Sofosbuvir–velpatasvir in adults with hepatitis C virus infection and compensated cirrhosis in Japan

Abstract

Background & Purpose Protease‐free regimens for chronic hepatitis C virus (HCV) infection are safe and effective for persons with either compensated or decompensated cirrhosis. We examined the efficacy and safety of sofosbuvir–velpatasvir in participants with HCV and compensated cirrhosis in Japan. Methods This was a Phase 3, multi‐center, open‐label study. At 20 sites, 37 individuals with chronic HCV infection of any genotype and compensated cirrhosis received sofosbuvir–velpatasvir (400 mg/100 mg) daily for 12 weeks. Participants were treatment‐naïve or treatment‐experienced with interferon‐based treatments with or without HCV NS3/4A protease inhibitors. Prior exposure with HCV NS5A or NS5B inhibitors was prohibited. The primary study endpoint was sustained virologic response 12 weeks after treatment (SVR12). Results Among participants, 62% had HCV genotype 1 infection, and 38% had HCV genotype 2. More than three quarters (29/37, 78%) were HCV treatment naïve. All participants (37/37, 100%) achieved SVR12. Seventeen participants (46%) and three participants (8%) had pretreatment resistance‐associated substitutions to HCV NS5A and NS5B nucleoside inhibitors respectively, yet no on‐treatment breakthrough or relapse occurred. Sofosbuvir–velpatasvir for 12 weeks treatment was safe and well tolerated. The most commonly reported adverse events were headache (8%, 3/37) and diarrhea (5%, 2/37). One serious adverse event, patella fracture, occurred and was considered not treatment related. No participants discontinued study treatment due to an adverse event. Three participants (8%) had a Grade 3 laboratory abnormality; all were hyperglycemia. Conclusion Sofosbuvir–velpatasvir resulted in high SVR rates and was well tolerated among Japanese patients with HCV and compensated cirrhosis. This single‐tablet regimen offers a highly effective, protease‐inhibitor free regimen for treating HCV. ClinicalTrials.gov Identifier: NCT04112303.

Effect of treatment periods on efficacy of glecaprevir and pibrentasvir in chronic hepatitis C: A nationwide, prospective, multicenter study

“…[2][3][4][5][6][7] The development of newer direct-acting antiviral agents (DAAs) for HCV has improved the rate of sustained virological response (SVR), and DAA therapy has expanded the indication for antiviral therapy. [8][9][10][11][12][13] Recently, new interferon-free DAA regimens have become available, including glecaprevir (GLE) and pibrentasvir (PIB). GLE/PIB therapy has high anti-HCV activity and is effective against pan-genotype HCV.…”

“…Since chronic hepatitis C can lead to liver cirrhosis and hepatocellular carcinoma (HCC), HCV elimination is important to prevent the progression to liver disease 2–7 . The development of newer direct‐acting antiviral agents (DAAs) for HCV has improved the rate of sustained virological response (SVR), and DAA therapy has expanded the indication for antiviral therapy 8–13 …”

Sofosbuvir and Velpatasvir Regimen Outcome for Chronic Hepatitis C Patients With End-Stage Renal Disease Undergoing Hemodialysis

“…Among these, pan-genotypic DAAs are widely considered for HCV-infected patients to obtain a sustained virologic response (SVR) due to their tolerability, effectiveness, and affordability [ 6 ]. An FDA-approved pyrimidine nucleotide analog called sofosbuvir (SOF) inhibits the ribonucleic acid-dependent RNA polymerase produced by non-structural viral protein 5B (NS5B), whereas velpatasvir (VEL) inhibits non-structural viral protein 5A (NS5A) [ 7 ].…”

Sofosbuvir/velpatasvir and glecaprevir/pibrentasvir: how should we choose among these two latest and probably the last regimens?

“…However, the study by Takehara et al clearly demonstrated the safety, efficacy, and tolerability of sofosbuvir/velpatasvir in patients with compensated cirrhosis. 3 It reported a 100% SVR rate in 37 study patients. No patients experienced serious adverse events associated with the regimen, including those with impaired renal function, and completed the therapy.…”

“…However, the study by Takehara et al. clearly demonstrated the safety, efficacy, and tolerability of sofosbuvir/velpatasvir in patients with compensated cirrhosis 3 . It reported a 100% SVR rate in 37 study patients.…”