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AASLD 2013: Sofosbuvir + Ribavirin Effective Against Hepatitis C Genotype 4

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A dual oral regimen of sofosbuvir plus ribavirin taken for 24 weeks led to an early cure at 4 weeks post-treatment for difficult-to-treat patients with hepatitis C virus (HCV) genotype 4, according to a poster presented at the 64th AASLD Liver Meeting last month in Washington, DC.

HCV genotype 4 is the predominant type in the Middle East and Africa -- where it accounts for more than 80% of cases -- and it is increasingly also seen in the U.S. and Europe. Genotype 4, like genotype 1, is traditionally considered hard to treat (compared with genotypes 2 and 3), but it has not been as extensively studied.

Peter Ruane from Light Source Medical in Los Angeles and colleagues evaluated an interferon-free dual regimen combining the nucleotide HCV polymerase inhibitor sofosbuvir (formerly GS-7977) plus ribavirin for people of Egyptian descent with HCV genotype 4. The estimated hepatitis C prevalence in Egypt is around 10%-15% and more than 90% have this genotype.

The Phase 3 NEUTRINO study previously showed that sofosbuvir plus pegylated interferon and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 90% overall for people with genotypes 1, 4, 5, and 6, rising to 96% in a sub-analysis of the 28 treatment-naive participants with genotype 4. The genotype 4 cure rate for pegylated interferon/ribavirin alone has ranged from 40% to 70% in prior studies.

The current Phase 2b pilot study aimed to determine if sofosbuvir plus ribavirin without interferon is adequate for people with genotype 4, as has been demonstrated for genotypes 2 and 3. FDA approval of the dual regimen for these easier-to-treat genotypes is expected soon.

The analysis included 60 patients born in Egypt and living in the U.S. About two-thirds were men and the mean age was 54 years. 28 were treatment-naive and 32 were treatment-experienced; in the latter group, 63% were prior non-responders, 19% had viral breakthrough or relapse, and 13% could not tolerate interferon. Most had unfavorable (CT or TT) IL28B gene variants, more than half had high baseline HCV viral load, 23% had liver cirrhosis, and about 40% had previously had schistosomiasis (a parasitic infection that can damage the liver).

Participants in this open-label study were randomly assigned to receive with 400 mg once-daily sofosbuvir plus 1000-1200 mg/day weight-based ribavirin for either 12 or 24 weeks. The poster reported SVR12 results for the 12-week treatment arm and SVR4 data for the 24-week treatment arm. SVR12 is considered a cure, but relapse may still occur after SVR4.

Results

  • After 4 weeks on treatment, almost all patients experienced rapid virologic response (HCV RNA > 25 IU/mL).
  • No cases of virological breakthrough were observed while on treatment.
  • 79% of treatment-naive patients and 59% of treatment-experienced patients treated for 12 weeks achieved SVR12.
  • All treatment-naive patients and 93% of treatment-experienced patients treated for 24 weeks achieved SVR4.
  • People with cirrhosis and unfavorable IL28B variants had lower response rates with 12-week treatment, but differences were not apparent for 24-week treatment.
  • Sofosbuvir plus ribavirin was generally safe and well-tolerated.
  • 3 people in the 24-week arm experienced serious adverse events and 1 person in this group discontinued ribavirin early due adverse events.
  • The most common side effects were headache, insomnia, and fatigue.
  • No participants developed severe anemia

"An oral regimen containing sofosbuvir plus ribavirin provided rapid and consistent antiviral suppression in treatment-naive and -experienced patients with genotype 4 infection," the researchers concluded. "Patients receiving 24 weeks of sofosbuvir + ribavirin achieved high SVR4 rates (97% overall) regardless of prior treatment experience, cirrhotic status, or other prognostic factors.

12/4/13

Reference

PJ Ruane, D Ain, J Riad, et al. Sofosbuvir Plus Ribavirin in the Treatment of Chronic HCV Genotype 4 Infection in Patients of Egyptian Ancestry. 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013). Washington, DC, November 1-5, 2013. Abstract1090.