Friday, June 23, 2017

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.


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

Thursday, June 22, 2017

Listen Or Watch: Mark Sulkowski, MD discuss current treatment options for all HCV genotypes

Managing Chronic Hepatitis C in the Primary Care Setting: Best Practices From Screening to Treatment

Source: PeerView CME/CE Audio Podcast - Gastroenterology

Podcast
Listen to Mark Sulkowski, MD discuss HCV screening, diagnosis, noninvasive tests for assessing liver fibrosis and current treatment options for all HCV genotypes (1-6). Although this podcast and online CME is aimed at clinicians the use of clinical vignettes make it easy for patients to understand.

Either listen only to the podcast or click here to access the complete two part presentation. The second part of this learning activity will discuss: A Closer Look at Current Recommendations and Options for the Treatment of HCV. Topics include HCV guidelines, liver disease staging "FibroTest" and treating HCV according to genotype.

Pick Me
I highly suggest you choose the patient friendly online learning activity, the program is uncomplicated and easy to navigate. The user can skip through any part of the program by clicking on the "next" button located in the upper right hand corner of the presentation.



Managing Chronic Hepatitis C in the Primary Care Setting: Best Practices From Screening to Treatment
Activity Overview
Join us for one of the live, in-person meetings we will be carrying out at state chapters of the AAFP. A nationally recognized expert will review age-based and risk-based HCV screening recommendations, approaches to diagnosis, optimal treatment and counseling strategies for HCV-infected patients, and the parameters that warrant referral to specialist care.

Activity Description
Enormous progress has been made in recent years toward effectively treating and curing patients with chronic hepatitis C. However, at least half of the possible 7 million individuals infected with hepatitis C virus (HCV) in the US remain undiagnosed. The formidable task of increasing the number of patients diagnosed, and subsequently linked to appropriate care has fallen to primary care clinicians. In this activity, the guest speaker will address the challenges encountered by primary care clinicians faced with the increasing societal need to screen for HCV and make appropriate diagnoses. The importance of counseling patients regarding current HCV treatment options will be examined, and the guest speaker will also provide a discussion focused on identifying HCV-infected patients who can be managed in primary care versus those requiring linkage to specialist care.

Recommended Links
HCVguidelines.org

On This Blog
HCV Education

Helpful Links
Premier Hepatitis C Websites, Blogs and Support Forums

10 year HCV treatment programme in people who inject drugs: No effect of recent or former injecting drug use on treatment adherence or SVR

Outcomes from a large 10 year hepatitis C treatment programme in people who inject drugs: No effect of recent or former injecting drug use on treatment adherence or therapeutic response
Omar Elsherif , Ciaran Bannan, Shay Keating, Susan McKiernan, Colm Bergin, Suzanne Norris

Full Text Article
Download PDF
View Online

Abstract
Background and aims
People who inject drugs (PWID) are historically viewed as having “difficult to treat” hepatitis C disease, with perceived inferior treatment adherence and outcomes, and concerns regarding reinfection risk. We evaluated for differences in treatment adherence and response to Peginterferon-alfa-2a/Ribavirin (Peg-IFNα/RBV) in a large urban cohort with and without a history of remote or recent injection drug use.

Methods
Patient data was retrospectively reviewed for 1000 consecutive patients—608 former (no injecting drug use for 6 months of therapy), 85 recent (injecting drug use within 6 months) PWID, and 307 non-drug users who were treated for chronic hepatitis C with Peg-IFNα/RBV. The groups were compared for baseline characteristics, treatment adherence, and outcome.

Results
There was no significant difference in treatment non-adherence between the groups (8.4% in PWID vs 6.8% in non-PWIDs; RR = 1.23, CI 0.76–1.99). The overall SVR rate in PWID (64.2%) was not different from non-PWIDs (60.9%) [RR = 1.05, 95% CI 0.95–1.17]. There was no significant difference in SVR rates between the groups controlling for genotype (48.4% vs 48.4% for genotype 1; 74.9 vs 73.3% for genotype 3). Former and recent PWID had similar adherence rates.

Conclusions
PWID have comparable treatment adherence and SVR rates when compared to non-drug users treated with Peg-IFNα/RBV. These data support a public health strategy of HCV treatment and eradication in PWID in the DAA era.

Published: June 21, 2017 https://doi.org/10.1371/journal.pone.0178398
PLOS ONE

Wednesday, June 21, 2017

Medscape New HCV Video Series - Hepatitis C Virus: Containing the Threat

Medscape - New Video Series
Hepatitis C Perspective

Hepatitis C Virus: Containing the Threat
About this Series
In the past few years, a new class of direct-acting antiviral agents has made the treatment of HCV easier and more effective than ever before, with cure rates nearing 100%, even among HIV-positive patients. But not all patients with HCV who are eligible for antiviral treatment are identified, and even fewer are being referred for care. Thus, HCV infection remains a significant risk for progression to cirrhosis, liver failure, and hepatocellular carcinoma. Liver specialists at two prestigious Chicago medical centers confront the key issues in the management of patients with chronic HCV infection.

View: Episode 1/ Strides and Obstacles

Coming Soon


Begin here
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Safety of the 2D/3D direct acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis - a pooled analysis

Journal of Hepatology -
Articles in Press

DOI: http://dx.doi.org/10.1016/j.jhep.2017.06.011
Publication stage: In Press Accepted Manuscript
Published online: June 20, 2017

Safety of the 2D/3D direct acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis - a pooled analysis
Fred Poordad Correspondence information about the author Fred Poordad Email the author Fred Poordad , David R. Nelson, Jordan J. Feld, Michael W. Fried, Heiner Wedemeyer, Lois Larsen, Daniel E. Cohen, Eric Cohen, Niloufar Mobashery, Fernando Tatsch, Graham R. Foster

Highlights
  • OBV/PTV/r ± DSV ± RBV was well-tolerated in patients with Child-Pugh A cirrhosis.
  • Low rates of serious adverse events and those leading to discontinuation of study drugs.
  • Events consistent with hepatic decompensation occurred in 1.2% of patients (13/1066)
  • Decompensation events occurred across the treatment period and post-treatment.
  • Rates of decompensation events were comparable in treated and untreated patients.

Abstract
Background & aims

Chronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit–risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r ± DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis.

Methods

Twelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r ± ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r + DSV ± RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported.

Results

In 1066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% CI: 4.1–6.8) and 2.2% (95% CI: 1.4–3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7–2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2).

Conclusions

This pooled analysis in 1066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r ± DSV ± RBV in this population. These results support the use of OBV/PTV/r ± DSV ± RBV in this high-priority population.

Lay summary

This pooled safety analysis in 1066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was comparable to rates from historical reports for untreated patients.

Hepatitis C - CDC New Surveillance for Viral Hepatitis

Of Interest
Medscape - New Video Series
About this Series
In the past few years, a new class of direct-acting antiviral agents has made the treatment of HCV easier and more effective than ever before, with cure rates nearing 100%, even among HIV-positive patients. But not all patients with HCV who are eligible for antiviral treatment are identified, and even fewer are being referred for care. Thus, HCV infection remains a significant risk for progression to cirrhosis, liver failure, and hepatocellular carcinoma. Liver specialists at two prestigious Chicago medical centers confront the key issues in the management of patients with chronic HCV infection.
View: Episode 1/ Strides and Obstacles



Surveillance for Viral Hepatitis – United States, 2015
The Centers for Disease Control and Prevention’s (CDC) National Notifiable Diseases Surveillance System (NNDSS) (1) receives viral hepatitis case reports electronically each week from state and territorial health departments in the United States (U.S.) via CDC’s National Electronic Telecommunications System for Surveillance (NETSS), a computerized public health surveillance system. The surveillance system accepts case reports of acute and chronic infections from all states and the District of Columbia, though not all jurisdictions report their data. In 2015, a total of 48 states submitted reports of acute hepatitis B virus (HBV) infection, 40 submitted reports of acute hepatitis C virus (HCV) infection, 40 submitted reports of chronic HBV infection, and 40 submitted reports of chronic HCV infection.

View Report Online - Commentary

Hepatitis C: 
Reported cases of acute HCV infection increased more than 2.9-fold from 2010 through 2015, rising annually throughout this period. Examining annual trends beginning in 2011, reported cases of acute HCV infection increased 44.3% from 2011 to 2012 (n=1,232 and 1,778 cases, respectively), increased 20.3% to 2,138 cases in 2013, increased 2.6% to 2,194 cases in 2014, and increased 11% to 2,436 cases in 2015. The increase in acute HCV case reports reflects new infections associated with rising rates of injection-drug use, and, to a much lesser extent, improved case detection (15). Several early investigations of newly acquired HCV infections reveal that most occur among young, white persons who live in non-urban areas (particularly in states within the Appalachian, Midwestern, and New England regions of the country) (16); trends in these states likely indicate an overall increase in HCV incidence throughout the country (15, 17). States with the highest rate of new HCV infections (e.g., West Virginia, Kentucky, and Tennessee) did not receive CDC support for case finding during these reporting years (2011-2015). After adjusting for under-ascertainment and under-reporting (2), an estimated 33,900 (95% CI=26,800–115,000) new HCV infections occurred in 2015.

Based on the data from national health surveys conducted in the 2003-2010 time period, approximately 3.5 million persons are currently infected with HCV (18). Mortality among HCV-infected persons—primarily adults aged 55–64 years—increased during 2006-2010 (19, 20). In 2013, HCV associated deaths exceeded the combined number of deaths with 60 other infectious diseases as underlying causes (21). CDC data indicate the number of HCV-associated deaths increased 10.9% from 2011 through 2014 and decreased 0.2% to 19,629 in 2015. Approximately one-half of all deaths in 2015 occurred among persons aged 55-64 years. However, deaths associated with HCV are largely underestimated; the only large U.S. study of deaths among persons with confirmed HCV infection indicated that only 19% had HCV listed anywhere on the death certificate despite 75% having evidence of substantial liver disease (20). To increase the proportion of persons with HCV who are tested and linked to recommended care including curative treatment for HCV (12, 13), CDC and USPSTF recommend one-time testing for HCV infection among all adults born during 1945–1965 and among others at increased risk for HCV infection (22).

Continue reading report @ https://www.cdc.gov/hepatitis/statistics/2015surveillance/commentary.htm

Funding the war on hepatitis – deploying innovative finance mechanisms to eliminate hepatitis C in Europe

Funding the war on hepatitis – deploying innovative finance mechanisms to eliminate hepatitis C in Europe

"In this blog, co-authors Rob Walton (
Cello Health Public Affairs), Jeffrey V Lazarus (CHIP, WHO Collaborating Centre on HIV and Viral Hepatitis at Rigshospitalet, the University of Copenhagen and Editor-in-Chief of Hepatology, Medicine and Policy), Homie A. Razavi (Center for Disease Analysis), Jagpreet Chhatwal (Harvard Medical School), Charles Gore (Hepatitis C Trust), Pierre Van Damme (Vaccine & Infectious Disease Institute – VAXINFECTIO, University of Antwerp), Luís Mendão (GAT –Treatment Activist Group), and Angelos Hatzakis (Athens University Medical School and Hepatitis B & C Public Policy Association), discuss an innovative financing mechanism to eliminate Hepatitis C in Europe."

Rob Walton
20 Jun 2017
It is no coincidence that the emerging international consensus to tackle HCV has come at the same time as the arrival of new and highly effective range of direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV). These new drugs offer, for the first time, a realistic opportunity for the elimination of the disease across Europe by 2030. While effective, the high price of these treatments could pose a significant financial challenge to healthcare systems. But the costs of failing to take action could potentially be even higher. If HCV is left untreated, in many cases it can lead to liver failure and liver cancer which means that a liver transplant is the only viable course of treatment available.

"Speak Up" on World Hepatitis Day - The Hepatitis C Trust Patient Conference programme announced

The Hepatitis C Trust Patient Conference programme announced



The Hepatitis C Trust is delighted to confirm the programme for this year's Patient Conference, which is being held in London on 28th July to coincide with World Hepatitis Day. Speakers will include Professor Graham Foster (Professor of Hepatology, Queen Mary University), Sam May (Head of Support Services, The Hepatitis C Trust), and Dr Magdalena Harris (Lecturer, London School of Hygiene and Tropical Medicine), and there will also be an opportunity to share personal stories about the impact of hepatitis C.

The event is free to attend for all patients and professionals and you can secure your place here.

Continue reading....

Investigational Hepatitis C Drugs Show Promising Results

Investigational Hepatitis C Drugs Show Promising Results



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...

Monday, June 19, 2017

Letter: the influence of direct acting agents for hepatitis C, on hepatitis B reactivation

Volume 46, Issue 2
July 2017  Page 208

LETTERS TO THE EDITORS
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Letter: the influence of direct acting agents for hepatitis C, on hepatitis B reactivation
C.-C. Wang, J.-H. Kao
First published: 15 June 2017
Full publication history DOI: 10.1111/apt.14116  

SIRS,
We read with great interest the article by Londono et al.[1] In this study, baseline HBsAg positivity or isolated anti-HBc positivity were 2.8% and 18% in 352 chronic hepatitis C (CHC) patients receiving direct-acting antivirals (DAAs), respectively. They found that 50% of HBsAg-positive and 1.6% of anti-HBc-positive patients had hepatitis B virus (HBV) viral reactivation (> 1 log increase in HBV-DNA level). In addition, the increase in HBV-DNA was modest and early during the course of DAAs treatment. There were no serious clinical events in such patients. They thus suggested that HBV viral reactivation is frequent and early during DAAs treatment; however, the reactivation is modest and without clinical impact. Although these data provide more evidence about the risk of HBV reactivation during DAAs for CHC, several issues are worthy of discussion and further investigations.

First, this study found HBV reactivation is frequent in HBsAg-positive patients receiving DAAs against HCV. However, only 10 HBV/HCV co-infected patients were included, and they had a higher risk of HBV viral reactivation than those positive for anti-HBc antibody. Among these HBsAg-positive patients, six were inactive carriers and four received anti-HBV agents. Therefore, the frequency and severity of HBV viral reactivation may be underestimated as is observed in clinical practice. It is recommended that HBV status, either chronic active infection, inactive carrier or resolved infection, must be confirmed before starting DAAs, especially in HBV endemic area by measuring serum HBsAg, HBV-DNA, anti-HBc, and anti-HBs antibody. On-treatment HBV-DNA monitoring at Week 4 of DAAs treatment is required for early detection of HBV viral reactivation to prompt anti-HBV treatment and prevent the occurrence of hepatitis flare as well as subsequent fulminant hepatic failure.[2, 3] Second, 24.8% of HBV/HCV co-infected patients had HBeAg-negative chronic hepatitis in our previous study.[4] Our data showed that combination of pegylated interferon plus ribavirin is equally effective for patients with HCV mono-infection and those with dual HBV/HCV infection. In addition, post-treatment HBsAg seroclearance was observed in 11.2% of 161 HBV/HCV co-infected patients. Interferon-based regimen is known active against both HBV and HCV; however, DAAs are only effective for HCV. Whether combination of DAAs and anti-HBV agents is cost-effective for HBV/HCV co-infected patients with high HBV-DNA levels (> 2000 IU/mL) deserves additional studies. Third, a recent study showed a high rate of hepatocellular carcinoma (HCC) recurrence in HCV-related HCC patients receiving DAAs after curative treatment.[5] The possible explanation is the disruption of host immune surveillance after HCV clearance. Since host immune responses play an important role in the interaction between HBV and HCV in HBV/HCV co-infected patients, the dynamic change in immune markers during DAAs therapy for CHC deserves further investigations.

REFERENCES
Londono MC, Lens S, Marino Z, et al. Hepatitis B reactivation in patients with chronic hepatitis C undergoing anti-viral therapy with interferon-free regimens. Aliment Pharmacol Ther. 2017;45:1156-1161.
  • 2De Monte A, Courjon J, Anty R, et al. Direct-acting antiviral treatment in adults infected with hepatitis C virus: reactivation of hepatitisB virus coinfection as a further challenge. J Clin Virol. 2016;78:27-30.
  • 3Ende AR, Kim NH, Yeh MM, et al. Fulminant hepatitis B reactivation leading to liver transplantation in a patient with chronic hepatitis C treated with simeprevir and sofosbuvir: a case report. J Med Case Rep. 2015;9:164.
  • 4Liu CJ, Chen PJ, Chen DS, Tseng TC, Kao JH. Perspectives on dual hepatitis B and C infection in Taiwan. J Formos Med Assoc. 2016;115:298-305.
  • 5Reig M, Marino Z, Perello C, et al. Unexpected early tumor recurrence in patients with hepatitis C virus –related hepatocellular carcinoma undergoing interferon-free therapy: a note of caution. J Hepatol. 2016;65:719-726.
  • Saturday, June 17, 2017

    In an uncertain world, viral hepatitis is one problem we can solve

    In an uncertain world, viral hepatitis is one problem we can solve
    By Ryan Clary, opinion contributor -     

    These days, it feels like there’s no shortage of threats. Fears of national security breaches, terrorism, global warming and more all play in surround sound in the media and on Capitol Hill.

    With all of these dangers dominating the news cycle and the congressional calendar, it’s easy to forget the silent threats that also deserve our attention. One of these noiseless threats is viral hepatitis.

    Wednesday, June 14, 2017

    Acute kidney injury in chronic Hep C treated with sofosbuvir-based regimens

    Acute kidney injury in chronic Hep C treated with sofosbuvir-based regimens
    The frequency of acute kidney injury in patients with chronic hepatitis C virus infection treated with sofosbuvir-based regimens, reports the latest issue of the Alimentary Pharmacology & Therapeutics

    Guidelines recommend withholding sofosbuvir in patients with an estimated glomerular filtration rate of less than 30 mL/min.

    Dr Andres Duarte-Rojo and colleagues from Arizona, USA assessed the risk of acute kidney injury in patients with no renal contraindications for sofosbuvir-based treatment.

    The team performed a multicenter retrospective observational study included all consecutive patients that were treated with sofosbuvir-based regimens at 2 tertiary university centers in North America.

    Acute kidney injury was defined as an increase of 0.3 mg/dL or more in serum creatinine level.

    The scope of the position statement included evidence that serrated lesions have premalignant potential

    In total, 426 patients were included and treated with a sofosbuvir-based regimen or telaprevir/boceprevir-based regimen.

    The team found that among patients treated with a telaprevir/boceprevir-based regimen, 18% experienced acute kidney injury compared to 11% of patients treated with sofosbuvir-based regimens.

    The researchers showed that the presence of ascites, and the use of NSAIDs were associated with a risk of acute kidney injury during sofosbuvir-based antiviral therapy.

    Creatinine levels returned to normal at end of follow-up in 88% of patients who experienced acute kidney injury with a sofosbuvir-based regimen, and had a creatinine level available during follow-up.

    Dr Duarte-Rojo's team comments, "Although the risk for acute kidney injury was lower than for patients treated with telaprevir/boceprevir-based regimens, acute kidney injury was seen during 11% of sofosbuvir-based regimens and was mostly reversible."

    "Patients with ascites and patients using NSAIDs have an increased risk for acute kidney injury during sofosbuvir-based antiviral therapy."

    Global health experts say elimination of hepatitis C in the US is possible: How do we make it happen?

    Global health experts say elimination of hepatitis C in the US is possible: How do we make it happen?
    With a growing consensus in the global health community that Hepatitis C (HCV) could be eliminated, a new report from the O'Neill Institute for National and Global Health Law at Georgetown University highlights a key missing element needed to achieving complete elimination adequate surveillance and monitoring and explains how modest investments would improve lives and save money. The report was published June 13 ahead of the National Viral Hepatitis Roundtable congressional briefing June 14.

    The report is available for free on the O'Neill Institute website

    The Centers for Disease Control and Prevention (CDC) estimates that at least 3.5 million Americans currently have HCV infection, and rates of new infections have increased nearly 2.9-fold between 2010 and 2015. The latest data from 2015 indicate that an estimated 33,900 new infections occurred that year alone.

    The report, "Monitoring the Hepatitis C Epidemic in the United States: What Tools are Needed to Achieve Elimination?" explains that effective medicines are available to treat and often cure hepatitis C, but information is lacking to know where to "deploy critical public health and health care resources to prevent new infections, screen and diagnose cases, and treat all of those who are infected with the virus," write the authors.

    Written by Institute Associate Sonia L. Canzater, JD, MPH and Jeffrey S. Crowley, MPH, program director of infectious disease initiatives and distinguished scholar at the O'Neill Institute, the report was developed following an expert consultation held in Washington, DC, in September 2016 with diverse stakeholders, including hepatitis C medical and non-medical providers, patient advocates, epidemiologists, and federal hepatitis C policy and program staff.

    Crowley and Canzater identify five critical actions that should be priorities for monitoring HCV: 1) expand and standardize reporting to the CDC, 2) utilize electronic medical records to collect data on HCV cases and the cure cascade, 3) fund epidemiologic research using clinical data sets, 4) integrate improved monitoring of HCV with responses to the opioid epidemic, and 5) establish and monitor HCV elimination plans across major US health systems.

    "Even with a constrained federal budget, more resources are needed for HCV surveillance and monitoring," Crowley said, adding, "Relatively modest investments, however, can have a big impact toward eliminating HCV."

    Canzater said that, "Most of the newly infected HCV cases are among injection opioid drug users, but we often do not have even basic information to adequately monitor where and how the HCV epidemic is unfolding in the US and we are not using the clinical data that is already collected." Canzater and Crowley say eliminating HCV would lead to a plummet in liver cancer rates (HCV was responsible for half of the nearly 23,000 liver cancer deaths in 2010). Almost $300 million a year in health care costs could be saved by avoiding the liver transplant surgeries caused by HCV.

    Canzater and Crowley conclude, "Unlike some pressing problems where the scope of need is so large it can be immobilizing, modest new investments can have a significant impact. Boosting the capacity to monitor the HCV epidemic can move the nation toward eliminating HCV as a public health threat in the United States."

    Story Source:
    Materials provided by O'Neill Institute for National & Global Health Law.

    Tuesday, June 13, 2017

    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.....

    Regulus Discontinuing clinical development of RG-101 for HCV

    Regulus Announces Pipeline Updates and Advancements

    Phase II RG-012 HERA and Renal Biopsy studies for Alport syndrome move forward
    Discontinuing clinical development of RG-101
    Pre-clinical pipeline progresses

    LA JOLLA, Calif., June 12, 2017 /PRNewswire/ -- Regulus Therapeutics Inc. (NASDAQ: RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced updates to its pre-clinical and clinical development programs.

    "We are squarely focused on taking the steps necessary to advance our pipeline and continue building shareholder value. To that end, we recognize that we must be disciplined in our investment choices and focus our resources and capital on our most promising discovery and development programs, including the application of important development, regulatory and commercial considerations," said Jay Hagan, President and Chief Executive Officer of Regulus. "MicroRNA therapeutics have the potential to become an important new class of drugs with broad therapeutic application. Regulus' focus will be in diseases with significant unmet medical need in organs to which we have been able to preferentially deliver oligonucleotide therapeutics effectively, such as the liver and kidney."

    RG-012 for Alport syndrome: Initiation of the Phase II clinical programs for RG-012 for the treatment of Alport syndrome is on track as planned. Important changes to the Phase II study design have been incorporated with the goal to accelerate patient enrollment, improve statistical power, and potentially achieve proof of mechanism data by the end of 2017. HERA, the Phase II randomized (1:1), double-blinded, placebo-controlled study evaluating the safety and efficacy of RG-012 in Alport syndrome patients, has been modified to increase enrollment to 40 patients to improve its statistical power. Dose frequency has also been adjusted to once every other week. The separate renal biopsy study will evaluate RG-012 renal tissue pharmacokinetics, target engagement and downstream effects on genomic disease biomarkers. Data from the renal biopsy study is anticipated by year-end and interim data from HERA is anticipated mid-2018. 

    RG-101 (anti-miR122) for HCV: The Company announced today that it plans to discontinue clinical development of RG-101 upon completion of the one remaining clinical study, which is expected to occur in July 2017. Comprehensive pre-clinical investigation and thorough evaluation of the clinical data from RG-101 has led to the identification of a bilirubin transport mechanism as the likely cause for the cases of hyperbilirubinemia in the RG-101 program. We believe that a combination of factors including inhibition of conjugated bilirubin transport by RG-101, impaired baseline bilirubin transport in HCV patients and the preferential uptake of RG-101 by hepatocytes contributed to this mechanism. Additional patient specific contributing factors cannot be excluded. Applying the learnings from the RG-101 program, alternative compounds targeting miR-122 have been identified that maintain potent HCV antiviral activity while lacking inhibition of the bilirubin transporter. These compounds have the potential for rapid clinical proof-of-concept of a novel, markedly shortened treatment regimen for HCV and will be considered for further development pending an updated global commercial market assessment for HCV.

    RGLS4326 (anti-miR-17) for autosomal dominant polycystic kidney disease (ADPKD): The IND for RGLS4326 is on track for filing by year end 2017. IND enabling toxicology, repeat pharmacology and manufacturing work have been completed as scheduled to support regulatory submissions. Data from the pre-clinical program have been recently published in Nature Communications and support the rationale for targeting miR-17 for the treatment of ADPKD, an orphan indication with no treatment options affecting approximately 600,000 people in the United States. 

    RGLS5040 (anti-miR-27) for cholestatic disease: RGLS5040, an unconjugated inhibitor of microRNA27, has been discontinued based on a positioning of the compound with respect to the competitive landscape coupled with the results from repeat pharmacology studies as part of IND-enabling work. The Company continues to work on developing highly effective therapeutics for genetic forms of cholestatic disease as part of its overall research activities targeting unmet diseases of the liver and kidney.
    "With the focus of our efforts on the most promising programs in our portfolio and the opportunity to explore additional novel clinical applications of miRNA targeted therapeutics, I am more excited than ever about the opportunity to deliver game-changing therapeutics for patients with great unmet medical need," said Dr. Timothy Wright, Regulus' Chief R&D Officer.
    Separately, AstraZeneca informed the Company that it intends to terminate the clinical development program for AZD4076(RG-125) for the treatment of NASH in Type 2 Diabetes/Pre-diabetes. Pursuant to the terms of the licensing agreement, AstraZeneca's rights with respect to AZD4076(RG-125) will revert to Regulus when the termination becomes effective in twelve months.  AZD4076(RG-125) was jointly identified and selected as a clinical candidate in April 2015 by AstraZeneca under the companies' strategic alliance to discover, develop and commercialize microRNA therapeutics.
    http://ir.regulusrx.com/releasedetail.cfm?ReleaseID=1029833

    Saturday, June 10, 2017

    CROI 2017: Highlights of Advances in Viral Hepatitis and Liver Fibrosis.

    Top Antivir Med. 2017 May/Jun;25(2):84-92.

    CROI 2017: Highlights of Advances in Viral Hepatitis and Liver Fibrosis.
    Luetkemeyer AF1, Wyles DL2.

    ABSTRACT:
    At the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington, hepatitis C virus (HCV) infection was a major focus in the context of HIV-associated liver disease. Well-tolerated direct-acting antiviral (DAA) regimens have enabled effective treatment of the populations that are hardest to cure, including those with decompensated cirrhosis, and many studies examined the impact of HCV cure on hepatitis and extrahepatic outcomes. Scaling up access to DAAs and the impact that their universal availability can have on reducing prevalence were key topics. There was much discussion of what is needed to eliminate HCV on local and global levels and a focus on ensuring that the populations hardest to reach can access treatment. Prevention of new infections and reinfection will be key to sustaining the benefits of scaled-up HCV treatment, with particular attention to populations at elevated risk for HCV reinfection, including HIV-infected men who have sex with men (MSM) as well as some HIV-uninfected MSM on preexposure prophylaxis. In the hepatitis B virus (HBV) arena, a landmark phase III trial demonstrated that tenofovir disoproxil fumarate given to HBV-infected pregnant women at week 28 of gestation, in combination with postpartum HBV vaccination and hepatitis B immunoglobulin, resulted in zero mother-to-child transmissions of HBV.

    Keywords: CROI, 2017, hepatitis, HBV, HCV, viral hepatitis, direct acting antivirals  

    Authors Bio: Dr Luetkemeyer is Associate Professor at the University of California San Francisco. Dr Wyles is Chief of the Infectious Diseases Division at Denver Health in Colorado. Send correspondence to Anne F. Luetkemeyer, MD, 995 Potrero Ave, Box 0874, San Francisco, CA 94110.

    Selected Topics
    HCV Natural History and Markers of Clinical Fibrosis
    HCV Treatment Outcomes: Impact of Generics and Genotype
    Toxicity and Drug Interactions During DAA Treatment
    HCV Treatment in Cirrhosis and Post-Liver Transplant
    Impact of HCV on Extrahepatic Disease, Lipid Profiles, and Overall Mortality
    Hepatocellular Carcinoma


    All cited abstracts appear in the CROI 2017 Abstracts eBook, available online at www.CROIconference.org.

    Recommended Links
    CROI 2017 - Conference on Retroviruses and Opportunistic Infections (CROI)
    February 13-16, 2017, Seattle WA

    Sorry, You're Not Sick Enough: Approach to Hep C Defies Logic

    Sorry, You're Not Sick Enough: Approach to Hep C Defies Logic
    You've never heard Randy's story before, but you probably have patients just like him.

    Randy tested positive for hepatitis C two years ago, just one of roughly 34,000 Americans diagnosed with the disease in 2015. That year, the number of new hepatitis C virus infections reported to the CDC reached a 15-year high, nearly triple the number from 2010.

    The CDC attributes that spike, in part, to increased use of injection drugs, and the agency estimates that 3.5 million Americans are infected with hepatitis C virus. That staggering number makes it the most common bloodborne infection in the country. At least 75 percent of those patients will develop chronic infection, which can lead to cirrhosis or liver cancer.

    Source
    American Family Physician
    The AAFP’s peer-reviewed, evidence-based clinical journal offers concise, easy-to-read clinical review articles for physicians and other health care professionals.

    Friday, June 9, 2017

    Response to Cochrane Collaboration review in to Hepatitis C medicines

    Update - June 13, 2017
    The Guardian has published a response to their original article that reviewed a report by Cochrane Collaboration suggesting there was no evidence new HCV treatments improve outcomes in patients infected with hepatitis C.

    The Guardian June 13, 2017
    Hepatitis C antiviral drugs are effective
    The Cochrane analysis casting doubt on this life-saving therapy is flawed and may deter patients from seeking it, say clinicians and scientists
    We are clinicians and scientists who have studied and treated patients with chronic hepatitis C virus infection over many years and patient groups that represent those affected by hepatitis C. We write in response to your article on the effectiveness of antiviral therapy (Hepatitis ‘wonder drug’ may be clinically ineffective, say experts, 9 June). The Cochrane review that you highlight analysed clinical trials, which are by nature short term, where the sole purpose was to evaluate the virological efficacy of new antiviral drugs. The trials were neither designed, nor powered, to assess mortality, so it is hardly surprising that the Cochrane review was unable to identify any impact on mortality.
    Continue reading....

    Recommended Reading
    Read a rebuttal published in Gastroenterology & Endoscopy News concerning the Cochrane report: Direct-acting antivirals for chronic hepatitis C (the Cochrane article was about the effectiveness of HCV therapy) and a response from Hepatitis C Trust addressing the latest media coverage.


    Of Interest
    Research article suggested by Graham Cooke‏ @grahamscooke
    Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response
    The results suggest that there is a significant survival benefit of achieving an SVR compared with unsuccessful treatment in a range of populations infected with hepatitis C virus.


    As a former HCV patient I would like to thank @HenryEChang, @gastroendonews - Dr. Dieterich , for pointing out the flaws in the Cochrane review article and @ABPI_UK, @HepatitisCTrust (Hepatitis C Trust) for responding to the recent media coverage.

    Response to Cochrane Collaboration review in to Hepatitis C medicines
    ​​​​​​This review was reported in the Guardian​ on Thursday 8 June.

    Dr Paul Catchpole, Director of Value & Access, at the ABPI said:

    'It can take decades for a person to realise that they are infected with Hepatitis C, by which time their liver may have been significantly damaged.

    As such, the objective of clinical trials is to demonstrate clearance of the virus in the blood (SVRs) to predict the effectiveness of treatment, rather than studying mortality which would require studies to run over periods of up to 30 years. This objective measure, along with other 'surrogate markers', are an internationally recognised and accepted benchmark used by medicines regulators, clinicians and researchers alike.

    There is also a wealth of evidence which demonstrates the impact of being infected with the Hepatitis virus on progression - from early cirrhosis of the liver through to end stage liver failure and liver transplant or liver cancer. This is why the markers that measure how much virus a patient is carrying, and whether the virus has been eradicated, are of crucial importance.

    All of this is taken into account by NICE as part of their strict assessment process.

    Our concern is that the Cochrane Collaboration research has been reported in a way that only tells half of this story, which is unhelpful for patients who are currently living through the pain of progressive liver disease or end stage liver failure.'

    http://www.publicnow.com/view/60EF3687B2F4B4E01EC3578590FD9ABAB965E53F?2017-06-09-17:31:29+01:00-xxx8318

    ABPI - The Association of the British Pharmaceutical Industry
    06/08/2017 | Press release | Distributed by Public on 06/09/2017 09:48

    Media enquiries​
    ABPI Press Office
    ​Email: pressoffice@abpi.org.uk​
    Telephone (24hrs): +44 (0) 20 7747 7147​​ About the ABPI

    The ABPI represents innovative resea​rch-based biopharmaceutical companies, large, medium and small, leading an exciting new era of biosciences in the UK.

    Our industry, a major contributor to the economy of the UK, brings life-saving and life-enhancing medicines to patients. We represent companies who supply more than 80 per cent of all branded medicines used by the NHS and who are researching and developing the majority of the current medicines pipeline, ensuring that the UK remains at the forefront of helping patients prevent and overcome disease.

    Globally our industry is researching and developing more than 7,000 new medicines.

    The ABPI is recognised by government as the industry body negotiating on behalf of the branded pharmaceutical industry for statutory consultation requirements including the pricing scheme for medicines in the UK.​​​​​​​​​

    Why do we continue to put our children at unnecessary risk of liver cancer?

    Why do we continue to put our children at unnecessary risk of liver cancer?
    On International Children’s Day (1June), the World Hepatitis Alliance calls for widespread coverage of the hepatitis B birth dose vaccine to protect our children’s futures.

    By Raquel Peck, CEO of the World Hepatitis Alliance

    Children are our future. It’s an utter cliché, but it’s true. Children are our future adults, leaders, carers. And so, we have a duty to provide children with the best start in life possible, and that means ensuring their health and wellbeing from day one. A no-brainer, right?

    Worldwide, almost two out three babies are being denied access to the hepatitis B birth dose vaccine, a simple measure which can avert a virus that can cause cirrhosis and liver cancer and accounts for over 880,000 deaths a year, globally.

    Despite the alarming figures, inexplicably not all children are receiving this life-saving intervention. Across the globe 84% of infants receive three doses of the hepatitis B vaccine. It’s a good start but to ensure full protection, the vaccine must be given shortly after birth to prevent both infection that may occur early in life and to protect against potential mother-to-child transmission if the mother is living with hepatitis B.

    In the South-East Asia region only 34% receive the birth dose vaccine; in the Eastern Mediterranean region just 23% of babies are vaccinated and in the African region as few as just 10% receive the birth dose. There are many reasons for this: vaccines are unavailable, health services are poorly provided or inaccessible, populations live in remote locations, or because families are uninformed about the importance of vaccination.

    As a mother myself, I know it might be hard to imagine putting a newborn baby through the pain of a shot but this small prick is a crucial first step to protecting a child against a deadly disease for life. What’s more, where vaccination has been implemented, it has already proven a success. The proportion of children under 5 years of age who are chronically infected with hepatitis B has fallen from 4.7% in the pre-vaccine era to 1.3% now. The fact that the majority of those living with hepatitis B are adults born before the hepatitis B was available and that the prevalence of hepatitis B among children under 5 is still at 3% in the African region shows just how crucial vaccination is in protecting children’s futures.

    The 257 million people currently living with chronic hepatitis B infection were denied this protection, but we cannot deny our children protection. In May 2016, 194 governments committed to increasing coverage of the hepatitis B birth dose vaccine to 90% by 2030.

    Today on International Children’s Day, we call on all governments to uphold their commitment by implementing vaccination programme for infants from day one. Let’s join together and raise our voices to ensure that every baby across the world gets the best possible start in life. Now, that’s a no-brainer.

    http://www.worldhepatitisalliance.org/news/jun-2017/why-do-we-continue-put-our-children-unnecessary-risk-liver-cancer

    Researchers identify how class of drugs blocks Hepatitis C virus replication

    Researchers identify how class of drugs blocks Hepatitis C virus replication
    Findings reveal a difference between strains of HCV

    Date:June 8, 2017
    Source: University of North Carolina Health Care
    Summary: For the first time, researchers show how the antiviral class of drugs called NS5A inhibitors interacts with the hepatitis C virus, and these findings show a difference between strains of HCV.

    Globally, an estimated 71 million people are living with chronic hepatitis C virus (HCV). Over decades of infection, chronic HCV infection results in progressive damage to the liver and an increased risk for end stage liver disease and liver cancer, making the virus the leading cause of liver-related deaths in the United States today.

    While effective combination therapies have recently been developed, HCV can evolve to become resistant to these antiviral drugs, potentially resulting in treatment failures. Resistance is particularly important for one class of medications used in treatment, for which the mechanism by which it stops growth of the virus is poorly understood. For the first time, researchers at the University of North Carolina at Chapel Hill have identified how the class of antiviral drugs known as NS5A inhibitors interacts with the virus, and their findings show a difference between strains of HCV. These results were published in PLOS Pathogens.

    "When HCV infects a liver cell, it establishes replication complexes (RCs) within the cell," said David McGivern, Ph.D., lead-author and an associate professor in the UNC Division of Infectious Diseases. "These may be thought of as factories that replicate the virus genetic material. We wanted to understand how long these factories persist in an infected cell after treatment with an NS5A inhibitor."

    The research team has shown previously NS5A inhibitors block the formation of new RCs, but do not affect existing RCs, which are ultimately lost from the cell during treatment. The team used NS5A inhibitors to estimate the half-life of the existing RCs and found a difference in the speed of decline depending upon the strain of HCV.

    "The majority of people who undergo antiviral treatment clear their HCV infection," said McGivern. "But about 5 percent of people experience treatment failure, often associated with drug resistance. Our findings have potentially important implications for this group of people. Did the treatment fail because replication complexes turned over more slowly? Do some strains of HCV need longer treatment? A better understanding of these issues may lead to more effective therapies active against a broader range of viruses."

    Story Source:
    Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.

    Journal Reference:
    NS5A inhibitors unmask differences in functional replicase complex half-life between different hepatitis C virus strains
    Tiffany Benzine, Ryan Brandt, William C. Lovell, Daisuke Yamane, Petra Neddermann, Raffaele De Francesco, Stanley M. Lemon, Alan S. Perelson, Ruian Ke, David R. McGivern
    PLOS Pathogens, 2017; 13 (6): e1006343 DOI: 10.1371/journal.ppat.1006343

    https://www.sciencedaily.com/releases/2017/06/170608202150.htm

    Wednesday, June 7, 2017

    Liver Cancer, Fastest-Growing Cause of Cancer Death in U.S. Incidence, rising since the 1970s, expected to continue through at least 2030

    Death Rate From Liver Cancer in US Now Double That in 1980s
    Mortality rates from liver cancer in the US are increasing faster than for any other cancer, with considerable disparities across ethnic groups.

    Report Looks at Liver Cancer, Fastest-Growing Cause of Cancer Death in U.S. Incidence, rising since the 1970s, expected to continue through at least 2030
    A new report provides an overview of incidence, mortality, and survival rates and trends for liver cancer, a cancer for which death rates have doubled in the United States since the mid-1980s, the fastest rise of any cancer in the U.S.

    The report notes that liver cancer incidence has been rising in the U.S. since at least the mid-1970s, a trend that is expected to continue through at least 2030. One major factor contributing to the increase is a higher rate of hepatitis C virus (HCV) infection among baby boomers (born between 1945 through 1965). Among this age group, HCV prevalence is approximately 2.6%, a rate 6-fold greater than that of other adults. A rise in obesity and type II diabetes over the past several decades has also likely contributed to the trend. Other risk factors include alcohol, which increases liver cancer risk by about 10% per drink per day, and tobacco use, which increases liver cancer risk by approximately 50%. Despite improvements in liver cancer survival in recent decades, only one in five patients survives five years after diagnosis.

    The report appears in CA: A Cancer Journal for Clinicians, and says differences in major risk factors as well as inequalities in access to care have led to significant racial disparities in liver cancer mortality.

    The American Cancer Society estimates that liver cancer will account for about 41,000 new cancer cases and 29,000 cancer deaths in the United States in 2017. It is the fifth leading cause of cancer death in men and the eighth leading cause of cancer death in women. About 1.0 percent of men and women will be diagnosed with liver cancer in their lifetimes.

    The report notes that liver cancer incidence has been rising in the U.S. since at least the mid-1970s, a trend that is expected to continue through at least 2030. One major factor contributing to the increase is a higher rate of hepatitis C virus (HCV) infection among baby boomers (born between 1945 through 1965). Among this age group, HCV prevalence is approximately 2.6%, a rate 6-fold greater than that of other adults. A rise in obesity and type II diabetes over the past several decades has also likely contributed to the trend. Other risk factors include alcohol, which increases liver cancer risk by about 10% per drink per day, and tobacco use, which increases liver cancer risk by approximately 50%. Despite improvements in liver cancer survival in recent decades, only one in five patients survives five years after diagnosis.

    The report identifies substantial disparity in liver cancer death rates by race/ethnicity, ranging from 5.5 per 100,000 in non-Hispanic whites to 11.9 per 100,000 in American Indians/Alaska Natives. There are also wide disparities by state, with the lowest death rates in North Dakota (3.8 per 100,000), and the highest in the District of Columbia (9.6 per 100,000). The report says the wide racial and state disparities in liver cancer mortality reflect differences in the prevalence of major risk factors and, to some extent, inequalities in access to high-quality care. “However, most liver cancers are potentially preventable,” write the authors. “Interventions to curb the rising burden of liver cancer and reduce racial/ethnic and geographic disparities should include the targeted application of existing knowledge in prevention, early detection, and treatment, including improvements in [hepatitis B virus] vaccination, screening and treatment of HCV, maintaining a healthy body weight, access to highquality diabetes care, prevention of excessive alcohol drinking, and tobacco control.
    Article: Disparities in Liver Cancer Occurrence in the United States by Race/Ethnicity and State, CA Cancer J Clin 2017: doi: 10.3322/caac.21402.
    Disparities in liver cancer occurrence in the United States by race/ethnicity and state
    Farhad Islami MD, PhD, Kimberly D. Miller MPH, Rebecca L. Siegel MPH, Stacey A. Fedewa PhD, MPH, Elizabeth M. Ward PhD, Ahmedin Jemal DVM, PhD

    Full Text Online
    First published: 6 June 2017

    Abstract
    Liver cancer is highly fatal, and death rates in the United States are increasing faster than for any other cancer, having doubled since the mid-1980s. In 2017, it is estimated that the disease will account for about 41,000 new cancer cases and 29,000 cancer deaths in the United States. In this article, data from the Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics are used to provide an overview of liver cancer incidence, mortality, and survival rates and trends, including data by race/ethnicity and state. The prevalence of major risk factors for liver cancer is also reported based on national survey data from the Centers for Disease Control and Prevention. Despite the improvement in liver cancer survival in recent decades, only 1 in 5 patients survives 5 years after diagnosis. There is substantial disparity in liver cancer death rates by race/ethnicity (from 5.5 per 100,000 in non-Hispanic whites to 11.9 per 100,000 in American Indians/Alaska Natives) and state (from 3.8 per 100,000 in North Dakota to 9.6 per 100,000 in the District of Columbia) and by race/ethnicity within states. Differences in risk factor prevalence account for much of the observed variation in liver cancer rates. Thus, in contrast to the growing burden, a substantial proportion of liver cancer deaths could be averted, and existing disparities could be dramatically reduced, through the targeted application of existing knowledge in prevention, early detection, and treatment, including improvements in vaccination against hepatitis B virus, screening and treatment for chronic hepatitis C virus infections, maintaining a healthy body weight, access to high-quality diabetes care, preventing excessive alcohol drinking, and tobacco control, at both the state and national levels.
    CA Cancer J Clin 2017. © 2017 American Cancer Society.

    View Full Text Article, here....

    Cochrane Database of Systematic Reviews - Direct-acting antivirals for chronic hepatitis C

    Cochrane Database of Systematic Reviews  - Direct-acting antivirals for chronic hepatitis C

    Read a rebuttal published in Gastroenterology & Endoscopy News concerning the Cochrane report: Direct-acting antivirals for chronic hepatitis C (on the effectiveness of HCV therapy) and a response from Hepatitis C Trust on the flawed media coverage.

    Of Interest
    Research article suggested by Graham Cooke‏ @grahamscooke
    Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response
    The results suggest that there is a significant survival benefit of achieving an SVR compared with unsuccessful treatment in a range of populations infected with hepatitis C virus.

    A rebuttal published in:  Gastroenterology & Endoscopy News

    Clinical Benefit of Direct-Acting Antivirals Beyond SVR Not Yet Shown in Hepatitis C Infection
    Boston—A Cochrane review of clinical trials with the new generation of drugs to treat hepatitis C infection has concluded no evidence exists yet that the drugs improve outcomes in patients infected with the virus.
    Not surprisingly, the assertion that improved outcomes from DAA therapy require proof is not widely shared by experts. The relationship of SVR after DAA therapy to protection from bad outcomes may not have been demonstrated in a randomized, placebo-controlled trial, but Douglas T. Dieterich, MD, director of the Institute for Liver Medicine at the Icahn School of Medicine at Mount Sinai, in New York City, insisted that plenty of evidence supports this conclusion.
    “For just one example of many, there is very good data from the Rotterdam cohort that failure to achieve SVR is associated with an approximately 300% increase in all-cause mortality,” Dr. Dieterich observed.
    Continue reading..

    As a former HCV patient thank you @HenryEChang, @gastroendonews - Dr. Dieterich for pointing out the flaws in the following Cochrane review article.....

    Thank you Hepatitis C Trust
    The Hepatitis C Trust issues a response to recent media coverage on the report
    In recent days there has been media coverage of a new study that casts doubt upon the effectiveness of new hepatitis C treatments. Given the potential that the coverage of this study has to mislead patients, The Hepatitis C Trust wishes to make clear that we have fundamental doubts as to the credibility of the research. Along with leading clinicians and scientists, we have written to The Guardian to express our concern.
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    Review Article
    Cochrane Database of Systematic Reviews
    Cochrane Database Syst Rev.2017 Jun 6;6:CD012143.
    doi: 10.1002/14651858.CD012143.pub2. [Epub ahead of print]

    Direct-acting antivirals for chronic hepatitis C
    Janus C Jakobsen, Emil Eik Nielsen, Joshua Feinberg, Kiran Kumar Katakam, Kristina Fobian, Goran Hauser, Goran Poropat, Snezana Djurisic, Karl Heinz Weiss, Milica Bjelakovic, Goran Bjelakovic, Sarah Louise Klingenberg, Jian Ping Liu, Dimitrinka Nikolova, Ronald L Koretz, Christian Gluud

    Abstract
    Background
    Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs) are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate hepatitis C virus (HCV) from the blood (sustained virological response). However, it is still questionable if eradication of hepatitis C virus in the blood eliminates hepatitis C in the body, and improves survival and leads to fewer complications.

    Objectives
    To assess the benefits and harms of DAAs in people with chronic HCV.

    Search methods
    We searched for all published and unpublished trials in The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, LILACS, and BIOSIS; the Chinese Biomedical Literature Database (CBM), China Network Knowledge Information (CNKI), the Chinese Science Journal Database (VIP), Google Scholar, The Turning Research into Practice (TRIP) Database, ClinicalTrials.gov, European Medicines Agency (EMA) (www.ema.europa.eu/ema/), WHO International Clinical Trials Registry Platform (www.who.int/ictrp), the Food and Drug Administration (FDA) (www.fda.gov), and pharmaceutical company sources for ongoing or unpublished trials. Searches were last run in October 2016.

    Selection criteria
    Randomised clinical trials comparing DAAs versus no intervention or placebo, alone or with co-interventions, in adults with chronic HCV. We included trials irrespective of publication type, publication status, and language.

    Data collection and analysis
    We used standard methodological procedures expected by Cochrane. Our primary outcomes were hepatitis C-related morbidity, serious adverse events, and quality of life. Our secondary outcomes were all-cause mortality, ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non-serious adverse events (each reported separately), and sustained virological response. We systematically assessed risks of bias, performed Trial Sequential Analysis, and followed an eight-step procedure to assess thresholds for statistical and clinical significance. The overall quality of the evidence was evaluated using GRADE.

    Main results
    We included a total of 138 trials randomising a total of 25,232 participants. The 138 trials assessed the effects of 51 different DAAs. Of these, 128 trials employed matching placebo in the control group. All included trials were at high risk of bias. Eighty-four trials involved DAAs on the market or under development (13,466 participants). Fifty-seven trials administered withdrawn (or discontinued) DAAs. Trial participants were treatment-naive (95 trials), treatment-experienced (17 trials), or both treatment-naive and treatment-experienced (24 trials). The HCV genotypes were genotype 1 (119 trials), genotype 2 (eight trials), genotype 3 (six trials), genotype 4 (nine trials), and genotype 6 (one trial). We identified two ongoing trials.

    Meta-analysis of the effects of all DAAs on the market or under development showed no evidence of a difference when assessing hepatitis C-related morbidity or all-cause mortality (OR 3.72, 95% CI 0.53 to 26.18, P = 0.19, I2 = 0%, 2,996 participants, 11 trials, very low-quality evidence). As there were no data on hepatitis C-related morbidity and very few data on mortality (DAA 15/2377 (0.63%) versus control 1/617 (0.16%)), it was not possible to perform Trial Sequential Analysis on hepatitis C-related morbidity or all-cause mortality.

    Meta-analysis of all DAAs on the market or under development showed no evidence of a difference when assessing serious adverse events (OR 0.93, 95% CI 0.75 to 1.15, P = 0.52, I2 = 0%, 15,817 participants, 43 trials, very low-quality evidence). The Trial Sequential Analysis showed that the cumulative Z-score crossed the trial sequential boundary for futility, showing that there was sufficient information to rule out that DAAs compared with placebo reduced the relative risk of a serious adverse event by 20%. The only DAA that showed a significant difference on risk of serious adverse events when meta-analysed separately was simeprevir (OR 0.62, 95% CI 0.45 to 0.86). However, Trial Sequential Analysis showed that there was not enough information to confirm or reject a relative risk reduction of 20% and when one trial with an extreme result was excluded then the meta-analysis result showed no evidence of a difference.

    Withdrawn DAAs had no evidence of a difference when assessing hepatitis C-related morbidity and all-cause mortality (OR 0.64, 95% CI 0.23 to 1.79, P = 0.40, I2 = 0%; 5 trials, very low-quality evidence). However, withdrawn DAAs seemed to increase the risk of serious adverse events (OR 1.45, 95% CI 1.22 to 1.73, P = 0.001, I2 = 0%, 29 trials, very low-quality evidence), and Trial Sequential Analysis confirmed this meta-analysis result.

    DAAs seemed to reduce the risk of no sustained virological response (RR 0.44, 95% CI 0.37 to 0.52, P < 0.00001, I2 = 77%, 6886 participants, 32 trials, very low-quality evidence), and Trial Sequential Analysis confirmed this meta-analysis result.

    Only 1/138 trials assessed the effects of DAAs on health-related quality of life (SF-36 mental score and SF-36 physical score).

    The majority of all outcome results were short-term results, so we could neither confirm nor reject any long-term effects of DAAs. None of the 138 trials provided useful data to assess the effects of DAAs on the remaining secondary outcomes (ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, and hepatocellular carcinoma).

    Authors' conclusions
    Overall, DAAs on the market or under development do not seem to have any effects on risk of serious adverse events. Simeprevir may have beneficial effects on risk of serious adverse event. In all remaining analyses we could neither confirm nor reject that DAAs had any clinical effects. DAAs seemed to reduce the risk of no sustained virological response. The clinical relevance of the effects of DAAs on no sustained virological response is questionable, as it is a non-validated surrogate outcome. All trials and outcome results were at high risk of bias so our results presumably overestimate benefit and underestimate harm. The quality of the evidence was very low.

    Plain language summary
    Review question
    To assess the beneficial and harmful effects of direct-acting antivirals (DAAs) for chronic hepatitis C.

    Background
    Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Numerous previous interventions have been used for hepatitis C, but none of these interventions have proven effective on patient-centred outcomes. DAAs are relatively new but expensive interventions for hepatitis C, and preliminary results have shown that DAAs seem to eradicate hepatitis C virus from the blood (sustained virological response). However, it is questionable if an eradication of hepatitis C virus in the blood leads no hepatitis C in the body and improved survival and fewer complications. In this Cochrane Review, the authors assessed the evidence on the clinical effects of DAAs for hepatitis C.

    Study characteristics
    The authors included 351 publications of 138 randomised clinical trials. All included trials were at high risk of bias. The 138 trials used 51 different DAAs. Of these, 84 trials assessed DAAs on the market or under development; 57 trials were on DAAs withdrawn from the market. Trials were conducted from 2004-2016. The trials were from all over the world including 34 different countries. We included 17 trials where all the participants had previously been treated for hepatitis C (treatment-experienced) before being included in the trial. There were 95 trials that included only participants who had not been previously treated for hepatitis C (treatment-naive). The intervention periods ranged from one day to 48 weeks with an average of 14 weeks. The combined intervention period and follow-up period ranged from one day to 120 weeks with an average of 34 weeks.

    Key results
    DAAs do not seem to have any effects on the risk of hepatitis C-related morbidity or all-cause mortality. In fact, there were no data on hepatitis C-related morbidity and very few data on mortality (15 deaths/2377 direct-acting antiviral participants (0.63%) versus 1 death/617 control participants (0.16%) resulting in an odds ratio of 3.72, 95% CI 0.53 to 26.18, P = 0.19, I2 = 0%, 2996 participants, 11 trials, very low-quality evidence). DAAs do not seem to have any effects on the risk of serious adverse events (376/13,574 (2.77%) direct-acting antiviral participants had one or more serious adverse events versus 125/2,243 (5.57%) control participants during the observation period resulting in an odds ratio of 0.93, 95% CI 0.75 to 1.15, P = 0.52, I2 = 0%, 15,817 participants, 66 trials, very low-quality evidence). When analysed separately, simeprevir was the only direct-acting antiviral that showed evidence of a beneficial effect when assessing risk of a serious adverse event. Our analyses, however, showed that the validity of this result is questionable and that 'play of chance' might be the cause for the difference. There was not enough information to confirm or reject if DAAs have clinically relevant effects on other clinically relevant outcomes. Our results confirm that DAAs seem to have an effect on the risk of no sustained virological response, but all of the trial results were at high risk of systematic error ('bias'), and the clinical relevance of results on virological response is questionable. The lack of valid evidence and the possibility of potentially harming people with chronic hepatitis ought to be considered before treating people with hepatitis C with DAAs.

    Quality of the evidence
    Due to several limitations, we assessed the quality of the evidence in this review as very low quality. First, all trials and outcome results were at high risk of bias, which means that our results presumably overestimate the beneficial effects of DAAs and underestimate any potential harmful effects. Second, there were limited data on most of our clinical outcomes, that is, there were only relevant clinical data for meta-analyses on all-cause mortality and serious adverse events, and for these, data were sparse. Third, most trials primarily focused and assessed the effects of DAAs on sustained virological response; however, it is questionable if sustained virological response has any clinical relevance to the person with chronic hepatitis C (see ‘Background’ in this Plain language summary).
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