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.

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....

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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.....

The Changing HCV Landscape: Pangenotypic Regimens

Gastroenterology & Endoscopy News

Review Articles
MAY 18, 2017

The Changing HCV Landscape: Update on Treatment

Toward the Future: Pangenotypic Regimens
A novel once-daily RBV-free doublet regimen of ABT-493 (a protease inhibitor) and ABT-530 (an NS5A inhibitor) was studied in an intent-to-treat population of treatment-naive and treatment-experienced patients for 8 to 12 weeks (phase 2 SURVEYOR-1 and SURVEYOR-2). Both drugs are second-generation members of their respective classes, with pangenotypic coverage and coverage of most or all known RAVs relevant to their classes. The results are summarized as follows: SVR12 by 97% to 98% with 8 weeks of treatment in GT1 and GT2 noncirrhotic patients by intention-to-treat analysis,64 96% SVR12 in GT1 patients with cirrhosis treated for 12 weeks,65 and 100% SVR4 for patients with GT4-6 without cirrhosis treated for 12 weeks.66 Additional studies in GT3 patients yielded SVR12 in 97% of noncirrhotics treated for 8 weeks,67 and 100% in cirrhotics treated for 12 weeks.68 These data from phase 2 trials reflect the potential for this regimen to be available in the future as a truly pangenotypic regimen without RBV if phase 3 trials recapitulate these results. A fixed-dose coformulated regimen consisting of SOF-VEL and GS-9857 (a second-generation NS5A inhibitor) received breakthrough therapy designation by the FDA for the treatment of chronic GT1 patients who have previously failed an NS5A-containing regimen. Lawitz et al treated 128 GT1-6 patients, mostly with GT1-3, including 48% with cirrhosis for 12 weeks with the triplet regimen.69 Nearly 80% of patients had prior DAA exposure, including 63 of 63 GT1 patients (100%), and 60% had baseline RAVs. Overall, 127 of 128 (99%) attained SVR12, with the only virologic failure in a GT3 patient. Of 35 patients with prior NS5A exposure, all had SVR12.

Continue reading....

AbbVie takes aim at Gilead and BMS with 8-week hep C treatment

Of Interest

AbbVie takes aim at Gilead and BMS with 8-week hep C treatment
Richard Staines
AbbVie is aiming to steal sales from hep C drugs from Gilead and BMS with a new combination offering a shorter, eight-week treatment for the most difficult-to-treat form of the disease.

Results presented at the International Liver Congress (ILC) in Amsterdam showed 95% of genotype 3 patients on its pan-genotypic regimen of glecaprevir+pibrentasvir were free of disease, 12 weeks after completing an eight-week treatment course.

The results were based on a previously untreated, cirrhosis-free, 157-patient arm of the ENDURANCE-3 study.

Another arm of the trial also met its goal, matching the performance of BMS’ Daclinza(daclatasvir) plus Gilead’s Sovaldi (sofosbuvir) over 12 weeks in genotype 3.

The Daclinza and Sovaldi combination is current standard of care for genotype 3 hepatitis, but AbbVie is attempting to produce a more patient-friendly alternative with a shorter regimen.
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Hep C 5-minute videos - Summary Of The International Liver Congress™ (ILC) 2017

ILC 2017 Glecaprevir/pibrentasvir 95% SVR12 in HCV Geno 3 treatment naïve, non-cirrhotic patients

ILC 2017: Study demonstrates the efficacy of an investigational, pan-genotypic treatment in patients with a difficult to cure subgroup of Hepatitis C

Co-formulation of glecaprevir/pibrentasvir achieved a 95% SVR12 rate in treatment naïve, non-cirrhotic patients with chronic Hepatitis C virus genotype 3 

April 21, 2017, Amsterdam, The Netherlands: Study results presented today demonstrate that the oral, once-daily treatment regimen of glecaprevir/pibrentasvir (G/P) resulted in 95% sustained virologic response rates at 12 weeks post treatment (SVR12) in patients with Hepatitis C virus (HCV) genotype 3. In the ENDURANCE-3 study, presented at The International Liver Congress™ 2017 in Amsterdam, The Netherlands, patients infected with HCV genotype 3 without cirrhosis and who had no previous treatment history were treated with the new regimen for eight or 12 weeks, which was well tolerated. G/P had a similar safety profile to the commonly used combination of sofosbuvir and daclatasvir for 12 weeks, to which G/P was actively compared in the study.

Around 180 million people globally have chronic HCV infection,1 including approximately 15 million people in the EU.2 Genotype 3 patients have become the most difficult subgroup of patients to cure.3 Although there have been recent advances in direct-acting antiviral therapies for HCV genotype 1, genotype 3 remains a challenge and is a highly prevalent strain of the virus globally.3

"While there has been great progress made in the treatment of patients with Hepatitis C, there remain limited options for those with genotype 3 disease. As such, we are pleased to see that the investigational combination of glecaprevir/pibrentasvir achieved high SVR12 rates, in treatment naïve, non-cirrhotic patients,” said Dr Graham Foster, Queen Mary University of London, United Kingdom and lead study author. “Treatment with this once-daily regimen for eight weeks could provide a highly efficacious and well-tolerated option for treatment naïve, non-cirrhotic patients with Hepatitis C, genotype 3, if approved by the regulatory authorities.”

ENDURANCE-3 is a Phase 3, open-label, active-controlled study in which 348 treatment naïve, non-cirrhotic HCV genotype 3 patients were randomised to receive 12 weeks of oncedaily therapy with either co-formulated glecaprevir/pibrentasvir, or with sofosbuvir plus daclatasvir. Subsequently, 157 patients were enrolled to receive glecaprevir/pibrentasvir for eight weeks. The primary endpoint of the study was the percentage of patients who achieved SVR12. 

SVR12 was achieved in 222/233 (95%) (95% confidence interval 93-98) of patients treated with glecaprevir/pibrentasvir for 12 weeks, and in 111/115 (97%) (95% confidence interval 91-99) of patients treated with sofosbuvir plus daclatasvir for 12 weeks. In patients treated with glecaprevir/pibrentasvir for eight weeks, SVR12 was achieved in 149/157 (95%) (95%

confidence interval 92-98) of patients. Relapse occurred in 1% of patients in both 12 week treatment regimens, and in 3% of patients in the eight week regimen. Adverse events (71%) were mostly mild and there were no serious treatment-related adverse events. 

“These results are more than encouraging, considering that treatment options for HCV genotype 3 are still suboptimal,” said Prof Francesco Negro, Divisions of Gastroenterology and Hepatology of Clinical Pathology, University Hospital of Geneva, Switzerland, and EASL Governing Board Member.

Press Release
Eight Weeks of Treatment with AbbVie’s Investigational, Pan-Genotypic, Ribavirin-Free HCV Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved High SVR Rates in Challenging-to-Treat Genotype 3 Chronic HCV Patients
AbbVie announced high SVR rates were achieved with 8 weeks of treatment with its investigational, once daily, ribavirin-free, pan-genotypic regimen of glecaprevir/pibrentasvir (G/P) in patients with challenging-to-treat genotype 3 (GT3) chronic hepatitis C virus (HCV) infection. In results from AbbVie’s Phase 3 ENDURANCE-3 study, 95 percent (n=149/157) of GT3 chronic HCV-infected patients without cirrhosis and who were new to treatment achieved sustained virologic response at 12 weeks post-treatment (SVR₁₂) following 8 weeks of treatment with G/P.¹ These results will be featured as an oral presentation today at The International Liver Congress™ (ILC) 2017 in Amsterdam, The Netherlands.

In addition to evaluating 8 weeks of treatment with G/P, the ENDURANCE-3 study was designed to evaluate whether 12 weeks of G/P treatment is non-inferior to 12 weeks of sofosbuvir plus daclatasvir (SOF+DCV), a current standard of care for GT3 chronic HCV-infected patients.¹ SVR₁₂ rates of 95 percent were seen in both 8 weeks (n=149/157) and 12 weeks (n=222/233) of treatment with G/P.¹ Additionally, 12 weeks of treatment with G/P was demonstrated to be non-inferior to 12 weeks of treatment with SOF+DCV (97 percent, n=111/115).¹

GT3 is the second most common genotype globally, accounting for 18 percent of patients worldwide and 26 percent of patients in Europe.² Patients with GT3 HCV have more rapid disease progression, with the highest rates of associated fibrosis, steatosis (fatty liver), and hepatocellular carcinoma (HCC).³ Treatment guidelines with current standards of care recommend 12 weeks of treatment in GT3 patients without cirrhosis and who are new to treatment.⁴

Full results from ENDURANCE-3 are the latest to be released from AbbVie’s registrational studies in its G/P clinical development program, designed to investigate a faster path to virologic cure* for all major HCV genotypes (GT1-6) and with the goal of addressing areas of continued unmet need.

In the ENDURANCE-3 study, no patients who received 8 weeks of G/P discontinued treatment due to adverse events (AEs).¹ AEs were mostly mild (71 percent) in patients receiving both 8 and 12 weeks of G/P. The most common AEs (≥10 percent) in patients receiving 8 weeks and 12 weeks of G/P were headache (20 and 26 percent), fatigue (13 and 19 percent) and nausea (12 and 14 percent), respectively and with patients receiving 12 weeks of SOF+DCV treatment (headache 20 percent, fatigue 14 percent and nausea 13 percent).¹

Authorization applications for G/P are currently under review by regulatory authorities around the world. G/P has been granted accelerated assessment by the European Medicines Agency, and priority review designations by the U.S. Food and Drug Administration and Japanese Ministry of Health, Labour and Welfare. G/P is an investigational regimen and its safety and efficacy have not been established.

The ENDURANCE-3 study will be featured in the official ILC press conference on Friday, April 21 from 11:30 a.m. - 12:30 p.m. local time.

About the ENDURANCE-3 Study
ENDURANCE-3 is a Phase 3, open-label, active-controlled study evaluating patients who are new to treatment with HCV GT3 infection without cirrhosis. The study included 505 patients who were randomized to receive either 12 weeks of G/P (Arm A, n= 233) or 12 weeks of SOF+DCV (Arm B, n=115), with subsequently enrolled patients receiving 8 weeks of G/P (Arm C, n=157). The primary endpoint was the percentage of patients achieving SVR12. The rate of virologic failure was 1.7 percent (n=4/233) in Arm A, 0.8 percent (n=1/115) in Arm B and 3.8 percent (n=6/157) in Arm C.

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

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

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AbbVie's Investigational Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved 99 Percent SVR(12) Rate in Chronic Hepatitis C Patients with Compensated Cirrhosis

AbbVie's Investigational Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved 99 Percent SVR(12) Rate in Chronic Hepatitis C Patients with Compensated Cirrhosis

MEDPAGE TODAY
New Hep C Combo Cures Most Patients with Cirrhosis

by Liz Highleyman
Glecaprevir/pibrentasvir highly effective against most hepatitis C genotypes.

Direct-acting antiviral drugs used in interferon-free regimens can now cure most people with hepatitis C, but there is still room for better options for hard-to-treat patients, as well as medications that are active against all types of HCV.

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Press Release
AbbVie's Investigational, Pan-Genotypic, Ribavirin-free Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved 99 Percent SVR(12) Rate in Chronic Hepatitis C Patients with Compensated Cirrhosis
AMSTERDAM, April 20, 2017 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that 99 percent (n=145/146) of chronic hepatitis C virus (HCV) infected patients with genotype 1, 2, 4, 5 or 6 and compensated cirrhosis (Child-Pugh A) achieved sustained virologic response at 12 weeks post-treatment (SVR12) with its investigational, pan-genotypic regimen of glecaprevir/pibrentasvir (G/P). These high SVR12 rates were seen following 12 weeks of G/P treatment without ribavirin. Patients with specific virus strains associated with resistance or with a high quantity of the virus in their bloodstream before treatment initiation were not excluded from the study. These new data, from the Phase 3 EXPEDITION-1 study, will be featured as an oral presentation today at The International Liver Congress™ (ILC) 2017 in Amsterdam, The Netherlands.

"We have already seen great progress in the treatment of HCV patients with compensated cirrhosis. However, treatment challenges remain related to the use of ribavirin," said Xavier Forns, M.D., head of hepatitis unit, Hospital Clinic de Barcelona, Spain. "The positive findings from the EXPEDITION-1 study, along with previously reported data, show that G/P has the potential to become a ribavirin-free treatment for patients with compensated cirrhosis across these genotypes."

In the EXPEDITION-1 study, the majority of adverse events (AEs) were mild and no patients discontinued treatment due to an AE. The most common AEs (≥10 percent) were fatigue and headache.

"With our G/P clinical development program, our goal is to provide a cure for as many patients living with HCV as possible, across all genotypes and regardless of whether their disease has progressed to compensated cirrhosis," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "The EXPEDITION-1 study results, along with a number of other ILC presentations from our G/P clinical development program, explore the potential of our regimen in patients with specific treatment challenges."

Approximately 130 to 150 million people worldwide are living with chronic HCV, for whom the risk of cirrhosis of the liver is between 15-30 percent within 20 years.2 Treatment guidelines around the world recommend that all patients with cirrhosis should be considered for treatment, yet the treatment of specific patients with HCV and compensated cirrhosis is still challenging.3,4

AbbVie is presenting additional data at ILC in patients with specific treatment challenges, including in those with chronic kidney disease (SAT-273), HIV-1 co-infection (LBP-522), post liver and renal transplant patients (LBO-03) and in patients who did not achieve SVR12 with previous direct-acting antiviral (DAA) treatment (PS-156). Additional information on the clinical trials for G/P is available at http://www.clinicaltrials.gov.

Authorization applications for G/P are currently under review by regulatory authorities around the world. G/P has been granted accelerated assessment by the European Medicines Agency (EMA), and priority review designations by the U.S. Food and Drug Administration (FDA) and Japanese Ministry of Health, Labour and Welfare (MHLW). G/P is an investigational regimen and its safety and efficacy have not been established.

About the EXPEDITION-1 Study EXPEDITION-1 is a single arm, multicenter, open-label study evaluating the efficacy and safety of 12 weeks of G/P in adults with GT1, 2, 4, 5 or 6 chronic HCV infection and compensated cirrhosis (Child-Pugh A). The study enrolled 146 patients, including those new to treatment or had prior treatment experience with IFN-based treatments (IFN/pegIFN ± RBV, or sofosbuvir + RBV ± pegIFN). The primary endpoint was the percentage of patients achieving SVR12. SVR12 was achieved by 145/146 (99 percent) patients, with one GT1a-infected patient experiencing relapse.

No patients experienced ALT elevations equal to or above Grade 3. Of the 11 patients (7.5 percent) who experienced serious AEs, none were considered treatment-related.

About AbbVie's HCV Clinical Development ProgramAbbVie'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 being evaluated as a potential cure in 8 weeks for HCV patients without cirrhosis and who are new to treatment with direct-acting antivirals (DAA)**, 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. G/P is a fixed-dose combination of glecaprevir (300mg), an NS3/4A protease inhibitor, and pibrentasvir (120mg), an NS5A inhibitor, dosed once-daily as three oral tablets.

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

*Patients who achieve a sustained virologic response at 12 weeks post treatment (SVR12) are considered cured of hepatitis C. **Patients who are treatment-naive or had prior treatment experience with IFN-based treatments ([peg]IFN +/- RBV or SOF/RBV +/- pegIFN).


1 Forns, X et al. EXPEDITION-1: Efficacy and Safety of Glecaprevir/Pibrentasvir in Adults with Chronic Hepatitis C Virus Genotype 1, 2, 4, 5 or 6 Infection and Compensated Cirrhosis. Presented at The International Liver Congress™ (ILC) in Amsterdam, The Netherlands, April 19-23, 2017.
2 Hepatitis C. World Health Organization. World Health Organization, July 2016. Web. http://www.who.int/mediacentre/factsheets/fs164/en/.
3 EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol (2016), http://dx.doi.org/10.1016/j.jhep.2016.09.001.
4 Spach D, Scott J. Treatment of Hepatitis C in Patients with Cirrhosis. Hepatitis C Online. http://cdn.hepatitisc.uw.edu/pdf/special-populations-situations/treatment-cirrhosis/core-concept/all Published 2015. Accessed April 03, 2017.

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ILC 2017 Glecaprevir/pibrentasvir 95% SVR12 in HCV Geno 3 treatment naïve, non-cirrhotic patients

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.”
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Glecaprevir and Pibrentasvir Yield High response Rates in Patients with HCV Genotype 1-6 without Cirrhosis

Journal of Hepatology

Available online 13 April 2017

Glecaprevir and Pibrentasvir Yield High response Rates in Patients with HCV Genotype 1-6 without Cirrhosis

Paul Y. Kwo1, Fred Poordad, Armen Asatryan, Stanley Wang, David L. Wyles, Tarek Hassanein, Franco Felizarta, Mark S. Sulkowski, Edward Gane, Benedict Maliakkal, J. Scott Overcash,

Highlights

An all oral, once-daily, RBV-free, pangenotypic HCV treatment option is described.

8- or 12-week treatment with glecaprevir + pibrentasvir yielded high rates of SVR12

Treatment was well-tolerated with a favorable safety profile.

Abstract
Background and Aims
Hepatitis C virus (HCV) therapy that is highly efficacious, pangenotypic, with a high barrier to resistance and short treatment duration is desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) was evaluated in non-cirrhotic patients with chronic HCV genotype 1–6 infection.

Methods
SURVEYOR-I and SURVEYOR-II were phase 2, open-label, multicenter, dose-ranging trials including patients with chronic HCV genotype 1–6 infection who were either previously untreated or treated with pegylated interferon plus ribavirin. Patients received once-daily glecaprevir plus pibrentasvir at varying doses with or without ribavirin for 8 or 12 weeks. The primary efficacy endpoint was the percentage of patients with a sustained virologic response at post-treatment week 12 (SVR12).

Results
Of the 449 patients who received varying doses of glecaprevir plus pibrentasvir, 25%, 29%, 39%, and 8% had HCV genotype 1, 2, 3, and 4–6 infection, respectively. Twelve-week treatment achieved SVR12 in 97–100%, 96–100%, 83–94%, and 100% in genotypes 1, 2, 3, and 4–6, respectively. Eight-week treatment with 300 mg glecaprevir plus120 mg pibrentasvir in genotype 1–, 2–, or 3–infected patients yielded 97–98% SVR12 with no virologic failures. Three (0.7%) patients discontinued treatment due to adverse events; most events were mild (Grade 1) in severity. No post-nadir alanine aminotransferase elevations were observed.

Conclusions
Glecaprevir plus pibrentasvir was well tolerated and achieved high sustained response rates in HCV genotypes 1–6–infected patients without cirrhosis following 8- or 12-week treatment durations.

Lay Summary
The combination of direct-acting antivirals glecaprevir and pibrentasvir comprise a once-daily, all-oral, pangenotypic treatment for HCV genotype 1-6 infection. This article describes results from two Phase 2 trials investigating a range of doses at treatment durations of 8 or 12 weeks in 449 patients without cirrhosis. Efficacy of the optimal dose, as determined by rates of sustained virologic response at post-treatment week 12, ranged from 92%-100%; treatment was well-tolerated and significant laboratory abnormalities were rare.

Journal of Hepatology

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Glecaprevir and Pibrentasvir

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Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment

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Grazoprevir/Elbasvir Effectively Induces SVR in HCV with Prior Failure

Enanta Announces Presentations at The International Liver Congress™ 2017

Enanta Pharmaceuticals Announces Data Presentations at The International Liver Congress™ 2017

WATERTOWN, Mass.--(BUSINESSWIRE)--

• New data to be presented on Enanta’s FXR agonist EDP-305 for non-alcoholic steatohepatitis (NASH) and primary biliary cholangitis (PBC)
• New data to be presented on AbbVie’s investigational, pan-genotypic, ribavirin-free HCV regimen that combines two distinct antiviral agents, including glecaprevir, Enanta’s second protease inhibitor

Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a research and development-focused biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, today announced that several abstracts regarding Enanta’s wholly-owned EDP-305 development program for NASH and PBC, as well as abstracts regarding AbbVie’s investigational, pan-genotypic regimen of glecaprevir/pibrentasvir (G/P) for the treatment of chronic hepatitis C virus (HCV) infection, have been accepted for presentation at The International Liver Congress™ (ILC) 2017, April 19-23, in Amsterdam.

Three poster presentations will demonstrate that EDP-305 is a potent Farnesoid X Receptor (FXR) agonist that has been shown to reduce fibrosis progression and improve non-alcoholic fatty liver disease (NAFLD) activity scores (NAS) in a variety of preclinical models.

In addition, several oral and poster presentations will report data from AbbVie’s G/P clinical development program. G/P is an investigational, pan-genotypic, once-daily regimen that combines two distinct direct-acting-antiviral (DAA) agents, glecaprevir, Enanta’s second protease inhibitor, and pibrentasvir, AbbVie’s NS5A inhibitor.

The following abstracts regarding EDP-305 and G/P will be presented during the International Liver Congress:

Enanta Presentations: EDP-305 FXR Agonist:

Thursday, April 20

Poster Presentation, 08:00 - 18:00

• Poster #THU-377: A Novel Farnesoid X Receptor (FXR) Agonist, EDP-305, Reduces Fibrosis Progression in Animal Models of Fibrosis (Presenter: Bryan C. Fuchs)

Friday, April 21

Poster Presentation, 08:00 - 18:00

• Poster #FRI-363: EDP-305, a Novel and Highly Potent Farnesoid X Receptor (FXR) Agonist, Improves Liver Steatosis, Ballooning and Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) in a Diet-Induced Murine Model of Non-Alcoholic Steatohepatitis (NASH) (Presenter: Li Juan Jiang)

Saturday, April 22

Poster Presentation, 08:00 - 18:00

• Poster #SAT-459: A Novel FXR Agonist EDP-305 Potently Suppresses Liver Injury and Fibrosis in Mouse Models of Biliary and Metabolic Liver Disease (Presenter: Yury Popov)

AbbVie Presentations: glecaprevir/pibrentasvir (G/P) for HCV:

Thursday, April 20

Oral Presentation, 15:15 - 15:30

• Abstract GS-006: EXPEDITION-I: Efficacy and Safety of Glecaprevir/Pibrentasvir in Adults with Chronic Hepatitis C Virus Genotype 1, 2, 4, 5 or 6 Infection and Compensated Cirrhosis (Presenter: Xavier Forns)

Poster Presentations, 08:00 - 18:00

• Poster #THU-263: Pharmacokinetics and Safety of Glecaprevir/Pibrentasvir in Adults with Chronic Genotype 1-6 Hepatitis C Virus Infection and Compensated Cirrhosis: an Integrated Analysis (Presenter: Edward Gane)
• Poster #THU-305: Resistance Selection Using Glecaprevir and Pibrentasvir in Replicons of Major Hepatitis C Virus Genotypes (Presenter: Teresa Ng)

Late Breaking Poster April 20-22, 08:00 - 18:00

• Poster #LBP-522: Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients Co-infected With Hepatitis C Virus and Human Immunodeficiency Virus-1: the EXPEDITION-2 Study (Presenter: Juergen Rockstroh)

Friday, April 21

Oral Presentation, 08:30 - 08:45

• Abstract GS-007: ENDURANCE-3: Safety and Efficacy of Glecaprevir/Pibrentasvir Compared to Sofosbuvir Plus Daclatasvir in Treatment-Naïve HCV Genotype 3-Infected Patients without Cirrhosis (Presenter: Graham R. Foster)

Poster Presentations 08:00 - 18:00

• Poster #FRI-205: Pooled Resistance Analysis in HCV Genotype 1-6-infected Patients Treated with Glecaprevir/Pibrentasvir in Phase 2 and 3 Clinical Trials (Presenter: Preethi Krishnan)
• Poster #FRI-238: Safety of Glecaprevir/Pibrentasvir in Adults with Chronic Genotype 1-6 Hepatitis C Virus Infection: An Integrated Analysis (Presenter: Jean-Francois Dufour)
• Poster #FRI-262: CERTAIN-1: Efficacy and Safety of Glecaprevir/Pibrentasvir in Japanese Patients with Chronic Genotype 1 Hepatitis C Virus Infection with and without Cirrhosis (Presenter: Kazuaki Chayama)
• Poster #FRI-263: Efficacy and Safety of Glecaprevir/Pibrentasvir in Japanese Patients with Chronic Genotype 2 Hepatitis C Virus Infection with and without Cirrhosis (Presenter: Kazuaki Chayama)

Saturday, April 22

Oral Presentations

• 08:45 - 09:00: PS-156: MAGELLAN-1, Part 2: Glecaprevir and Pibrentasvir for 12 or 16 weeks in Patients with Chronic Hepatitis C Virus Genotype 1 or 4 and Prior Direct-Acting Antiviral Treatment Failure (Presenter: Fred Poordad)
• 16:30 - 16:45: LBO-03: MAGELLAN-2: safety and efficacy of Glecaprevir/Pibrentasvir in Liver or Renal Transplant Adults with Chronic Hepatitis C Genotype 1-6 Infection (Presenter: Nancy Reau)

Poster Presentations, 08:00 - 18:00

• Poster #SAT-204: Resistance Analysis in the MAGELLAN-1 Study (Part 2): Glecaprevir/Pibrentasvir Therapy in HCV-infected Patients who had Failed Prior DAA Regimens Containing NS3/4A protease and/or NS5A Inhibitors (Presenter: Tami Pilot-Matias)
• Poster #SAT-233: High SVR Rates with Eight and Twelve Weeks of Pan-Genotypic Glecaprevir/Pibrentasvir: Integrated Efficacy and Safety Analysis of Genotype 1-6 Patients without Cirrhosis (Presenter: Massimo Puoti)
• Poster #SAT-273: Safety and Efficacy of Glecaprevir/Pibrentasvir in Adults with Chronic Hepatitis C Virus Infection Genotype 1 – 6 and Chronic Kidney Disease: an Integrated Analysis (Presenter: Stan Pol)

The full ILC 2017 scientific program can be found at http://ilc-congress.eu/.

About G/P

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

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

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