Investigational direct-acting antivirals in hepatitis C treatment: the latest drugs in clinical development

ABSTRACT

Introduction: Therapeutic options for patients with HCV-related liver disease have increased over the last two decades. In fact, the old standard of care based on the combination of pegylated interferon and ribavirin did not result in satisfactory eradication rates, particularly in patients with liver cirrhosis. With the advent of direct-acting antivirals (DAAs), higher rates of viral clearance became possible and, patients with contraindications to interferon obtained access to treatment. However, several concerns have been raised regarding first-generation DAAs, namely their high costs, and the emergence of resistant-associated variants with low susceptibility to these drugs.

Areas Covered: In this review, the authors discuss the data about the efficacy and safety of the main anti-HCV direct-acting antivirals currently in the pipeline. Furthermore, they evaluate the impact of these drugs on the therapeutic options currently available for HCV patients.

Expert opinion: The results of trials evaluating the effectiveness of new DAAs are encouraging. These new antivirals lead to high rates of viral eradication without relevant adverse reactions and seem to be effective regardless of viral genotypes, presence of resistant-associated variants or advanced liver disease. Consequently, with the advent of this new family of drugs, chronic HCV-related hepatitis may become a curable disease.

KEYWORDS:

• HCV
• cirrhosis
• resistance
• velpatasvir
• sofosbuvir
• grazoprevir
• elbasvir

Article highlights

• Anti-HCV DAAs have radically changed the prognosis of patients.

• Current DAA-based regimens, although generally effective and safe, may not lead to a satisfactory SVR12 rate, or be well tolerated in some categories of patients.

• Most DAAs currently in the pipeline resulted in a very high SVR12 rate, and a low rate of serious adverse reactions in both patients with and patients without cirrhosis.

• Some DAA-based regimens currently pending approval were very effective in patients who experienced previous anti-HCV treatment or who harbored HCV resistant-associated variants.

• Given the evidence of the high efficacy and safety of several new DAAs in the pipeline even for difficult-to-treat patients with chronic HCV infection, their availability is highly desirable.This box summarizes key points contained in the article

Acknowledgements

The authors are grateful to Jean Ann Gilder (Scientific Communication srl, Naples, Italy) for text editing.

Financial and competing interests disclosure

I Gentile has received a grant from Gilead Sciences for Hepatitis B and Hepatitis C research. He has also acted as a consultant for AbbVie. 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.