ABT-450: a novel agent for the treatment of CHC genotype 1: focus on treatment-experienced patients

Abstract

Chronic hepatitis C (CHC) constitutes a major health concern. Hepatitis C virus eradication by antiviral treatment can markedly reduce the risk of developing cirrhosis, hepatocellular carcinoma and liver-related death. A plethora of new direct antiviral agents have been developed and are being explored in clinical trials. One of the newest members of this family is the NS3/4A protease inhibitor ABT-450. The multi-targeted approach combining ritonavir-enhanced ABT-450 with ombitasvir and dasabuvir has been evaluated for the treatment of CHC Gt1 in treatment-naïve and treatment-experienced adults. In this article, we sought to discuss the current knowledge on ABT-450-containing regimens, with special emphasis on treatment-experienced CHC Gt1 patients. This new combination was found to be potent, safe and well tolerated. Future Phase III trials with larger sample size in patients with decompensated cirrhosis, non-Gt1, end-stage renal disease and liver transplant recipients are eagerly awaited.

Keywords:

• ABT-450
• antiviral treatment
• dasabuvir
• HCV
• interferon-free
• NS3/4A
• ombitasvir

Financial & competing interests disclosure

P Andreone declares that he has received research support from Roche, MSD, and Gilead Sciences and served on advisory committees for Roche, MSD, Janssen Cilag, AbbVie, Boehringer Ingelheim, Gilead Sciences and BMS. 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. English language editing and revision was undertaken by American Journals Experts.

No writing assistance was utilized in the production of this manuscript.

Key issues

• A better understanding of Hepatitis C virus (HCV) genome and lifecycle is vital for developing a successful cure with new molecules.

• Chronic hepatitis C infection is considered to be a ‘silent’ disease because it progresses slowly and rarely causes symptoms until decades after infection. Raising awareness of such infection is critical.

• The standard-of-care treatment of genotype 1 HCV infection has improved with the introduction of telaprevir and boceprevir, which are given in combination with pegylated interferon/ribavirin as a triple therapy. Nonetheless, these drugs have some limitations that lead to deferral or even refusal of initiation of antiviral therapy.

• Currently available data about direct antiviral agents regimens vary significantly in terms of efficacy, HCV genotype coverage and their barrier to resistance.

• Many host and viral factors might affect the response to the new direct antiviral agents regimens. Previous non-responders, infection with HCV Gt1a and non-favorable IL28B polymorphism are considered negative predictive factors of sustained virologic response. However, their clinical implication differs greatly according to the IFN-sparing regimen used.

• The use of ribavirin, in certain all-oral regimens, might be unnecessary, especially in those with high genetic barrier and robust antiviral activity.

• A proper evaluation of the potential drug–drug interactions with the IFN-sparing regimens along with pre-treatment assessment of the concomitant medications is indispensable.

• The promising results published recently about the new ABT-450 containing regimens will bring considerable changes to the treatment algorithm of HCV Gt1 infection.

• To conclude, it is still quite challenging for the clinician to choose between all the available IFN-free regimens owing to their comparable rates of sustained virologic response. Nevertheless, a proper selection of such regimens can be achieved by evaluating the patient’s baseline clinical characteristics, cost–effectiveness along with the pharmacological profile of the antiviral combination used.