Thursday, December 29, 2016

Hepatitis C Hot Topics - Research and News of 2016

Hepatitis C Hot Topics - Research and News of 2016

Today we 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.

Recent News
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). In Phase 3 clinical studies, eight weeks of therapy with G/P achieved high sustained virologic response (SVR) rates across all major genotypes (GT 1-6) in patients without cirrhosis, which represents the majority of HCV patients. In patients with compensated cirrhosis, high SVR rates were achieved after 12 weeks of therapy. High SVR rates were also achieved in patients with limited treatment options, such as those with severe chronic kidney disease (CKD). In historically difficult to treat populations, including those not cured* by prior direct-acting antiviral (DAA) treatment regimens, high SVR rates were achieved with durations as short as 12 weeks.

Of Interest
Press Release
Nov 11, 2016
Eight Weeks of Treatment with AbbVie's Investigational, Pan-Genotypic Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved High SVR Rates Across All Major Genotypes of Chronic Hepatitis C
NORTH CHICAGO, Ill., Nov. 11, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced high SVR12 rates with 8 weeks of treatment with its investigational, pan-genotypic regimen of glecaprevir (ABT-493)/pibrentasvir (ABT-530) (G/P) across all major chronic hepatitis C virus (HCV) genotypes. In more than 700 genotype 1-6 (GT1-6) chronic HCV infected patients without cirrhosis and who are new to treatment, 97.5 percent (n=693/711) achieved sustained virologic response at 12 weeks post treatment (SVR12), regardless of baseline viral load. The rate of virologic failure was 1 percent (n=9/711).

November 13, 2016
Glecaprevir/Pibrentasvir: High SVR Rates in HCV GT 2, 4, 5, 6 Without Cirrhosis

Dec 8, 2016
Gilead Submits New Drug Application to U.S. Food and Drug Administration for the Investigational Single Tablet Regimen Sofosbuvir/Velpatasvir/Voxilaprevir
Gilead Sciences, Inc. announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily single tablet regimen containing sofosbuvir 400 mg, velpatasvir 100 mg, and voxilaprevir 100 mg (SOF/VEL/VOX) for the treatment of direct-acting antiviral (DAA)-experienced chronic hepatitis C virus (HCV)-infected patients. The data submitted in the NDA support the use of the regimen for 12 weeks in DAA-experienced patients with genotype 1 to 6 HCV infection without cirrhosis or with compensated cirrhosis.

Of Interest
October 2016
Gilead Announces SVR12 Rates From Four Phase 3 Studies of a Once-Daily, Fixed-Dose Combination of Sofosbuvir, Velpatasvir and Voxilaprevir in Treatment-Naïve and Treatment-Experienced Genotype 1-6 Chronic HCV-Infected Patients
Gilead Sciences, Inc. (NASDAQ: GILD) today announced topline results from four international Phase 3 clinical studies (POLARIS-1, POLARIS-2, POLARIS-3 and POLARIS-4) evaluating an investigational, once-daily, fixed-dose combination of sofosbuvir (SOF), a nucleotide analog NS5B polymerase inhibitor; velpatasvir (VEL), a pangenotypic NS5A inhibitor; and voxilaprevir (VOX; GS-9857), an investigational pangenotypic NS3/4A protease inhibitor, for the treatment of genotype 1-6 chronic hepatitis C virus (HCV) infection.                      

From The Journals

Journal of Hepatology 2017 Issue
Summary @ MD
Dec 16, 2016
Hepatitis C Still Increases Mortality Rate After Being Cured

NATAP - Full Text Article
Mortality in hepatitis C patients who achieve a sustained viral response compared to the general population

Of Interest
Correspondence: Prof. Dr. J.K. Rockstroh
2016/2017 - New HCV two and three drug regimens on their way: what do they promise?
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

The Lancet Gastroenterology & Hepatology
Dec 12, 2016
Editorial Access to HCV treatments: hurdles not barriers

Infectious Diseases and Therapy
Evidence shows value of treating all stages of chronic HCV
November 1, 2016
Available evidence suggests that HCV treatment with the new direct-acting antivirals (DAAs) should not be limited to patients with advanced liver disease.

Liver Cancer After Treatment For Hepatitis C
November 23, 2016
A collection of 2016 articles retrieved online from press releases, conferences (The Liver Meeting® 2016 and the International Liver Congress 2016) and peer-reviewed journals featuring long-term risk for liver cancer in those who were cured of Hepatitis C.

December 2016
The following article appeared in the December print edition of HCV NEXT, published online at Healio; Screening for HCC in the Post-SVR12 Setting

Gastroenterology & Hepatology
December 2016
Interview
The Possible Association Between DAA Treatment for HCV Infection and HCC Recurrence
Download the PDF
G&H  How common is the coexistence of hepatocellular carcinoma and hepatitis C virus infection in a patient?


RB  Among patients with hepatitis C virus (HCV) infection and cirrhosis, the risk of hepatocellular carcinoma (HCC) is estimated to be 1% to 3% per year. Thus, in any given year, the risk is relatively low, but over a decade, the risk is considerable. More importantly, with the rise in the number of baby boomers who have had HCV infection for more than 2 decades, we are seeing an increasing prevalence of HCC. Although the rate of new cases of HCV infection is falling, the prevalence of HCV infection with cirrhosis is still rising, as is the number of patients who have HCV infection and HCC.
Continue reading...

Research Article
November 25, 2016
What’s Important to the Patient? Informational Needs of Patients Making Decisions About Hepatitis C Treatment
Patients contemplating hepatitis C virus treatment want a great deal of information to make informed treatment decisions.

Journal Of Gastroenterology and Hepatology
November 2016
Comparative Treatment Effectiveness of Direct Acting Antiviral Regimens for Hepatitis C:  Data from the Veterans Administration
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jgh.13652

Journal Of Hepatology
New Perspectives in HCV Infection
October 2016 Issue
Second generation direct-acting antivirals – Do we expect major improvements?
Future landscape of hepatitis C research – Basic, translational and clinical perspectives

Liver International
October 2016
The value of cure associated with treating treatment- naïve chronic hepatitis C genotype 1: Are the new all- oral regimens good value to society?

Gastroenterology
October 1, 2016
Hepatitis C Therapy: Game Over!
Alessio Aghemo, Maria Buti
DOI: http://dx.doi.org/10.1053/j.gastro.2016.09.034
Publication stage: In Press Accepted Manuscript
NS5B polymerase inhibitor sofosbuvir, NS5A inhibitor velpatasvir, and the new protease inhibitor GS-9857 (voxilaprevir)
Download PDF

Hepatology
Emerging complexities with HCV DAA regimens: Less is still way more.
September 2016
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/hep.28832

Clinical Gastroenterology and Hepatology
SVR Linked to Long-Term Reduction in Fibrosis, Cirrhosis
July Issue 2016
The Changing HCV Landscape:
October 26, 2016
Hepatitis C virus (HCV) continues to be a significant global burden, with more than 170 million people...

Conferences, Learning Activities and Guidelines

International Congress on Drug Therapy in HIV Infection
Generic hepatitis C drugs purchased online achieve high cure rates
October 27, 2016
Use of generic versions of direct-acting antivirals resulted in very high cure rates for people who obtained the products through three buyers’ clubs, indicating that the generic products are effective, according to three presentations at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow) this week.

Of Interest
AASLD 2016: Generic Sofosbuvir Underperforms in Real World, May Be Due to Suboptimal Regimens
Dec 15, 2016
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.

Watch - An Introduction to Access to Generic Hepatitis C Medicines
November 8, 2016
Following the success of the first two webinars in the Knowledge for Change series covering access to diagnostics and medicines, we were pleased to deliver the next in the series, ‘An Introduction to Accessing Generic Hepatitis C Medicines’ on 1 November. The webinar explored the generics landscape for hepatitis C with discussions on legalities, quality and performance of generics medicines as well as providing examples of how people across the globe are accessing them.

EASL- AASLD Special Conference New perspectives in hepatitis C virus infection - The roadmap for cure
September 23, 2016
Watch Summary Presentation - EASL Recommendations on Treatment of Hepatitis C 2016

EASL Recommendations on Treatment of Hepatitis C
Download 2016 - Update of the HCV EASL recommendations

American Association for the Study of Liver Diseases 67th Annual Meeting 2016
November 18, 2016
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. Review three programs offering a review of key studies presented at the American Association for the Study of Liver Diseases 67th Annual Meeting 2016.

New at Healio
December 26, 2016

Related
Healio - Highlights from The Liver Meeting

AASLD Coverage @ HIV and Hepatitis

ALL CONFERENCE COVERAGE
HIV and Hepatitis

VIDEO: Cost to treat HCV could be as low as $80 in the US
November 19, 2016
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.

American College of Gastroenterology (ACG) 2016 Annual Scientific Meeting
November 22, 2016
LAS VEGAS — Rapid advances in the treatment of hepatitis C have clinicians seeing outcomes they never thought possible, and experts are optimistic that more complex and challenging patients will respond to therapy.

Healio
See more from American College of Gastroenterology Annual Meeting

National AIDS Treatment Advocacy Project (NATAP)
View All 2016 HCV and HIV conference reports at NATAP

 2016 Updates

HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C

HCV Guidelines Update: People with HCV Should Be Tested for HBV Before Starting Antiviral Therapies
September 16, 2016
All patients beginning hepatitis C (HCV) treatment using direct acting antiviral (DAA) therapies should be assessed for hepatitis B (HBV), according the American Association for the Study of Liver Diseases/Infectious Diseases Society of America Guidance Panel, which provides up-to-date guidance on the treatment of hepatitis C on its website, HCVguidelines.org.

AASLD Offers Two New Practice Guidelines
New Practice Guidelines covering the treatment of hepatocellular carcinoma and portal hypertensive bleeding in cirrhosis have been released by AASLD.

These evidence-based guidelines are developed and updated regularly by a committee of experts and include recommendations of preferred approaches to the diagnostic, therapeutic, and preventative aspects of care.

Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management was published in December. Treatment of Hepatocellular Carcinoma has a January 2017 publication date.

For details about AASLD’s practice guidelines, click here.

FDA MedWatch/Direct-Acting Antivirals for Hepatitis C: Drug Safety Communication - Risk of Hepatitis B Reactivating
October 4, 2016
The FDA is warning about the risk of hepatitis B virus (HBV) becoming an active infection again in any patient who has a current or previous infection with HBV and is treated with certain direct-acting antiviral (DAA) medicines for hepatitis C virus. In a few cases, HBV reactivation in patients treated with DAA medicines resulted in serious liver problems or death. HBV reactivation usually occurred within 4-8 weeks.

July 6, 2016
This version of the Guidance has been updated to reflect several important developments, including the recent approval of sofosbuvir/velpatasvir, together with new information regarding the use of testing for HCV resistance associated variants....
Read more 

February 24, 2016
This version of the Guidance has been updated to reflect several important developments, including the recent approval of elbasvir/grazoprevir, together with new information regarding the use of testing for HCV resistance associated variants....
Read more 

 Emerging Hepatitis C Treatment Strategies For Difficult‐to‐Cure Patients
November 12, 2016
Sit back and watch a panel of HCV experts discuss the recent updates and changes to AASLD-IDSA recommendations for testing, managing, and treating hepatitis C. Other topics include: efficacy of various DAA regimens in patients who have failed prior DAA therapies and efficacy and safety of different DAA regimens in the new difficult-to-cure patients.

Top Hepatitis Stories From Around The Web

Healio
HCV Next Cover Story - 2017 A Year in Transition
2017: A Year in Transition
"HCV Next" features cutting edge news on the latest HCV research developments. With in-depth articles on a range of topics; diagnosis, hepatitis c treatment regimens, side effects, drug/drug interaction, guidelines, practice management issues, to name a few.
Begin here.....

 HIVandHepatitis.com
Top 10 HIV and Hepatitis Stories of 2016
Simplification and optimization of antiretroviral therapy for HIV, wider use of pre-exposure prophylaxis (PrEP), a growing appreciation that people with undetectable viral load do not transmit HIV, and an expanded armamentarium of treatments for hepatitis C were among the top HIV and viral hepatitis headlines this year. Here's a look back at some of our biggest news from 2016.

Hepatitis B Foundation
Ten Things You Should Know About Hepatitis B and Do in 2017
It’s 2017, and experts around the world continue to study the complex life cycle of the hepatitis B virus in order to find a chink in its armor that will lead to a cure. In 2016, there were successes and disappointments in the research and healthcare arena. Here is what you need to know about hepatitis B in 2017.

Healio: Top Ten Most Read Articles In 2016
ILC coverage, HCV guidelines, FDA approvals among 2016 hot topics in hepatology
New data presented at the 2016 International Liver Congress, new guidelines on the management of hepatitis C virus infection from EASL and the WHO, and several new FDA approvals were among the most popular news topics covered by Healio.com/Hepatology this year.

HEP Your Guide To Hepatitis
Here are the stories and blogs with the most shares across social media this year;
2016 Top Shared Stories

1. FDA Approves Gilead’s Hepatitis C Regimen Epclusa (Sofosbuvir/Velpatasvir)
Posted: June 28

2. Epclusa: The Newest Hepatitis C Treatment
Posted: June 28

3. Looks Like Boomers Didn’t Get Hepatitis C From Youthful Drug Use After All
Posted: April 13

4. Hepatitis C Is Now the Biggest Killer Among All Infectious Diseases
Posted: May 4

5. Success for 8 Weeks of Gilead’s All-Genotype Hepatitis C Regimen
Posted: April 25

6. Zepatier: The Newest Hepatitis C Drug
Posted: February 1

7. After Curing Hepatitis C, Risk of Liver Cancer Remains Elevated
Posted: June 15

8. All Veterans With Hepatitis C, Without Restrictions, to Get Treatment
Posted: March 15

9. Near Perfect Hepatitis C Cure Rate For Ravidasvir and Sovaldi Among Those With Genotype 4
Posted: March 6

10. Hepatitis C is Killing Americans in Record Numbers While Patients Cannot Access Life Saving Medicine
Posted: May 16

11. Harvoni is Safe and Effective in Seniors With Hepatitis C
Posted: March 30

12. Hep C Relapses Are Uncommon Among Those Proclaimed Cured, But Reinfection is a Concern
Posted: March 7

13. Tattoos and Hepatitis C: What Are the Risks?
Posted: July 14

14. How Long Does Recovery From Hep C Treatment Take?
Posted: July 13

15. Hepatitis C Treatment Side Effects
Posted: May 31

Specialty Pharmacy Times
Lauren Santye, Assistant Editor
Publish Date: Wednesday, December 28, 2016
AbbVie Hepatitis C Drug Granted Breakthrough Therapy Designation
Experimental hepatitis C medication treats genotypes 1 through 6.

A Patient's Long, Difficult Journey to a Cure for Hepatitis C
Burdened by the symptoms of hepatitis C, an Australian man faced an uncertain future before new antiviral drugs offered hope.

Zepatier Tops Other Hepatitis C Drugs in Safety Comparison
Researchers compare top selling hep C medications Zepatier, Sovaldi, Harvoni, and Viekira Pak.

Merck Wins Nearly $2.5 Billion from Gilead in Hepatitis C Drug Royalties Verdict
Jury declares Merck’s acquired HCV drug patent valid.

First Drug for All Major Hepatitis C Genotypes Approved by FDA
Epclusa showed up to 99% viral suppression after 12 weeks across major hepatitis C genotypes.

Experts Call for End of Restricted Access to Hepatitis C Antivirals for Drug Users
Achieving global elimination of the virus starts with illicit drug users accessing curative hepatitis C virus treatments.

Is Prior Authorization Creating a Barrier to Eradicating Hepatitis C?
Nearly 1 of 4 initial requests for Harvoni were denied in a recent study of hepatitis C drug coverage.

Pharmacist Pleads Guilty in Hepatitis C Drug Fraud Case
Tennessee pharmacist admits to falsifying prior authorizations, medical lab reports, and drug test results for at least 51 hepatitis C patients prescribed Sovaldi, Harvoni, Viekira Pak, and Daklinza.

Black Plague Left Clues for Fighting Hepatitis C, HIV
Aberrant protein mutation associated with the black plague may lead to treatments for HIV and hepatitis C.

Improved Hepatitis C Screening Still Needed for Baby Boomers
Baby boomer generation are five times more likely to be diagnosed with hepatitis C virus.

Most Physicians Believe High-Cost Hepatitis C Drugs Are Worth the Price Tag
Debate continues surrounding cost versus cure in hepatitis C treatment.

Express Scripts Adds Hepatitis C Drug Harvoni to 2017 National Formulary
After 2 years of exclusion, Harvoni has been added to the Express Scripts national formulary for the treatment of hepatitis C.

New Hepatitis C Drug Expected to Challenge Dominance of Gilead in HCV Market
Zepatier is priced considerably lower with similar efficacy to Harvoni and Sovaldi.

As Out-of-Pocket Costs Rise, Hepatitis C Drug Adherence Drops
Manufacturer coupons found to show significant benefits reducing Sovaldi cost share.

GoodRx
2016 Year in Review: Good News, Bad News, and Looking Ahead to 2017
The two largest prescription insurance companies, Express Scripts and Caremark, dropped coverage for 40 popular drugs in 2016. Most notably, medications like the popular insulin Lantus, and venlafaxine ER (Effexor XR) for depression have been dropped by Caremark. Express Scripts dropped Taltz for psoriasis, and Orencia for rheumatoid arthritis, among others, and Viekira Pak now has only limited coverage. Insurers are also restricting coverage for many of the expensive (but effective) hepatitis C drugs like Zepatier and Olysio, leaving only Sovaldi and Harvoni as options.
                          
Wishing you all a safe and healthy 2017!
Tina
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This Army Vet Is Fighting Hep C With Big Pharma’s Help

This Army Vet Is Fighting Hep C With Big Pharma’s Help
by Doni Bloomfield
@DoniBloomfield
More stories by Doni Bloomfield
‎December‎ ‎29‎, ‎2016‎ ‎5‎:‎00‎ ‎AM‎ ‎EST

Burkett specializes in lining up testing and treatment for patients, and most of his work is funded by companies including Gilead Sciences Inc., AbbVie Inc. and Merck & Co. that have sold almost $50 billion of the new antivirals since they began hitting the market in 2013. Stiff competition has driven prices down and discounts up, and many insured patients have already been treated. That’s been bad news for the market leader, Gilead, which must increasingly find patients through the social service networks that target drug users and the poor. Many patients don’t even know they have the infection, which can take years to show symptoms.

“They are seeing patient volume declines even though there are 1 or 2 million patients out there,” said Michael Yee, an analyst with RBC Capital Markets. “They have to go out and find those 1 to 2 million.”
Continue reading...
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Wednesday, December 28, 2016

Faldaprevir–Deleobuvir - Hepatitis C Virus Genotype-1b-Infected Patients w-Cirrhosis and Moderate Hepatic Impairment

Research Article

In conclusion, in this small study in treatment-naïve and treatment-experienced patients with chronic HCV genotype-1b infection and mild or moderate hepatic impairment, the response to 24 weeks of treatment with faldaprevir, deleobuvir and ribavirin was not durable, with 74% of patients achieving SVR4 but only 57% achieving SVR12. Since this study was initiated, the HCV field has changed rapidly with the advent of new DAAs and all-oral DAA combinations. Because of this and based on the results of the phase 3 HCVerso1 and HCVerso2 trials [16], the development of the faldaprevir–deleobuvir combination has been terminated.

HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment
Christoph Sarrazin , Michael Manns, Jose Luis Calleja, Javier Garcia-Samaniego, Xavier Forns, Renee Kaste, Xiaofei Bai, Jing Wu, Jerry O. Stern

Abstract
This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh A [CPA], n = 18). Patients received faldaprevir 120 mg and deleobuvir (600 mg [CPA], 400 mg [CPB]) twice-daily with weight-based ribavirin for 24 weeks. Baseline characteristics were similar between groups. Among CPA patients, 13/18 completed treatment; discontinuations were for adverse events (AEs, n = 1), lack of efficacy (n = 3) and withdrawal (n = 1). Among CPB patients, 8/17 completed treatment; discontinuations were for AEs (n = 6), withdrawal (n = 1) and ‘other’ (n = 2). Sustained virologic response at post-treatment Week 12 (SVR12) was achieved by 11 (61%) CPA patients (95% confidence interval: 38.6%–83.6%) and 9 (53%) CPB patients (95% confidence interval: 29.2%–76.7%), including most CPA (11/16) patients with Week 4 HCV RNA <25 IU.mL-1 (target detected or not detected) and most CPB (8/9) patients with Week 4 HCV RNA <25 IU.mL-1 (target not detected); 0/4 CPB patients with Week 4 HCV RNA <25 IU.mL-1 (target detected) achieved SVR12. The most common AEs in both groups were nausea, diarrhoea and vomiting. Serious AEs were observed in 9 (53%) CPB patients and 1 (6%) CPA patient. Plasma trough concentrations of deleobuvir and faldaprevir were not substantially different between the CPA and CPB groups. In conclusion, in this small study the safety and efficacy profiles for 24 weeks of treatment with faldaprevir+deleobuvir+ribavirin in patients with mild or moderate hepatic impairment were consistent with the safety and efficacy profile of this regimen in non-cirrhotic patients. Faldaprevir+deleobuvir+ribavirin resulted in SVR12 in 53–61% of patients: proportions achieving SVR4 but not SVR12 were higher than in non-cirrhotic patients and overall response rates were lower than rates reported with other all-oral regimens in patients with cirrhosis.
Trial Registration: ClinicalTrials.gov NCT01830127.

Discussion Only
View Full Text Research Article Here
In this small study in treatment-naïve and treatment-experienced patients with chronic HCV genotype-1b infection and mild or moderate hepatic impairment, the overall safety and efficacy profiles for 24 weeks of treatment with deleobuvir and faldaprevir in combination with ribavirin were generally consistent with the safety and efficacy profiles observed in non-cirrhotic patients [16].

Overall the majority of patients achieved SVR4 (74%) and SVR12 (57%); however, response rates were lower than rates achieved with other all-oral DAA regimen in HCV-infected patients with cirrhosis (>90% SVR12) [18, 19]. Notably, the trough concentrations of deleobuvir and faldaprevir over 4 weeks of treatment were not substantially different between the CPA and CPB groups and similar proportions of patients achieved SVR4 and SVR12. The proportion of patients who were SVR4 but not SVR12 responders was higher than reported in phase 3 studies in non-cirrhotic patients. In non-cirrhotic patients, 95% of patients achieving SVR4 went on to achieve SVR12 [16]; whereas, in the present study, only 77% (20/26) of patients with SVR4 also achieved SVR12 (Table 2).

This is consistent with data from other all-oral combinations that require longer treatment durations (24 weeks rather than 12 weeks) to achieve SVR in patients with cirrhosis than in those without cirrhosis [2, 18, 19]. Response at treatment Week 4 appeared to predict SVR12 after 24 weeks of treatment, although the small number of patients precluded statistical analysis. This was particularly notable in patients with moderate hepatic impairment (CPB), where none of the 4 patients having Week 4 HCV RNA <25 IU.mL-1, but with target detected, achieved SVR12, whereas 8/9 (89%) of those with undetectable HCV RNA at Week 4 achieved SVR12. It is conceivable that the combination of faldaprevir and deleobuvir with ribavirin is not sufficient to prevent on-going viral replication in patients where residual virus is detected at Week 4. Of note, with more potent DAA combinations, detectable Week 4 HCV RNA is not predictive of treatment failure [2, 18, 19]. Consistent with a more severe disease state, discontinuations, AEs and SAEs were more common in patients with moderate hepatic impairment than in those with mild hepatic impairment. The higher rates of AEs in CPB patients is likely related to these patients having more severe liver disease and a more unstable condition. SAEs reported in CPB patients were primarily related to worsening of the underlying disease (including hepatic cirrhosis, acute hepatic failure, hepatic encephalopathy, ascites, haemorrhage and general physical health deterioration).

In conclusion, in this small study in treatment-naïve and treatment-experienced patients with chronic HCV genotype-1b infection and mild or moderate hepatic impairment, the response to 24 weeks of treatment with faldaprevir, deleobuvir and ribavirin was not durable, with 74% of patients achieving SVR4 but only 57% achieving SVR12. Since this study was initiated, the HCV field has changed rapidly with the advent of new DAAs and all-oral DAA combinations. Because of this and based on the results of the phase 3 HCVerso1 and HCVerso2 trials [16], the development of the faldaprevir–deleobuvir combination has been terminated.

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HBV/HCV dual infection impacts viral load, antibody response, and cytokine expression differently from HBV or HCV single infection

HBV/HCV dual infection impacts viral load, antibody response, and cytokine expression differently from HBV or HCV single infection
Fei Chen, Jian Zhang, Bo Wen, Shan Luo, Yingbiao Lin, Wensheng Ou, Fengfan Guo, Ping Tang, Wenpei Liu & Xiaowang Qu

Received:15 July 2016
Accepted:23 November 2016
Published online:23 December 2016

Scientific Reports 6, Article number: 39409 (2016)
doi:10.1038/srep39409
Download Citation

Abstract
Hepatitis B virus/hepatitis C virus (HBV/HCV) dual infection is common among high-risk individuals. To characterize the virological and immunological features of patients with HBV/HCV dual infection, we enrolled 1,049 individuals who have been identified as injection drug users. Patients were divided into single and dual infection groups according to the serological markers. We found the average HCV RNA level was significantly lower; however, HBV viral load was significantly higher in HBV/HCV dual-infected patients (n = 42) comparing HCV single infection (n = 340) or HBV single infection (n = 136). The level of anti-HBs in patients who experienced spontaneous HBV clearance was higher than that in HCV single-infected patients with HBV spontaneous clearance. The level of anti-HCV E2 in HBV/HCV dual infection was lower than that detected in HCV single infection. Serum levels of IL-6, IL-8, and TNF-α were significantly lower in HBV/HCV dual-infected patients than in patients infected with HBV or HCV alone. Taken together, two viral replications are imbalanced in dual infected patients. The anti-HBs and anti-HCV E2 antibody production were impaired and proinflammatory IL-6, IL-8, and TNF-α also downregulated due to dual infection. These findings will help further understanding the pathogenesis of HBV/HCV dual infection.

Discussion Only
Full Text Available at Nature.

In this study, we found that HBV DNA levels were higher and HCV viral load were lower in HBV/HCV dual infection as compared with HBV or HCV single infection. Our results clearly suggest a competition between HBV and HCV infection when the liver is infected with both viruses, and HBV replication is dominant in dual-infected subjects.

The different HBV and HCV replication levels are typically attributed to direct interference9,11,18. However, we believe that the observed difference in the two viral replications derived from a competition for uninfected hepatocytes rather than from viral interference. It is well known that the prevalence of HBV infection is much higher than that of HCV infection in the Chinese general population16,31. Furthermore, our previous study, which examined HBV and HCV infection patterns between IDUs and the general population using the similar cohort with this study, demonstrated that HBV infections shared similar patterns by IDUs and the general populations, and HCV infection exhibited distinct features between two populations32. From these studies, we infer that most of the patients with HBV/HCV dual infection infected HBV were though perinatal, while some of these patients were infected though injection drug use. However, the study herein shows that HCV was acquired at a later age. Therefore, it is conceivable that the HBV/HCV dual-infected individuals were already infected with HBV before contracting HCV infection. As the majority of the hepatocytes are already infected with HBV, these cells are generally resistant to viral superinfection. Only a small number of hepatocytes are uninfected, which may be available for HCV infection. Besides, HBV has a long-lived nuclear form of its genome (covalently closed circular DNA) that is able to persist in the face of potent inhibition of viral replication. In contrast, HCV does not have a long-lived genome form; HCV is therefore much more susceptible to eradication by potent immunity33. Moreover, a lower HCV level may reflect a small number of HCV-infected cells, which is a possible explanation for the dominant HBV replication in our cohort.

Further to the rationale for our study results is an explanation for the higher HBV DNA levels in the dual-infected patients than in HBV single-infected patients. Patients with HBV single infection, especially those who acquired the infection in adulthood, likely experienced spontaneous viral clearance, and the number of infected cells was significantly reduced as the natural course of the virus progressed. On the other hand, the subjects with dual infection were likely to have been repeatedly infected with HBV during transmission of HCV, leading to more HBV-infected cells despite the ongoing viral clearance. Due to no treatment guidelines for HBV/HCV dual-infection patients, so it is important to determine the “dominant” virus by serological and virological testing prior to initiating therapy. For patients with dominant HCV infection, IFN or pegylated IFN in addition to ribavirin can achieve comparable sustained virus response as expected with HCV monoinfection. For patients with dominant HBV infection, pegylated IFN plus ribavirin and a nucleos(t)ide analog appears to be a feasible option2,34,35,36.

Wiedmann et al. showed that chronic HCV-infected patients tended to have poor HBV vaccination response and low anti-HBs antibody levels25. In this study, we found both the percentage of anti-HBs antibody titers ≥10 mIU/mL and anti-HBs levels in the HCV single-infected patients with HBV spontaneous clearance were lower than that found in patients who experienced spontaneous HBV clearance. The results of various studies revealed that higher concentrations of serum antibody may lead to a longer duration of immunity. The anti-HBs titer correlated to the frequency of IFN-γ-producing HBs-specific T cells. Reports show that HBs-specific T cell and antibody responses did not differ between vaccines and HBV-recovered patients37,38. This finding suggests that greater levels of antibody production would lead to enhanced immunity, and that HCV infection may directly or indirectly influence HBV surface antibody production. Therefore, it is necessary to strengthen the HBV vaccine and increase the monitoring of the anti-HBs antibody levels in the high risk population of HCV infection.

Moorman et al. showed an impaired response to HBV vaccination in chronic HCV-infected patients, which was partly attributed to the upregulated expression of PD-1 and PD-L1 on CD4+ T cells26. We also found that the anti-HCV E2 antibody response was weaker in HBV/HCV dual infection than in HCV single infection. The HCV envelope glycoproteins E2 are codified by E2 genomic regions. Envelope glycoprotein E2 comprises two hypervariable regions. The two hypervariable regions are subject to immune pressure, which leads to the formation of escape mutants. Patients infected with HCV develop a humoral immune response against HCV envelope proteins; therefore, anti-HCV E1 and E2 may have the capability of neutralizing HCV infection39. This finding suggests that HBV infection may negatively impact HCV antibody response. Of great consideration, our findings do not support the suggestion that the upregulation of expression of immune checking molecules was partially responsible for lower anti-HBs or anti-HCV E2 levels in the dual infection, since viral proteins are also expressed in single infection if they inhibited the immune response. We believe that the HBV/HCV dual infection placed a heavier burden on the immune system of the host, and that the antibody production has to deal with two viral infections, which leads to a weak antibody response to each virus.

Pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α are involved in HBV- or HCV-induced liver inflammation and treatment outcomes27,40,41,42,43. The expression levels of these cytokines in HBV/HCV dual infection are unclear. Here, we showed that the serum levels of IL-6, IL-8, and TNF-α expression were significantly lower in HBV/HCV dual infection compared with HCV or HBV single infection, which is consistent with an in vitro study that showed that co-culturing HBV and HCV core proteins with human dendritic cells significantly increased the production of immune-suppressive cytokine, IL-10, and decreased the expression of pro-inflammatory cytokines. IL-6, IL-12, and TNF-α. In addition, the results of this study suggested that viral core proteins can synergistically induce the immune tolerance of dendritic cells and overproduce IL-10, which can inhibit the production of pro-inflammatory cytokines such as IL-6 and TNF-α28.

In summary, our study showed that there likely exists competition for uninfected hepatocytes when the liver is infected with both HBV and HCV. The viral dominance in dual infection was largely determined by the virus that firstly established the infection. Hepatitis B replication was dominant in this cohort because HBV was likely the first to infect the majority of liver cells. In addition, dual infection placed a heavier burden on the immune system of the host and weakened the antibody production capacity, leading to a lower level of protective antibody to each virus. Taken together, our data may contribute to further understanding the biology of viral infection and immune response in patients with a dual infection of HBV and HCV.

http://www.nature.com/articles/srep39409
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Monday, December 26, 2016

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

2018 - Updates
Letter to the editor
Jan 2018

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

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.






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Mortality in hepatitis C patients who achieve a sustained viral response compared to the general population

Journal of Hepatology 2017 vol. 66 j 19–27

Mortality in hepatitis C patients who achieve a sustained viral response compared to the general population
Hamish Innes, Scott McDonald, Peter Hayes, John F. Dillon, Sam Allen, David Goldberg, Peter R. Mills, Stephen T. Barclay, David Wilks, Heather Valerio, Ray Fox, Diptendu Bhattacharyya, Nicholas Kennedy, Judith Morris, Andrew Fraser, Adrian Stanley, Peter Bramley, Sharon J. Hutchinson


Abstract
Background & Aims
The number of people living with previous hepatitis C infection that have attained a sustained viral response (SVR) is expected to grow rapidly. So far, the prognosis of this group relative to the general population is unclear.

Methods
Individuals attaining SVR in Scotland in 1996–2011 were identified using a national database. Through record-linkage, we obtained cause-specific mortality data complete to Dec 2013. We calculated standardised mortality ratios (SMRs) to compare the frequency of mortality in SVR patients to the general population. In a parallel analysis, we used Cox regression to identify modifiable patient characteristics associated with post-SVR mortality.

Results
We identified 1824 patients, followed on average for 5.2 years after SVR. In total, 78 deaths were observed. Overall, all-cause mortality was 1.9 times more frequent for SVR patients than the general population (SMR: 1.86; 95% confidence interval (CI): 1.49–2.32). Significant cause-specific elevations were seen for death due to primary liver cancer (SMR: 23.50; 95% CI: 12.23–45.16), and death due to drug-related causes (SMR: 6.58, 95% CI: 4.15–10.45). Together these two causes accounted for 66% of the total excess death observed. All of the modifiable characteristics associated with increased mortality were markers either of heavy alcohol use or injecting drug use. Individuals without these behavioural markers (32.8% of cohort) experienced equivalent survival to the general population (SMR: 0.70; 95% CI: 0.41–1.18)



Conclusions
Mortality in Scottish SVR patients is higher overall than the general population. The excess was driven by death from drug-related causes and liver cancer. Health risk behaviours emerged as important modifiable determinants of mortality in this population.

Lay summary
Patients cured of hepatitis C through treatment had a higher mortality rate overall than the general population. Most of the surplus mortality was due to drug-related causes and death from liver cancer. A history of heavy alcohol and injecting drug use were associated with a higher mortality risk.

Keywords:
Excess mortality, Hepatitis C, Cure, Epidemiology
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Thursday, December 22, 2016

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.

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AbbVie Awaits NDA Approval For Hepatitis C Treatment

Dec 21
A New Drug Application (NDA) by AbbVie Inc (NYSE:ABBV) that will be used for the treatment of Hepatitis C is at the mercy the U.S. Food and Drug Administration. Glecaprevir/pibrentasvir (G/P), which will be in direct competition with another treatment from Gilead Sciences, Inc. (NASDAQ:GILD), has been submitted for an investigational pan-genotypic regimen. The application was supported by encouraging results that had been collected from over 2,300 patients in 27 countries who had used glecaprevir/pibrentasvir (G/P) regimen on trial basis.

Press Release
NORTH CHICAGO, Ill., Dec. 19, 2016 -- (Healthcare Sales & Marketing Network) -- 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). In Phase 3 clinical studies, eight weeks of therapy with G/P achieved high sustained virologic response (SVR) rates across all major genotypes (GT 1-6) in patients without cirrhosis, which represents the majority of HCV patients. In patients with compensated cirrhosis, high SVR rates were achieved after 12 weeks of therapy. High SVR rates were also achieved in patients with limited treatment options, such as those with severe chronic kidney disease (CKD). In historically difficult to treat populations, including those not cured* by prior direct-acting antiviral (DAA) treatment regimens, high SVR rates were achieved with durations as short as 12 weeks.

"Our regimen of glecaprevir and pibrentasvir shows promise for patients by achieving high cure rates in Phase 3 clinical studies across all major hepatitis C genotypes," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We look forward to working with the FDA as they review our New Drug Application, which we believe represents another important step toward a faster path to virologic cure for hepatitis C patients."

The NDA is supported by data from eight registrational studies in AbbVie's G/P clinical development program, which evaluated more than 2,300 patients in 27 countries across major HCV genotypes and special populations. Patient populations studied included genotypes 1-6, those new and experienced to treatment, those with compensated cirrhosis and without cirrhosis and patients with specific treatment challenges, including those with severe CKD, and those not cured with a prior DAA containing regimen.

AbbVie previously announced registrational data that demonstrated with eight weeks of treatment 97.5 percent (n=693/711) of chronic HCV GT1-6 patients without cirrhosis and new to treatment achieved sustained virologic response at 12 weeks post treatment (SVR12). Additional data submitted show that with 12 weeks of treatment 98 percent (n=102/104) of severe CKD patients achieved SVR12 in a primary intent-to-treat (ITT) analysis. In a modified intent-to-treat (mITT) analysis of severe CKD patients, 100 percent (n=102/102) of patients achieved SVR12. The mITT analysis excludes patients who did not achieve SVR for reasons other than virologic failure. The most commonly reported adverse events (AEs) for severe CKD patients were pruritus, fatigue and nausea. The most commonly reported AEs for GT1-6 patients without cirrhosis and new to treatment were headache and fatigue. These data were presented at The American Association for the Study of Liver Diseases (AASLD) annual meeting in November 2016. Data for other registrational studies will be shared in future meetings.

On September 30, 2016, AbbVie announced that the FDA granted Breakthrough Therapy Designation (BTD) for G/P for the treatment of patients with HCV who were not cured with prior DAA therapy in genotype 1 (GT1), including therapy with an NS5A inhibitor and/or protease inhibitor. The BTD is supported by positive results seen in AbbVie's Phase 2 MAGELLAN-1 clinical study. According to the FDA, BTD is intended to expedite the development and review of therapies for serious or life threatening conditions.1

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

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

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 a 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 (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 U.S. Food and Drug Administration. Fact Sheet: Breakthrough Therapies. http://www.fda.gov
Accessed November 23, 2016.
Source: AbbVie

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"Significant Unmet Needs" Remain in Hepatitis C


"Significant Unmet Needs" Remain in Hepatitis C
Dec 22, 2016
By Pharmaceutical Executive Editors
 
Although recent years have seen a revolution in the hepatitis C space, as interferon-free direct-acting antiviral (DAA) combination therapies have started replacing interferon-based therapies, a number of considerable unmet needs remain, according GBI Research.

The company’s latest report emphasises that although the proportion of hepatitis C patients who do not respond to or cannot tolerate DAA combination therapies is small, as over 90% can now be cured within 3–6 months, a failure rate of even 5% may still leave up to 10 million people with unmet needs due to the high prevalence. In addition, it is estimated that 1-2% of people who reach a sustained virologic response may experience a subsequent relapse over a 4-5 year period.

The need to develop drugs for non-responsive and relapsing patients means the hepatitis C space is a commercially attractive one, reports GBI. Currently, the hepatitis C pipeline is relatively active, with 198 products in development, and differs significantly from the market landscape, which is dominated by interferon immune mediators and ribavirin products.
See the report here.

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Thursday, December 8, 2016

Gilead Submits NDA to FDA for Sofosbuvir/Velpatasvir/Voxilaprevir HCV Genotype 1-6

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 -
     
FOSTER CITY, Calif.--()--Gilead Sciences, Inc. (Nasdaq: GILD) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily single tablet regimen containing sofosbuvir 400 mg, velpatasvir 100 mg, and voxilaprevir 100 mg (SOF/VEL/VOX) for the treatment of direct-acting antiviral (DAA)-experienced chronic hepatitis C virus (HCV)-infected patients. The data submitted in the NDA support the use of the regimen for 12 weeks in DAA-experienced patients with genotype 1 to 6 HCV infection without cirrhosis or with compensated cirrhosis.

“The remaining clinical need to treat HCV patients is a safe and effective cure for patients who have failed previous therapy with DAA regimens, including those with NS5A inhibitors,” said Norbert Bischofberger, Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “SOF/VEL/VOX has the potential to fill that need by offering single tablet dosing and high cure rates across all HCV genotypes for patients with and without cirrhosis, who have failed prior treatment with other highly effective regimens.”
  
The NDA for SOF/VEL/VOX is based on data from two Phase 3 studies (POLARIS-1 and POLARIS-4), which evaluated 12 weeks of the fixed-dose combination in DAA-experienced patients with hepatitis C genotypes 1-6, including those who failed prior treatment with an NS5A-containing regimen. Of the 445 patients treated with SOF/VEL/VOX, 430 (97 percent) achieved the primary efficacy endpoint of SVR12. The NDA is further supported by two additional Phase 3 studies (POLARIS-2 and POLARIS-3) in which 611 DAA-naïve HCV-infected patients received 8 weeks of SOF/VEL/VOX. The most common adverse events among patients who received SOF/VEL/VOX were headache, fatigue, diarrhea and nausea. These data were presented at the American Association for the Study of Liver Diseases (AASLD) annual meeting in November 2016.

About SOF/VEL/VOX
The SOF/VEL/VOX fixed-dose combination is an investigational product and its safety and efficacy have not been established. It has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration for the treatment of chronic genotype 1 HCV patients who have previously failed an NS5A inhibitor-containing regimen.

About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.
Source

AASLD 2016 - Liver Meeting​
Phase 3 POLARIS-1 Study
NATAP ​- Reported by Jules Levin review slides
Sofosbuvir/Velpatasvir/Voxilaprevir for 12 Weeks as a Salvage Regimen in NS5A Inhibitor-Experienced Patients With Genotype 1-6 Infection: The Phase 3 POLARIS-1 Study - (11/15/16)

Phase 3 POLARIS-2 Study
NATAP ​- Reported by Jules Levin review slides
A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevir for 8 Weeks Compared to Sofosbuvir/Velpatasvir for 12 Weeks in DAA-Naïve Genotype 1-6 HCV Infected Patients: The POLARIS-2 Study - (11/15/16)

POLARIS-2: Voxilaprevir safe, effective with Epclusa in multiple HCV genotypes

Phase 3 POLARIS-3 Study
NATAP ​- Reported by Jules Levin review slides
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 - (11/15/16)

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

Phase 3 POLARIS-4 Study
NATAP ​- Reported by Jules Levin review slides
A Randomized, Controlled, Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevir or Sofosbuvir/Velpatasvir for 12 Weeks in Direct-Acting Antiviral-Experienced Patients With Genotype 1-6 HCV Infection: The POLARIS-4 Study - (11/14/16)

SOF/VEL/VOX Effective as Retreatment for Non-NS5A DAA Failures
By Debra Hughes, MS November 14, 2016
Treatment with single tablet sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks "is a highly effective salvage therapy" for patients who did not previously achieve sustained virologic response (SVR) following treatment with non-NS5A inhibitor-containing direct-acting antivirals (DAAs), results from the POLARIS-4 study presented at The Liver Meeting® 2016 have shown

NATAP ​- Reported by Jules Levin review slides​
Integrated Analysis of Sofosbuvir +Ribavirin, Ledipasvir/Sofosbuvir or Sofosbuvir/Velpatasvir for the Treatment of Genotype 4 Chronic HCV Infection - (11/15/16)

NATAP ​- Reported by Jules Levin review slides​
Integrated Resistance Analyses of HCV-Infected Patients Treated With Sofosbuvir, Velpatasvir, and Voxilaprevir for 8 and 12 Weeks From Phase 2 Studies - (11/14/16)
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Monday, December 5, 2016

December HCV Newsletters And Updates: Epclusa most effective for HCV genotype 3 vs. other DAAs

December HCV Newsletters And Updates

Greetings everyone, here is your digest of December Newsletters, along with today's news and updates. 

News In Review

Healio
Top Story
Epclusa most effective for HCV genotype 3 vs. other DAAs
December 5, 2016
Researchers in the Netherlands found that Sovaldi plus velpatasvir, known as Epclusa in the United States, was the most effective regimen for the treatment of hepatitis C genotype 3 infection compared with other direct-acting antiviral regimens, according to published findings.

“The findings of our network meta-analysis can be used to prioritize DAA regimens for HCV genotype 3 patients in guidelines and clinical practice,” Joost P.H. Drenth, MD, PhD, professor of gastroenterology and hepatology, Radboud University Medical Center, the Netherlands, and colleagues wrote.
Begin here...

Family Practice News
Frontline Medical News
Hepatitis Outlook
Publish date: November 29, 2016
By: Richard Pizzi
A single-center trial of direct-acting antivirals in treatment-naive patients with chronic hepatitis C virus genotype (GT)1 or 3 infection supported the use of 8-week DAA treatment regimens that maintain high efficacy, even for patients infected with HCV GT3 infection.

Results from the OSIRIS study revealed that simeprevir plus sofosbuvir for 12 weeks achieved a 100% sustained virologic response rate in hepatitis C virus genotype 4-infected patients with or without compensated cirrhosis.
Continue reading...

 BASL - British Association for the Study of the Liver
Hepatocellular carcinoma increase rate slows in USA
The overall rate of increase in hepatocellular carcinoma (HCC) slowed between 2010 and 2012, found a nationwide US study. However, it did increase in some sub-groups such as men aged 55 to 64, and whites/Caucasians.

Researchers at Baylor College of Medicine in Texas analysed data from the US Cancer Statistics registry, which covers 97% of the population of all 50 states.

They found that the HCC incidence increased from 4.4/100,000 in 2000 to 6.7/100,000 in 2012, increasing by 4.5% annually between 2000 and 2009, but only by 0.7% annually between 2010 and 2012.

The average annual percentage change (AAPC) between 2000 and 2012 was higher in men (increase of 3.7%) than women (increase of 2.7%), and highest in 55 to 59-year-olds (AAPC 8.9%) and 60 to 64-year-olds (AAPC 6.4%).

By 2012, rates in Hispanics surpassed those in Asians, and rates in Texas surpassed those in Hawaii (9.71/100,000 vs 9.68/100,000). Geographic variation within individual race and ethnic groups was observed, but rates were highest in all major race and ethnic groups in Texas.

Reference - Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012. White DL, Thrift AP, Kanwal F et al. Gastroenterology. 2016 Nov 23 [Epub ahead of print]

Read all research and news updates, here...

Dr. Joseph S. Galati
Discussions about the liver and everything else related to health and wellness.
Visit The Blog of Dr. Joseph S. Galati

 Fatty Liver: What Treatment is Available?
Published on Dec 4, 2016
Joe Galati, M.D.
Dr. Joe Galati and Liver Specialists of Texas has research protocols for those diagnosed with NASH, fatty liver disease, or non-alcoholic fatty liver disease.

Fatty liver can be complicated by cirrhosis and liver cancer, and the need for liver transplant. Fatty liver disease should not be ignored. New research drugs and medicines are being developed.



 In The News

DHHR Secretary gives update on practices used to fight West Virginia’s drug epidemic
CHARLESTON, W.Va. — Karen Bowling, cabinet secretary for the State Department of Health and Human Resources Bureau for Public Health, told members of a legislative interim committee what’s working and what’s not when it comes to fighting West Virginia’s drug epidemic.

Hundreds of VA dental patients possibly exposed to HIV, hepatitis
(CNN) — Nearly 600 patients who received dental care at a Wisconsin Veterans Affairs medical center may have been exposed to HIV, hepatitis B and C and now face an anxious wait to find out if they were infected.

WHO Prequalifies First Hepatitis C Diagnostic
Regulatory Focus-12 minutes ago
The World Health Organization (WHO) on Monday announced it has prequalified its first hepatitis C virus (HCV) rapid diagnostic test, which will help diagnose ...

1.9 million pounds of undercooked chicken recalled
(CNN)National Steak and Poultry issued a recall of more 1.9 million pounds of its ready-to-eat chicken products, the Unites States Department of Agriculture said Monday. The products are sold as fully cooked for consumers to heat and serve, but they may be undercooked. Undercooked poultry can harbor bacteria. . A complete list of recalled products can be found on the USDA website

VA dentist resigns after possibly infecting 600 veterans with HIV and hepatitis
TOMAH, Wis., Dec. 3 (UPI) -- An unidentified Department of Veterans Affairs dentist in Wisconsin resigned after possibly exposing hundreds of patients to HIV and hepatitis B and C.

Officials at Tomah Veterans Affairs Medical Center announced Friday the dentist, who placed veterans at risk by reusing his tools, resigned after initially moving to an administrative role, The Milwaukee Journal Sentinel reported.

The latest figures have outlined 10 most prescribed and most expensive drugs on the Pharmaceutical Benefits Scheme (PBS) in the past year.
The figures are particularly notable due to the introduction of two new hepatitis C drugs, which were introduced to the PBS in March.

People who consistently smoked an average of less than one cigarette per day over their lifetime had a 64 percent higher risk of earlier death than never smokers, and those who smoked between one and 10 cigarettes a day had an 87 percent higher risk of earlier death than never smokers, according to a new study from researchers at the National Cancer Institute (NCI). Risks were lower among former low-intensity smokers compared to those who were still smokers, and risk fell with earlier age at quitting. The results of the study were reported Dec. 5, 2016, in JAMA Internal Medicine. NCI is part of the National Institutes of Health.

Newsletters

HCV Advocate
The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education

Check out what we have in store for you in the December Newsletter

Dear Advocaters,
It’s hard to believe that it’s December and 2017 is right around the corner.  It’s been a busy year at the HCV Advocate and this month’s issue is no exception.  Lucinda K. Porter RN and I have each picked some of our favorite abstracts from this year’s AASLD’s Liver Meeting.  Matthew Zielske’s article continues on the theme of research to discuss turning research and education into practice.

The Five by Alan Franciscus – I have picked five abstracts that I think are some of the most interesting including alcohol and treatment, HBV reactivation during and after HCV treatment, patient descriptions of fatigue (my favorite), curing HCV and diabetes, and the cost of generic direct-acting antiviral medications.

HealthWise by Lucinda K. Porter—AASLD – Lucinda has picked various abstracts such as payer treatment restrictions, pre-existing liver disease treatment and outcomes of breast cancer, hepatitis C reactivation in patients with cancer, alcohol and treatment outcome, fatigue, HAV and HBV vaccination in people with liver disease, and surveillance and screening of liver cancer.

Under the Umbrella by Matthew Zielske –The challenges of proving what we know – Matthew writes about the importance of communication and some of the discrimination that people face when seeking information and medical care.

HCV Advocate Pipeline has been updated with phase 2 information about AbbVie’s combination of glecaprevir plus pibrentasvir to treat genotype 1, 3,4, 5, and 6.  Hint – very high cure rates.

What’s Up!
Check out our new Easy C fact sheets:
What are RAVs
Taking HCV Meds – Adherence
We have updated our HCSP fact sheet:
Adherence to HCV Therapy

Coming Next Month
The Top News Stories of 2016
A New Fact Sheet Series: Harm Reduction

Many thanks for your continued support,
Alan and the HCV Advocate team

Infohep
Latest treatment news and information for patient advocates and people working in hepatitis in Europe.

November 2016 Newsletter
Contents
News from the 2016 AASLD Liver Meeting
New pangenotypic combinations
Hepatitis C genotype 3
Real world treatment performance matches the best clinical trial results
Treatment scale-up and the continuum of care
Liver cancer in people treated with direct-acting antivirals
Hepatitis B treatment
Generic hepatitis C drugs
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Hepatitis B and C Public Policy Association
 The Hepatitis Public Policy Association aims to urge and facilitate the formulation of public policies at national and international level for the communication, prevention and management of the spread of viral Hepatitis B and C. The Association’s unique approach in furtherance of this aim is to gather together, and work in partnership with, the major stakeholders in the field of these diseases including regulators, patients, clinicians, public health and civil society communities and the private sector.

Treatment of HCV with Direct Acting Antivirals in Italy
1) The real cost of DAAs
2) The potential savings to be made for the INHS by treating all HCV patients
3) The number of patients to treat
4) The real capacity of the hospitals authorized to prescribe DAAs;
Side effects of prohibition
The biggest and unexpected side effect of denying treatment to more than 100,000 patients, is the use of generic drugs imported from other countries. We have seen an exponential increase in the import of generic drugs against HCV from India and Egypt. Given that Italian regulations are extremely restrictive concerning this issue, this has caused controversies and problems also for the Italian physicians who were unprepared to deal with this situation. It is almost impossible to know exactly how many patients have imported these drugs, but certainly we could speculate at least 500.
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 HEP
Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and Hep Magazine are the go-to source for educational and social support for people living with hepatitis.

HEP Winter 2016 - Special Issue
Highlights
Through the Uprights
Alive and Kicking
Beware Herbal and Dietary Supplements
Read this issue online, here...
View interactive publication, here...
Past issues, here...

The New York City Hepatitis C Task Force
The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community.

Check out the new Hep C resources addressing needs of people who use drugs
Share this road map of resources for New York City immigrants with clients.
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Newsletter Archives..

 HCV Action
HCV Action brings together hepatitis C health professionals from across the patient pathway with the pharmaceutical industry and patient representatives to share expertise and good practice.

HCV Action e-update: November 2016
New HCV Action case studies highlight effective testing services

 GI & Hepatology News
Over 17,000 gastroenterologists and hepatologists rely on GI & Hepatology News every month to cover the world of medicine with breaking news, on-site medical meeting coverage, and expert perspectives both in print and online. The official newspaper of the AGA Institute was launched in partnership with IMNG in January 2007.
December 2016 issue of GI & Hepatology
Past Issues

NIH News in Health
Check out the December issue of NIH News in Health, the monthly newsletter bringing you practical health news and tips based on the latest NIH research.

Features
Making a Healthier Home
Cast Toxins From Your Living Space

Tai Chi and Your Health
A Modern Take on an Ancient Practice
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In Case You Missed It

Acetaminophen, supplements and other medications may trigger drug-induced liver injury
More than 1,000 medications, with acetaminophen being the most common, have been associated with drug-induced liver injury (DILI).

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