Discovery and preclinical development of dasabuvir for the treatment of hepatitis C infection

ABSTRACT

Introduction: Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality. Positively, the introduction of new directly-acting antivirals (DAAs) have led to dramatic improvements in response rates to antiviral therapy. Furthermore, newer generations of DAAs have demonstrated better safety profiles as well as efficacy than older generations. Current treatment recommendations are based on different combinations of DAAs. Current combination therapies rely on agents that target the different steps of viral replication by using different molecules from various DAAs families.

Areas covered: In this review, the authors summarize data from of one of the recently developed NS5B polymerase inhibitors, dasabuvir, formerly known as ABT-333. Herein, the authors discuss the drug discovery data for dasabuvir including data from preclinical, toxicological resistance studies. The authors also review dasabuvir’s clinical efficacy across various clinical challenges, in addition to its limitations in clinical practice.

Expert opinion: Dasabuvir represents an important medical advance when used as a combination therapy for HCV. Unfortunately, it does present limitations like low genotypic coverage and further research is still required to address some of the lingering issues

KEYWORDS:

• Hepatitis C virus
• dasabuvir
• preclinical
• drug discovery

Article highlights

• Dasabuvir is a direct-acting antiviral agent approved for use in combination therapy for treating hepatitis C infection.

• Dasabuvir acts by inhibiting NS5B polymerase, an enzyme required for HCV replication.

• Dasabuvir has a proven and clear effective synergistic role when used in combination with other DAAs despite showing moderate antiviral efficacy.

• The drug is safe and carries no major side effects with fewer requirements for drug stoppage.

• Dasabuvir has limitations in terms of its limited genotypic coverage. It also has difficulties in terms of its use in advanced cirrhotic patients. There is also a large pill burden when added to combination therapy.

Acknowledgment

This manuscript was language edited by ManuscriptEdit by Reseapro.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.