Efficacy and Safety of 12-week Interferon-based Danoprevir Regimen in Patients with Genotype 1 Chronic Hepatitis C

Abstract

Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 μg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate.Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9–99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident.Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated.Trial Registration Clinical-Trials.gov Identifier: NCT03020082

What to expect from different drugs used in the treatment of COVID-19: A study on applications and in vivo and in vitro results

“…The results of a clinical assay performed with 140 patients showed that danoprevir, potentialized by ritonavir and interferon, produced a sustained virologic response (SVR12) rate of 97.1% after 12 weeks of treatment for the hepatitis C virus. These results show that the combination danoprevir/ritonavir is highly effective, safe, and well tolerated in HCV patients ( Wei et al, 2019 ).…”

SARS-CoV-2 therapeutics: how far do we stand from a remedy?

“…Approved and marketed in China since 2018, Danoprevir is an antiviral used to treat chronic hepatitis C patients by inhibiting HCV protease (NS3/4A) and is demonstrated to be safe and well tolerated in HCV patients. It is often boosted with ritonavir (an HIV protease inhibitor in itself at high dosage), to enhance its plasma concentration [ 73 , 74 ]. Danoprevir is predicted to bind to 3′–5′ exoribonuclease (Nsp14), endoribonuclease (Nsp15) of SARS-CoV-2 [ 75 ] .…”

Existing Antiviral Options Against SARS-CoV-2 Replication in COVID-19 Patients

“…Danoprevir (Ganovo), an oral Hepatitis C virus NS3 serine protease inhibitor, has been already approved in China to treat the noncirrhotic genotype 1b chronic hepatitis C [ 55 , 56 ]. Due to structural and functional similarity between HCV NS3 protease and SARS-CoV-2 3CLpro [ 57 ] the HCV protease inhibitors such as danoprevir are hypothesized to have therapeutic potential against SARS-CoV-2 infection.…”