MAVIRET - AbbVie reaches an agreement with the pan-Canadian For HCV Drug

AbbVie reaches an agreement with the pan-Canadian Pharmaceutical Alliance (pCPA) for its hepatitis C treatment MAVIRET™

Feb. 21, 2019, 12:09 PM

Ontario will be the first province to reimburse MAVIRET as of February 28, 2019

MAVIRET is the first and only 8-week, pan-genotypic treatment for chronic hepatitis C patients without cirrhosis and who are new to treatment*1

MAVIRET previously received positive reimbursement recommendations from the CADTH Canadian Drug Expert Committee (CDEC)2 in January 2018 and the Institut national d'excellence en santé et services sociaux (INESSS) in February 2018

MAVIRET is the only pan-genotypic treatment approved for use in patients across all stages of chronic kidney disease

MONTREAL, Feb. 21, 2019 /CNW/ - AbbVie (NYSE: ABBV), a global, research and development-based biopharmaceutical company, announced an agreement was reached with the pan-Canadian Pharmaceutical Alliance (pCPA) regarding MAVIRET™ (glecaprevir/pibrentasvir tablets), a once-daily, ribavirin-free treatment for adults with chronic hepatitis C virus (HCV) infection across all major genotypes (GT1-6)2. MAVIRET is the only 8-week, pan-genotypic treatment for patients without cirrhosis and who are new to treatment,* who make up a large portion of HCV patients in Canada. 

Following the positive conclusion with the pCPA, Ontario will be the first province to reimburse MAVIRET on its public formulary as of February 28, 2019. As listed on the Ontario Drug Benefit (ODB)3 Formulary as a Limited Use product, MAVIRET will be covered for treatment-naïve and treatment-experienced adult patients with chronic hepatitis C infection (regardless of fibrosis stage)3:

Laboratory confirmed hepatitis C genotype 1,2,3,4,5,6
HCV RNA value within the last six months

***Prescription by a hepatologist, gastroenterologist or an infectious disease specialist (or other physician experienced in treating hepatitis C).

"After more than 20 years of treating hepatitis C, I am hopeful that soon we will successfully eliminate this virus. But in order to reach this goal in Canada and across the world, we need to work together to test, diagnose and bring these high curative treatments to every individual, regardless of their genotype, fibrosis stage and background," explains Dr. Magdy Elkhashab, Gastroenterologist/Hepatologist, Director of the Toronto Liver Centre. "As a hepatologist, MAVIRET offers me the opportunity to put my patients on an effective, short duration therapy that has a proven track record."

Approximately 300,000 Canadians are infected with hepatitis C.4 Over time chronic hepatitis C can lead to chronic liver diseases, with a risk of developing cirrhosis of up to 30 per cent within 20 years5 of infection. Additionally, HCV is common among people with severe chronic kidney disease (CKD), and some of these patients previously did not have a direct-acting antiviral (DAA)-based treatment option.6

"The Canadian Liver Foundation is committed to seeing Canada meet the target set by the World Health Organization's Global Strategy on Viral Hepatitis. And that target is to eliminate hepatitis C by 2030. It is within our reach, but all our elimination efforts require support, plans and concrete actions at the local level to combat the increasing burden of HCV infection and the associated stigma," says Dr. Morris Sherman, Chairman of the Canadian Liver Foundation and Toronto-based hepatologist. "To be successful, we need a comprehensive screening strategy based on risk factors, plus a one-time test for all Canadians born 1945 – 19757, as well as adapted linkage to care to allow access to all available treatment options for all Canadians."

The efficacy and safety of MAVIRET was evaluated in nine Phase 2-3 clinical trials, in over 2,300 patients with genotype 1, 2, 3, 4, 5 or 6 HCV infection and with compensated liver disease (with or without cirrhosis).

"AbbVie is committed to the World Health Organization's targets and looks forward to working with governments, health care professionals and patient associations in their concerted efforts to achieve HCV elimination in Canada," explains Stéphane Lassignardie, General Manager, AbbVie Canada. "MAVIRET brings value in order to achieve elimination and all Canadians should have access to innovative and curative therapies."

https://markets.businessinsider.com/news/stocks/abbvie-reaches-an-agreement-with-the-pan-canadian-pharmaceutical-alliance-pcpa-for-its-hepatitis-c-treatment-maviret-1027973100

Mavyret - Safety and efficacy in patients receiving opioid substitution therapy/HCV genotypes 1-6

Int J Drug Policy. 2019 Feb 5;66:73-79. doi: 10.1016/j.drugpo.2019.01.011. [Epub ahead of print]

Safety and efficacy of glecaprevir/pibrentasvir in patients with chronic hepatitis C genotypes 1-6 receiving opioid substitution therapy.
Grebely J1, Dore GJ2, Alami NN3, Conway B4, Dillon JF5, Gschwantler M6, Felizarta F7, Hézode C8, Tomasiewicz K9, Fredrick LM3, Dumas EO3, Mensa FJ3.

Open Access

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Abstract
BACKGROUND:

International guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST.

METHODS:

Pooled data from patients with HCV genotypes 1-6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST.

RESULTS:

Among 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2-99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3-98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12.

CONCLUSION:

Glecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST.

Full-text article available online: https://www.sciencedirect.com/science/article/pii/S0955395919300192?via%3Dihub

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

KEYWORDS: Glecaprevir/pibrentasvir; Hepatitis C virus; Opioid substitution therapy; People who inject drugs

Hepatitis C: Mavyret (glecaprevir/pibrentasvir) in patients aged 65 years or older

Safety and efficacy of glecaprevir/pibrentasvir for the treatment of chronic hepatitis C in patients aged 65 years or older

Graham R. Foster , Tarik Asselah, Sarah Kopecky-Bromberg, Yang Lei, Armen Asatryan, Roger Trinh, Neddie Zadeikis, Federico J. Mensa

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Abstract
Finding safe and effective treatments for chronic hepatitis C virus (HCV) infection in the elderly is of clinical interest given the comorbidities and associated polypharmacy in this population. However, the number of patients older than age 65 years enrolled into clinical trials of anti-HCV medications generally have been limited and thus reaching meaningful conclusions for this demographic has been difficult. Glecaprevir/pibrentasvir is a once-daily, all-oral, ribavirin-free, pangenotypic direct-acting antiviral (DAA) combination therapy that has demonstrated high sustained virologic response rates at post-treatment week 12 (SVR12) and a favorable safety profile in patients with chronic HCV infection. This analysis evaluated the safety and efficacy of glecaprevir/pibrentasvir in patients aged ≥65 years. Data were pooled for treatment-naïve and -experienced patients with chronic HCV genotype (GT) 1–6 infections who received glecaprevir/pibrentasvir for 8, 12, or 16 weeks in 9 Phase 2 and 3 trials. SVR12 and adverse events (AEs) were evaluated for patients aged ≥65 versus <65 years. Of the 2369 patients enrolled, 328 (14%) were aged ≥65 years. Among patients aged ≥65 years, 42% and 34% had GT1 and GT2, respectively; 40% were treatment-experienced and 20% had compensated cirrhosis. Glecaprevir/pibrentasvir treatment resulted in SVR12 rates of 97.9% (95% CI, 96.3–99.4; n/N = 321/328) for patients aged ≥65 years and 97.3% (95% CI, 96.6–98.0; n/N = 1986/2041) for patients aged <65 years. The rates were not significantly different between the two age groups (P = 0.555). DAA-related AEs leading to treatment discontinuation, or serious AEs were similarly rare (<0.5%) for patients ≥65 and <65 years old. Glecaprevir/pibrentasvir is an efficacious and well-tolerated treatment option for patients aged ≥65 years with chronic HCV infection.
Full article: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208506 

Mavyret for HCV/HIV Coinfection and Genotype 3: A Report of Three Cases

Intern Med. 2018 Nov 19. doi: 10.2169/internalmedicine.1856-18.
[Epub ahead of print]

Glecaprevir and Pibrentasvir for Japanese Patients with Human Immunodeficiency Virus and Genotype 3 Hepatitis C Virus Coinfection: A Report of Three Cases
Takuya Sho1, Goki Suda1, Megumi Kimura1, Tomoe Shimazaki1, Osamu Maehara1, Taku Shigesawa1, Kazuharu Suzuki1, Akihisa Nakamura1, Masatsugu Ohara1, Machiko Umemura1, Takaaki Izumi1, Naoki Kawagishi1, Masaru Baba2, Masato Nakai1, Mitsuteru Natsuizka1, Kenichi Morikawa1, Koji Ogawa1 and Naoya Sakamoto1; for the NORTE Study Group

Abstract:
The efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with human immunodeficiency virus (HIV) and/or genotype 3 hepatitis C virus (HCV) infection is yet to be clarified. This is because no or only a few patients have been included in Japanese phase 3 trials. We herein report for the first time the successful treatment of glecaprevir and pibrentasvir in three Japanese patients with HIV and genotype 3 HCV coinfection as well as hemophilia. Glecaprevir and pibrentasvir treatment is safe and effective for Japanese patients with genotype 3 HCV and HIV coinfection.

Full-text article
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8-week Maviret HCV genotype 1-6 & compensated cirrhosis:The EXPEDITION-8 Study

Meeting Coverage @ infohep

8 weeks of Maviret cures 98% of people with hepatitis C and cirrhosis

Keith Alcorn / 14 November 2018
An 8-week course of the combination of glecaprevir and pibrentasvir (Maviret) is highly effective in curing hepatitis C in people with compensated cirrhosis, across a wide range of genotypes, Robert S. Brown of Weill Cornell Medical College reported at the AASLD Liver Meeting in San Francisco this week. Maviret is a highly effective combination of an HCV protease inhibitor (glecaprevir) and an NS5A inhibitor (pibrentasvir) that has been shown to cure hepatitis C in 98% of people without cirrhosis after eight weeks of treatment. A previous study showed that a 12-week course of the combination cured hepatitis C in 99% of people with compensated cirrhosis. The EXPEDITION-8 study was designed to test whether an 8-week treatment course was as effective in previously untreated people with compensated cirrhosis as the rate of cure achieved in the previous 12-week study.

Read more: http://www.infohep.org/page/3366911/

Meeting Coverage @ infohep Twitter - @infohep

HCV Combo Pill a Winner in Untreated Cirrhotic Patients

High SVR12 rate suggests 8-week treatment could be used for this population
Read more: https://www.medpagetoday.com/meetingcoverage/aasld/76333
Coverage @ MedPage Today Twitter @medpagetoday

Recommended Coverage

View updates on this blog (LINK), recommended coverage (LINK).

Presented at the AASLD: The Liver Meeting®

Preliminary efficacy & safety of 8-week GLE/PIB in patients with #HCV genotype 1-6 infection & compensated cirrhosis: The EXPEDITION-8 Study 

LINK

Download Slides: https://jumpshare.com/v/hfK0UhdJXgTFvWEY97tB

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AbbVie's MAVYRET™ (glecaprevir/pibrentasvir) Shows High Virologic Cure* Rates in Treatment-Naïve Hepatitis C Patients with Compensated Cirrhosis

The Liver Meeting® 2018

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High SVR12 rate for 16 week glecaprevir/pibrentasvir regimen in HCV GT1

Today's Press Release

AbbVie's MAVYRET™ (glecaprevir/pibrentasvir) Shows High Virologic Cure* Rates in Treatment-Naïve Hepatitis C Patients with Compensated Cirrhosis

- EXPEDITION-8 is the first Phase 3b study evaluating 8 weeks of MAVYRET™ in treatment-naïve chronic hepatitis C virus (HCV)-infected patients with compensated cirrhosis across all major genotypes (GT1-6)[1] 

- In cohort one, 100 percent of genotype 1, 2, 4, 5 and 6 treatment-naïve chronic HCV patients with compensated cirrhosis achieved SVR[12] with 8 weeks of MAVYRET per protocol analysis[1]

- Cohort two of the study is ongoing, evaluating treatment-naïve genotype 3 (GT3) patients with compensated cirrhosis 

- MAVYRET is currently approved as an 8-week, pan-genotypic treatment for treatment-naïve patients without cirrhosis

NORTH CHICAGO, Ill., Nov. 13, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced new data for its pan-genotypic chronic hepatitis C virus (HCV) treatment, MAVYRET™ (glecaprevir/pibrentasvir), in treatment-naïve patients with compensated cirrhosis. Results from the Phase 3b EXPEDITION-8 study showed that with 8 weeks of MAVYRET, 100 percent (n=273/273) of genotype 1, 2, 4, 5 and 6 patients achieved a sustained virologic response 12 weeks after treatment (SVR12) per protocol analysis.1

These data are being presented today as a late-breaking, oral presentation at The Liver Meeting® 2018 organized by the American Association for the Study of Liver Diseases (AASLD) in San Francisco, California.

"Current guidelines recommend a 12-week pan-genotypic regimen for people who have hepatitis C, are treatment-naïve and have compensated cirrhosis," said Robert S. Brown, Jr., M.D., the Gladys and Roland Harriman professor of medicine, Weill Cornell Medical College. "We are interested in investigating shorter treatment options, which may simplify care for patients with compensated cirrhosis while providing high cure rates."

This analysis is part of the ongoing Phase 3b EXPEDITION-8 study evaluating the safety and efficacy of MAVYRET in treatment-naïve chronic HCV patients with compensated cirrhosis across all major genotypes (GT1-6).1 The study includes two cohorts; cohort one with genotype 1, 2, 4, 5, 6 chronic HCV-infected patients, and cohort two with genotype 3 (GT3) chronic HCV-infected patients.1

"MAVYRET is already having a significant impact on people living with HCV. However, there are still groups of patients who may benefit from a shorter treatment option," said Janet Hammond, M.D., Ph.D., vice president, infectious diseases development, AbbVie. "We continue to investigate and understand the value of an 8-week treatment regimen for patients, something we recognize as an important step towards HCV elimination."

To date, no virologic failures have been reported in cohort one of the study and no patients have discontinued treatment due to adverse events.1 Adverse events (>5%) reported of the study populations include pruritus (9.6%), fatigue (8.6%), headache (8.2%) and nausea (6.4%).1 Six serious adverse events (2%) have occurred during the study, none of which were deemed to be related to glecaprevir/pibrentasvir.1 No new safety signals were identified in this study.

Data from the ongoing EXPEDITION-8 Phase 3b study will be presented as a late-breaking, oral presentation during the Late-breaking Abstract Oral Session II on November 13 at 8:30 a.m. PST.

MAVYRET is approved in the U.S. as a 12-week pan-genotypic treatment for treatment-naïve patients with compensated cirrhosis.2

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

About the EXPEDITION-8 Study1
EXPEDITION-8 is an ongoing non-randomized, single arm, open-label, multicenter Phase 3b study evaluating the safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve GT1-6 chronic HCV patients with compensated cirrhosis. The study investigated two cohorts of patients:
Cohort one: treatment-naïve genotype 1, 2, 4, 5, 6 patients with compensated cirrhosis (n=280)
Cohort two: treatment-naïve GT3 patients with compensated cirrhosis (n=60)

The primary endpoint is the percentage of patients achieving SVR12 in a per-protocol analysis and the secondary endpoints are on-treatment virologic failure and relapse rates. For cohort one, 280 patients were enrolled and seven patients were excluded from the SVR12 per-protocol analysis (n=273); five patients were lost to follow up, and two patients received less than 8 weeks of treatment (one of these two patients achieved SVR12).

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

About MAVYRET™ (glecaprevir/pibrentasvir)
MAVYRET™ is approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic hepatitis C virus (HCV) infection in adults across all major genotypes (GT1-6). MAVYRET is a pan-genotypic, once-daily, ribavirin-free treatment that combines glecaprevir (100mg), an NS3/4A protease inhibitor, and pibrentasvir (40mg), an NS5A inhibitor, dosed once-daily as three oral tablets, taken with food.

MAVYRET is an 8-week, pan-genotypic option for patients without cirrhosis and who are new to treatment, who comprise the majority of people living with HCV. MAVYRET is also approved as a treatment for patients with specific treatment challenges, including those (GT1) not cured by prior treatment experience to either a protease inhibitor or NS5A inhibitor (but not both), and in patients with limited treatment options, such as those with severe chronic kidney disease (CKD) or those with genotype 3 chronic HCV. MAVYRET is a pan-genotypic treatment approved for use in patients across all stages of CKD.

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.

Full prescribing information can be found here.

The Medicines Patent Pool Signs Licence With AbbVie to Expand Access to Key Hepatitis C Treatment, glecaprevir/pibrentasvir

The Medicines Patent Pool Signs Licence With AbbVie to Expand Access to Key Hepatitis C Treatment, glecaprevir/pibrentasvir 

SAN FRANCISCO, November 12, 2018 /PRNewswire/ --
Important collaboration will ensure affordable hepatitis C treatment options in low- and middle-income countries.

The Medicines Patent Pool (MPP) has today announced a new, royalty-free licence agreement with AbbVie for glecaprevir/pibrentasvir (G/P) - a World Health Organization (WHO)-recommended treatment for people living with chronic hepatitis C (HCV). The licence will enable quality-assured manufacturers to develop and sell generic medicines containing G/P in 99 low- and middle-income countries (LMICs) and territories at affordable prices, enabling access to and treatment scale-up with the most effective pan-genotypic regimens. The agreement was launched at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2018 in San Francisco.

"G/P is a priority therapy for licensing for the MPP, so this agreement with AbbVie is very good news for public health," said Dr Marie-Paule Kieny, Chair of the MPP Governance Board. "It is a really important new option for a significant proportion of HCV patients throughout the world. As with previous MPP licences, we look forward to facilitating access to generic versions of this product as quickly as possible in as many territories as possible."

Globally, 71 million people are currently living with chronic HCV, many of them in LMICs. By the end of 2015, only 20 percent had been diagnosed and a mere seven percent of them had received treatment. In February 2017, the MPP issued its annual report on priority medicines for in-licensing. Given its favourable clinical profile and high potential in LMICs, G/P was listed as a key priority treatment.

G/P is an all-oral, once-daily, pan-genotypic combination regimen and was originally approved in 2017. It has achieved high cure (SVR12) rates of 98 per cent in treatment-naïve non-cirrhotic patients across all six genotypes of the virus. It is recommended by the WHO as a first-line treatment for eight weeks in treatment- naïve non-cirrhotic patients. Treatment-naïve patients with compensated liver cirrhosis require a 12-week treatment course.

Further, the regimen is also indicated for use in HCV patients with any degree of renal impairment, including patients on dialysis. Globally between five and ten percent of all people living with chronic HCV infection are estimated to be living with kidney disease and this treatment will be very helpful for them.

There are 95 countries and four territories included in the MPP/AbbVie licence for G/P at this point.

More Details: www.medicinespatentpool.org 

High SVR12 rate for 16 week glecaprevir/pibrentasvir regimen in HCV GT1

Combo HCV Pill Effective in Certain Refractory Patients

High SVR12 rate for 16 week glecaprevir/pibrentasvir regimen in HCV GT1 patients

by Molly Walker, Staff Writer, MedPage Today November 11, 2018 

November 11, 2018
A 16-week treatment course had a SVR 12 of 95%, including 94% in non-cirrhotic patients and 97% in cirrhotic patients who had failed prior treatment containing NS5A inhibitors, with no virologic failure among those with HCV genotype 1b infection, reported Mark S. Sulkowski, MD, of Johns Hopkins Hospital in Baltimore.

He said that glecaprevir/pibrentasvir was approved by the FDA in 2017 for treatment of NS5A inhibitor-experienced patients with genotype 1 infection and no NS3/4A protease inhibitor therapy.

A 16-week course of treatment was approved based on a small group of 17 patients in a trial where 16 of 17 achieved SVR12, Sulkowski explained at a press conference at the annual Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD).

But that wasn't enough for the AASLD/Infectious Diseases Society of America (IDSA) guidelines panel, which labeled the therapy an "alternative regimen" and did not put it in the recommended category for treatment for this population, with "concerns based on the small number of human beings treated."
Read More: https://www.medpagetoday.com/meetingcoverage/aasld/76266

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Coverage > Liver Meeting

Mavyret SVR high in patients with Sovaldi, NS5A inhibitor experience
November 11, 2018

SAN FRANCISCO — Mavyret was highly effective and well-tolerated in patients with chronic hepatitis C genotype 1 who had experience with a combination of Sovaldi, NS5A inhibitor and ribavirin, according to data presented at The Liver Meeting 2018.

“The context of this study was that the FDA granted approval in August 2017 for [Mavyret] for 16 weeks in persons who failed an NS5A-containing regimen that did not also contain a protease inhibitor,” Mark S. Sulkowski, MD, from Johns Hopkins Hospital in Maryland, said during a press conference presentation.

Read More: https://www.healio.com/hepatology/hepatitis-c/news/online/%7B4d6fa6b5-eb3b-4dc5-9617-6c4b0411437f%7D/mavyret-svr-high-in-patients-with-sovaldi-ns5a-inhibitor-experience

Website Healio - Twitter @HealioHep

Combined Glecaprevir/Pibrentasvir Highly Effective in HCV Patients Who Have Failed Other Therapies 

SAN FRANCISCO – Data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found the combination of glecaprevir and pibrentasvir is highly effective and well tolerated in patients with chronic hepatitis C virus (commonly called HCV) genotype-1 infections who have prior treatment experience with sofosbuvir/NS5A inhibitor.

https://hepatitiscnewdrugs.blogspot.com/2018/11/the-liver-meeting-combined.html

Meeting Updates 

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Abstract

American Association for the Study of Liver Diseases

Source Reference: Sulkowski MS, et al "High efficacy of glecaprevir/pibrentasvir in patients with chronic HCV GT1 infection who failed prior treatment with NS5A-inhibitor plus sofosbuvir regimens" AASLD 2018; Abstract o226.

Website AASLD Twitter @AASLDtweets

The Liver Meeting® - Combined Glecaprevir/Pibrentasvir Highly Effective in HCV Patients Who Have Failed Other Therapies

Combined Glecaprevir and Pibrentasvir Found Highly Effective in Chronic Hepatitis C Patients Who Have Failed Other Therapies

SAN FRANCISCO – Data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found the combination of glecaprevir and pibrentasvir is highly effective and well tolerated in patients with chronic hepatitis C virus (commonly called HCV) genotype-1 infections who have prior treatment experience with sofosbuvir/NS5A inhibitor.

Although most patients with HCV genotype 1 infection can be cured of the infection with first-line direct-acting antiviral therapies, those who do not respond have few retreatment options, presenting a challenge to clinicians.

To address this, researchers from multiple centers in the United States took part in a randomized, controlled trial of a fixed-dose combination of once-daily 300 milligrams of glecaprevir (an NS3/4A protease inhibitor) and 120 milligrams of pibrentasvir (an NS5A inhibitor, also known as G/P).

“The G/P regimen given for 16 weeks was approved by the U.S. Food and Drug Administration for retreatment of HCV GT1-infected patients who failed a prior NS5Ai-containing regimen without prior exposure to a protease inhibitor, explains Mark Sulkowski, MD who is a professor of medicine at Johns Hopkins and the principle investigator of the study at the Hopkins site. “However, due the relatively small number of patients included in the registration trial, the AASLD/IDSA guidelines panel recommended this regimen as an alternative treatment option leading to uncertainty regarding the use this regimen in clinical practice for the re-treatment of persons with HCV genotype 1 infection who failed prior treatment with an NS5Ai-containing regimen,” he explains of what prompted the study.

One hundred seventeen patients participated in the study, which evaluated the G/P regimen for 16 weeks in compensated cirrhotic and non-cirrhotic patients with HCV genotype 1 infection who had previously failed on the combination of an NS5Ai with sofosbuvir. The patients were predominately male (82 percent) who ranged in age from 60-64 years, and the study included patients with HIV infection as well as patients who had undergone prior liver transplantation.

Patients who did not have cirrhosis were randomly assigned to receive G/P for either 12 or 16 weeks at a 2:1 ratio, and patients with cirrhosis were randomly assigned to receive G/P with ribavirin for 12 weeks or G/P alone for 16 weeks at a 1:1 ratio.

Patients were grouped by HCV genotype 1 subtype (1a and 1b), and the researchers monitored them to see if/when they achieved sustained virologic response (as marked by having no detectible HCV virus in their blood for 12 or more weeks after the last dose of treatment).

As of October 2018, sustained virologic outcomes data was available for 172 of the 177 study participants. Of those 172, 157 achieved sustained virologic response.

Among 126 patients without cirrhosis (data on one patient is still pending), 91 percent have reached sustained virologic response. Within this group, 78 patients received G/P for 12 weeks (a 90 percent sustained virologic response rate), and 48 patients received G/P for 16 weeks (a 94 percent sustained virologic response rate).

Among 46 patients with cirrhosis (data on four patients is still pending), 91 percent have reached sustained virologic response. Ninety-six percent of patients in this group who were randomized to 16 weeks of G/P achieved sustained virologic response.

Overall, the researchers found G/P was well-tolerated among study participants with fatigue, headache and nausea reported in 17 percent, 19 percent and 9 percent of participants, respectively. The addition of ribavirin was associated with more side effects. Eleven serious adverse events have been observed among nine participants in the study, including one death due to hepatocellular carcinoma; none of these events were classified as treatment-related. Complete safety, efficacy and resistance associated substitution data will be presented at The Liver Meeting®.

Editor’s note: This press release contains updated data that is not reflected in the published abstract but will be presented at The Liver Meeting®.

Dr. Mark Sulkowski will present these findings at AASLD’s press conference in Room 312-314 at the George R. Moscone Convention Center in San Francisco on Saturday, November 10 from 4:00 PM – 5:30 PM. The study entitled “High Efficacy of Glecaprevir/Pibrentasvir in Patients with Chronic HCV GT1 Infection Who Failed Prior Treatment with NS5A-Inhibitor Plus Sofosbuvir Regimens” will be presented on Sunday, November 12 at 10:30 AM in Room 154/156. The corresponding abstract (number 0226) can be found in the journal, HEPATOLOGY (link is external).

About AASLD
AASLD is the leading organization of clinicians and researchers committed to preventing and curing liver disease. The work of our members has laid the foundation for the development of drugs used to treat patients with viral hepatitis. Access to care and support of liver disease research are at the center of AASLD’s advocacy efforts.

Press releases and additional information about AASLD are available online at www.aasld.org.

Mavyret (glecaprevir/pibrentasvir) 8 Wks Improved Cardiovascular and Metabolic Outcomes and Stable Renal Function

Infect Dis Ther. 2018 Oct 27. doi: 10.1007/s40121-018-0218-x. [Epub ahead of print]

Pan-Genotypic Hepatitis C Treatment with Glecaprevir and Pibrentasvir for 8 Weeks Resulted in Improved Cardiovascular and Metabolic Outcomes and Stable Renal Function: A Post-Hoc Analysis of Phase 3 Clinical Trials. 
Tran TT1, Mehta D2,3, Mensa F3, Park C3, Bao Y3, Sanchez Gonzalez Y4.

First Online: 27 October 2018

Treatment with Glecaprevir and Pibrentasvir G/P for as short as 8 weeks showed improved glucose and triglyceride levels by post-treatment week 4 irrespective of treatment history and cirrhosis status. These benefits were especially pronounced in patients with elevated triglycerides, pre-diabetes and diabetes at baseline. Treatment with G/P also resulted in stable eGFR function in both during and post-treatment periods. Future studies are needed to determine whether these effects are maintained over longer periods of time.

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Abstract

Introduction
Chronic hepatitis C (CHC) infection is associated with extrahepatic manifestations (EHMs) which can affect renal, cardiovascular and other comorbidities. The effect of CHC treatment with short-duration regimens on these EHMs is not well defined. Hence, we examined longitudinal estimated glomerular filtration rate (eGFR), triglycerides and glucose values to assess the impact of short-duration CHC therapy on renal, cardiovascular and metabolic diseases, respectively.

Methods
We conducted analyses of all patients without cirrhosis treated with glecaprevir and pibrentasvir (G/P) for 8 weeks in two phase 3 clinical trials. In addition, one phase 3 trial was carried out to explore the effects of treatment on renal EHMs in patients with advanced renal impairment at baseline. As a sensitivity analysis, we included all CHC patients treated with G/P for 8 or 12 weeks enrolled across five phase 3 trials. Adjusting for baseline demographics and clinical properties via mixed regression models enabled evaluation of changes in EHMs through end of treatment.

Results
G/P treatment for 8 weeks resulted in statistically significant declines in triglycerides (− 28.6 mg/dl) and glucose (− 11.2 mg/dl), while there was no statistically significant decline in eGFR. Biomarker improvements were greatest among patients with elevated triglycerides and elevated glucose at baseline. Similar effects were observed across all patients treated with G/P for 8 or 12 weeks.

Conclusion
Short-duration treatment with G/P resulted in stable renal function and improvements in cardiovascular and metabolic EHM markers, especially in patients with severe EHMs at baseline.

Continue reading: https://link.springer.com/article/10.1007%2Fs40121-018-0218-x

Additional Reading
HCV Advocate
Hepatitis C is NOT just a liver disease-it affects the entire body. Check out our fact sheet that lists some of the more common and uncommon extrahepatic manifestations of hepatitis C.

Click here to download

Navigate this blog 

Sift through current research articles on the extrahepatic manifestations of hepatitis C.

FDA: Hepatitis C Drug Labeling Updated to Include New Clinical Data

Pharmacy Times

FDA: Hepatitis C Drug Labeling Updated to Include New Clinical Data

The FDA has approved updates to the labeling for hepatitis C virus (HCV) drug glecaprevir and pibrentasvir (Mavyret) to include new data from 2 clinical studies, according to a press release.

Labeling revisions include updates to the dosing recommendations, as well as safety and efficacy outcomes data from the HCV/HIV-1 coinfection study (M14-730) and from the liver and renal transplant study (M13-596).

The Dosage and Administration section was updated to include dosing recommendations for 12 weeks in liver or kidney transplant recipients and a 16-week treatment duration in genotype 1-infected patients who are NS5A inhibitor-experienced without prior treatment with an NS3/4A protease inhibitor or in genotype (GT) 3-infected patients who are pegylated interferon, ribavirin, and sofosbuvir (PRS) treatment-experienced.

Additionally, the Adverse Reactions and Clinical Studies sections were updated to include safety and efficacy data from the trials for HCV/HIV-1 coinfected individuals and patients with liver or kidney transplant.

Continue to article: 

https://www.pharmacytimes.com/news/fda-hepatitis-c-drug-labeling-updated-to-include-new-clinical-data

Healio

FDA updates Mavyret label for new safety, efficacy data

The FDA recently approved safety and efficacy revisions to the Mavyret label based on data from a hepatitis C/HIV-1 collection study and a liver and renal transplant study.

Ongoing studies from the past year have shown Mavyret (glecaprevir/pibrentasvir, AbbVie) to be a pangenotypic treatment that is highly effective over an 8-week course for most patients.

According to the released revisions, the FDA recommends a 12-week course of glecaprevir/pibrentasvir for liver or kidney transplant recipients. 

The FDA also recommends a 16-week course for patients with genotype 1 and NS5A inhibitor-experienced without prior treatment with an NS3/4A protease inhibitor, and for patients with genotype 3 who are treatment-experienced with Sovaldi (sofosbuvir, Gilead Sciences) and ribavirin.

Continue reading:
https://www.healio.com/hepatology/hepatitis-c/news/online/%7B16476477-5087-4d86-b8e9-021cb73a828b%7D/fda-updates-mavyret-label-for-new-safety-efficacy-data

FDA Hepatitis Updates
FDA recently approved revisions to the MAVYRET™ (glecaprevir and pibrentasvir)
The FDA recently approved revisions to the MAVYRET™ (glecaprevir and pibrentasvir) tablets label to include safety and efficacy data from the HCV/HIV-1 coinfection study (M14-730) and from the liver and renal transplant study (M13-596). A summary of the major revisions includes the following:

Section 2: DOSAGE AND ADMINISTRATION was updated to include the following dosing recommendations.

2.3 Liver or Kidney Transplant Recipients

MAVYRET is recommended for 12 weeks in liver or kidney transplant recipients. A 16-week treatment duration is recommended in genotype 1-infected patients who are NS5A inhibitor- experienced without prior treatment with an NS3/4A protease inhibitor or in genotype 3-infected patients who are PRS treatment-experienced.

Section 6: ADVERSE REACTIONS was updated to include the following safety data.

Adverse Reactions in HCV/HIV-1 Co-infected Subjects

The safety of MAVYRET in subjects with HIV-1 co-infection with genotypes 1, 2, 3, 4 or 6 chronic HCV infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) was assessed in 153 subjects (EXPEDITION-2) who received MAVYRET for 8 or 12 weeks. Thirty- three subjects with HIV-1 coinfection also received 8 or 12 weeks of therapy in ENDURANCE- 1.

The overall safety profile in HCV/HIV-1 co-infected subjects (ENDURANCE-1 and EXPEDITION-2) was similar to that observed in HCV mono-infected subjects. Adverse reactions observed in greater than or equal to 5% of subjects receiving MAVYRET in EXPEDITION-2 for 8 or 12 weeks were fatigue (10%), nausea (8%), and headache (5%).

Adverse Reactions in Subjects with Liver or Kidney Transplant

The safety of MAVYRET was assessed in 100 post-liver or -kidney transplant recipients with genotypes 1, 2, 3, 4, or 6 chronic HCV infection without cirrhosis (MAGELLAN-2). The overall safety profile in transplant recipients was similar to that observed in subjects in the Phase 2 and 3 studies, without a history of transplantation. Adverse reactions observed in greater than or equal to 5% of subjects receiving MAVYRET for 12 weeks were headache (17%), fatigue (16%), nausea (8%) and pruritus (7%). In subjects treated with MAVYRET who reported an adverse reaction, 81% had adverse reactions of mild severity. Two percent of subjects experienced a serious adverse reaction, and no subjects permanently discontinued treatment due to adverse reactions.

Section 14: CLINICAL STUDIES was updated to include the following efficacy outcomes data.

14.7 Treatment-Naïve or PRS Treatment-Experienced Adults with HCV/HIV-1 Coinfection without Cirrhosis or with Compensated Cirrhosis

EXPEDITION-2 was an open-label study in 153 HCV/HIV-1-coinfected subjects. Subjects without cirrhosis received MAVYRET for 8 weeks and subjects with compensated cirrhosis received MAVYRET for 12 weeks. The study included subjects who were HCV treatment-naïve or treatment-experienced to combinations of (peg)interferon, ribavirin, and/or sofosbuvir, with the exception of GT3-infected subjects who were all treatment naïve.

Of the 153 subjects treated, the median age was 45 years (range: 23 to 74); 63% had HCV genotype 1, 7% had HCV genotype 2, 17% had HCV genotype 3, 11% had HCV genotype 4, 2% had HCV genotype 6; 11% had cirrhosis; 84% were male; and 16% were Black.
In EXPEDITION-2, the SVR12 rate in HCV/HIV-1 co-infected subjects was 98% (150/153). One subject experienced on-treatment virologic failure and no subjects relapsed.

14.8 Treatment-Naïve or PRS Treatment-Experienced Adults with Liver or Kidney Transplant without Cirrhosis

MAGELLAN-2 was a single-arm, open-label study in 100 post-liver or -kidney transplant HCV GT 1, 2, 3, 4, or 6 infected subjects without cirrhosis who received MAVYRET for 12 weeks. The study included subjects who were HCV treatment-naïve or treatment-experienced to combinations of (peg)interferon, ribavirin, and/or sofosbuvir, with the exception of GT3-infected subjects who were all treatment-naïve.

Of the 100 subjects treated, the median age was 60 years (range: 39 to 78); 57% had HCV genotype 1, 13% had HCV genotype 2, 24% had HCV genotype 3, 4% had HCV genotype 4, 2% had HCV genotype 6; 75% were male; 8% were Black; 80% of subjects were post-liver transplant and 20% were post-kidney transplant. Immunosuppressants allowed for co- administration were cyclosporine ≤100 mg, tacrolimus, sirolimus, everolimus, azathioprine, mycophenolic acid, prednisone, and prednisolone.

The overall SVR12 rate in post-transplant subjects was 98% (98/100). There was one relapse and no on-treatment virologic failures.
The updated label will soon be available at drugs@fda or DailyMed
Mavyret - FDA Approval Date(s) and History, Letters, Labels, Reviews

Kimberly Struble
Division of Antiviral Products
Food and Drug Administration

Elizabeth Thompson
Division of Antiviral Products
Food and Drug Administration

Michael Stanfield Jr.
Division of Antiviral Products
Food and Drug Administration

Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection

Journal of Hepatology
Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection

JohannesVermehren, James S. Park, Ira Jacobson, StefanZeuzem

https://doi.org/10.1016/j.jhep.2018.07.002

Full-Text

PDF Download

Follow On Twitter 

The following full-text articles downloaded and shared by Henry E. Chang.

Abstract

Treatment of chronic hepatitis C virus (HCV) infection has been revolutionized with the development of direct-acting antiviral agents (DAAs). Eight to twelve weeks of all-oral, once-daily treatments is now the standard of care and viral eradication can be achieved in >95% across different patient populations. Despite these advances, several unresolved issues remain, including treatment of HCV genotype 3, chronic kidney disease, and in patients in whom DAA therapy has failed. Glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are the most recently approved DAA regimens. Given the overwhelming success of modern DAA-based therapies, GLE/PIB and SOF/VEL/VOX are also likely to represent the last DAAs to be approved. Both are pangenotypic, once-daily, all-oral DAA combinations that have the potential to close the gaps in the current DAA treatment portfolio. Here, we review the challenges associated with current DAAs and how these two regimens may be implemented in existing treatment algorithms.

Continue to article: https://jumpshare.com/v/UyqlFMHW9EjHQW9vWFYJ

Of Special Interest
Commentary
Hepatitis C Management Simplification From Test to Cure:A Framework for Primary Care Providers
SOF/VEL or GLE/PIB), both highly tolerated and effective for all genotypes.

Sofosbuvir and Ledipasvir is Associated with High Sustained Virologic Response and Improvement of Health-Related Quality of Life in East Asian Patients with Hepatitis C Virus Infection
In summary, our data clearly show the superiority of IFN-free RBV-free LDV/SOF in East Asian patients with chronic HCV genotype 1 infection. The advantages of that regimen are related not only to its high efficacy and excellent tolerability but also to significantly better quality of life during treatment and after achieving SVR. These data provide evidences up porting the comprehensive benefit of LDV/SOF for eligible patients which should inform all stakeholders, including providers, payers, and policy makers in East Asian countries

Absolute Insurer Denial of Direct-Acting Antiviral Therapy for Hepatitis C: A National Specialty Pharmacy Cohort Study

Absolute denials of DAA regimens by insurers in the U.S. have remained high & increased over time, regardless of type of insurance.

High SVR12 with 8-week and 12-week glecaprevir/pibrentasvir therapy: An integrated analysis of HCV genotype 1–6 patients without cirrhosis

High SVR12 with 8-week and 12-week glecaprevir/pibrentasvir therapy: An integrated analysis of HCV genotype 1–6 patients without cirrhosis

DOI: https://doi.org/10.1016/j.jhep.2018.03.007

Open Access

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Highlights

•A short-duration, pangenotypic cure for HCV infection may help treat more patients.

•Glecaprevir plus pibrentasvir (G/P) therapy for 8 weeks had an overall cure rate of 98%.

•The efficacy of 12-week G/P therapy (99%) was not significantly higher than that of 8-week G/P therapy (p = 0.2).
•Treatment responses were high irrespective of any baseline patient or viral trait.

•G/P demonstrated a favourable safety profile regardless of treatment duration.

Background & Aims
Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase II or III clinical trials, G/P therapy achieved rates of sustained virologic response 12 weeks after treatment (SVR12) of 93–100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P therapy in patients without cirrhosis with HCV GT 1–6 infection was performed.

Methods
Data were pooled from nine phase II and III trials including patients with chronic HCV GT 1–6 infection without cirrhosis who received G/P (300 mg/120 mg) for either 8 or 12 weeks. Patients were treatment naïve or treatment experienced with peginterferon, ribavirin, and/or sofosbuvir; all patients infected with HCV GT 3 were treatment naïve. Efficacy was evaluated as the SVR12 rate.

Results
The analysis included 2,041 patients without cirrhosis. In the intent-to-treat population, 943/965 patients (98%) achieved SVR12 when treated for eight weeks, and 1,060/1,076 patients (99%) achieved SVR12 when treated for 12 weeks; the difference in rates was not significant (p = 0.2). A subgroup analysis demonstrated SVR12 rates > 95% across baseline factors traditionally associated with lower efficacy. G/P was well tolerated, with one DAA-related serious adverse event (<0.1%); grade 3 laboratory abnormalities were rare.

Conclusions
G/P therapy for eight weeks in patients with chronic HCV GT 1–6 infection without cirrhosis achieved an overall SVR12 rate of 98% irrespective of baseline patient or viral characteristics; four additional weeks of treatment did not significantly increase the SVR12 rate, demonstrating that the optimal treatment duration in this population is eight weeks.

Lay summary

In this integrated analysis of nine clinical trials, patients with chronic HCV genotype 1–6 infection without cirrhosis were treated for either 8 or 12 weeks with the direct-acting antiviral regimen glecaprevir/pibrentasvir (G/P). The cure rate was 98% and 99% following 8 and 12 weeks of treatment, respectively; the difference in rates was not significant (p = 0.2), nor was there a significant difference in the cure rates across the two treatment durations on the basis of baseline patient or viral characteristics. These results, along with a favourable safety profile, indicate that G/P is a highly efficacious and well-tolerated pangenotypic eight-week therapy for most patients with chronic HCV infection.

View Article Online: https://www.journal-of-hepatology.eu/article/S0168-8278(18)30165-X/fulltext

First real-world data on Mavyret showing safety & effectiveness in HCV Genotype 1-6

Shared on Twitter today by @HenryEChang - First real-world data from the Deutsches Hepatitis C-Register (DHC-R) showing favorable safety & excellent effectiveness of G/P in HCV GT1-6 patients with 97% SVR12 & no virologic failures to date.

FIRST REAL - WORLD DATA ON SAFETY AND EFFECTIVENESS OF GLECAPREVIR/PIBRENTASVIR FOR THE TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION: DATA FROM THE GERMAN HEPATITIS C - REGISTRY

Download it here.... http://jmp.sh/VthHp48

Related:
Real-life effectiveness & safety of G/P among 723 Italian patients with chronic HCV: interim analysis of data from the NAVIGATOR-II study

Download here... https://jumpshare.com/v/DqbiLqRyrsNreitpAE12

Mavyret (glecaprevir/pibrentasvir)

Liver Congress™ 2018 First real-world studies report glecaprevir/pibrentasvir to be effective and well tolerated in chronic HCV infection
April 12, 2018
The results of the first real-world studies assessing the effectiveness and safety of glecaprevir/pibrentasvir (G/P) in patients with chronic hepatitis C virus (HCV) infection have confirmed high rates of viral suppression and a favourable safety profile in patients receiving 8-16 weeks of treatment.

Real-world experience confirms Mavyret efficacy in HCV
April 12, 2018
PARIS — Two real-world studies presented at the International Liver Congress 2018 confirmed the efficacy and safety of Mavyret in Italy and…

Liver Congress™ 2018 First real-world studies report glecaprevir/pibrentasvir to be effective and well tolerated in chronic HCV infection

Related: Real-world experience confirms Mavyret efficacy in HCV
April 12, 2018
PARIS — Two real-world studies presented at the International Liver Congress 2018 confirmed the efficacy and safety of Mavyret in Italy and…

First real-world studies report glecaprevir/pibrentasvir to be effective and well tolerated in chronic HCV infection 

European Association for the Study of the Liver

12 April 2018, Paris, France: The results of the first real-world studies assessing the effectiveness and safety of glecaprevir/pibrentasvir (G/P) in patients with chronic hepatitis C virus (HCV) infection have confirmed high rates of viral suppression and a favourable safety profile in patients receiving 8-16 weeks of treatment. Two real-world studies from Italy and Germany which will be presented at this week's International Liver Congress™ 2018 in Paris, France, reported high rates of sustained virological response (SVR), defined as undetectable HCV RNA, at 4 and 12 weeks after the end of treatment.

'The efficacy and safety of G/P as a treatment for HCV-infected patients have so far only been evaluated in controlled clinical trials', explained Dr Roberta D'Ambrosio from the University of Milan in Italy. 'Our real-world study involving more than 700 patients with chronic HCV infection confirmed that the effectiveness and safety profile of G/P were excellent across a range of different patient types'.

Glecaprevir (an NS3/4A protease inhibitor) coformulated with pibrentasvir (an NS5A inhibitor) is a relatively new direct-acting antiviral (DAA) combination that was approved in multiple countries during 2017 for the treatment of chronic HCV infection in adults.1 Phase 2 and 3 studies involving tightly defined patient groups with HCV infection have reported high rates of SVR12 and a favourable safety profile.1-6 Until now, no real-world studies with G/P in broader groups of patients with HCV infection have been reported.

The Italian study being presented this week is an interim analysis evaluating the outcomes of 723 consecutively treated patients within the Lombardy Navigator-II Network, with G/P administered according to the drug label. Of those with available data, 99.7% achieved SVR4 (346/347). HCV RNA was reported to be undetectable in 74% of patients at Week 4, and in 98% of patients at end of treatment for the entire cohort. The prevalence of treatment-related adverse events was low, mainly of mild severity, and only three patients discontinued G/P treatment prematurely.

The ongoing German real-world study, also being reported this week, evaluated 638 patients from the German Hepatitis C-Registry (DHC-R) who received G/P treatment according to the local label. Adult patients with HCV genotypes 1-6, with or without compensated cirrhosis, who were either treatment-naïve or treatment-experienced were included in this interim analysis. The majority of patients were treatment-naïve without cirrhosis and treated with 8 weeks of G/P.

According to Prof. Dr Thomas Berg from the University of Leipzig in Germany, who will present the study findings in Paris, among the 49 patients with available data, 100% achieved SVR12, excluding four patients who prematurely discontinued treatment for reasons other than virological failure. Of those four patients, two discontinued treatment due to adverse events. No grade 3 or higher elevations in alanine aminotransferase (ALT) have been observed.

'Our real-world study in patients receiving G/P in everyday clinical practice has yielded favourable effectiveness and safety results that were consistent with the clinical trial data', said Prof. Dr Thomas Berg. 'We have found G/P to be a very useful addition to our HCV treatment armamentarium as it simplifies treatment decisions for the majority of patients; G/P has the potential to expand the treated population and support the goal of HCV elimination'.

'These data are important because they confirm the high cure rates of more than 98% observed in Phase 3 trials', said Prof. Markus Cornberg from the Hannover Medical School, Germany, and EASL Governing Board Member. '8 weeks of therapy is possible for all naïve, non-cirrhotic patients, regardless of genotype, and although we still lack data in some difficult-to-treat genotype 3 patients, prevalence of these seems to be declining as shown by the German registry'.

References
1. AbbVie Limited. Maviret Summary of Product Characteristics, 28 February 2018. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004430/WC500233677.pdf. Last accessed: March 2018.

2. Zeuzem S, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N Engl J Med. 2018;378(4):354-69.

3. Gane E, et al. Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment. N Engl J Med. 2017;377(15):1448-55.

4. Forns X, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis. 2017;17(10):1062-8.

5. Asselah T, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 weeks in patients with hepatitis C virus genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol. 2018;16(3):417-26.

6. Kwo PY, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol. 2017;67(2):263-71.

AbbVie receives a positive recommendation from the CADTH Canadian Drug Expert Committee for MAVIRET™

AbbVie receives a positive recommendation from the CADTH Canadian Drug Expert Committee for MAVIRET™ - an oral therapy for the treatment of patients with hepatitis C

MAVIRET is the first and only 8-week, pan-genotypic treatment for chronic hepatitis C patients without cirrhosis and who are new to treatment*1
MAVIRET previously received a Notice of Compliance from Health Canada on August 16, 2017
MAVIRET is the only pan-genotypic treatment approved for use in patients across all stages of chronic kidney disease

MONTREAL, Feb. 6, 2018 /CNW/ - AbbVie (NYSE: ABBV), a global, research and development-based biopharmaceutical company, announced that the CADTH Canadian Drug Expert Committee (CDEC) issued a positive recommendation for MAVIRET™ (glecaprevir/pibrentasvir tablets), a once-daily, ribavirin-free treatment for adults with chronic hepatitis C virus (HCV) infection across all major genotypes (GT1-6)2. MAVIRET is the only 8-week, pan-genotypic treatment for patients without cirrhosis and who are new to treatment,* who make up a large portion of HCV patients in Canada. 

The recommendation states that glecaprevir/pibrentasvir be reimbursed for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection with or without compensated cirrhosis, including patients with HCV genotype 1 infection who were previously treated with either a regimen of NS5A inhibitor or with a NS3/4A protease inhibitor but not both classes of inhibitors, if specific conditions are met.3

"Continued efforts are fundamental to the ultimate goal of eliminating hepatitis C, which is a serious and complex disease in Canada. It is vital that as many patients as possible are able to achieve a virologic cure, as quickly as possible, and we hope that patients throughout Canada will be able to benefit from this latest treatment, which has the potential to cure most HCV patients in eight weeks," states Dr. Samuel Lee, Hepatologist and Professor, Cumming School of Medicine, University of Calgary.

Approximately 300,000 Canadians are infected with hepatitis C.4 In 2012 alone, more than 10,000 new cases of hepatitis C were reported, but 40 percent of patients are estimated to be living unaware of their disease.5 GT1 is the most common genotype in Canada and GT3 is the most difficult to treat.4,6 Over time chronic hepatitis C can lead to chronic liver diseases, with a risk of developing cirrhosis of up to 30 percent within 20 years7 of infection. Additionally, HCV is common among people with severe chronic kidney disease (CKD), and some of these patients previously did not have a direct-acting antiviral (DAA)-based treatment option.8

"Our goal is to see Canada meet its commitment to the World Health Organization's Global Strategy on Viral Hepatitis by eliminating hepatitis C by 2030. This is within our reach, but we need a coordinated national response with a comprehensive action plan to prevent, screen, diagnose and treat Canadians living with hepatitis C," says Dr. Morris Sherman, Chairman of the Canadian Liver Foundation and Toronto-based hepatologist. "The Canadian Liver Foundation recommends screening for hepatitis C based on risk factors, plus a one-time test for all Canadians born 1945 – 19759. Furthermore, treatment eligibility restrictions that currently exist need to be removed, so that physicians and their patients have affordable and equitable access to all available treatment options, regardless of background, disease severity or the province in which they live."

The efficacy and safety of MAVIRET was evaluated in nine Phase 2-3 clinical trials, in over 2,300 patients with genotype 1, 2, 3, 4, 5 or 6 HCV infection and with compensated liver disease (with or without cirrhosis).

"AbbVie is deeply committed to curing Canadians of hepatitis C. We strongly believe in providing patient and doctor choice when selecting the appropriate medication," explains Stéphane Lassignardie, General Manager, AbbVie Canada. "The CADTH positive recommendation reinforces our belief that there is a need for innovative therapies like MAVIRET in order to reach the goal set out by the World Health Organization to eliminate HCV by 2030 in Canada and across the world."

About MAVIRET™
MAVIRET™ is approved in Canada for the treatment of chronic hepatitis C virus (HCV) infection in adults across all major genotypes (GT1-6).2 MAVIRET is a new, pan-genotypic, once-daily, ribavirin-free treatment that combines glecaprevir (100 mg), an NS3/4A protease inhibitor, and pibrentasvir (40 mg), an NS5A inhibitor, dosed once-daily as three oral tablets.2

MAVIRET is an 8-week, pan-genotypic virologic cure** for use in patients without cirrhosis and who are new to treatment,*1 such patients comprising the majority of people living with HCV. MAVIRET is also approved as a treatment for patients with specific treatment challenges, including those with compensated cirrhosis across all major genotypes, and those who previously had limited treatment options, such as patients with severe chronic kidney disease (CKD) and those with genotype 3 infection.2 It is the only pan-genotypic treatment approved for use in patients across all stages of CKD.2

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 without cirrhosis and new to treatment with DAAs [either treatment-naive or not cured with previous 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.

About AbbVie
AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.ca and www.abbvie.com. Follow @abbvieCanada and @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

1 Decisions Resources Group. Hepatitis C virus: disease landscape & forecast 2016. January 2017.
2 MAVIRET (glecaprevir/pibrentasvir tablets) Product Monograph. Date of Preparation: August 16, 2017.
3 CADTH Canadian Drug Expert Committee Recommendation – Final: https://www.cadth.ca/sites/default/files/cdr/complete/SR0523_Maviret_complete-Jan-25-18.pdf. Accessed February 2018.
4Messina, JP et al. "Global distribution and prevalence of hepatitis C virus genotypes." Hepatology, 2015; 61: 77–87. Supporting information http://onlinelibrary.wiley.com/wol1/doi/10.1002/hep.27259/full. Accessed January 2018.
5 Hepatitis C: Get the Facts. Government of Canada. https://www.canada.ca/en/public-health/services/publications/diseases-conditions/poster-hepatitis-c-get-facts.html. Accessed February 2018.
6 Wyles, D et al. SURVEYOR-II, Part 3: Efficacy and Safety of ABT-493/ABT-530 in Patients with Hepatitis C Virus Genotype 3 Infection with Prior Treatment Experience and/or Cirrhosis. Presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, US on November 11-15, 2016.
7 Hepatitis C Fact Sheet. World Health Organization. World Health Organization, July 2017. Web. http://www.who.int/mediacentre/factsheets/fs164/en/. Accessed February 2018.
8 Fabrizi F, Poordad FF, Martin P. Hepatitis C infection in the patient with end stage renal disease. Hepatology. 2002;36(1):3-10.
9 The Canadian Liver Foundation, press release: https://www.newswire.ca/news-releases/not-getting-the-message-too-many-canadians-born-between-1945-1975-unaware-of-their-increased-risk-of-undiagnosed-hepatitis-c-587783871.html. Accessed February 2018.

SOURCE AbbVie Canada

HCV Updates & A Look At The Most Intense Flu Season In Years

Welcome, sit back and catch up on notable research articles and blog updates on the topic of viral hepatitis. However, we begin with updates on this year's flu season, with experts reporting it's the worst in nearly a decade. 

A Look At The Most Intense Flu Season In Years

CDC
Keep up with the latest flu news as it is posted on the CDC's website.

Transcript for CDC Update on Widespread Flu Activity
Tuesday, January 16, 2018

We called this briefing to get you the latest FluView numbers and to provide advice on preventing the flu and information about what people can do to reduce the risk of flu or serious illness.

Listen here

The American Council on Science and Health

This Year's Flu Is Different - It Kills In Two Ways
Jan 29, 2018
It is the 100th anniversary of the 1918 Spanish flu (1,2) pandemic, and the date is not the only similarity between the two. While it is impossible that the morbidity and mortality that is being caused by this year's H3N2 strain (3) will even approach that of the monster that infected 5% of the world, killing 2% of it, there is one troubling feature that this year's strain shares with its centennial cousin. Flu typically kills because of secondary infections, usually pneumonia. While both "18s" do this, they also kill people directly. This is the scary part. The latter is mercifully rare but it dominates the news. Children seem to be more susceptible rapid deaths. Cases have been recently reported in Florida, California, and Connecticut. And it may be growing, especially as new strains emerge (4). The cause of fast deaths is very different from that normally seen in flu death. It is more insidious, harder to prevent and can nothing can be done about it. One hundred years ago there were reports of people dying within hours of becoming ill.

Journal: New England Journal Of Medicine

January 25, 2018

Myocardial Infarction after Influenza Infection

J.C. Kwong and Others

Video

Abstract

Patients who had a positive laboratory test for influenza were six times as likely to be hospitalized for acute myocardial infarction during the 7 days after specimen collection (the “risk interval”) as during the year before and the year after the risk interval.

NPR

Flu Hitting Baby Boomers Unusually Hard
Gisele Grayson

Rob Stein
The flu is hitting the 65-and-over age group hardest, but the next-hardest hit is the 50-to-64 age group. Usually, children are the second-hardest hit. The reason is unclear. Jernigan says it may be because the strains of the flu to which baby boomers were exposed when they were young are different from the strains circulating this year, so they have less immunity.

Healio
CDC: Flu hospitalizations, deaths high; vaccination still urged
January 26, 2018
Influenza-related deaths this season have remained elevated for weeks, and hospitalization rates are comparable to the severe 2014-2015 influenza…

American Thinker

CDC: 50,000 Americans could die of influenza this year

January 28, 2018
By Rick Moran

“We often see different parts of the country light up at different times, but for the past three weeks the entire country has been experiencing lots of flu, all at the same time,” he said, adding: “We have several weeks to go.”

NBC News
Virus looks like flu, acts like flu, but it's not influenza
by Maggie Fox
Jan.28.2018
There’s another virus out there that could be adding to the seasonal misery, but it’s not being identified. The virus is called adenovirus, and it can cause very severe flu-like symptoms. It’s so risky that the U.S. military vaccinates recruits against two major strains.

In The News
England could become first country to eradicate Hepatitis C in 2025
Jan 29, 2018
NHS leaders today called on the pharmaceutical industry to work with them to provide best value for money for treatments so that in its 70th year, the NHS can commit to eliminating Hepatitis C in England at least five years earlier than the World Health Organisation goal of 2030.

HepCBC

Read today's news or check out the latest issue of Weekly Bull.

CDEC Recommends MAVIRET™ and VOSEVI™ for Reimbursement for Chronic HCV
January 27, 2018
On January 25, 2018 the federal CADTH Canadian Drug Expert Committee (CDEC) released its extensive reviews of two new "pan-genotypic" hepatitis C treatments: Maviret™ (AbbVie) and Vosevi™ (Gilead). In both cases, the drugs were recommended for reimbursement by provincial PharmaCares for "adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection with or without compensated cirrhosis." And, for both, reimburseme...

New Online

Medscape: CME Video

Treating Genotype 1-6
HCV Treatment: Incorporating Glecaprevir/Pibrentasvir and sofosbuvir/Velpatasvir/Voxilaprevir Into Clinical Practice
This 15-minute activity features a brief video introduction by faculty expert Dr. Muir in which he discusses how the new combination therapies glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir have changed the treatment landscape. The activity then continues with a text-based review of the recent advances in direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) and the clinical trials that led to the approval of these new agents.

Free registration is required 

Journal Updates
Journal: Alimentary Pharmacology and Therapeutics
Hepatitis C virus re-treatment in the era of direct-acting antivirals: projections in the USA
The introduction of oral direct-acting antivirals (DAAs) has dramatically changed the landscape of HCV treatment. However, a small percentage of patients fail to achieve sustained virologic response (SVR). Understanding the number of people who fail on DAAs and require re-treatment is important for budget impact and disease burden projections.

Journal: World Journal of Gastroenterology                   

Vitamin D deficiency and hepatitis viruses-associated liver diseases: A literature review

This review addresses general aspects of vitamin D deficiency and, in particular, the significance of vitamin D hypovitaminosis in the outcome of HBV- and HCV-related chronic liver diseases. Furthermore, current literature was reviewed in order to understand the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients.

Journal: World Journal of Hepatology
Efficacy of direct-acting antiviral treatment for chronic hepatitis C: A single hospital experience

Direct-acting antivirals have been approved for the treatment of hepatitis C virus (HCV) genotype 1 and 2 infections in Japan since 2011. In the new era of DAA therapy, predictors who fail to respond to DAA might be compromised by resistance-associated substitutions. There have been few reports of daclatasvir/asunaprevir failure because daclatasvir/asunaprevir is limited in Japan. Therefore, it might be important to report these cases for future research and treatment of HCV.

The following articles downloaded and shared by @HenryEChang via Twitter

Journal: Liver International

Ribavirin dose management in HCV patients receiving Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin

Journal: New England Journal Of Medicine
Mavyret - Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection (ENDURANCE-1 & ENDURANCE-3)

Blog Updates From Around The Web

National Viral Hepatitis Roundtable

Jan 25, 2018
Recent Additions
Webinar – Hepatitis C and the State of Medicaid Access

NVHR and the Center for Health Law Policy and Innovation at Harvard Law co-hosted this webinar on highlights from the "Hepatitis C: State of Medicaid Access" report, including methodology and key findings.

Contagion Live
Hepatitis C-Related Hospitalizations Rise By Almost 50%
EINAV KEET

The new report found that the number of inpatient hospital stays for patients seeking treatment solely for hepatitis C rose by nearly 49% from 2005 to 2014. In addition, hospital stays for hepatitis C patients also seeking treatment for hepatitis B, HIV, or alcoholic liver disease rose by about 11%. Overall, adults ages 52 to 72 years saw a more than 67% increase in hepatitis C-related hospitalizations –the most of any age group –while those ages 18 to 51 years saw a nearly 15% decrease in hospitalizations. Hospital stays involving hepatitis C were also longer, more expensive, and more likely to result in death than stays that did not involve hepatitis C.

HEPATITISC.NET

Life Changes Around Hep C 

By Kimberly Morgan Bossley - January 26, 2018
After curing hep C in 2014 many things changed in my life. I sold off half of my company and took the other with me and put in my home. After bringing the...

Getting Dumped with Hepatitis C 

By Karen Hoyt - January 25, 2018
After years of living with hepatitis C, I was very sick. My husband gave up on my low-energy self. He was about done with having a brain foggy wife. Within months of...

Self Treatment: Is it Safe?

By Daryl Luster - January 24, 2018
It has become evident to me that there are people who are treating their hep C with drugs that they purchase from countries where generic drugs are produced. These drugs are produced... 

HEP Blog
The Fire and Fury of Hep C 
January 26, 2018 

By Rick Nash

Growing up with Hep C colors the world very differently. Because I knew early, I avoided alcohol from the get-go. I’d like to think it allowed my liver to keep going to thirty. My biggest fear wasn’t dying, but accidentally infecting someone else. Over time I found my paranoia getting the better of me. I abhorred physical contact, because it added to the layered stress of social interaction. Having notified the school of my condition I was kept out of PE. I wasn’t shy about the topic, and the stigma merely fueled my rebellious teenage self. I clung to that rage, it felt justified, but often when we’re young we misidentify the real emotions at play.

On The Edge of a Smile  

By Karen Hoyt
A glimpse at an easily overlooked tool for healing.

Hepatitis C Reactivation: What It Is and What It Isn’t 
By Lucinda K. Porter, RN
Hepatitis C reactivation may occur in people receiving cancer treatment. However, hep C reactivation may not mean what you think it does.

Hepatitis C Treatment in Ireland 

By Greg Jefferys
In Ireland, the rate of Hepatitis C infection is one of the highest in the EU at about twice the international average.

Kevin MD
So the flu shot is only 10 percent effective. Here are 5 reasons to still get it.

Jennifer Variste, MD

January 27, 2018 

So you heard the flu shot is 10 percent effective. With so many sources of information available, the primary care provider’s role increasingly becomes that of educator. It is important to me that the parents of my patients make informed decisions, so when I have a parent decline the influenza vaccine, I make an effort to ask why. The number one response I hear has been “What’s the point? The flu ...

Hepatitis B Foundation

Journey to the Cure: What is Hepatitis B? 

Timothy Block, PhD

Welcome to Journey to the Cure. This is a web series that chronicles the progress at the Hepatitis B Foundation and Baruch S. Blumberg Institute towards finding the cure for hepatitis B.

Healthy You

Why herbal supplements taken with prescription drugs may be risky

Recommended Reading

Herbal Supplements May Be Dangerous When You Take Certain Prescription Drugs

By Amanda MacMillan
January 24, 2018 

A number of common herbal supplements, including green tea and Ginkgo biloba, can interact with prescription medications, according to a new research review published in the British Journal of Clinical Pharmacology. These interactions can make drugs less effective—and may even be dangerous or deadly. 

The new review analyzed 49 case reports of adverse drug reactions, along with two observational studies. Most people in the analysis were being treated for heart disease, cancer or kidney transplants, and were taking warfarin, statins, chemotherapy drugs or immunosuppressants. Some also had depression, anxiety or neurological disorders, and were being treated with antidepressant, antipsychotic or anticonvulsant medications.

Continue reading: http://time.com/5116664/are-herbal-supplements-safe/

Medical News Today

What to eat if you have hepatitis C
Last reviewed Thu 25 January 2018
By Tom Seymour
Reviewed by Natalie Olsen, RD, LD, ACSM EP-C

Hepatitis C can damage the liver and lead to cirrhosis, or scarring of the liver. Damage to the liver may mean that a person needs to modify their diet.

May we all remain healthy this flu season.

Tina