2016/2017 - New HCV two and three drug regimens on their way: what do they promise?

Summary for AASLD 2016 for Hepatitis C - New HCV two and three drug regimens on their way: what do they promise? And what do clinicians need to look out for under DAA combination therapy and beyond SVR?
Jurgen K. Rockstroh M.D., Professor of Medicine University of Bonn, Germany

Jules Levin Executive Director of National AIDS Treatment Advocacy Project (NATAP) recently added this complete summary of AASLD 2016 including links to each study cited in the article. Here is a summary of the topics and introduction with a few links of interest, click here to view the full text article.

Topic Summary
Risk of HBV reactivation after starting DAA therapy
Surveillance for hepatocellular carcinoma (HCC) and risk for HCC after achieving SVR following DAA therapy.
Intravenous drug users and patients on opioid substitution therapy
Patients in the prison setting
HIV/HCV coinfected patients
Patients with renal insufficiency or on hemodialysis
Patients older than 70 years
Patients receiving short treatment durations of 8 week
HCV three drug rescue combinations with licensed drugs
New dual DAA combinations
New three drug combinations

Introduction
At present, besides the Abbvie 3-D regimen, mostly dual hepatitis C (HCV) direct acting antiviral (DAA) combinations which are coformulated as single tablet regimens have become the gold standard for first line treatment of all HCV genotypes. Despite SVR rates on average above 95% there are still attempts in the field to develop three drug combinations (so called triplets) or very potent new dual regimens which may allow shortening of treatment duration and may also add to the antiviral pangenotypic activity of all oral DAA combination therapy. Obviously, even with the currently licensed HCV drugs, three drug combinations may play a role in retreatment of the few patients which experience virological failure under dual DAA-based HCV therapy. Various studies at AASLD this year where devoted to effectiveness and safety of these new three DAA regimens in treatment naïve as well as treatment experienced patients including prior DAA-based treatment failure (1-7). In addition, data on the new and very potent Abbvie dual combination (Glecaprevir (ABT-493)/Pibrentasvir (ABT-530)), again in treatment-naïve, experienced- and prior DAA-failures, was presented (8-10). Another important topic was feedback on safety and effectiveness of various all oral DAA combinations from real-world cohorts including a whole variety of special populations including intravenous drug users, patients on opioid substitution therapy, patients in the prison setting, HIV coinfected, patients with renal insufficiency, patients older than 70 years, patients receiving short treatment durations of 8 week and much more (11-19). As more and more data arises from very diverse patient populations it appears as if no special or hard to treat patient group seems to exist any longer. In the end it really is more about getting access to therapy feasible for some of those more marginalized patient groups. A further important topic was around clinically relevant issues which clinicians who treat HCV need to be aware of, including risk for hepatitis B (HBV) reactivation after starting DAA therapy, as well as the risk for development of hepatocellular cancer (HCC) after achieving SVR (20-24). Although HCV remained to be a widely recognized topic throughout AASLD, it is becoming apparent that other topics in hepatology including NASH, alcoholic hepatitis, hepatitis B, HCC and primary biliary cholangitis are gaining importance and presentation space especially in the late-breaker session. A more intensified discussion on national HCV screening programs, HCV treatment uptake and linkage to care at AASLD would be desirable to politically underline the need to continue the fight to ensure global access of HCV therapies throughout the world.

View full text article with slides over at National AIDS Treatment Advocacy Project (NATAP)

Of Interest
Hepatitis C Hot Topics - Research and News of 2016
Take a look back at the top HCV news stories of 2016. Sit back and review a collection of hepatitis C research articles, guideline updates, conference reports, learning activities, and news from around the web

AbbVie Awaits NDA Approval For Hepatitis C Treatment
Dec. 19, 2016
AbbVie (ABBV), a global biopharmaceutical company, announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the company's investigational, pan-genotypic regimen of glecaprevir/pibrentasvir (G/P), being evaluated for the treatment of chronic hepatitis C virus (HCV).

Gilead Submits NDA to FDA for Sofosbuvir/Velpatasvir/Voxilaprevir HCV Genotype 1-6
December 8, 2016
Gilead Submits New Drug Application to U.S. Food and Drug Administration for the Investigational Single Tablet Regimen Sofosbuvir/Velpatasvir/Voxilaprevir
- If Approved, SOF/VEL/VOX Would Be the First Once-Daily Single Tablet Regimen Available as a Salvage Therapy for Patients Infected with HCV Genotype 1-6 Who Have Failed Prior Treatment with DAA Regimens Including NS5A Inhibitors -