PAS 2017: Sofosbuvir Plus Ribavirin Cures Teens with Genotype 2 or 3 Hepatitis C

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A 2-drug regimen of sofosbuvir (Sovaldi) and ribavirin taken for 12 weeks led to sustained virological response in all treated adolescents with hepatitis C virus (HCV) genotype 2, while a 24-week course cured all but one teen with harder-to-treat genotype 3, according to a presentation at the 2017 Pediatric Academic Societies Meeting last week in San Francisco.

Experts estimate 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, mostly attributable to mother-to-child transmission.

The advent of direct-acting antivirals (DAAs) used in interferon-free regimens has transformed treatment of chronic hepatitis C, but the new drugs have not been extensively tested in adolescents or children, and until recently interferon-based therapy remained the standard of care for pediatric patients.

Regino Gonzalez-Peralta from the University of Florida Gainesville and colleagues evaluated sofosbuvir plus ribavirin for adolescents age 12 to 17 with HCV genotypes 2 or 3, which are less common in the U.S. but are a major public health problem in parts of Africa, Asia, and the Middle East.

The study enrolled 50 adolescents (average age 15 years) with chronic hepatitis C in the U.S., U.K., Europe, Russia, Australia, and New Zealand; 13 had genotype 2 and 37 had genotype 3. None of the genotype 2 patients had been previously been treated for hepatitis C, but 24% in the genotype 3 group were treatment-experienced. None were known to have liver cirrhosis, but 60% had unknown disease status.

Participants with HCV genotype 2 in this open-label study were treated with once-daily sofosbuvir (400 mg) plus ribavirin (15 mg/kg/day) for 12 weeks. Those with genotype 3 received the same combination for 24 weeks. The first 10 teens were included in a pharmacokinetic sub-study, which showed that plasma drug concentrations were comparable to those seen in adults.

Results

"Sofosbuvir plus ribavirin represents an important treatment option for adolescents with chronic HCV genotype 2 or 3 infection," the researchers concluded.

While these study results look good, hepatitis C drug approvals have been moving faster than the research can be completed, and this is already considered an obsolete regimen for adults.

In April the U.S. Food and Drug Administration approved sofosbuvir plus ribavirin for adolescents with HCV genotypes 2 or 3, and the sofosbuvir/ledipasvir coformulation (Harvoni) for those with genotypes 1, 4, 5, or 6.

A study presented at the 2016 EASL International Liver Congress showed that sofosbuvir/ledipasvir is highly effective for adolescents age 12 to 17 with genotype 1. Another study at this year's EASL meeting showed that this combination also worked well for younger children age 6 to 11.

As with Gonzalez-Peralta's study, most of the participants in these trials did not have confirmed liver cirrhosis, though many had not been evaluated for it.

A related presented at the PAS meeting described a case series of adolescents with cirrhosis who were treated with sofosbuvir/ledipasvir as part of a compassionate use program prior to its approval.

Kristina Reed, from the University of Oklahoma Health Sciences Center reported on 3 teens with HCV genotype 1a who did not respond to pegylated interferon and ribavirin. All had biopsy-proven cirrhosis. They all achieved SVR and no longer required liver transplants.

The current AASLD HCV treatment guidelines and EASL guidelines no longer recommend sofosbuvir plus ribavirin for adults, even those with easy-to-treat genotype 2. Instead, they recommend sofosbuvir plus daclatasvir (Daklinza) or the sofosbuvir/velpatasvir coformulation (Epclusa).

Gonzalez-Peralta acknowledged that a regimen containing 2 DAAs may also be a better option for teens. A study of sofosbuvir/velpatasvir for adolescents is now underway.

5/16/17

Sources

RP Gonzalez-Peralta, P Rosenthal, K Murray, et al. Sofosbuvir plus ribavirin is safe and effective in adolescents with genotype 2 or genotype 3 chronic hepatitis C infection. Pediatric Academic Societies Meeting. San Francisco, May 6-9, 2017. Abstract 1690.8.

K Reed, J Gamblin, J O'Connor, et al. Case Series- Treating Children with Hepatitis C 1a Who Are Treatment-experienced and Cirrhotic with Ledipasvir-Sofosbuvir under compassionate use. Pediatric Academic Societies Meeting. San Francisco, May 6-9, 2017. Abstract 1536.5.