Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection

Abstract

Glecaprevir (nonstructural protein 3/4A protease inhibitor) and pibrentasvir (nonstructural protein 5A inhibitor) (G/P), a coformulated once‐daily, all oral, ribavirin (RBV)‐free, direct‐acting antiviral regimen, was evaluated for safety and efficacy in hepatitis C virus genotype 2 (GT2)–infected Japanese patients, including those with compensated cirrhosis. CERTAIN‐2 is a phase 3, open‐label, multicenter study assessing the safety and efficacy of G/P (300/120 mg) once daily in treatment‐naive and interferon ± RBV treatment–experienced Japanese patients without cirrhosis but with GT2 infection. Patients were randomized 2:1 to receive 8 weeks of G/P (arm A) or 12 weeks of sofosbuvir (400 mg once daily) + RBV (600‐1000 mg weight‐based, twice daily) (arm B). The primary endpoint was noninferiority of G/P compared to sofosbuvir + RBV by assessing sustained virologic response at posttreatment week 12 (SVR12) among patients in the intent‐to‐treat population. SVR12 was also assessed in treatment‐naive and interferon ± RBV treatment‐experienced patients with GT2 infection and compensated cirrhosis who received G/P for 12 weeks in the CERTAIN‐1 study. A total of 136 patients were enrolled in CERTAIN‐2. SVR12 was achieved by 88/90 (97.8%) patients in arm A and 43/46 (93.5%) patients in arm B. No patient in arm A experienced virologic failure, while 2 did in arm B. The primary endpoint was achieved. In CERTAIN‐1, 100% (18/18) of GT2‐infected patients with compensated cirrhosis achieved SVR12. Treatment‐emergent serious adverse events were experienced by 2 patients without cirrhosis in each arm and no patient with cirrhosis. Conclusion: The results demonstrate high efficacy and favorable tolerability of G/P in GT2‐infected Japanese patients. (Hepatology 2018;67:505‐513).

Efficacy and safety of glecaprevir/pibrentasvir as retreatment therapy for patients with genotype 2 chronic hepatitis C who failed prior sofosbuvir plus ribavirin regimen

“…Theoretically, RAVs in Non‐structural protein (NS)3 and NS5A regions might influence the therapeutic efficacy of GLE/PIB in HCV GT2. However, the phase III trial of GLE/PIB for GT2 patients (CERTAIN‐2 trial) has reported that RAVs in NS3 and NS5A regions at the baseline did not affect the efficacy in either GT2a or GT2b . As the method for detecting RAVs in both NS3 and NS5A regions of HCV GT2 does not exist on a commercial basis, we could not investigate RAVs in this study.…”

Real‐world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group

“…In areas where regimens such as SOF + velpatasvir, glecaprevir/pibrentasvir, or SOF/ledipasvir are available, these regimens could be an alternative choice for HCV genotype 2 cirrhotic patients. For these patients, Japanese clinical trials have shown that the rate of SVR was 100% (18/18) for the glecaprevir/pibrentasvir regimen and 93% (13/14) for the SOF/ledipasvir regimen . The global ASTRAL‐2 study showed that the rate of SVR was 93% (40/43) by SOF + velpatasvir .…”

Efficacy and safety of elbasvir/grazoprevir for Japanese patients with genotype 1b chronic hepatitis C complicated by chronic kidney disease, including those undergoing hemodialysis: A post hoc analysis of a multicenter study

“…Considering the metabolism and excretion of these DAAs, it is presumed that they can be administered to patients with CKD. A phase 3 trial of glecaprevir/pibrentasvir demonstrated the high efficacy and safety in patients with CKD and those undergoing hemodialysis . IFN/ribavirin‐free, glecaprevir/pibrentasvir for pan‐genotype chronic hepatitis C patients is expected to treat genotype 2–6 chronic hepatitis C patients with CKD including hemodialysis, with high efficacy and safety.…”