounds or 35 kilograms, without liver cirrhosis or with compensated cirrhosis. Adolescents use the same Harvoni and Sovaldi doses as adults; ribavirin doses are adjusted based on weight.

HIV/HCV coinfected adolescents can use the same regimens, taking into consideration potential interactions with antiretroviral drugs. Harvoni and Sovaldi can lead to hepatitis B virus reactivation in HBV/HCV coinfected patients. The FDA cautioned that the safety and efficacy of Harvoni and Sovaldi have not been established in children under 12 years old or weighing less than 77 pounds.

The supplemental approval of Harvoni was supported by data from Gilead's Study 1116, an open-label clinical trial of 100 participants age 12-17 with HCV genotype 1, with or without liver cirrhosis. They received 400/90 mg sofosbuvir/ledipasvir once-daily for 12 weeks; there was no placebo arm.

As reported at last year's EASL International Liver Congress, 97% achieved sustained virological response, or continued undetectable HCV RNA at 12 weeks post-treatment (SVR12); a Gilead press release gave the final cure rate as 98%. There were no virological failures or relapses; those without SVR12 were lost to follow-up and also may have been cured. Adverse events were similar to those seen in adult studies, with headache and fatigue being most common.

Supplemental approval of sofosbuvir plus ribavirin was supported by data from Gilead's Study 1112, an open-label trial of 50 adolescents age 12-17 with or without cirrhosis. Those with genotype 2 received 400 mg once-daily sofosbuvir plus ribavirin for 12 weeks, while those with genotype 3 extended treatment to 24 weeks. All genotype 2 patients and 97% of genotype 3 patients were cured. Again, adverse events were similar to those seen in adults; despite using ribavirin, none developed anemia.

The cure rate in the Harvoni trial was similar to those seen in adult studies, while the adolescent cure rate for sofosbuvir plus ribavirin was somewhat higher. Although adolescents with cirrhosis were allowed in these studies, almost all were non-cirrhotic or had unknown cirrhosis status, which is a predictor of better treatment response with this regimen.

Sofosbuvir/ledipasvir is a recommended treatment option for adults with genotype 1. However, the latest AASLD/IDSA HCV treatment guidelines no longer recommend sofosbuvir plus ribavirin alone for genotypes 2 or 3, favoring the more effective sofosbuvir/velpatasvir or sofosbuvir plus daclatasvir (Daklinza) combinations.



Food and Drug Administration. FDA approves two hepatitis C drugs for pediatric patients. Press release. April 7, 2017.

Gilead Sciences. U.S. FDA Approves New Indications for Harvoni and Sovaldi in Pediatric Patients 12 Years and Older with Chronic Hepatitis C Infection. Press release. April 7, 2017.