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 -

Hepatitis C - Screening for HCC in the Post-SVR12 Setting

2018 - Updates

Letter to the editor

Jan 2018

Hepatocellular Carcinoma Screening in Patients Treated for Hepatitis C

SVR Reduced HCC by 71%
from Jules: there never was any doubt that SVR would reduce or eliminate risk for HCC. In this study cirrhosis prior to treatment had a higher HCC risk then for those without cirrhosis, but that is to be expected and merely reinforces how crucial it is to treat HCV as early as possible...
Full Text

Liver cancer incidence after HCV therapy linked to risk factors, not treatment

Direct-acting antiviral treatment for hepatitis C did not correlate with an increased risk for hepatocellular carcinoma in a large cohort study of both treated and untreated patients with or without cirrhosis. Those with incident HCC after DAA treatment had higher risk factors at baseline.

Dec 2016

Healio

The following articles appeared in the December print edition of HCV NEXT, published online at Healio.

Table of Contents
5 Questions
A Conversation With Zobair M. Younossi, MD, MPH

Cover Story
Screening for HCC in the Post-SVR12 Setting

Editorial
HCV Testing Needs Expansion Beyond Baby Boomers

The Take Home
The Liver Meeting 2016

Infectious Disease Week 2016

The Liver Meeting 2016: Beyond HCV

Trend Watch
CMS: Harvoni Outpaces Other Drugs in Total Spending
Canadian Patients With HCV Often Restricted From DAA Treatment

Begin here.....

Generic Sofosbuvir Underperforms in Real World, May Be Due to Suboptimal Regimens

AASLD 2016: Generic Sofosbuvir Underperforms in Real World, May Be Due to Suboptimal Regimens

HCV Treatment Published on Thursday, 15 December 2016

Written by Michael Carter

Generic sofosbuvir-based combinations for hepatitis C may not perform as well as branded sofosbuvir-containing regimens, according to a study conducted in Qatar and presented at the recent 2016 AASLD Liver Meeting. People treated with generics were less likely to be cured and more likely to experience adverse events compared to people who received branded drugs. But the investigators speculate that the generics may have underperformed because many people treated were with suboptimal regimens, and believe this deserves further research.

Continue reading...

VIDEO: Don’t be surprised by weight gain in men after HCV cure

VIDEO: Don’t be surprised by weight gain in men after HCV cure
Publish date: November 15, 2016
By: Kari Oakes Frontline Medical News

BOSTON – In the new era of direct-acting antiviral (DAA) therapy, physicians will be seeing more and more patients who have achieved a cure of their hepatitis C virus (HCV). Once freed from the burden of a chronic illness, patients feel better and may eat better. Unexpected weight gain and potential associated health effects may be the next set of challenges patients and their physicians will face.

A single-center retrospective study of patients who had achieved sustained virologic response (SVR) after treatment for HCV found a small but significant weight gain in men, but not women. Additionally, according to noninvasive assessments, liver fat increased significantly in men, but not women, after SVR was achieved

View the article and video, here.

(Epclusa) Sofosbuvir plus velpatasvir “best options” for HCV G3

Related
Epclusa for Hep C: What Pharmacists Should Know

JANUARY 04, 2017

Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). It is one of the leading causes of chronic liver disease in the United States with the CDC estimating that between 2.7 and 3.9 million people in the United States are infected with chronic HCV.¹ Over the past several years, a number of direct acting antivirals have been approved to treat the infection.

In June 2016, the FDA approved Epclusa, a fixed-dose combination product containing sofosbuvir, an HCV NS5B polymerase inhibitor, and velpatasvir, an HCV NS5A inhibitor, for treatment of chronic hepatitis C genotypes 1, 2, 3, 4, 5, or 6. With its approval, Epclusa became the first antiviral indicated for all 6 major forms of HCV.

This article highlights several key therapeutics areas with Epclusa that every pharmacist should know

Continue reading....

Sofosbuvir plus velpatasvir “best options” for HCV G3

An analysis of published studies on direct acting antivirals (DAAs) found that regimens containing sofosbuvir and velpatasvir were the best option for patients with HCV genotype three (G3).

The analysis indicated that ribavirin significantly increased rates of SVR and should be considered if tolerated.

Researchers at Radboud University Medical Centre in the Netherlands performed a Bayesian network meta-analysis using a random effects model to indirectly compare DAA regimens in HCV G3 patients with and without cirrhosis. They found 27 appropriate studies involving 3,415 patients.

Among patients without cirrhosis, the greatest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir with ribavirin (99%) and without ribavirin (97%), for sofosbuvir + daclatasvir + ribavirin (96%), and for sofosbuvir + peginterferon + ribavirin (95%), all for 12 weeks.

Among patients with cirrhosis, the highest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir for 24 weeks (96%), for sofosbuvir + daclatasvir + ribavirin for 24 weeks (94%), and for sofosbuvir + velpatasvir + ribavirin for 12 weeks (94%).

Ribavirin increases efficacy in patients with and without cirrhosis (odds ratios 2.6 and 4.5).

Reference
Identification of the best direct-acting antiviral regimen for patients with hepatitis C virus genotype 3 infection: a systematic review and network meta-analysis. Berden FA, Aaldering BR, Groenewoud H et al. Clin Gastroenterol Hepatol. 2016 Nov 10 [Epub ahead of print]

Nov 21, 2016
Sofosbuvir/velpatasvir improved patient-reported outcomes, knocked out HCV genotypes 1-6
BOSTON – When given with ribavirin, a fixed-dose combination of sofosbuvir/velpatasvir (Epclusa) achieved a sustained viral response at 12 weeks (SVR-12) in 94% of decompensated cirrhotic patients with hepatitis C virus (HCV) genotypes 1-6 infection, according to Zobair M. Younossi, MD.

Patients with and without cirrhosis also reported meaningful improvements across a variety of outcome measures after successfully completing treatment with Epclusa or sofosbuvir (Harvoni), said Dr. Younossi of Inova Fairfax Hospital in Falls Church, Va. “Although on-treatment patient-reported outcomes improved more with ribavirin-free regimens, post-SVR improvements were similar,” regardless of whether patients had received ribavirin, he reported at the annual meeting of the American Association for the Study of Liver Diseases.
Continue reading..

Of Interest
Nov 17, 2016
AbbVie Pangenotypic Combination Cures Hard-to-Treat People with HCV Genotype 3

Adding Voxilaprevir to Sofosbuvir/Velpatasvir Effective for HCV Genotype 3: Presented at AASLD

Nov 15, 2016
AASLD 2016 Grazoprevir/elbasvir (Zepatier) plus sofosbuvir (Sovaldi) highly effective for hard-to-treat genotype 3 hepatitis C patients

October 2016

Short-duration Treatment With Elbasvir/Grazoprevir and Sofosbuvir - HCV GT1 or GT3 with or without cirrhosis

Vol 4, Supplement 1 (October 2016): Annals of Translational Medicine

Sofosbuvir and velpatasvir: a stellar option for patients with decompensated hepatitis C virus (HCV) cirrhosis

           

VIDEO: Cost to treat HCV could be as low as $80 in the US

VIDEO: Cost to treat HCV could be as low as $80 in the US

BOSTON — In this exclusive video at The Liver Meeting, Andrew M. Hill, PhD, discusses data from a new study that show the price of a direct-acting antiviral generic regimen could be as low as $80 in the U.S. to cure hepatitis C virus infection in one patient.

“The potential to lower prices and treat far more people is enormous,” Hill said.

Hill and colleagues extracted data from an online database of Indian export ledgers for per-kilogram prices and volumes of direct-acting antiviral API’s exported from India between January and June 2016.

“We found these drugs are being exported from India as raw materials for very low prices,” Hill said.

Continue reading @ Healio

See more from The Liver Meeting

Direct-acting antiretrovirals in genotype 1 HCV patients with mental health conditions safe, well tolerated

Direct-acting antiretrovirals in genotype 1 HCV patients with mental health conditions safe, well tolerated
Publish date: November 18, 2016
By: Whitney McKnight Frontline Medical News

BOSTON – Direct-acting antiretroviral therapies are safe and well tolerated in hepatitis C virus patients with comorbid psychiatric conditions, a study showed.

The finding that sustained virologic response (SVR) rates at 1 year were similar in genotype 1 HCV patients with and without psychiatric comorbidities could help end the stigma against treating this patient subgroup, stemming from when treatment with interferon risked psychiatric decompensation. That’s according to nurse practitioner Anne Moore, winner of this year’s Poster of Distinction Award at the American Association for the Study of Liver Diseases

Continue reading..

AASLD 2016 Review - Watch Advances in Chronic Hepatitis C: Management and Treatment

After each conference this blog links to a series of education-related information on important findings related to ongoing challenges of managing and treating viral hepatitis. Listed below are three programs offering a review of key studies presented at the American Association for the Study of Liver Diseases 67th Annual Meeting 2016.

Internet symposium at ViralEd - Advances in Chronic Hepatitis C: Management and Treatment

The CME Internet Symposium: AASLD 2016 Expert Review will feature four HCV experts reviewing and discussing key presentations on chronic hepatitis C presented at AASLD 2016. The review and discussion will focus on HCV therapeutic options and developments, including: current treatment and management strategies, algorithms and recommendations; therapies in development; epidemiology; and diagnosis and clinical management of specific patient populations, including HCV/HIV co-infected and cirrhotic patients.

Click here to view program..

Clinical Care Options - Clinical Impact of New Hepatology Data From Boston 2016*

November 11-15, 2016 | Boston, Massachusetts

Examine Capsule Summaries, download slides, and review analysis by expert faculty on key studies from Boston 2016.

Begin here....

Free Registration Required, click here to register

Conference Coverage AASLD: Practice Point 5 Minute Video Clips
At Practice Point a series of 5 minute video clips highlighting hot hepatitis topics presented at the Liver Meeting 2016 is offered. 
This activity is jointly provided by the University of Nebraska Medical Center,
University of Florida College of Pharmacy
and Practice Point Communications

Click here to get started.....
Free Registration Required, click here to register

Adding Voxilaprevir to Sofosbuvir/Velpatasvir Effective for HCV Genotype 3: Presented at AASLD

Adding Voxilaprevir to Sofosbuvir/Velpatasvir Effective for HCV Genotype 3: Presented at AASLD

By Frances Morin

BOSTON -- November 17, 2016 -- Adding voxilaprevir to the combination tablet containing sofosbuvir and velpatasvir (Epclusa) for 8 weeks shows similar efficacy to sofosbuvir/velpatasvir alone for 12 weeks in the treatment of patients with hepatitis C virus (HCV) genotype 3 and cirrhosis.

“The results show that sofosbuvir/velpatasvir and voxilaprevir for 8 weeks and sofosbuvir/velpatasvir for 12 weeks each provide simple, safe, and effective treatment regimens for patients with HCV genotype 3 and cirrhosis,” said Graham R. Foster, MD, Royal London Hospital, London, United Kingdom, at The Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

In efforts to treat HCV with direct acting antivirals, genotype 3 infection has become notably difficult to cure, particularly in patients with cirrhosis.

For the phase 3 POLARIS-3 trial, the researchers investigated the addition of voxilaprevir 100 mg/day to sofosbuvir/velpatasvir 400 mg/100 mg/day for 8 weeks compared with sofosbuvir/velpatasvir 400 mg/100 mg/day alone for 12 weeks in 219 patients with genotype 3 HCV infection and cirrhosis.

The results showed that 96% of patients in each group achieved a sustained virologic response for at least 12 weeks after treatment (SVR12).

In the voxilaprevir group, there were 2 relapses, 1 patient withdrew consent, and there was 1 death. In the sofosbuvir/velpatasvir group, there was 1 on-treatment failure, 1 relapse, 1 discontinuation due to an adverse event (AE), and 1 lost to follow-up.

In looking at patients according to prior treatment, 96% of treatment-naïve patients in the voxilaprevir group (72/75) achieved SVR12 compared with 99% of the sofosbuvir/velpatasvir group (76/77). Among those who received prior treatment, 97% and 91% achieved SVR 12, respectively.

The most common AEs (>10% of patients) were fatigue and headache. Rates of nausea and diarrhoea were higher in the voxilaprevir group (21% and 15%, respectively), compared with the sofosbuvir/velpatasvir group (9% and 5%).

According to the researchers, baseline NS5A resistance-associated substitutions, including Y93H, did not impact treatment outcomes for either group.

Funding for this study was provided by Gilead Sciences.

[Presentation title: A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir/ Voxilaprevir for 8 Weeks and Sofosbuvir/Velpatasvir for 12 Weeks for Patients With Genotype 3 HCV Infection and Cirrhosis: The POLARIS-3 Study]

To read more Conference Dispatch articles, click here.

Source - https://www.firstwordpharma.com/node/1434143?tsid=28&region_id=4

Coffee Consumption and Herbal Tea Tied to Lower Liver Stiffness

Herbal Tea, Coffee Consumption Tied to Lower Liver Stiffness

Tea and coffee consumption is ubiquitous around the world. Both contain polyphenols, caffeine, as well as other chemical components. Polyphenols and caffeine are suspected to improve liver health; for example, previous research has suggested that coffee might prevent liver cirrhosis. However, whether or not this is true for fibrosis in the general population is not known.

AASLD Coverage
Nov 11, 2016
Herbal Tea, Coffee Consumption Tied to Lower Liver Stiffness
Herbal tea and coffee might protect the liver among healthy adults, according to findings presented at The Liver Meeting® 2016.

“High coffee consumption appears protective of liver stiffness even in individuals with no known liver disease,” reported lead study coauthor Louise J. Alferink, of the Gastroenterology and Hepatology of the Erasmus Medical Center, Rotterdam, Netherlands. 

Continue reading...

Additional updates @ MPR

People who drink coffee are less likely to develop nonalcoholic fatty liver disease (NAFLD), a new literature review suggests. And people with NAFLD who drink coffee regularly are less likely to develop liver fibrosis.

AASLD Coverage
Nov 12,2016

Drinking Coffee Found to Significantly Decrease NAFLD Risk
Coffee drinkers significantly decrease their risk of nonalcoholic fatty liver disease (NAFLD), and regular drinking also decreases risk of liver fibrosis, according to results of a systematic review and meta-analysis presented at The Liver Meeting® 2016.

“Whether consumption of coffee could be considered as a preventative measure against NAFLD needs further investigations,” reported Karn Wijarnpreecha, MD, of the department of internal medicine at Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, and colleagues.
Continue reading...

Additional updates @ MPR

AbbVie's Glecaprevir/Pibrentasvir (G/P) Shows High SVR Rates in Chronic Hepatitis C Patients with Severe Chronic Kidney Disease

AbbVie's Investigational, Pan-Genotypic Regimen of Glecaprevir/Pibrentasvir (G/P) Shows High SVR Rates in Chronic Hepatitis C Patients with Severe Chronic Kidney Disease

- 98 percent of patients across all major HCV genotypes (GT1-6) with severe chronic kidney disease (CKD), including patients on dialysis, achieved SVR12 with 12 weeks of G/P in the primary intent-to-treat analysis, regardless of previous treatment status or presence of compensated cirrhosis
- 100 percent of patients achieved SVR12 in a modified intent-to-treat analysis
- G/P is an investigational, pan-genotypic, once-daily, ribavirin-free, fixed-dose combination for the treatment of chronic HCV
- Development of new regimens to treat HCV patients with CKD remains a critical unmet medical need across genotypes1

NORTH CHICAGO, IL, USA I November 15, 2016 I AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced 98 percent (n=102/104) of chronic hepatitis C virus (HCV) infected patients with severe chronic kidney disease (CKD) achieved sustained virologic response following 12 weeks of treatment (SVR12) with its investigational, pan-genotypic regimen of glecaprevir (ABT-493)/pibrentasvir (ABT-530) (G/P) in the primary intent-to-treat (ITT) analysis. In a modified intent-to-treat (mITT) analysis, SVR12 was achieved in 100 percent (n=102/102) of severe CKD patients; mITT excludes patients who did not achieve SVR for reasons other than virologic failure. These new data from the Phase 3 EXPEDITION-4 study, evaluating patients with chronic HCV infection across all major genotypes (GT1-6) and severe CKD, will be presented as a late-breaker today at The Liver Meeting®, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.

The EXPEDITION-4 results are the latest to be released from registrational studies in AbbVie's G/P clinical development program, designed to investigate a faster path to virologic cure* for all major HCV genotypes (GT1-6) and with the goal of addressing areas of continued unmet need.

"HCV patients with severe chronic kidney disease present a complex challenge for physicians to treat, particularly as kidney disease progresses, and if the patient has genotype 2 or 3 or has compensated cirrhosis," said Ed Gane, M.D., professor of medicine at the University of Auckland in Auckland, New Zealand. "The results seen in EXPEDITION-4 are a positive development in AbbVie's investigation of the G/P regimen for patients with chronic kidney disease, who currently have limited HCV treatment options."

HCV is common among people with severe CKD, reaching prevalence of up to 80 percent in some regions of the world.2 In the U.S., it is estimated that over 500,000 people have both chronic HCV and CKD.3 Some chronic HCV infected patients with severe CKD, particularly those with GT2 and GT3 HCV infection, currently don't have access to direct-acting antivirals (DAAs). The development of new, safe and effective regimens to treat HCV in these patients remains a critical unmet medical need.1

"With our investigational, pan-genotypic regimen, our goal is to provide a safe and effective cure to patients across genotypes, including patients with severe chronic kidney disease, regardless of previous treatment status or presence of compensated cirrhosis," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "Our clinical development program reflects our ongoing commitment to addressing treatment areas of continued unmet need."

The EXPEDITION-4 study enrolled 104 patients with severe chronic kidney disease, including 85 patients (82 percent) who were receiving dialysis at enrollment and 20 patients (19 percent) who had compensated cirrhosis. The study also included those who were not cured with previous sofosbuvir (SOF) with ribavirin (RBV) or interferon (IFN) with RBV; with or without SOF (44 patients, 42 percent).

The majority of treatment related adverse events (AEs) were mild or moderate. The most commonly reported AEs included pruritus, fatigue and nausea. Of the 24 percent of patients who experienced serious AEs, none were considered related to G/P. Four AEs (4 percent) led to the discontinuation of G/P and one patient died after achieving SVR4 due to a serious AE (intracerebral hemorrhage) considered not-related to G/P.

*Patients who achieve a sustained virologic response at 12 weeks post treatment (SVR12) are considered cured of hepatitis C.

About the EXPEDITION-4 Study

EXPEDITION-4 is a single-arm, open-label, Phase 3 study evaluating the safety and efficacy of 12 weeks of G/P in patients with GT1-6 chronic HCV infection and chronic kidney disease, including those on dialysis. The primary efficacy endpoint is SVR12.

Patients had severe or end stage kidney disease (stage 4 and 5 CKD), with an eGFR < 30 mL/min/1.73 m2 required at screening. Prior treatment in the study is defined as treatment with IFN/pegIFN ± RBV, or SOF + RBV ± pegIFN therapy.

Additional information on the clinical trials for G/P is available at www.clinicaltrials.gov/.

About AbbVie's HCV Clinical Development Program

AbbVie's glecaprevir/pibrentasvir (G/P) clinical development program was designed to investigate a faster path to virologic cure* for all major HCV genotypes (GT1-6) and with the goal of addressing treatment areas of continued unmet need.

G/P is an investigational, pan-genotypic regimen that is being evaluated as a potential cure in 8 weeks for HCV patients without cirrhosis and who are new to treatment, who make up the majority of HCV patients. AbbVie is also studying G/P in patients with specific treatment challenges, such as genotype 3, patients who were not cured with previous DAA treatment and those with CKD, including patients on dialysis.

G/P is an investigational, once-daily regimen that combines two distinct antiviral agents in a fixed-dose combination of glecaprevir (300mg), an NS3/4A protease inhibitor, and pibrentasvir (120mg), an NS5A inhibitor. G/P is dosed once-daily as three oral tablets.

Glecaprevir (GLE) was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements

Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2015 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

1 American Association for the Study of Liver Diseases. Recommendations for Testing, Managing, and Treating Hepatitis C, February 24, 2016, http://www.hcvguidelines.org/full-report/monitoring-patients-who-are-starting-hepatitis-c-treatment-are-treatment-or-have. Accessed March 15, 2016.
2 Fabrizi F, Poordad FF, Martin P. Hepatitis C infection in the patient with end stage renal disease. Hepatology. 2002;36(1):3-10.
3 IMS Health, July 2016. Parsippany, NJ; Medivo, July 2016. New York, NY (Estimate based on IMS Health Dx Medical Claims 12/2013-4/2016; IMS Health Life Link Patient Level Data 12/2013-4/2016; Medivo Lab Data 12/2013-4/2016).

AASLD 2016 Grazoprevir/elbasvir (Zepatier) plus sofosbuvir (Sovaldi) highly effective for hard-to-treat genotype 3 hepatitis C patients

HIVandHepatitis conference coverage includes commentary with interim results from ongoing clinical studies by freelance medical writer, editor, and health educator Liz Highleyman. Additional  conference reports are available at aidsmap and Infohep.

HIVandHepatitis - Reported by Liz Highleyman

Grazoprevir/elbasvir + sofosbuvir highly effective for hard-to-treat genotype 3 hepatitis C patients
A triple regimen of grazoprevir/elbasvir (Zepatier) plus sofosbuvir (Sovaldi) without ribavirin cured 96% of previously untreated and 97% of treatment-experienced people with hepatitis C virus (HCV) genotype 3 and liver cirrhosis, matching
Continue reading....

Coverage reported by Jules Levin the Executive Director of NATAP - National AIDS Treatment Advocacy Project. Coverage at NATAP includes full text articles and slides to review without the hassle of going through a registration process.

NATAP ​- Reported by Jules Levin review slides​
ELBASVIR/GRAZOPREVIR PLUS SOFOSBUVIR ± RIBAVIRIN IN TREATMENT-NAIVE AND TREATMENT-EXPERIENCED PATIENTS WITH HEPATITIS C VIRUS GENOTYPE 3 INFECTION AND COMPENSATED CIRRHOSIS: THE C-ISLE STUDY

MPR by Bryant Furlow
EBR/GZR+SOF ± RBV is 'Highly Efficacious' for HCV GT3
Elbasvir/grazoprevir (EBR/GZR) and sofosbuvir (SOF) with and without ribavirin (RBV; EBR/GZR + SOF ± RBV) regimen was generally safe and effective for cirrhotic patients with hepatitis C virus (HCV) GT3 infections, according to an author of the UK-based randomized, open-label C-ISLE trial that were presented at The Liver Meeting® 2016.
Additional updates @ MPR

AASLD Updates - On This Website
Sift through highlights from The Liver Meeting arranged by the following topics;
Multimedia
​​Safety Profile
​Reinfection
Sofosbuvir or Daclatasvir-Based Regimens
Key data indexed by pharmaceutical company
Treatment with direct-acting antiviral (DAA) agents; Veterans and Elderly
HCV and Liver Disease; Fibrosis, Cirrhosis, Liver Cancer, Liver Transplant, Liver Failure,​ and Fatty Liver/non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
Latest News
​Begin here...

Updates On This Blog: AASLD 2016

Prometheus HepaStem - Therapeutic alternative to liver transplantation could be on horizon in NASH

Nov 11
Therapeutic alternative to liver transplantation could be on horizon in NASH
Kris Gellynck, PhD, manager of research and development at Promethera Biosciences in Brussels, will present data at this year’s annual meeting for the American Association for the Study of Liver Diseases showing that it was possible to decrease nonalcoholic liver disease scores by using what would be marketed as an “off the shelf” product. HepaStem has been classified by the European Medicines Agency as a medicinal product, and is comprised of human adult liver–derived mesenchymal stem cells cryopreserved and reconstituted as needed..
Continue reading....

Nov 14
Prometheus BioScience Inc. Provides Update On Hepastem NASH-Fibrosis Program With Late-Breaking Preclinical Data At 2016 American Association for Study of Liver Diseases Meeting

--HepaStem reduces liver inflammation and improves fibrosis symptoms in a NASH mouse model--

MONT-SAINT-GUIBERT, Belgium--(BUSINESS WIRE)--Promethera Biosciences SA, a world-leading cell therapy and regenerative medicine company targeting liver diseases, today announced the presentation of new preclinical NASH-Fibrosis data from its proprietary HepaStem program, demonstrating a beneficial effect of HepaStem in a nonalcoholic steatohepatitis (NASH) mouse model and confirming Hepastem’s unique and multifaceted mode of action. The results were presented on Sunday, November 13th by the Promethera R&D and Medical Affairs team, in a late-breaking poster presentation titled, “Clinical-grade human liver mesenchymal stem cells for the treatment of NASH-Fibrosis through immunomodulation” at The Liver Meeting® 2016, the 67th Annual Meeting of the American Association for the Study of Liver Disease (AASLD), currently being held in Boston, Massachusetts.

“These first data support that HepaStem has the strong potential to modulate and decrease inflammation and fibrosis, opening the route to promising clinical trials in NASH and other severe inflammatory conditions of the liver”

In the study, HepaStem was administered in a single and repeated dose setting with or without immunosuppression in a NASH STAMTM cell mouse model. HepaStem significantly reduced inflammation and Nonalcoholic Fatty Liver Diseases (NAFLD) Activity score (NAS), as well as fibrotic collagen deposition in liver sections at 9 weeks of age. In addition, Promethera’s in-house R&D could further elucidate the underlying immunomodulatory effect of HepaStem cells. In in vitro co-culturing systems with T-lymphocytes or dendritic cells, HepaStem was shown to decrease T-cell activation and dendridic cell generation and activation in vitro. HepaStem cells were also shown to secrete high levels of HGF (Hepatocyte Growth Factor), a growth factor known to inhibit stellate cells, the key in-situ players in liver fibrosis development.

“These first data support that HepaStem has the strong potential to modulate and decrease inflammation and fibrosis, opening the route to promising clinical trials in NASH and other severe inflammatory conditions of the liver,” said Prof. Dr. Etienne Sokal, Founder and CI and CSO of Promethera Biosciences. He added that Promethera is further investigating preclinical studies in various liver inflammatory and fibrotic models.

“Promethera is in the process of building on results such as these that firmly support our expansion to the larger indications of NASH, liver inflammation and fibrosis,” said Dr. John Tchelingerian, CEO of Promethera Biosciences. “With the good safety profile shown in the pediatric patients from our initial clinical studies, HepaStem cells offer a unique product profile which we believe will differentiate Promethera’s approach as a novel and impactful cell therapy platform in a highly-competitive environment as our industry seeks therapies for devastating liver diseases.”

HepaStem is a cell suspension constituted of heterologous human adult liver-derived mesenchymal stem cells isolated from ethically donated healthy adult human liver tissue. HepaStem treatment has been shown to be safe in a phase I/II study in 20 pediatric patients suffering from inherited metabolic disorders.

About Promethera Biosciences
Promethera Biosciences is a clinical stage biopharmaceutical company and the global leader in cell therapy and regenerative medicine for the treatment of inborn and acquired liver diseases with no effective therapeutic cure. Promethera uses allogeneic progenitor cells, stem cells and mature hepatocytes that are harvested and purified from non-transplantable, healthy human livers (Heterologous Human Adult Liver-derived Progenitor Cells, HHALPC and Heterologous Human Liver Cells, HHLivC). These technologies have resulted in the development of three different cell products, HepaStem and H2Stem (progenitor/stem cells) and Heparesc® (mature hepatocytes). Promethera specializes in the development of therapeutic options for the treatment of a broad variety of liver diseases. These range from orphan indications, such as rare inborn metabolic diseases including urea cycle disorders (UCD) to large indications such as acute-on-chronic liver failure (ACLF), and nonalcoholic steatohepatits (NASH)/fibrosis.

Promethera Biosciences is a spin-off of the Walloon Region-based Université catholique de Louvain (UCL) and was founded in 2009 by Prof. Dr. Etienne Sokal and Sopartec, the tech transfer office (TTO) of UCL. Promethera is headquartered in Mont-Saint-Guibert, Belgium with a U.S. based operation and a GMP compliant manufacturing facility in Durham, NC, US. For more information, visit www.promethera.com.

AASLD 2016 Study eyed zinc for slowing progression of chronic liver disease

Study eyed zinc for slowing progression of chronic liver disease

BOSTON – Oral zinc supplementation was associated with maintenance of liver function and suppression of hepatocellular carcinoma in a retrospective cohort study of 267 patients with chronic liver disease.

Additional analyses revealed stepwise inverse relationships between serum zinc levels and rates of de novo liver failure, hepatocellular carcinoma, and death, Atsushi Hosui, MD, PhD, said at the annual meeting of the American Association for the Study of Liver Diseases. No patients stopped zinc therapy because of adverse events, and there were no serious adverse events, although some patients experienced nausea, which can occur with zinc supplementation, noted Dr. Hosui of Osaka-Rosai Hospital, Japan.

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AASLD 2016 IFN-free DAA Regimens Found Safe and Effective for Elderly Patients

IFN-free DAA Regimens Found Safe and Effective for Elderly Patients
By Da Hee Han, PharmD
BOSTON, MA—Interferon (IFN)-free direct-acting antiviral agent (DAA) regimens are “as safe and effective” for elderly patients with hepatitis C virus (HCV)-related cirrhosis or severe fibrosis as they are for younger patients, according to research presented at The Liver Meeting® 2016.

“The lifetime utility of HCV eradication in the elder in terms of reduction of events and overall survival needs evaluation in long-term observational cohorts,” however, cautioned senior study author Vincenza Calvaruso, MD, PhD, of the University of Palermo, in Palermo, Italy.
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DAAs Effective for Chronic HCV, Even in Very Elderly
By Da Hee Han, PharmD November 14, 2016
BOSTON, MA—“Advanced age in and of itself should not be considered a barrier to direct-acting antiviral (DAA) treatment” in patients with chronic hepatitis C virus (HCV) infection, a study in more than 17,000 veterans presented at The Liver Meeting® 2016 concluded.

“DAAs are equally highly effective for the treatment of chronic HCV in all age groups, including very elderly patients,” added Feng Su, MD, University of Washington, Seattle, WA and Veterans Affairs Puget Sound Healthcare System, Seattle, WA, and colleagues.
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Additional updates @ MPR
Updates On This Blog: AASLD 2016

AASLD 2016 Liver Cancer Rare After HCV Therapy

Liver Cancer Rare After HCV Therapy

by Michael Smith Michael Smith
North American Correspondent, MedPage Today

But some patients develop aggressive form of the disease

BOSTON -- For patients with advanced liver disease owing to hepatitis C (HCV), treatment with direct-acting antiviral agents did not increase the risk of hepatocellular carcinoma, a researcher said here.

The risk of liver cancer in the first year after such therapy was pretty much the same as it is in untreated patients, according to Alfredo Alberti, MD, of the University of Padua in Italy.

On the other hand, the rare patients who developed cancer after HCV treatment were more likely to have an aggressive form of the disease, Alberti told reporters at the American Association for the Study of Liver Diseases (AASLD) annual meeting.

The findings, from a large prospective cohort of patients in northern Italy, should help to settle what has been a "controversial and confusing issue," Alberti said, with small studies yielding conflicting results on the issue.
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Additional Reading @ MedPage Today

Fibrosis Risk High in Kids With Transplanted Livers

Those with cirrhosis at risk of liver failure and graft loss

Marked Sex Difference Seen in Drug-Induced Liver Failure

Brain damage, polypharmacy more common in women with ALF

AASLD: HCV Outcomes Under Scrutiny

Treatment now 'predictably' good in trials but what about real world?

AASLD: Focus on Liver Broadens

Fatty liver disease expected to get lion's share of spotlight

Elsewhere
Current updates: Conference Reports
Updates On This Blog: AASLD 2016

AASLD 2016 Glecaprevir/Pibrentasvir: High SVR Rates in HCV GT 2, 4, 5, 6 Without Cirrhosis

Nov 13
Glecaprevir/Pibrentasvir: High SVR Rates in HCV GT 2, 4, 5, 6 Without Cirrhosis
By Debra Hughes, MS
Patients with chronic hepatitis C virus (HCV) genotypes (GT) 2, 4, 5, or 6 infection without cirrhosis had SVR12 rates of 97% after 8 weeks of treatment with co-formulated glecaprevir/pibrentasvir, investigators from the SURVEYOR-II, Part 4, concluded at The Liver Meeting® 2016.​

Press Release
Nov 11
Update AbbVie's Glecaprevir/Pibrentasvir (G/P) Acheive High SVR12 Rates at 8 Wks Genotypes 1-6
- 97.5 percent of chronic HCV infected patients without cirrhosis and new to treatment across all major genotypes (GT1-6) achieved SVR12 with 8 weeks of G/P
- Across the 8-week arms of three registrational studies, no patients discontinued treatment due to adverse events
- G/P is an investigational, pan-genotypic, once-daily, ribavirin-free regimen for the treatment of chronic HCV

Additional updates @ MPR
Current updates: Conference Reports
Updates On This Blog: AASLD 2016

AASLD 2016 Once-Daily Simeprevir, AL-335, and Odalasvir Combination Safe, Effective

Once-Daily Simeprevir, AL-335, and Odalasvir Combination Safe, Effective
By Bryant Furlow November 13, 2016

BOSTON, MA—Once-daily-administered combination of the investigative direct-acting antivirals AL-335 and odalasvir (ODV), and simeprevir (SMV) is well tolerated in healthy volunteers, and is now under study among patients with hepatitis C virus (HCV), according to findings from an open-label Phase 1 study presented at The Liver Meeting® 2016.
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Additional updates @ MPR
Current updates: Conference Reports
Updates On This Blog: AASLD 2016

AASLD 2016 Dr. George N. Ioannou on the Efficacy of Antiviral Agents for Hepatitis C in HCC Patients

Dr. George N. Ioannou on the Efficacy of Antiviral Agents for Hepatitis C in HCC Patients

George N. Ioannou, MD Published Online: Saturday, Nov 12, 2016

AASLD Updates @ OncLive

George N. Ioannou, MD, associate professor, VA Puget Sound Health Care System, University of Washington School of Medicine, discusses a study evaluating the effectiveness of direct antiviral agents for hepatitis C virus patients with hepatocellular carcinoma (HCC).
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AASLD 2016 Biomarkers Define Future Age of Immunotherapy in Cancer

Biomarkers Define Future Age of Immunotherapy in Cancer
Marilyn White Published Online: Sunday, Nov 13, 2016

The use of immunotherapy as a treatment for cancer is progressively increasing with a flood of recent approvals for immune checkpoint inhibitors directed against CTLA-4 and PD-1. These therapies have revolutionized cancer treatment, making immunotherapy the fourth pillar of cancer treatment.“Immunotherapy is the perfect anti-cancer agent, more patients are being treated with immunotherapy and it continues to increase,” stated Drew Pardoll, MD, PhD, John Hopkins University, at the AASLD Liver Meeting. Discovering ways to look at patients’ endogenous immune systems can lead to treating patients with the right type of immunotherapy by targeting, detecting, and destroying cancer cells, which will be important as these approaches are explored in hepatocellular carcinoma (HCC).

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AASLD Updates @ OncLive

Dr. George N. Ioannou on the Efficacy of Antiviral Agents for Hepatitis C in HCC Patients

Dr. Gonzalez on Cost-Benefit of Treating Hepatitis C in HCC Patients Before Transplant

Lack of Screening, Surveillance Leads to Rising HCC Rates in Hepatitis B Patients

Hepatocellular carcinoma‎ incidence continues to rise among patients with hepatitis B despite improvements in antiviral therapies, stressing the importance of screening and surveillance in this population.

ERK Inhibition May Explain Regorafenib Success in Sorafenib-Resistant HCC

Efforts are under way to further evaluate the effects of regorafenib on sorafenib-resistant HCC cells, including the role of suppressing the ERK signaling pathway.