Coblopasvir and sofosbuvir for treatment of chronic hepatitis C virus infection in China: A single-arm, open-label, phase 3 trial.

BACKGROUND & AIM: An affordable, pangenotypic regimen remains as an unmet medical need for chronic hepatitis C patients in China. This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of coblopasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic hepatitis C virus (HCV) infection. METHODS: Treatment-naïve and interferon-experienced adult patients, including those with advanced fibrosis (F3) or compensated cirrhosis (F4), were treated with a universal, combinational regimen of coblopasvir 60 mg and sofosbuvir 400 mg, once daily, for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12). RESULTS: Overall, 371 patients (men, 51%; age, 47 ± 11 years; genotype 1a < 1%, 1b 48%, 2a 26%, 3a 6%, 3b 7% and 6 12%) were enrolled from 19 sites. Fifty-one patients (14%) had F3, 39 patients (11%) had F4 and 39 patients (11%) were interferon experienced. The overall SVR12 was 97% (95% CI, [94%, 98%]) for the full analysis set and was equal to or above 90% for all predefined subsets. Ten patients (3%) experienced virological relapse and two patients did not complete follow-up. No adverse events (AEs) occurred at a frequency ≥5%, and the most often reported AEs (≥1%) were neutropenia and fatigue. The majority of AEs were mild to moderate and transient without specific medical intervention. CONCLUSIONS: The universal, pangenotypic combo of coblopasvir plus sofosbuvir is an efficacious and safe treatment for Chinese patients monoinfected with HCV of genotype 1, 2, 3 and 6, including those with compensated cirrhosis. LAY SUMMARY: The regimen of coblopasvir and sofosbuvir is a safe and effective treatment for Chinese patients with genotype 1, 2, 3 and 6 HCV infection, including those with compensated cirrhosis. Therefore, this regimen would be a novel choice of treatment for this patient population.

Sofosbuvir/velpatasvir for the treatment of hepatitis C in pediatric patients.

Introduction: Sofosbuvir/velpatasvir is a combination of direct-acting antivirals with pangenotypic activity for treatment of chronic hepatitis C virus infection. It was approved in 2020 for use in children aged 6-17 years and in June 2021 by the United States Food and Drug Administration for the age group 3-5 years.Areas covered: A literature search of PUBMED and EMBASE was conducted on April 30th and updated on June 10th. Other citations were identified in references of available literature and from ClinicalTrials.gov. The aim of the present research was to outline and discuss the pharmacokinetics, clinical efficacy, tolerability and safety of sofosbuvir/velpatasvir, exploring its actual and potential use in children and adolescents with chronic hepatitis C virus infection.Expert opinion: Five combinations of direct-acting antivirals, of whom three with pangenotypic activity, are now approved for children. No major differences in efficacy and safety profile have been described. Limited access to treatment still is a major issue, especially in low and middle-income countries.

Sofosbuvir and velpatasvir for the treatment of hepatitis C.

INTRODUCTION: Direct acting antivirals are revolutionizing the treatment of chronic hepatitis C. Specifically, the combination therapy sofosbuvir and velpatasvir offers a pangenotypic regimen with high sustained viral response (SVR). Areas covered: Reviewed here are the clinical trials that led to the FDA approval of sofosbuvir and velpatasvir combination therapy, the adverse events during registration trials, and drug-drug interactions. Sofosbuvir and velpatasvir is a fixed dose regimen that is both interferon- and ribavirin-free. It is administered for 12 weeks as a once-a-day pill, covers all genotypes of hepatitis C, and achieves SVR >95% in non-cirrhotic patients and patients with compensated cirrhosis. Addition of ribavirin is recommended for patients with decompensated cirrhosis (CTP B or C). Baseline resistance-associated substitutions do not appear to impair ability to achieve SVR with an initial course of treatment. Expert commentary: Availability of this highly efficacious, well tolerated, all oral regimen formulated as a single pill, can potentially simplify hepatitis C treatment. Its utility as a pangenotypic regimen additionally limits resource utilization.