Hepatitis C Genotype 3 - FDA Approved And Soon To Be Approved Therapies

September: Updated AASLD IDSA HCV Guidance
This page was updated on Aug 3, 2017 to include AbbVie's FDA approval of MAVYRET™ (glecaprevir/pibrentasvir). On July 18, 2017  Gilead announced the FDA approved VoseviTM (Sofosbuvir/Velpatasvir/Voxilaprevir  - EMA granted marketing authorization for both Vosevi, and AbbVie's MAVIRET® on July 28, 2017.

Hepatitis C genotype 3 isn't a death sentence

Published on Jul 14, 2017
By onewhoknows7
We begin with a family who struggle to access HCV therapy. A video with only one picture and a bit of text for us to read, for me - a powerful video. A story that almost anyone who has treated HCV can relate to; falling through the cracks, not receiving quality care, insurance companies deciding when or if to treat patients, is this your story too? In many ways this video hits home for me also, if not for HCV Advocate, I most certainty would have never treated successfully in 1999.  

An estimated 130-150 million people worldwide are living with chronic HCV infection, within the six major HCV genotypes, genotype 3 represents 22-30% of all infection, 10% in the United States.

Research has shown people infected with genotype 3 have significantly increased rates of steatosis (fatty liver), fibrosis, and hepatocellular carcinoma (liver cancer), thus making this genotype both difficult and urgent to treat. Here is a quick review of key HCV genotype 3 research articles,  with an update from the HCV Guidance .

FDA approved drugs to treat HCV genotype 3
September 2017
AASLD IDSA
HCV Guidance: Updated - Geno 1 & 3 Treatment-Naïve & Treatment-Experienced
Recommendations Reflecting Vosevi and Mavyret .
Stay current with all guideline updates, "click here."
Read more click here.....

October 2017
Over at NEJM Journal Watch, a small study for HCV genotype 3 patients is reviewed by Atif Zaman, MD, MPH, published last week in Hepatology. The study; Glecaprevir/pibrentasvir for HCV genotype 3 patients with cirrhosis and/or prior treatment experience: A partially randomized phase III clinical trial, is available for download over at NATAP. 

Watch

June 2017
HCV genotype 3: Work through virtual case study with Dr Doug Dieterich
The HCV Virtual Patient program is an interactive, case-based program featuring real-world case scenarios discussed by HCV thought leaders.

Recommended Reading

July 13, 2017
Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections—A Scandinavian real-life study
We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.

Commentary On This Study
Aug 1, 2017
Hepatitis C Cure Rate Tops 90% in Hard-to-Treat Genotype 3 Patients

Hepatitis C patients with hard-to-treat genotype 3 showed sustained virologic response (SVR) of greater than 90% in a real-life study of a therapy based on the direct-acting antiviral (DAA) drug sofosbuvir (Sovaldi, Gilead Sciences Inc.)

New Drugs FDA Approved 

FDA Approved - Gilead's VoseviTM (Sofosbuvir/Velpatasvir/Voxilaprevir 

On July 18, 2017 Gilead's VoseviTM (Sofosbuvir/Velpatasvir/Voxilaprevir) was FDA Approved, a few weeks later on July 28, the European Commission Granted Marketing Authorization for Vosevi.

Research Articles

Sofosbuvir, Velpatasvir and Voxilaprevir

Patients with prior DAA treatment failure, genotype 3, cirrhosis and/or unfavorable resistance profiles all achieved cure rates of 96% or greater.

Link - July 5, 2017: Sofosbuvir, Velpatasvir and Voxilaprevir combination for the treatment of hepatitis C- Review

This is a review of the preclinical and clinical development of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), an interferon-free, oral, once daily, pangenotypic treatment for chronic HCV infection.  All relevant literature from 2015 through June of 2017 is included..

FDA Approved AbbVie's MAVIRET (Glecaprevir/Pibrentasvir)
Aug 3, 2017 AbbVie Received U.S. FDA Approval of MAVYRET™ (glecaprevir/pibrentasvir). 

On June 28, 2017 the European Commission Granted AbbVie's MAVIRET® (glecaprevir/pibrentasvir) Marketing Authorization for the Treatment of Chronic Hepatitis C in All Major Genotypes (GT1-6)

Glecaprevir/Pibrentasvir

In patients with challenging-to-treat genotype 3 chronic HCV infection with cirrhosis, 95% achieved SVR12 after 8 weeks of therapy.

April 21, 2017 - AbbVie combination cures 97% of genotype 3 hepatitis C

AbbVie's pangenotypic direct-acting antiviral combination of two drugs cured 95% of people with early-stage genotype 3 hepatitis C virus (HCV), the hardest genotype to treat, according to results of the ENDURANCE-3 trial presented at the  International Liver Congress in Amsterdam on Friday. The AbbVie second-generation direct-acting antiviral combination consists of a protease inhibitor and an NS5A inhibitor. Glecaprevir is an HCV NS3/4A protease inhibitor active against all genotypes of hepatitis C. Pibrentasvir is an NS5A inhibitor also active against all genotypes of hepatitis C.

July 26, 2017
Glecaprevir/pibrentasvir is effective for people with HIV/HCV co-infection
Liz Highleyman
Produced in collaboration with hivandhepatitis.com
Published: 26 July 2017

AbbVie's new pangenotypic regimen combining glecaprevir and pibrentasvir cured almost all HIV-positive people with hepatitis C co-infection in the EXPEDITION-2 study, according to a presentation on Monday at the 9th International AIDS Society Conference on HIV Science (IAS 2017) in Paris.

Karine Lacombe of Saint-Antoine Hospital in Paris presented findings from AbbVie's phase 3 EXPEDITION-2 trial, which evaluated an 8-week regimen of glecaprevir/pibrentasvir for people with both HIV and hepatitis C.

Glecaprevir is an HCV NS3/4A protease inhibitor and pibrentasvir is an NS5A inhibitor. Both are pangenotypic, or active against all HCV genotypes. The two drugs have been co-formulated in a once-daily combination pill, to be marketed under the brand name Maviret.

Studies presented at this year's International Liver Congress showed that glecaprevir/pibrentasvir cured 99% of people with hepatitis C with multiple HCV genotypes, as well as 95% of people with hard-to-treat genotype 3.

Continue reading......

Recommended Reading

July 14, 2017

The relationship between hepatitis C infection and hepatic steatosis.

Metabolic Manifestations of Hepatitis C Virus

Lawrence Serfaty

Key Points
Out of excessive alcohol consumption, steatosis should be classified into 2 types according to hepatitis C virus (HCV) genotypes: metabolic steatosis, which is associated with features of metabolic syndrome and insulin resistance in patients infected with nongenotype 3, and viral steatosis, which is correlated with viral load and hyperlipemia in patients infected with genotype 3.

HCV interacts with host lipid metabolism by several mechanisms, such as promotion of lipogenesis, reduction of fatty acid oxidation, and decreases of lipids export, leading to hepatic steatosis and hypolipidemia.

A strong link between HCV infection and diabetes mellitus has been found in subject based studies and, to a lesser degree, in population-based studies.

Download PDF.

The above link was provided by @HenryEChang via Twitter, view an index of all HCV extrahepatic manifestations.

Video - March 2017

Genotype 3 Infection - Identification of the Best Direct-Acting Antiviral Regimen for Patients With Hepatitis C Virus
Drs. Drenth and Berden discuss their manuscript "Identification of the Best Direct-Acting Antiviral Regimen for Patients With Hepatitis C Virus Genotype 3 Infection: A Systematic Review and Network Meta-analysis."

HCV Advocate

Clinical Trials Reference Guide
Users can search for a hepatitis C clinical trial by category (genotype), or learn how to evaluate a clinical trial and become familiar with commonly used terms. HCV Advocate offers an easy to navigate HCV Medications Blog as well, organized by HCV genotype

Stay Updated

Sift through a collection of research articles related to treating HCV according to genotype.

Sofosbuvir, Velpatasvir and Voxilaprevir combination for the treatment of hepatitis C- Review Article

Expert Rev Gastroenterol Hepatol. 2017 Jul 4. doi: 10.1080/17474124.2017.1351295.
[Epub ahead of print]

Sofosbuvir, Velpatasvir and Voxilaprevir combination for the treatment of hepatitis C
Rebecca Voaklander & Ira M Jacobson

Received 19 Apr 2017, Accepted 03 Jul 2017, Accepted author version posted online: 04 Jul 2017

Full Text Article
Download PDF

Abstract

Introduction

The advent of direct-acting antiviral (DAA) treatments for chronic hepatitis C virus (HCV) infection has dramatically increased rates of cure. However, there remain difficult-to-treat populations, including patients with genotype 3 infection and cirrhosis, and limited salvage treatment options for those that have failed first-line DAA therapy.

Areas covered

This is a review of the preclinical and clinical development of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), an interferon-free, oral, once daily, pangenotypic treatment for chronic HCV infection. All relevant literature from 2015 through June of 2017 is included.

Expert commentary

Voxilaprevir, a second-generation HCV protease inhibitor, in combination with the already approved combination of sofosbuvir and velpatasvir, was evaluated in the POLARIS trials and found to be a safe and effective regimen. Patients with prior DAA treatment failure, genotype 3, cirrhosis and/or unfavorable resistance profiles all achieved cure rates of 96% or greater. The most distinctive role for this potent regimen may prove to be as a salvage regimen for patients who have failed previous DAA therapy.

Full Text Article
PDF link provided by Henry E. Chang via Twitter.
I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C.

Hepatitis C Therapies Perform Well in Challenging Patients

Medscape Coverage from
Digestive Disease Week (DDW) 2017

Hepatitis C Therapies Perform Well in Challenging Patients
William F. Balistreri, MD

At this year's Digestive Disease Week, several studies looked into the nuances of treating hepatitis C virus (HCV)infection. Of particular interest were new data regarding difficult-to-treat groups and the validation of shorter, simpler regimens

Glecaprevir and PibrentasvirIn several phase 2 and 3 clinical trials, patients who received the pangenotypic direct-acting antivirals (DAAs) glecaprevir (GLE) and pibrentasvir (PIB) achieved sustained virologic response (SVR) rates of 92%-100% across all six major HCV genotypes...

Sofosbuvir/Velpatasvir/Voxilaprevir
A pangenotypic combination of sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) was designed to inhibit three distinct HCV targets: the NS5B polymerase, the NS5A protein, and NS3/4A protease, respectively.

Flamm and colleagues^[3] presented cumulative data from 1056 patients with and without compensated cirrhosis who were infected with HCV genotype 1-6 and treated with the once-daily fixed-dose combination tablet of SOF/VEL/VOX in phase 3 studies....

Continue reading....

Free registration required

Pangenotypic regimens and the next generation hepatitis C virus therapy

The latest issue of Clinical Liver Disease
Clinical Liver Disease (CLD) is a digital educational resource published on behalf of the American Association for the Study of Liver Diseases (AASLD). CLD publishes easy to read reviews on relevant topics for clinicians diagnosing and managing patients with liver disease. Each article is accompanied by a podcast audio version, and a video interview with the author to help emphasize the key teaching points for a clinical audience.

Issue Publication: June 2017
Volume 9, Issue 6 Pages 131 - 149, June 2017

Reviews
Hepatitis C
Guest Edited by Andrew Muir, MD
Pangenotypic regimens and the next generation hepatitis C virus therapy (pages 131–133)
Nancy S. Reau
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.635
Three new antiviral therapies for viral hepatitis C are anticipated in the next several months: GP, glecaprevir (protease inhibitor [PI])/pibrentasvir (NS5A inhibitor); SOF/VEL/VOX, sofosbuvir (NS5B inhibitor)/velpatasvir (NS5A)/voxilaprevir (NS3); and MK3, grazoprevir (NS3) + MK-3682 (NS5B) + NS5A inhibitor (elbasvir or Ruzasvir).

Each is a pangenotypic all-oral fixed dose combination (FDC) with high potency and efficacy against common NS3 and NS5A polymorphisms. Multiple safety and efficacy abstracts were presented at the 67th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in November 2016. In this article, I will address why we need new therapies as well as what is still unaddressed in the arsenal against hepatitis C.
Watch a video presentation of this article
Watch the interview with the author
Full Text (HTML)
PDF (140.1KB) 

Noninvasive Diagnosis of Liver Fibrosis in Children and Adults
Guest Edited by Naim Alkhouri, MD and Jean Molleston, MD
Putting it all together: Noninvasive diagnosis of fibrosis in nonalcoholic fatty liver disease in adults and children (pages 134–137)
Naim Alkhouri
Multiple noninvasive tests have been developed and validated in the adult NAFLD population to predict the stage of fibrosis.[6] These tests are being widely used by gastroenterologists and hepatologists to risk-stratify patients with NAFLD without the need for liver biopsy. These tests can be divided into one of three categories: simple fibrosis scores that can be calculated from readily available clinical variables, complex fibrosis scores that rely on measuring serum biomarkers of fibrosis and extracellular matrix turnover, and imaging studies that are based on measuring liver stiffness as an indirect way to determine fibrosis stage.
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.636
Watch a video presentation of this article
Watch the interview with the author
Full Text (HTML)
PDF (178.2KB)  

Antifibrotic therapies in liver disease: Ready for primetime? (pages 138–140)
David A. Rudnick
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.641
Watch a video presentation of this article
Watch the interview with the author

LT in the High MELD Era: Perioperative Management of the Critically Ill Patient
Guest Edited by Julie Heimbach, MD and Michael Schilsky, MD
Transplantation for acute alcoholic hepatitis (pages 141–143)
Patrizia Burra and Giacomo Germani
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.629
Watch a video presentation of this article
Watch the interview with the author

The Practice of Hepatology in a Non-Traditional Setting
Guest Edited by Mitchell Shiffman, MD
Contrasting the academic and nonacademic hepatology practice settings (pages 144–146)
Alexander T. Lalos and Coleman I. Smith
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.638
Watch a video presentation of this article
Watch the interview with the author

Developing clinical research in a clinical hepatology practice (pages 147–149)
Oren K. Fix, Terri Spinelli and Kris V. Kowdley
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.639
Watch a video presentation of this article
Watch the interview with the author

Begin here.....

HCV Treatment Options in 2017/2018: What’s Here and What’s Coming Soon

HCV Treatment Options in 2017/2018: What’s Here and What’s Coming Soon
Clinical Care Options
*Free registration required

Greetings, hope everyone had a great weekend! When new research articles or educational resources related to managing and treating viral hepatitis become available a link to the activity is provided with a short description, view previous programs here.  

What's New

Recently published over at Clinical Care Options, Ira M. Jacobson, MD, and Norah Terrault, MD, MPH present an update on current and future HCV therapies.

HCV Treatment Options in 2017/2018: What’s Here and What’s Coming Soon

Coming Soon At Clinical Care Options
Video Modules
Initial HCV Therapy
Challenging Cases
Begin here.....

Hepatitis C: AbbVies MAVIRET (glecaprevir/pibrentasvir) and Gilead’s Vosevi (Sofosbuvir/Velpatasvir/Voxilaprevir) Receives CHMP Positive Opinion

AbbVies  MAVIRET (glecaprevir/pibrentasvir) and Gilead’s Vosevi (Sofosbuvir/Velpatasvir/Voxilaprevir) Receives CHMP Positive Opinion

Two new medicines recommended for the treatment of chronic hepatitis C

Maviret and Vosevi evaluated under accelerated assessment

The European Medicines Agency has recommended granting marketing authorisations in the European Union (EU) for Maviret and Vosevi, two new medicines indicated for the treatment of chronic hepatitis C virus (HCV) infection in adults.

HCV infection is a major public health challenge. It affects between 0.4% and 3.5% of the population in different EU Member States and is the most common single cause of liver transplantation in the EU. Approximately 15 million people are chronically infected with HCV throughout Europe.

Both Maviret and Vosevi are active against all genotypes of the virus and, with some differences between the two medicines, may be specifically useful in some patients who failed or cannot use previously available therapies. As this is considered to be of major public health interest in terms of therapeutic innovation, both medicines were evaluated under the EU’s accelerated assessment mechanism, which aims to speed up patients’ access to new medicines where there is an unmet medical need.

Maviret and Vosevi belong to the direct acting antivirals against HCVs which have reshaped the way chronic HCV infection is treated. By blocking the action of proteins essential for HCV replication, this type of medicine achieves high cure rates of the infection and does not require the concomitant use of interferons, medicines which are associated with poor tolerability and potentially serious side effects.

Despite the rapid development of new therapies there is still a need for a range of alternative treatment options to serve the different medical needs of the millions of people suffering from the disease. The more treatment options that are available, the better chance a patient has to get the right treatment to cure the disease and to lead a longer and healthier life.

Maviret and Vosevi are the first medicines for which accelerated assessment has been carried out within 120 days, after a recent review of the timetable for this mechanism.

Maviret contains two next generation direct-acting and antiviral agents: glecaprevir, an inhibitor of HCV NS3/4A protease, and pibrentasvir, an inhibitor of HCV NS5A. Both components are pangenotypic.

The effects of Maviret were studied in a total of 2,376 patients who participated in eight pivotal and three supportive clinical trials. The hepatitis C virus could no longer be detected in over 90% of patients 12 weeks after the end of treatment. If the blood of patients is clear of hepatitis C virus for more than 12 weeks they are generally considered as being cured of the infection. Adverse events reported with Maviret were generally mild, including headache, fatigue, diarrhoea, nausea and abdominal pain.

The applicant for Maviret received scientific advice from the Agency during the development of the medicine.

Vosevi is composed of sofosbuvir (a nucleotide analogue non-structural protein NS5B polymerase inhibitor), velpatasvir (an HCV NS5A inhibitor), which were previously approved in other medicinal product, to which is added voxilaprevir (a novel pangenotypic HCV NS3/4A protease inhibitor).

The effects of Vosevi were studied in four main clinical trials involving over 1,700 patients. Two studies were in previously untreated patients and two in patients in whom previous treatment (in some cases with an NS5A inhibitor) had not cleared the virus. Treatment was given for 12 weeks in the previously treated patients and eight weeks in the untreated. The hepatitis C virus could no longer be detected in over 90% of patients 12 weeks after the end of treatment with Vosevi. Mild nausea, headache and diarrhoea were the most common side effects observed. Other potentially related adverse effects were decreased appetite, vomiting, muscle spasms and rash.

The opinions adopted by the CHMP at its June 2017 meeting are an intermediary step on Maviret's and Vosevi’s path to patient access. The CHMP opinions will now be sent to the European Commission for the adoption of decisions on EU-wide marketing authorisations through an accelerated procedure. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of these medicines in the context of the national health system of that country.

Notes
The applicant for Maviret is AbbVie Ltd.
The applicant for Vosevi is Gilead Sciences International Ltd.

http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2017/06/news_detail_002768.jsp&mid=WC0b01ac058004d5c1

Press Release
European CHMP Adopts Positive Opinion for Gilead’s Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir) for the Treatment of All Chronic Hepatitis C Genotypes

– Vosevi is Gilead’s Fourth Sofosbuvir-Based Treatment to Receive CHMP Positive Opinion for the Treatment of Chronic HCV Infection –

  

FOSTER CITY, Calif.--(BUSINESS WIRE)--Jun. 23, 2017-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion on the company’s Marketing Authorization Application (MAA) for Vosevi^®, an investigational, once-daily, single tablet regimen of sofosbuvir 400 mg, velpatasvir 100 mg, and voxilaprevir 100 mg (SOF/VEL/VOX) for the treatment of chronic hepatitis C virus (HCV)-infected patients. The data included in the application support the use of SOF/VEL/VOX in patients with and without compensated cirrhosis, with all genotypes (GT1-6) of HCV infection regardless of prior therapy, including 8 weeks of treatment for HCV direct-acting antiviral (DAA)-naïve patients without cirrhosis, as well as 12 weeks of treatment for patients who have previously failed therapy with a DAA-containing regimen.
  
The CHMP positive opinion was adopted following an accelerated assessment procedure, reserved for medicinal products expected to be of major public health interest. The recommendation will now be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union, Norway and Iceland.
  
The MAA for SOF/VEL/VOX is supported by data from four Phase 3 studies. Two studies (POLARIS-1 and POLARIS-4), evaluated 12 weeks of the single tablet regimen in patients with genotypes 1-6 HCV infection previously treated unsuccessfully with DAA-containing regimens, including NS5A inhibitors. Two other studies (POLARIS-2 and POLARIS-3) evaluated 8 weeks of SOF/VEL/VOX in DAA-naïve patients with genotypes 1-6 HCV infection. Across POLARIS-1 and POLARIS-4, 97 percent of patients treated with SOF/VEL/VOX (n=431/445) achieved the primary efficacy endpoint of SVR12. In POLARIS-2, 95 percent of patients with genotypes 1-6 HCV infection with and without cirrhosis treated with SOF/VEL/VOX (n=477/501) achieved the primary efficacy endpoint of SVR12. In POLARIS-3, 96 percent of patients with genotype 3 infection and cirrhosis treated with SOF/VEL/VOX (n=106/110) achieved the primary efficacy endpoint of SVR12. The most common adverse events among patients who received SOF/VEL/VOX in the POLARIS studies were headache, fatigue, diarrhea and nausea.
  
Sofosbuvir as a single agent was granted marketing authorization in the European Union on January 16, 2014, under the trade name Sovaldi^®, for use in combination with other agents. The single tablet regimen of sofosbuvir (400 mg) and ledipasvir (90 mg) received marketing authorization in the European Union on November 18, 2014, under the trade name Harvoni^®. The single tablet regimen of sofosbuvir (400 mg) and velpatasvir (100 mg) received marketing authorization in the European Union on July 8, 2016, under the trade name Epclusa^®.
  
Gilead has also submitted a regulatory application for SOF/VEL/VOX in the United States. Gilead filed the New Drug Application for SOF/VEL/VOX on December 8, 2016, and the Food and Drug Administration (FDA) has set a target action date under the Prescription Drug User Fee Act of August 8, 2017.
  
SOF/VEL/VOX is an investigational product and its safety and efficacy has not been established and is not approved anywhere globally.
http://www.gilead.com/news/press-releases/2017/6/european-chmp-adopts-positive-opinion-for-gileads-vosevi-sofosbuvirvelpatasvirvoxilaprevir-for-the-treatment-of-all-chronic-hepatitis-c-genotypes

Press Release

AbbVie Receives CHMP Positive Opinion for MAVIRET™ (glecaprevir/pibrentasvir) for the Treatment of Chronic Hepatitis C in All Major Genotypes (GT1-6)

- If approved, MAVIRET™ will provide a shorter, 8-week, pan-genotypic (GT1-6), once-daily option for the majority of people living with the hepatitis C virus (HCV)(1)*
- MAVIRET would also be an additional HCV treatment option for patients with specific treatment challenges, such as those with compensated cirrhosis, chronic kidney disease and genotype 3
- Final European Commission decision expected Q3 2017

NORTH CHICAGO, Ill., June 23, 2017 /PRNewswire/ -- AbbVie ABBV 0.32%, a global biopharmaceutical company, today announced that the European Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted a positive opinion recommending marketing authorization of MAVIRET™ (glecaprevir/pibrentasvir), an investigational, pan-genotypic treatment for adults with chronic hepatitis C virus (HCV) infection. If approved, MAVIRET will be a once-daily, ribavirin-free, 8-week option for patients without cirrhosis and who are new to treatment across all genotypes (GT1-6), who comprise the majority of people living with HCV.¹ The European Commission will now review the CHMP opinion and a final decision is expected in Q3 2017.

"MAVIRET represents a new generation of HCV therapy and has the potential to be a shorter, 8-week option for patients living with this serious, chronic illness," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "Today's CHMP positive opinion takes us closer to delivering on AbbVie's mission to address continued unmet needs by bringing a new pan-genotypic option to people living with HCV in Europe."

The CHMP positive opinion is supported by 97.5 percent (n=807/828) SVR₁₂ rates with 8 weeks of MAVIRET across GT1-6 chronic HCV infected patients without cirrhosis and who are new to treatment, with varied patient and viral characteristics.² In an integrated analysis (n=2,265), less than 0.4 percent of patients discontinued treatment.³ The reported adverse reactions (incidence greater than or equal to 10 percent) were headache and fatigue.³ The type and severity of adverse reactions in patients with cirrhosis were overall comparable to those seen in patients without cirrhosis.³

"While the HCV treatment landscape has transformed significantly over recent years, the disease continues to be a global public health problem and treatment challenges remain," said Stefan Zeuzem, M.D., chief of the department of medicine at the J.W. Goethe University Hospital in Frankfurt, Germany. "In clinical studies, MAVIRET demonstrated high SVR rates across all genotypes of HCV patients (GT1-6). If approved, MAVIRET would remove many of the complexities of pre-treatment patient evaluation and has the potential to help facilitate the care and management of HCV."

MAVIRET is also intended to be an additional option for patients with specific treatment challenges. This includes chronic HCV patients with compensated cirrhosis (Child-Pugh A), and those who currently have limited treatment options, such as patients with severe chronic kidney disease, including those on dialysis, and patients infected with genotype 3.

The marketing authorization application (MAA) for MAVIRET is under an accelerated assessment by the EMA, which is granted to new medicines of major public health interest. The MAA evaluation is conducted under the centralized licensing procedure, and if approved, will result in a marketing authorization valid in all 28 member states of the European Union, as well as Iceland, Liechtenstein and Norway. AbbVie's investigational, pan-genotypic regimen has also been granted accelerated review designations by other regulatory authorities including the U.S. Food and Drug Administration and Japanese Ministry of Health, Labour and Welfare. MAVIRET is an investigational regimen and its safety and efficacy have not been established. 

About MAVIRET™ (glecaprevir/pibrentasvir)
AbbVie's MAVIRET™ (glecaprevir/pibrentasvir) clinical development program was designed to investigate a pan-genotypic, once-daily, ribavirin-free treatment with the potential to provide a faster path to virologic cure** for all major HCV genotypes (GT1-6) and with the goal of addressing specific treatment challenges, including compensated cirrhosis (Child-Pugh A), chronic kidney disease and genotype 3. MAVIRET is being evaluated as a potential 8-week, pan-genotypic treatment for the majority of people living with HCV,¹ those without cirrhosis and who are new to treatment,* and regardless of viral and patient characteristics.

MAVIRET is a fixed-dose combination of two distinct antiviral agents: glecaprevir (100mg), an NS3/4A protease inhibitor, and pibrentasvir (40mg), an NS5A inhibitor, dosed once-daily as three oral tablets.

Glecaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals ENTA 1.16% for HCV protease inhibitors and regimens that include protease inhibitors.

*Patients who are treatment-naive or had prior treatment experience with IFN-based treatments ([peg]IFN +/- RBV or SOF/RBV +/- pegIFN).
**Patients who achieve a sustained virologic response at 12 weeks post treatment (SVR₁₂) are considered cured of hepatitis C. 
http://www.prnewswire.com/news-releases/abbvie-receives-chmp-positive-opinion-for-maviret-glecaprevirpibrentasvir-for-the-treatment-of-chronic-hepatitis-c-in-all-major-genotypes-gt1-6-630334863.html

Investigational Hepatitis C Drugs Show Promising Results

Investigational Hepatitis C Drugs Show Promising Results

By Barbara Jungwirth

From TheBodyPRO.com

June 20, 2017

Newer hepatitis C (HCV) drugs have shown very good sustained viral response (SVR) rates and little risk of resistance-associated substitutions, David L. Wyles, M.D., of Denver Health Medical Center reported in an International Antiviral Society-USA (IAS-USA) webinar.

He summarized studies on various direct-acting antiviral agents (DAAs) from the recent International Liver Congress (EASL) in Amsterdam.
Continue reading...

Medscape - Early Look at Two New Hepatitis C Pangenotypic Therapies

Medscape Coverage from
Digestive Disease Week (DDW) 2017

COMMENTARY
Early Look at Two New Hepatitis C Pangenotypic Therapies
Digestive Disease Week (DDW) 2017
Nancy S. Reau, MD

Despite the incredible evolution in hepatitis C (HCV) therapeutics, much remains to be done to affect the incidence, prevalence, and morbidity caused by this silent but curable disease. Several presentations at the recent Digestive Disease Week (DDW) meeting offer new perspectives in screening, reinfection, and therapy.

Risk-based screening was the primary way to identify individuals with chronic HCV until 2012, when the Centers for Disease Control and Prevention released recommendations to screen Americans born between 1945 and 1965, the birth cohort with the highest prevalence of chronic HCV and the most chronically infected with advanced fibrosis.
Continue reading.....

Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection

New England Journal of Medicine

Full Text PDF Download

http://freepdfhosting.com/1fcc820940.pdf?platform=hootsuite

Abstract

Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection

Marc Bourlière, M.D., Stuart C. Gordon, M.D., Steven L. Flamm, M.D., Curtis L. Cooper, M.D., Alnoor Ramji, M.D., Myron Tong, M.D., Natarajan Ravendhran, M.D., John M. Vierling, M.D., Tram T. Tran, M.D., Stephen Pianko, M.D., Meena B. Bansal, M.D., Victor de Lédinghen, M.D., Robert H. Hyland, D.Phil., Luisa M. Stamm, M.D., Ph.D., Hadas Dvory-Sobol, Ph.D., Evguenia Svarovskaia, Ph.D., Jie Zhang, Ph.D., K.C. Huang, Ph.D., G. Mani Subramanian, M.D., Diana M. Brainard, M.D., John G. McHutchison, M.D., Elizabeth C. Verna, M.D., Peter Buggisch, M.D., Charles S. Landis, M.D., Ph.D., Ziad H. Younes, M.D, Michael P. Curry, M.D., Simone I. Strasser, M.D., Eugene R. Schiff, M.D., K. Rajender Reddy, M.D., Michael P. Manns, M.D., Kris V. Kowdley, M.D., and Stefan Zeuzem, M.D., for the POLARIS-1 and POLARIS-4 Investigators^*

N Engl J Med 2017; 376:2134-2146

June 1, 2017 DOI: 10.1056/NEJMoa1613512

Background
Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options.

Methods
We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir–velpatasvir–voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir–velpatasvir–voxilaprevir (163 patients) or sofosbuvir–velpatasvir (151 patients) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir–velpatasvir–voxilaprevir group.

Results
In the three active-treatment groups, 46% of the patients had compensated cirrhosis. In POLARIS-1, the rate of sustained virologic response was 96% with sofosbuvir–velpatasvir–voxilaprevir, as compared with 0% with placebo. In POLARIS-4, the rate of response was 98% with sofosbuvir–velpatasvir–voxilaprevir and 90% with sofosbuvir–velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea. In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower.

Conclusions
Sofosbuvir–velpatasvir–voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed. (Funded by Gilead Sciences; POLARIS-1 and POLARIS-4 ClinicalTrials.gov numbers, NCT02607735 and NCT02639247.)

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Abstract Source
http://www.nejm.org/doi/full/10.1056/NEJMoa1613512?query=featured_home

NEJM Journal Watch - Commentary On The Article

When DAA Treatment for Hepatitis C Fails, 3-Drug Regimen "Highly Effective"

By Kelly Young
Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, DFASAM
The combination of sofosbuvir, velpatasvir, and voxilaprevir is effective for hepatitis C in patients with virologic failure after direct-acting antiviral agent (DAA) treatment, according to two phase 3, industry-funded trials in the New England Journal of Medicine.

For POLARIS-1, roughly 300 patients with genotype-1 hepatitis C infection whose prior NS5A-inhibitor treatment had failed were randomized to either daily sofosbuvir-velpatasvir-voxilaprevir or placebo for 12 weeks. An additional 100 patients with non-genotype 1 infection were enrolled in the treatment group.

For POLARIS-4, over 300 patients with hepatitis C who had taken a direct-acting antiviral other than an NS5A inhibitor were randomized to receive sofosbuvir-velpatasvir with or without voxilaprevir.

Sustained virologic response 12 weeks after treatment ended was 96% for the POLARIS-1 treatment group (vs. 0% with placebo).

In POLARIS-4, the three-drug regimen had a 98% response rate, compared with 90% for sofosbuvir-velpatasvir. Sustained response rates were high for all genotypes.

Infectious disease expert Dr. Paul Sax comments: "This triple-therapy treatment strategy provides a highly effective option for that small proportion of patients who failed prior treatment for hepatitis C with non-interferon-based regimens. Although few in number, candidates for this treatment (and their clinicians) will welcome this treatment when it is FDA approved."
http://www.jwatch.org/fw112944/2017/06/01/when-daa-treatment-hepatitis-c-fails-3-drug-regimen

MEDPAGE TODAY
Triple-DAA Pill Offers HCV Retreatment Option
Most patients, all unsuccessful on previous DAA regimens, cleared the virus
combination of three drugs that act directly to block hepatitis C (HCV) replication successfully cured most patients who had previously failed therapy with such agents, researchers reported.

In two phase III trials, the investigational combination of sofosbuvir, velpatasvir, and voxilaprevir cleared the virus in 96% and 98% of patients, regardless of whether they had compensated cirrhosis or not, according to Marc Bourlière, MD, of Hôpital Saint-Joseph in Marseille, France, and colleagues.
Continue reading...

Media Coverage Of This Article

New Combo Pill Offers Hope to Hepatitis C Patients Who Fail Other Treatment

Updated: May 31, 2017 — 7:00 PM EDT

by Steven Reinberg HealthDay Reporter

WEDNESDAY, May 31, 2017 (HealthDay News) -- A pill that contains three powerful antiviral drugs might offer a cure for many hepatitis C patients who have failed other treatments, researchers report.

The pill -- which contains the antiviral drugs sofosbuvir (Sovaldi), velpatasvir and voxilaprevir -- was nearly 100 percent effective in curing hepatitis C in patients whose disease returned after treatment with other antiviral drugs, the researchers said.

"Currently, we have very good treatments for hepatitis C, and we are able to achieve a cure in over 90 percent of patients. So globally, although only a few patients relapse, it still is a significant number," said lead researcher Dr. Marc Bourliere, from the Hospital Saint Joseph in Marseilles, France.

This new pill is being developed as a rescue treatment for patients who have failed other therapy, he said. When it was used as an initial treatment in another study, the combination pill fared no better than the usual treatment, he added.

The data from these and other trials, funded by Gilead Sciences, the maker of the combination pill, is in the hands of the U.S. Food and Drug Administration, where it is undergoing the approval process, Bourliere said.

The bottom line, according to Bourliere, is: "We have other options even if you fail the first treatments."

The new combination pill is likely to be expensive. In 2014, Gilead introduced a combination drug for hepatitis C called Harvoni, which was priced at more than $1,000 a dose with a 12-week course of treatment running $94,500, the Associated Press reported.

Hepatitis is an inflammation of the liver that can be caused by several viruses, including hepatitis C. Hepatitis C is usually spread when blood from an infected person enters the body of someone not infected. Most people become infected with hepatitis C by sharing needles or other equipment to inject drugs, the U.S. Centers for Disease Control and Prevention says.

Approximately 75 percent to 85 percent of people who have hepatitis C will develop chronic infection. In the United States, as many as 4 million people have chronic hepatitis C, according to the CDC.

Many people infected with hepatitis C don't know they have it because they don't look or feel sick.

Chronic hepatitis C is serious and can result in long-term health problems, including liver damage, liver failure, liver cancer or death. Hepatitis C is the leading cause of cirrhosis and liver cancer, and the most common reason for liver transplantation in the United States.
In two, phase 3 trials, Bourliere and his colleagues treated patients with the combination pill or a placebo or other antiviral drugs.

In the first trial, 300 patients were randomly assigned to the combination pill or a placebo. These patients all had hepatitis C genotype 1. In addition, 114 patients with other genotypes of hepatitis C were given the combination pill. Patients took the pill daily for 12 weeks.

Among patients taking the combination pill, 96 percent responded to treatment. None on the placebo showed a response, the researchers found.

The second trial included 314 patients with hepatitis C genotypes 1, 2 or 3. All had failed other treatments, but hadn't been given a NS5A inhibitor, such as velpatasvir or daclatasvir. This group received either the combination pill (163 patients) or sofosbuvir-velpatasvir (151 patients).
In addition, 19 patients with genotype 4 hepatitis C were given the combination pill.

In this trial, 98 percent of the patients taking the combination pill responded to 12 weeks of treatment. And 90 percent of those who received sofosbuvir-velpatasvir responded to treatment, the findings showed.

The most common side effects were headache, fatigue, diarrhea and nausea, Bourliere said. Only 1 percent or fewer patients stopped treatment because of the side effects, he said.

Dr. David Bernstein is chief of hepatology at Northwell Health in Manhasset, N.Y. He called the new drug "a very important advance. This is really for salvage therapy. I don't think this is first-line therapy, but it gives hope to the people who fail the current therapies we have."
The report was published June 1 in the New England Journal of Medicine.

https://consumer.healthday.com/infectious-disease-information-21/hepatitis-news-373/new-combo-pill-offers-hope-to-hepatitis-c-patients-who-fail-other-treatment-723205.html

Emerging Therapies for Genotype 3 HCV

EASL 2017: Emerging Therapies for Genotype 3 HCV

Nancy Reau MD, FAASLD, AGAF - 5/12/2017

Genotype 3 HCV infection is concerning, not just because of its natural history but also because of its potential role in reinfection. New data from EASL offer promise for the treatment of this challenging patient population.

Experimental Pangenotypic Therapies
When we consider the data presented for the next wave of HCV therapy, I believe we are approaching this objective. The currently approved pangenotypic fixed-dose combination of sofosbuvir (SOF)/velpatasvir (VEL) for 12 weeks offers high cure rates (95%) for genotype 3 HCV infection regardless of cirrhosis status. The 3 pangenotypic therapies in development promise even more options..

Free registration required

https://www.clinicaloptions.com/Hepatitis.aspx

ILC 2017: SOF/VEL with or without VOX- High efficacy with investigational direct-acting antiviral treatment combination is accompanied with substantial gains in patient-reported outcomes

ILC 2017: High efficacy with investigational direct-acting antiviral treatment combination is accompanied with substantial gains in patient-reported outcomes

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High efficacy is accompanied with substantial gains in patient reported outcomes in cirrhotic patients with chronic hepatitis C treated with sofosbuvir (SOF), velpatasvir with or without voxilaprevir (VOX): Data from Polaris 1, 2, 3 and 4

Patients with Hepatitis C and cirrhosis experience the greatest improvements in patient-reported outcomes with sofosbuvir/velpatasvir with or without voxilaprevir compared to those without cirrhosis 

April 20, 2017, Amsterdam, The Netherlands:  Analysis of patient outcome data from the POLARIS-1, 2, 3 and 4 studies presented today demonstrate that patients with Hepatitis C virus (HCV) and cirrhosis experience the greatest improvement of patient-reported outcome (PRO) scores when taking treatment with sofosbuvir (SOF) + velpatasvir (VEL), with or without voxilaprevir (VOX), an anti-HCV regimen that has been shown to be safe and effective against all HCV genotypes in different populations. The analysis of the four studies, presented at The International Liver Congress™ 2017 in Amsterdam, The Netherlands, showed that achievement of sustained virologic response at 12 weeks (SVR12) was associated with significant improvements in PROs, which were more prominent in patients with cirrhosis than those without.

Hepatitis C is one of the most widespread transmissible diseases.1 HCV is a leading cause of chronic liver disease, end-stage cirrhosis and liver cancer.2 It is estimated to infect over 185 million people worldwide, of whom 350,000 die each year, with 84,000 of those being in Europe.3 In Europe, liver cirrhosis is responsible for 1–2% of all deaths,4 and was the leading cause of adult liver transplants between 1988 and 2013.5 Until the approval of direct-acting antiviral (DAA) drugs, HCV was treated with pegylated interferon alpha and ribavirin, which caused serious adverse effects in many patients, often leading to premature termination of therapy.1 DAAs have revolutionised treatment, as they are well tolerated and highly efficacious.6 

“This analysis showed that although patients with HCV and cirrhosis have significantly impaired patient-reported outcomes, they experience the greatest improvement during treatment with SOF/VEL with or without VOX, when compared to those without cirrhosis,” said Dr Zobair Younossi, Center for Liver Diseases, Washington, United States, and lead author of the study. “We also found that achieving a sustained virologic response with the drugs was associated with substantial gains in outcomes.”

This analysis combined data from 1,908 patients with chronic HCV who were enrolled in four Phase 3 studies (POLARIS 1 to 4) that assessed the efficacy and safety of SOF/VEL/VOX in the treatment of HCV-infected patients. Outcomes from 26 PRO domain scores relating to quality of life, fatigue, work productivity and activity impairment were assessed using questionnaires.     

The overall cure rate (SVR12) was 94% for patients with and without cirrhosis in both the SOF/VEL/VOX and SOF/VEL treatment groups. Patients with cirrhosis experienced significant improvements in their PRO scores compared to the start of treatment, which were similar or greater than those in patients without cirrhosis. Individuals with cirrhosis treated with placebo did not have any PRO improvements.    “Successful treatment of HCV-related cirrhosis with DAA therapy improves patient-reported outcomes, and this will certainly impact not only the direct but also the significant indirect costs linked to this progressive disease,” said Prof Francesco Negro, Divisions of Gastroenterology and Hepatology of Clinical Pathology, University Hospital of Geneva, Switzerland and EASL Governing Board Member.

POLARIS 1, 2, 3 and 4 POLARIS-1 was a double-blind, placebo-controlled study of SOF/VEL/VOX for 12 weeks in adults with chronic HCV infection who had been treated previously with DAA therapy.7 POLARIS-2 was an open-label study that randomised patients with chronic HCV infection who had not previously received DAA therapy to treatment with SOF/VEL/VOX for eight weeks or SOF/VEL for 12 weeks.8 POLARIS-3 was an open-label study that randomised patients with genotype 3 HCV infection and cirrhosis to receive SOF/VEL/VOX daily for eight weeks or SOF/VEL for 12 weeks.9 The open-label POLARIS-4 study randomised patients with chronic HCV infection who had previously received DAAs, but not an NS5A inhibitor (a DAA that is a protease inhibitor), to treatment with either SOF/VEL/VOX or SOF/VEL for 12 weeks.10

About The International Liver Congress™ This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ 2017 will take place from April 19 – 23, at the RAI Amsterdam, Amsterdam, The Netherlands.

About The European Association for the Study of the Liver (EASL) (www.easl.eu) Since its foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European Association with international influence, with an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Onsite location reference  
Session title: Late breaker posters Time, date and location of session: 08:00 – 18:00, Thursday 20 April – Saturday 22 April, Hall 1 Presenter: Zobair Younossi, United States of America Abstract: High efficacy is accompanied with substantial gains in patient reported outcomes in cirrhotic patients with chronic hepatitis C treated with sofosbuvir (SOF), velpatasvir with or without voxilaprevir (VOX): data from POLARIS 1, 2, 3 and 4 (LBP-544)

Author disclosures Research funds or consultation fees from BMS, Gilead Sciences, Intercept, Allergan and GSK.

References 1 World Health Organization. Access to new medicines in Europe: technical review of policy initiatives and opportunities for collaboration and research. March 2015. Available from: http://apps.who.int/medicinedocs/documents/s21793en/s21793en.pdf. Last accessed: April 2017.  2 Mühlberger N et al. HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health 2009;9:34. 3 World Health Organization. Hepatitis C in the WHO European Region Fact Sheet. July 2015. Available from: http://www.euro.who.int/__data/assets/pdf_file/0010/283357/factsheet-en-hep-c.pdf?ua=1. Last accessed: April 2017.  4 European Association for the Study of Liver. The burden of liver disease in Europe. A review of epidemiological data. Available from: http://www.easl.eu/medias/EASLimg/Discover/EU/54ae845caec619f_file.pdf. Last accessed: April 2017.  5 European Liver Transplant Registry. Specific results by disease. Available from: http://www.eltr.org/Specific-results-by-disease.html. Last accessed: April 2017.  6 Liang T, Ghany M. Current and future therapies for hepatitis C virus infection. N Engl Med 2013;369(7):679–680. 7 ClinicalTrials.gov. NCT02607735. Safety and efficacy of sofosbuvir/velpatasvir/voxilaprevir in adults with chronic HCV infection who have previously received treatment with directacting antiviral therapy (POLARIS-1). Available from: https://clinicaltrials.gov/ct2/show/NCT02607735. Last accessed: April 2017.  8 ClinicalTrials.gov. NCT02607800. Safety and efficacy of sofosbuvir/velpatasvir/voxilaprevir and sofosbuvir/velpatasvir in adults with chronic HCV infection who have not previously received treatment with direct-acting antiviral therapy (POLARIS-2). Available from: https://clinicaltrials.gov/ct2/show/NCT02607800. Last accessed: April 2017.  9 ClinicalTrials.gov. NCT02639338. Safety and efficacy of SOF/VEL/VOX FDC for 8 weeks and SOF/VEL for 12 weeks in adults chronic genotype 3 HCV infection and cirrhosis. Available from: https://clinicaltrials.gov/ct2/show/NCT02639338. Last accessed: April 2017.  10 ClinicalTrials.gov. NCT02639247. Safety and efficacy of SOF/VEL/VOX FDC for 12 weeks and SOF/VEL for 12 weeks in DAA-experienced adults with chronic genotype HCV infection who have not received an NS5A inhibitor. Available from: https://clinicaltrials.gov/ct2/show/NCT02639247. Last accessed: April 2017.

Recommended reading @ Healio - International Liver Congress- Three HCV drugs may not be better than two

International Liver Congress
Updates On This Blog

International Liver Congress/Healio - Three HCV drugs may not be better than two

Expert: Three HCV drugs may not be better than two
AMSTERDAM — The benefits of both double and triple direct-acting antiviral therapy combinations depend on myriad patient and disease factors, according to findings presented at the International Liver Congress.

Pawlotsky ran down a laundry list of agents in the pipeline, including NS5A inhibitors odalasvir (Achillion), pibrentasvir (AbbVie), and ruzasvir (Merck), and NS5B inhibitors AL-335 (Achillion), pibrentasvir (AbbVie) and uprifosbuvir (Merck). Although trials are currently underway, he suggested that ruzasvir has improved on previous compounds. “This drug has a virtually no resistance in vitro,” he said, noting that the resistance barrier was lower than Daklinza (daclatasvir, Bristol-Myers Squibb) or ledipasvir (Gilead). “You can see we’re making progress.”
Continue reading....

Recommended Reading
See more from International Liver Congress

In Case You Missed It - Review Gilead's HCV Investigational Regimen Sofosbuvir/Velpatasvir/Voxilaprevir

Review Sofosbuvir/Velpatasvir/Voxilaprevir

It can be overwhelming trying to sift through research about newly approved or investigational agents to treat HCV, especially if you were recently diagnosed with hepatitis C. Hopefully, this short review will give you a better understanding of cure rates for Gilead's pan-genotypic fixed-dose combination tablet consisting of Sofosbuvir/Velpatasvir/Voxilaprevir - that sure is a mouthful. Gilead's regimen has been shown to be highly effective in treatment-naive and treatment-experienced patients with HCV genotype 1–6. This is good news for people who have treated previously with direct-acting antivirals but relapsed. I'm sure you all know that in December Gilead submitted a new drug application (NDA) to the U.S. Food and Drug Administration, and in January Sofosbuvir/Velpatasvir/Voxilaprevir was granted an Accelerated Assessment by the European Medicines Agency.  The fixed-dose combination 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.

Lets start with expert commentary (video with slides) discussing the 3 drug regimen using data presented at the American Association for the Study of Liver Diseases (AASLD) annual meeting in November, the program is available online at ViralEd.

Show Me A Video - Sofosbuvir/Velpatasvir/Voxilaprevir.
Listen to Dr. Dieterich review and discuss Sofosbuvir/Velpatasvir/Voxilaprevir, in this short in-depth ten minute segment, over at ViralEd.

View the program with Dr. Dieterich, here......

Download Slides from the presentation, here.....

Watch the entire presentation; The Advances in Chronic Hepatitis C: Management and Treatment

Highlights Include

POLARIS-2 Study

Genotype 1–6

A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevirfor 8 Weeks Compared to Sofosbuvir/Velpatasvir for 12 Weeks in DAA-Naïve Genotype 1–6 HCV Infected Patients

Genotype 3

The POLARIS-3 Study

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

April 2017
The European Association for the Study of the Liver (EASL) International Liver Congress (ILC 2017) will take place April 19-23 in Amsterdam
Hep C 5-minute videos - Summary Of The International Liver Congress™ (ILC) 2017

On this page of the blog visitors are provided with an index of links pointing to comprehensive coverage of the meeting.  Start by viewing a short video series over at Practice Point presented by Dr. Tran, highlights include clinical studies on new antiviral therapy, data on drug toxicity/adverse events, drug interactions, and strategies for HCV management. On May 1, ViralEd will launch: The Advances in Chronic Hepatitis C: Management and Treatment, a comprehensive program featuring HCV experts reviewing and discussing the most important studies on chronic hepatitis C presented at EASL 2017. Other videos include EASL press conference, and opening ceremony.

Data submitted in Gilead's NDA

What Data Was Used In The New Drug Application (NDA)
The following data supports the use of the regimen for 12 weeks in DAA treatment experienced patients with HCV genotype 1 - 6 who have or don’t have liver cirrhosis.

The NDA for SOF/VEL/VOX is based on data from two Phase 3 studies (POLARIS-1 and POLARIS-4). The NDA is further supported by two additional Phase 3 studies (POLARIS-2 and POLARIS-3)

Show Me The Data
Phase 3 POLARIS trials, included people who were previously treated with direct-acting antivirals and those with hepatitis C virus (HCV) genotype 3 and compensated cirrhosis.

In POLARIS-1, 96% of NS5A-experienced patients with HCV genotypes 1-6 were cured with 12 weeks of sofosbuvir/velpatasvir/voxilaprevir, compared with none of the placebo recipients.

POLARIS-4 showed that the triple combination for 12 weeks worked better than a dual combination of sofosbuvir/velpatasvir for DAA-experienced patients who had not used NS5A inhibitors (SVR12 97% vs 90%).

POLARIS-3 demonstrated that 8 weeks of sofosbuvir/velpatasvir/voxilaprevir worked as well as 12 weeks of sofosbuvir/velpatasvir for patients with hard-to-treat genotype 3 and liver cirrhosis.

However POLARIS-2, with a more diverse group of mostly non-cirrhotic DAA-naive patients with genotypes 1-6, did not reach the threshold for non-inferiority.

Study		Population		Genotype		Treatment		Duration		SVR12 Rates
POLARIS-1		NS5A inhibitor-experienced 41 percent (172/415) had cirrhosis		1, 2, 3, 4, 5, 6		SOF/VEL/VOX		12 Weeks		96% (253/263)
						Placebo		12 Weeks		0% (0/152)
POLARIS-4		DAA-experienced (No NS5A inhibitor) 46 percent (153/333) had cirrhosis		1, 2, 3, 4		SOF/VEL/VOX		12 Weeks		97% (177/182)
						SOF/VEL		12 Weeks		90% (136/151)
POLARIS-2		DAA-naïve 18 percent (174/941) had cirrhosis		1, 2, 3, 4, 5, 6		SOF/VEL/VOX		8 Weeks		95% (476/501)
						SOF/VEL		12 Weeks		98% (432/440)
POLARIS-3		DAA-naïve All had cirrhosis		3		SOF/VEL/VOX		8 Weeks		96% (106/110)
						SOF/VEL		12 Weeks		96% (105/109)

Source - http://hivandhepatitis.com/hcv-treatment/experimental-hcv-drugs/5891-new-triple-combo-cures-most-daa-experienced-and-hard-to-treat-hepatitis-c-patients-without-ribavirin

Summary
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.

In The Journals

HCV Genotype 1
Abstract
Published in Hepatology 2017 Feb 21,  Sofosbuvir-velpatasvir-voxilaprevir with or without ribavirin in DAA-experienced patients with genotype 1 HCV.

Media Coverage of this study: Source - Hepatitis: Monthly Essentials March 2017

Takeaway

• Once-daily sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX) tablets show high efficacy as salvage therapy for HCV-1 after failure of direct-acting antivirals (DAAs).

Key results

• Most patients (88%) had received only 1 prior regimen; 41% had previously received an NS5A inhibitor±another DAA; 20% had been exposed to ≥3 DAA classes.
• Of 48 patients with baseline deep-sequencing data, 73% had resistance-associated substitutions (RAS; 27% had multiple-class RASs).
• SVR12 with SOF/VEL/VOX±ribavirin (RBV) was 96% and 100%, respectively.
• 1 relapse occurred in a patient with HCV-1a, cirrhosis, and VEL-associated NS5A L31M RASs.
• The most common adverse events with SOF/VEL/VOX were diarrhea and bronchitis.
• With SOF/VEL/VOX+RBV, fatigue, anemia, gastroenteritis, and nausea were most common.

Study design

• Phase 2 monocentric US open-label randomized study of 49 patients with DAA-refractory HCV-1 (1a, 88%; 51% had cirrhosis).
• Participants received a 12-wk regimen of SOF/VEL/VOX with (n=25) and without (n=24) RBV.
• Primary endpoint was sustained virologic response at 12 wk posttherapy (SVR12).
• Funding: Gilead Sciences.

Recommended Reading

April 28, 2017

8-week Sofosbuvir-velpatasvir-voxilaprevir Less Effective for HCV

By Lorraine L. Janeczko
NEW YORK (Reuters Health) - For patients with chronic hepatitis C virus (HCV) infection, eight weeks of combined sofosbuvir-velpatasvir-voxilaprevir may not be as effective as 12 weeks of only sofosbuvir-velpatasvir, results from two phase 3 open-label trials suggest.

But patients with HCV genotype 3 and cirrhosis may have similar rates of sustained virologic response (SVR) to either treatment, researchers report in Gastroenterology, online April 5.

"Among patients who have not been treated with direct-acting antiviral agents (DAAs), the triple regimen of the DAAs sofosbuvir/velpatasvir/voxilaprevir for eight weeks achieved very high rates of efficacy, curing 95% of patients with chronic HCV infection; however, it failed to achieve noninferiority against the 12-week regimen of sofosbuvir/velpatasvir, which cured 98% of patients," said lead author Dr. Ira M. Jacobson of the Icahn School of Medicine at Mount Sinai, in New York City.

Continue reading....

Fixed-Dose Sofosbuvir/Velpatasvir/Voxilaprevir Cures 97% of Treatment-Experienced Hepatitis C Patients

Discussion Forum
SOF/VEL and SOF/VEL/VOX

Other Investigational HCV Agents
Novel emerging treatments for hepatitis C infection: a fast-moving pipeline

National AIDS Treatment Advocacy Project (NATAP)
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?

Of Interest
Rapid Response from Barcelona: New Data in HCV Treatment
Healio Gastroenterology, March 2017
Source - http://www.healio.com/gastroenterology/education-lab/2016/05_may/rapid-response-from-barcelona-new-data-in-hcv-treatment/new-data-in-hcv-treatment

Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis, end-stage liver disease, hepatocellular carcinoma, and death from liver disease in the United States. Rapid advancements in the field and interferon-free regimens approved for HCV, as well as several on the horizon, offer improved outcomes, shorter treatment durations, and unique adverse event profiles; therefore, clinicians must stay informed of the evolving data to counsel patients appropriately. Clinicians face challenges regarding how to make treatment choices among the numerous interferon-free regimens to improve treatment uptake and optimize outcomes in patients with HCV. This roundtable discussion among leading experts in HCV was recorded immediately following the 2016 EASL meeting in Barcelona, Spain, exploring some of the most recent findings and addressing the evidence-based clinical application of these data for HCV patients.

For downloadable slides, please click here.

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Clinical Trials Reference Guide
Users can search for a hepatitis C clinical trial by category (genotype), or learn how to evaluate a clinical trial and become familiar with commonly used terms. HCV Advocate offers an easy to navigate HCV Medications Blog as well, organized by HCV genotype.

Happy St. Paddy's Day folks!