Saturday, July 15, 2017

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

This page has been updated to include: Gilead's FDA approved VoseviTM (Sofosbuvir/Velpatasvir/Voxilaprevir announcement, and TAG HCV Pipeline update, links provided below.

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 current FDA approved treatment for HCV genotype 3, with a look at newer therapies soon to be approved.

UPDATED July 18, 2017U.S. Food and Drug Administration Approves Gilead's VoseviTM (Sofosbuvir/Velpatasvir/Voxilaprevir) for Re-Treatment of Adults with Chronic Hepatitis C Virus
U.S. Food and Drug Administration (FDA) has approved VoseviTM (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) tablets, a single-tablet regimen for the re-treatment of chronic hepatitis C virus (HCV) infection in adults with genotype 1, 2, 3, 4, 5 or 6 previously treated with an NS5A inhibitor-containing regimen, or with genotype 1a or 3 previously treated with a sofosbuvir-containing regimen without an NS5A inhibitor. The approval is based on data from the Phase 3 POLARIS-1 and POLARIS-4 studies, which evaluated 12 weeks of Vosevi in direct-acting antiviral-experienced chronic HCV-infected patients without cirrhosis or with compensated cirrhosis.

FDA approved drugs to treat HCV genotype 3
If you have never been on HCV therapy and do not have cirrhosis theses two regimens are recommended: daclatasvir plus sofosbuvir for 12 weeks, or sofosbuvir-velpatasvir (Epclusa) also for 12 weeks.

If you have never been on HCV therapy but have compensated cirrhosis the two regimens recommended remain the same, with the following changessofosbuvir-velpatasvir for 12 weeks, or daclatasvir plus sofosbuvir, with or without ribavirin for 24 weeks.

However, if you are treatment-experienced, or have treated hepatitis C before with PEG-IFN/Ribavirin or Sofosbuvir but treatment failed you, check out the links provided below or learn more here: HCV Guidelines, a living document published by (The American Association for the Study of Liver Diseases/Infectious Disease Society of America/International Antiviral Society-USA Recommendations for Testing, Managing and Treating Hepatitis)

PEG-IFN/Ribavirin Experienced, Genotype 3 Patients Without Cirrhosis
PEG-IFN/Ribavirin Experienced, Genotype 3 Patients with Compensated Cirrhosis
Sofosbuvir-experienced, Genotype 3 Patients

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.

New Drugs Soon To Be FDA Approved 
FDA Approved - Gilead's VoseviTM (Sofosbuvir/Velpatasvir/Voxilaprevir 
On July 18, 2017 Gilead's VoseviTM (Sofosbuvir/Velpatasvir/Voxilaprevir) was FDA Approved
Last month CHMP - the scientific committee of the European Medicines Agency adopted a positive opinion on the company’s marketing authorization application for Vosevi sofosbuvir/Velpatasvir/Voxilaprevir.

In Case You Missed ItTAG Pipeline Report HIV, TB, and HCV
Published July 5, 2017
Hepatitis C
HCV Pipeline: DAAs and Diagnostics in the Pangenotypic Era
Annette Gaudino
AbbVie, Gilead, Merck, and Janssen have presented data at international congresses on efficacy across the six major genotypes; in difficult-to-treat populations, including patients with genotype 3 and cirrhosis; and patients with advanced kidney disease. Gilead also recently received approval for previously untreated adolescents, and presented data on ongoing clinical trials in young children. It would not be hyperbole to state that science has solved chronic HCV infection for all but individuals with decompensated cirrhosis—yet another powerful argument for early treatment. It must be noted that, as historically has been the case, all clinical trial data is based on majority male patient populations, with few people of color, particularly African Americans, taking part in clinical trials....

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.
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..

Awaiting FDA Approval For AbbVie's Glecaprevir/Pibrentasvir
On Dec. 19, 2016 in the U.S. AbbVie submitted a new drug application to the FDA for Glecaprevir/Pibrentasvir (G/P) for the treatment of genotypes 1-6. Estimated date under the Prescription Drug User Fee Act is August 2, 2017.

In June AbbVies MAVIRET (glecaprevir/pibrentasvir) was granted marketing authorisations in the European Union. The European Commission will now review the CHMP opinion and a final decision is expected in Q3 2017.

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 2017
Drug Pipeline – Monthly Report
Investigational HCV Drugs
Merck's MK-3682 (polymerase inhibitor), grazoprevir (protease inhibitor) plus ruzasvir (NS5A inhibitor) with and without ribavirin to treat HCV genotypes 1, 2 and 3.


Pangenotypic regimens and the next generation hepatitis C virus therapy
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)

Recommended Reading
July 14, 2017
The relationship between hepatitis C infection and hepatic steatosis.

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.

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.

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