Beclabuvir in combination with asunaprevir and daclatasvir for hepatitis C virus genotype 1 infection: A systematic review and meta‐analysis

Abstract

Daclatasvir, asunaprevir (ASV), and beclabuvir (BCV) are direct-acting antivirals (DAAs) for patients with hepatitis C virus genotype 1 infection. This systematic review and meta-analysis investigating the efficacy and safety of this three-drug combination in HCV genotype 1 infection. Eleven electronic search engines were searched for relevant publications. Studies were screened for eligibility and data was extracted. The outcomes were pooled as event rate and risk ratio (RR). The protocol was registered in PROSPERO (CRD42017054391). Among the included six studies, five studies were included for the meta-analysis (n = 1261). The three-drug combination showed a high response rate in naïve patients with sustained virologic response at week-12 posttreatment (SVR ) rate = 95.7% (95%CI [93.8-97.1]) and no difference detected by adding ribavirin (RBV) (the pooled RR = 0.98, 95%CI [0.90-1.08], P = 0.70) or comparing with interferon-experienced patients (RR = 1.02, 95%CI [0.98-1.07], P = 0.31) regardless the genotype 1 subtypes or IL28B genotype. Treatment failure was minimal and showed no difference regarding the previous comparisons. Increasing the dose or the duration did not show a significant increase in the efficacy. In conclusion, this analysis showed high response rates in HCV genotype 1-infected patients treated with daclatasvir, ASV, and BCV irrespective of RBV use, prior interferon-based therapy, or restriction on non-cirrhotic patients, IL28B genotype, or baseline resistance-associated variants.

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

“…Beclabuvir is a non-nucleoside polymerase inhibitor that potentially inhibit nonstructural protein 5B (NS5B) of HCV [25]. Previous studies, including phase 3 clinical trials have suggested beclabuvir have a high response rate at post-treatment week [26,27]. Moreover, the pharmacokinetic, efficiency and tolerability were also reported very favorable [28].…”

The Discovery and Early Clinical Evaluation of the HCV NS3/4A Protease Inhibitor Asunaprevir (BMS-650032)

“…The licensing of 1 and 2 represented the first approval of a combination of DAAs for the treatment of HCV infection although the combination of 52 and the nucleoside-based HCV NS5B inhibitor prodrug sofosbuvir (53) was approved by the FDA in December of 2013 [86,87]. Extending the therapeutic utility of 1 and 2 to include the treatment of HCV GT-1a infections required the addition of a third agent, the NS5B inhibitor beclabuvir (3), which was ultimately developed as a fixed dose combination comprising of 200 mg of 1, 30 mg of 2, and 75 mg of 3 administered on a BID schedule for 12 weeks [88][89][90][91][92][93]. In an international phase III clinical study designated the UNITY 1 trial that was conducted in 415 patients infected with HCV GT-1 who were non-cirrhotic, 91% of the patients achieved SVR 12 .…”

The Discovery and Development of Daclatasvir: An Inhibitor of the Hepatitis C Virus NS5A Replication Complex

“…Broadening the utility of 1 and 54 to treat HCV GT-1a infections required the addition of a third agent, the allosteric RNA-dependent RNA polymerase inhibitor beclabuvir (56) which was developed as a fixed-dose combination comprising of 30 mg of 1, 200 mg of 54, and 75 mg of 56 administered as a BID regimen for 12 weeks [120][121][122][123][124][125][126]. In the UNITY 1 international study which was conducted in 415 non-cirrhotic patients with HCV GT-1 infection, 91% of the patients achieved SVR 12 .…”