Efficacy and safety of a fixed dose combination tablet of asunaprevir + beclabuvir + daclatasvir for the treatment of Hepatitis C

ABSTRACT

Introduction: Hepatitis C virus (HCV) is estimated to infect approximately 70 million people worldwide. If left untreated, chronic infection can progress to cirrhosis, liver failure or hepatocellular carcinoma. The advent of new direct-acting antivirals (DAA) has revolutionized patients’ chances of treatment and viral elimination. Currently, several DAA options are available on the market.

Areas covered: This review focuses on the pharmacokinetics, efficacy, tolerability and safety profile of DCV-TRIO, a twice-daily fixed-dose combination of daclatasvir, asunaprevir and beclabuvir approved in Japan for the treatment of genotype 1 HCV infection.

Expert opinion: The DCV-TRIO combination achieved good response rates in genotype 1 patients (SVR12 ≥ 95% in naïve subtype 1b), independently from IL28B genotype, cirrhotic status and prior interferon exposure. On the other hand, unsatisfying response rates were reported in DAA-experienced patients and the risk of RAS selection should not be underestimated. Moreover, DCV-TRIO lacks differentiation from its earlier-launched DAA rivals, presents an inconvenient twice-daily dosing schedule and is not recommended in patients with advanced liver and kidney disease. All these drawbacks considerably limit its effective commercial potential. However, it can be a therapeutic option against HCV in tailored approaches according to the needs of different markets across the world.

Abbreviations AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ASV: asunaprevir; AUC: area under the curve; BCRP: Breast Cancer Resistance Protein; BCV: boceprevir; BID: bis in die; CI: confidence intervals; CLcr: creatinine clearance; DAA: direct acting antivirals; DCV: daclatasvir; EC50: Half maximal effective concentration; GT: genotype; HCV: Hepatitis C virus; IFN: Interferon; NHL: non-Hodgkin lymphoma; OATP: Organic anion transporting polypeptides; OR: odds ratio; P-gp: P-glycoprotein; PK: pharmacokinetics; QD: quo die; RAS: resistance-associated substitutions; SVR: sustained virological response; USD: Unites States dollar

KEYWORDS:

• BMS-79125
• DAA
• DCV-TRIO
• interferon-free combinations
• HCV
• Ximency®

Box 1. Drug summary box.

Declaration of interest

I Gentile has acted as a consultant for Merck Sharp and Dohme, AbbVie and Correvio Pharma. He has also received grants from Gilead Sciences in the framework of a fellowship program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• Several DAA options are currently approved worldwide, with different efficacy and safety profiles across HCV genotypes and patients’ subpopulations.

• DCV-TRIO is a twice-daily fixed-dose combination of daclatasvir, asunaprevir and beclabuvir licensed in Japan for the treatment of GT-1 chronic HCV infection.

• The combination administered for 12 weeks achieves SVR rates ≥ 90%, regardless of cirrhosis status, IL28B genotype, ribavirin addition or prior interferon-exposure.

• Nevertheless, its commercial potential is significantly limited by inconvenient twice-daily dosing schedule, safety issues in patients with end-stage liver and kidney disease, minimal potency against HCV genotypes other than GT-1 and low response rate in DAA-experienced patients.

• Therefore, DCV-TRIO can be considered an additional DAA option only in restricted subgroups of patients.

Additional information

Funding

This manuscript has not been funded.