A phase 3b study of sofosbuvir plus ribavirin in treatment‐naive and treatment‐experienced Korean patients chronically infected with genotype 2 hepatitis C virus

Abstract

Summary In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon‐alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon‐free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38–46% in Korea. This single‐arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12‐week duration) in chronic genotype 2 HCV‐infected treatment‐naive and treatment‐experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment‐naive and 100% (24/24) of treatment‐experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on‐treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment‐emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all‐oral, interferon‐free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection.

Safety, Tolerability, and Efficacy of Sofosbuvir Plus Ribavirin in Elderly Patients Infected with Hepatitis C Virus Genotype 2

“…Consistent with the results from the previous reports [6,8,9], all patients were negative for serum HCV at EOT, suggesting a high barrier against the emergence of resistant strain for nucleotide NS5B inhibitor. Of the 4 patients who failed to achieve SVR12, only the patient in the non-aged group discontinued the 12-week treatment because of hyperbilirubinemia.…”

“…Similar results were reported for this combination therapy in several regions, such as Japan, Taiwan, Korea where the reported SVR12 rate was 97, 100, and 97%, respectively [6,8,9]. Reportedly, a high SVR12 rate was observed even in patients with liver cirrhosis, treatment-experienced, and elderly patients.…”

“…Although previous reports suggested a high SVR12 rate irrespective of liver cirrhosis and age [6,8,9], the reported cohorts in most previous literature classified the elderly group as the group comprising patients aged ≥65, and did not include patients aged ≥75. Therefore, it might be possible that advanced liver fibrosis and history of HCC that were associated with the presence of liver cirrhosis might be a cause of a lower SVR12 rate in the aged patients.…”

“…Reportedly, a high SVR12 rate was observed even in patients with liver cirrhosis, treatment-experienced, and elderly patients. However, according to previous reports, almost every patient reported in the literature was younger than 75 years; the efficacy and safety of sofosbuvir plus RBV treatment in patients older than 74 years have not been elucidated [5,6,8,9]. Information regarding the safety, tolerability, and efficacy in aged patients is critical for the management of CHC patients in an aging society such as Japan [16]; we compared the efficacy and safety of this combination therapy between patients aged ≥75 and those aged ≤74.…”

“…Recently, an IFN-free regimen for CHC was developed, which led to a drastic improvement in sustained virological response (SVR) [4]. With regard to the treatment of CHC patients infected with HCV genotype 2 (G2), data from a phase III trial on treatment using combination of nucleotide HCV non-structural protein 5B (NS5B) polymerase inhibitor, sofosbuvir, and ribavirin (RBV) for 12 weeks have been published for different ethnic cohorts including the Japanese population; 93-100% of the patients reportedly achieved SVR at 12 weeks (SVR12) after the end of the treatment (EOT) [5,6,7,8,9]. More importantly, the high SVR12 rate could be achieved regardless of age, gender, background status of liver fibrosis, and history of antiviral therapy [6,8,9], which have been known to be associated with failure of IFN-based treatment.…”