Showing posts with label A-New targets for antiviral therapy. Show all posts
Showing posts with label A-New targets for antiviral therapy. Show all posts

Friday, January 8, 2016

The Hepatitis C Revolution Part 2


The Hepatitis C Revolution Part 2
What additional treatment strategies may be employed in difficult-to-treat hepatitis C patients?

Abstract
Purpose of review Novel direct-acting antiviral (DAA) agents are highly effective in the treatment of hepatitis C, achieving unprecedented rates of sustained virological response, a functional cure. However, a significant minority of patients belong to 'difficult-to-treat' groups, in which efficacy of DAAs appears less robust. The review article aims to discuss additional treatment strategies which may be employed in these patient cohorts, as well as evidence for the potential role of experimental DAAs.

Recent findings Patients with genotype 3 infection have consistently lower rates of virological clearance following DAA therapy when compared with other genotypes. However, in combination with sofosbuvir, the novel nonstructural protein 5A inhibitor daclatasvir has demonstrated high efficacy in the treatment of noncirrhotic genotype 3 infection. Recent data from phase 2 and 3 clinical studies support the use of currently approved DAA regimens in the treatment of patients with hepatitis C virus and human immunodeficiency virus (HIV) coinfection. Sustained virological response rates in coinfected patients are analogous to those observed in monoinfection, such that HIV infection itself does not pose a barrier to DAA efficacy. In posttransplant populations, DAAs have again shown great potential, with trial data validating use of sofosbuvir/ledipasvir.

Summary Unmet need persists in certain subsets of the hepatitis C patient population. The arrival on scene of novel DAAs is likely to further expand the repertoire of available therapy for these 'difficult-to-treat' groups.
Continue to full text article....

January 08, 2016
The Hepatitis C Revolution Part 1
This review article discusses novel hepatitis C virus treatment options in hopes to clarify best available evidence for clinicians treating patients with HCV.

The rapid evolution in the therapeutic landscape of hepatitis C presents a minefield to clinicians seeking to optimize therapy for their patients. Efficacy, evidence-base, side-effects, and drug combinations must be tailored to individual patients, taking into account comorbidities, degree of fibrosis, evidence of hepatic decompensation, and life expectancy. The review article aims to discuss novel hepatitis C virus (HCV) treatments with an overview of recent breakthrough research validating their potential. It is hoped that this systematic evaluation will clarify best available evidence for clinicians treating patients with HCV on a regular basis.


Wednesday, November 5, 2014

Promise and Peril: The New Hep C Drugs

Promise and Peril: The New Hep C Drugs

By Liz Highleyman
From AIDS Community Research Initiative of America
November 4, 2014

In the Pipeline
A 12-week regimen of AbbVie's "3D" combo pill (the protease inhibitor ABT-450, NS5A inhibitor ombitasvir, and polymerase inhibitor dasabuvir) has also demonstrated high cure rates. In the PEARL-III trial, SVR rates reached 99% for previously untreated genotype 1 patients without liver cirrhosis. AbbVie expects approval by the end of 2014. 
Similarly, a regimen of daclatasvir, asunaprevir, and the polymerase inhibitor BMS-791325 taken for 12 weeks cured 92% of previously untreated patients. Merck also has a promising combo in the works: the protease inhibitor MK-5172 and NS5A inhibitor MK-8742. 
Continue reading @ The Body 

Wednesday, October 8, 2014

Sovaldi - What Can We Learn from Recent Hepatitis C Treatments?

What Can We Learn from Recent Hepatitis C Treatments?

Published on Oct 2, 2014
On October 1, the Engelberg Center for Health Care Reform and the USC Schaeffer Center for Health Policy and Economics hosted a half-day forum to discuss the serious coverage challenges that accompany breakthrough treatments, such as the much-discussed new treatment for Hepatitis C, Sovaldi.



Links:
Reducing the cost of new hepatitis C drugs
An index of articles pointing the reader to the current controversy over the high price of Sovaldi.

Thursday, August 28, 2014

Hepatitis C - New Therapies Are Coming Soon: The Case To Wait

New Therapies Are Coming Soon:  The Case To Wait

Good morning folks, sit back and watch an entertaining webcast presented in a trial and jury format, which examines the "Treat Now Or Wait" scenario in patients with HCV.

The program was recently launched for your viewing pleasure over at CLDF, listen to the judge and expert witnesses discuss new HCV regimens under development with or without ribavirin in this light-hearted innovative presentation.

Click here..........

Monday, June 30, 2014

Genotype 1 HCV–Infected Cirrhotic Patients: Still Hard to Treat?

Posted Today: HCV therapies for genotype 1: A final good-bye to interferon

ClinicalThought™ 
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Genotype 1 HCV–Infected Cirrhotic Patients: Still Hard to Treat?
Mark S. Sulkowski, MD - 6/27/2014
More from this author

After years of telling our patients that better HCV treatments are coming soon, we finally have access to potent, safe, oral direct-acting antivirals (DAAs) in our clinics and we expect more oral DAA regimens to be approved over the next 18 months. As clinicians, the ability to offer the opportunity for HCV cure to our patients with the greatest medical need—those with cirrhosis—is truly great news.

Patients with HCV-related cirrhosis have the greatest risk for the development of hepatic decompensation, hepatocellular carcinoma (HCC), and the need for transplantation. They are also at the greatest risk for liver-related death in the absence of liver transplantation. At the same time, we are increasingly confident that we can decrease the risk of these life-threatening outcomes in patients with compensated cirrhosis if their underlying HCV infection is cured, appropriate lifestyle modifications are adopted (eg, cessation of alcohol and reduction of caloric intake coupled with more exercise in obese patients), and medical interventions are provided (eg, serial liver imaging studies for HCC and endoscopic surveillance and/or treatment of esophageal varices). But the bottom line is this: Patients with compensated HCV-related cirrhosis need to be cured of their chronic HCV infection with some degree of urgency.

Poor Cure Rates, High Adverse Events With Previous Therapies
So, let’s set aside the decompensated patients and those with HCC for now and focus on compensated cirrhosis. In my practice, these patients tend to be older adults infected with HCV genotype 1 or 3 and are previous nonresponders to peginterferon/ribavirin or one of the first-generation protease inhibitors. Many are poor candidates for interferon-based treatments, as this drug simply does not work well for cirrhotics; this was demonstrated as far back as the IDEAL study evaluating peginterferon alfa-2a vs alfa-2b both with ribavirin (once an important question—my, how times have changed in the world of HCV therapeutics!). With peginterferon alfa plus ribavirin, the cure rate for genotype 1 HCV–infected patients with F3/F4 fibrosis or cirrhosis was low (24% with peginterferon alfa-2a and 21% to 30% with peginterferon alfa-2b across two dosing arm), and approximately one half that seen in patients with minimal fibrosis (44%). In later studies that added one of the first-generation HCV protease inhibitors to peginterferon/ribavirin, rates of HCV cure in cirrhotic patients with genotype 1 infection were higher, in the low 60% range, but not as high as those reported in patients without cirrhosis (approximately 80%).

However, when we drill down further to the most “difficult-to-treat” patients—those with genotype 1 infection, cirrhosis, and previous null response to peginterferon/ribavirin—the cure rate with telaprevir plus peginterferon/ribavirin was an abysmal 15%. Comparable data on boceprevir use in this population are limited. Two of 4 previous null responders with F3/F4 fibrosis who received boceprevir plus peginterferon/ribavirin in the PROVIDE study achieved SVR. To make matters worse, we commonly saw significant adverse effects in these patients, including anemia and infections, not to mention liver failure in some. Good riddance to that—boceprevir and telaprevir earned a “not recommended” designation in the 2014 AASLD/IDSA guidance, and I agree they should no longer be used in settings where the newer DAAs are now available.

The Current Era of HCV Therapies
Late 2013 saw the launch of the current era of HCV treatment with sofosbuvir, the first of a brand new class of antivirals, nucleotide analogue NS5B polymerase inhibitors, and simeprevir, a vastly improved HCV NS3/4A protease inhibitor with once-daily dosing and no discernible risk of anemia. After a couple years of administering epoetin alfa and blood transfusions to our boceprevir- and telaprevir-treated patients, I am grateful for that particular attribute. My clinic has been bustling with patients wanting treatment and, not surprisingly, many are treatment-experienced cirrhotic patients.

I would like to describe one such patient, a 55-year-old black man with genotype 1b HCV compensated cirrhosis (MELD score: 10) and previous null response to peginterferon/ribavirin (his HCV RNA level actually went up at Week 12 of peginterferon/ribavirin treatment). He is healthy otherwise and anxious to take treatment, even willing to take interferon if required.

Is an interferon-based regimen his best option? In the phase III NEUTRINO study, the SVR rate in treatment-naive, genotype 1 HCV–infected cirrhotic patients treated with sofosbuvir plus peginterferon/ribavirin was approximately 80%, a good response rate compared with the past regimens. Once again, noncirrhotic patients did better: In this group, more than 90% were cured. The NEUTRINO regimen was not tested in cirrhotic previous null responders like our case patient, but an FDA analysis estimated the likely SVR rate in such patients to be approximately 70%. A few years ago, if I could have gotten my hands on an HCV regimen that could cure 70% of black cirrhotic, null responders, I would have prescribed the regimen in a heartbeat. But, today, there are treatment regimens with a higher likelihood of success available for patients like this one, including the “off-label” combination of sofosbuvir plus simeprevir.

The Coming Wave of All-Oral DAA Therapy
The data are crystal clear: For previous null responders with cirrhosis and perhaps for treatment-naive cirrhotic patients too, the best chance for a potentially life-saving HCV cure is an oral combination regimen of potent DAAs. By the end of 2014, we expect the FDA approval of the first agents in a new class of HCV DAAs called NS5A inhibitors. These agents will be an important part of 2 potent, interferon-free, all-oral regimens: the once-daily, single tablet, fixed-dose combination of sofosbuvir/ledipasvir and a 3-drug regimen that includes a fixed-dose combination of a ritonavir-boosted HCV protease inhibitor (ABT-450) plus ombitasvir (an NS5A inhibitor) administered with dasabuvir (a nonnucleoside polymerase inhibitor). The New England Journal of Medicine has published results from a series of historic phase III studies, also presented at the 2014 EASL annual meeting, in which HCV cure rates were between 82% and 100% across treated and untreated genotype 1 HCV–infected cirrhotic patients receiving these novel regimens with or without ribavirin.

Some fine-tuning of therapy may still be needed in this group of patients. In the phase III ION-1 study of sofosbuvir/ledipasvir in untreated patients, there appeared to be some drop off in response rate among cirrhotic patients who did not receive additional ribavirin compared with those who did (94% vs 100%, respectively). In the phase III ION-2 study of the same regimen in previously treated patients, cirrhotic individuals appeared to benefit more from the 24-week regimens than from 12 weeks of therapy (100% vs 82% to 86%, respectively). And in the phase III TURQUOISE-II study of the 3-drug regimen plus ribavirin in cirrhotic patients, previous null responders with genotype 1a infection also appeared to do better with 24 weeks of therapy compared with 12 weeks (93% vs 80%, respectively). Overall, however, the development of these therapies remains a remarkable achievement, and we are really looking forward to these regimens as they will permanently transform how we think about this important disease.

What About Cirrhotic Patients Who Cannot Delay Therapy?
What about my patient? To recap, he’s a 55-year-old black cirrhotic null responder with HCV genotype 1b infection. Should I wait for these future treatment options in his case? After all, we have been waiting for new therapies since he first failed peginterferon/ribavirin in 2006. This is a long time to wait for treatment that can yield an HCV cure, while hoping that HCC is not found on the next liver ultrasound.

I opted to treat him in accordance with the AASLD/IDSA HCV guidance recommendation for genotype 1 patients with previous nonresponse to therapy. I prescribed a 12-week course of sofosbuvir and simeprevir, a potent once-daily regimen. Is this his best option? The final results of the phase II COSMOS study that evaluated this regimen were hard to beat for cirrhotic patients with genotype 1b HCV : All genotype 1b patients were cured, as were most cirrhotic null responders.

The response rates in this study for patients with genotype 1a infection were also quite good, although a number of patients with this subgenotype receiving the 12-week regimens did experience viral relapse, whereas those treated for 24 weeks did well: SVR rates in the 12-week arms were between 88% to 100% across arms vs 100% in both treatment arms for the 24-week regimens. Use of ribavirin did not appear to make a difference to SVR rates, but this is not definitive. I know that some of my colleagues are adding ribavirin to the regimen for patients with genotype 1a infection who are receiving sofosbuvir plus simeprevir, on the basis that other studies have demonstrated some benefit from this approach. While I understand the limitations of the COSMOS study—it is a small phase 2 trial—currently, it is the best option for HCV cure for this cirrhotic patient who has been waiting a long time for treatment. Achieving HCV cure will dramatically reduce the likelihood that he will develop HCC or liver failure and need a liver transplant, complications of HCV that are both expensive and, for at least 15,000 Americans each year, deadly.

Your Thoughts
I am interested to hear about your own current practice for treating cirrhotic patients. In light of the new data on all-oral regimens for genotype 1 HCV, what is your management approach? Please use the comments section below to provide your insights.

Topics: HCV - Treatment
Of Interest @ CCO
My Approach to Identifying Treatment Candidates and Maintaining Patients on Long-term HBV Therapy
Highlights From EASL 2014 
Antiretroviral Therapy Update 2014

Saturday, June 28, 2014

Future Therapies for HCV: The Importance of New Treatment Paradigms and Interferon-free Regimens

Future Therapies for CHC: The Importance of New Treatment Paradigms and Interferon-free Regimens

Good afternoon folks, its time to catch up on what you missed with another edition of Weekend Reading.

Today we have a documentary exploring the high cost of HCV treatment in the UK (BAD BLOOD), a bit of news, and a must watch learning activity released last month by ViralEd. The latter; Improving the Care Patients with Chronic Hepatitis C Online Program will focus on guidelines, diagnosis, and new all oral treatments for hepatitis C.  Although the CME is for healthcare professionals, the patient will benefit greatly by viewing all three narrated presentations. The activity is easy on the ears, and even easier to follow, especially because the CME is presented in a video and slide format. However, if the program is consuming too much of your Saturday, and the family is waiting in the wings for some weekend action, skip to the last presentation - you won't be disappointed.

Each teaching module is hosted by a different CHC specialist; Mark Sulkowski, MD., Professor of Medicine, and Medical Director of Viral Hepatitis Center, Johns Hopkins University School of Medicine, will host 1) Current Guidelines for the Diagnosis and Management of Patients with HCV Infection; K. Rajender Reddy, MD., Professor of Medicine, University of Pennsylvania, presents 2) Overcoming Host and Viral Barriers to Successful Hepatitis C Therapy; and finally Nezam H. Afdhal, MD., Professor of Medicine, Harvard School of Medicine, and Chief of Hepatology, Director of Liver Center, Beth Israel Deaconess Medical Center, will end with 3) Future Therapies for CHC: The Importance of New Treatment Paradigms and Interferon-free Regimens.

After viewing each module a link is provided for anyone interested in receiving a CME credit. Finally, a menu offering all three modules will once again appear allowing us to continue. 

Registration
Just like any CME a quick free registration is required, click here to register. Enter your name, email address, and degree. If you are not a physician or nurse, type in My Degree, it worked for me.


http://www.viraled.com/modules/contact/?form_id=282

Topic Highlights


Patient Case
Baby Boomers
Revised Screening
Who Should Be Tested
Progression
Staging Disease
Morbidity and Mortality Predictions
Cure and Outcome
Genotypes
FDA Approved Drugs


Patient Case 
Undiagnosed HCV
Evolution Of HCV Treatment
SVR
Drug To Drug Interactions
Side Effects
Current Treatments
Regimens (Genotype)
SVR - Cirrhosis
 Treating Patients With Advanced Liver Disease
Transplant
Sofosbuvir - Decompensated Liver Disease


HCV - Past, Present, and Future
Patient Case
Ledipasvir  - Sofosbuvir
And MORE.......

Begin here 

Video 

BAD BLOOD 

Published on Jun 26, 2014 

A documentary exploring the treatment of Hepatitis C in the UK

 

New From Healio  

NICE seeks information from Gilead regarding cost-effectiveness of Sovaldi 

 The National Institute for Health and Care Excellence in the UK is requesting Gilead Sciences to provide more information on sofosbuvir to determine if it is cost effective to treat hepatitis C virus, according to a press release.

The antiviral oral drug sofosbuvir (Sovaldi) currently has marketing authorization in the UK for use in combination with other drugs for treating hepatitis C virus (HCV).
The National Institute for Health and Care Excellence (NICE) request is included in draft guidance on the drug, which is available for public consultation. Comments on the draft will be accepted until July 4, according to the release.

In the draft, the NICE committee does not recommend sofosbuvir within its marketing authorization for treating chronic HCV in adults. It also requests further analyses from Gilead for sofosbuvir in combination with ribavirin, with or without pegylated interferon-alfa vs. peginterferon-alfa and ribavirin in patients with HCV genotypes 1 and 3, regarding revised analyses to cost-effectiveness for patients with and without cirrhosis, HIV coinfection, along with patients’ treatment history. Sensitivity analyses that address any incremental cost-effectiveness ratios also are sought, the release said.

“Poor diagnosis rates, combined with a high number of new infections annually means that chronic hepatitis C presents a major public health challenge,” Carole Longson, PhD, director of the NICE Centre for Health Technology Evaluation, said in the release. “The available evidence shows that sofosbuvir is an effective treatment for chronic hepatitis C in certain patients. However, evidence is lacking for some subgroups of patients with chronic hepatitis C, and there are also substantial uncertainties in the evidence base presented by the manufacturer. The committee has therefore requested further information from the manufacturer before it can decide whether sofosbuvir is a cost-effective use of [National Health Service] resources.”

According to the release, approximately 160,000 people are infected with HCV in England, and a majority have genotypes 1 (46%) and 3 (43%).

 Heads Up In Canada 

SOVALDI (sofosbuvir) WEBINAR July 3, noon (PST) with Dr. Alnoor Ramji

HepCBC is co-hosting a Webinar with the Pacific Hepatitis C Network on July 3rd at noon Pacific time. Dr. Alnoor Ramji will present the most accurate and most current information about SOVALDI (sofosbuvir), and will be available to answer your questions. Registration information will be available at this website soon. Stay tuned!

HepCBC is asking everyone’s help in approving all the new hepatitis drugs for coverage by BC PharmaCare. Between now and July 10th, you can contribute your voice to HepCBC’s Patient Group SOVALDI (sofosbuvir) submission: http://hepcbc.ca/sovaldi-give-personal-input-hepcbcs-patient-group-submission/.

You can also find the forms for individual patient and caregiver submissions at http://www.health.gov.bc.ca/pharmacare/yourvoice/. Deadline for these submissions is midnight, July 11th.

In Today's News

Health insurer Anthem Blue Cross and Blue Shield asks state for 12.5% rate hike

By SUSAN HAIGH Associated Press

Michael Bears, Anthem's vice president of actuary, spelled out a number of reasons for the proposed rate increase. The list included higher costs for medical services and pharmaceuticals, especially drugs for treating Hepatitis C, and fees levied by the federal government as part of the Affordable Care Act. 

Hartford - Consumers and advocates urged state insurance regulators on Friday to deny a 12.5 percent rate increase proposed by Anthem Blue Cross and Blue Shield, Connecticut's largest health insurer.

The proposed rate increase for individual plans, beginning
Jan. 1, would affect nearly 66,200 policyholders, including some who recently purchased their policies through the state's health insurance exchange, Access Health CT.

"Anthem is only one insurer asking for a rate increase, but it is an insurer that enjoys a large share of the Connecticut market," Jill Zorn, senior program officer for the Universal Health Care Foundation of Connecticut, told the Department of Insurance hearing officer reviewing the rate request. "We urge you to sharpen your pencils and carefully review all input in this rate review hearing, most especially the comments of policyholders who could not be here today."

Zorn said the state owes it to the state's policyholders "not to just rubber stamp Anthem's request to raise premiums."

Anthem was the only established Connecticut insurance company that offered both individual and small group health care plans in the state's health insurance exchange during the recent open enrollment period. It is providing coverage to the bulk of the customers who signed up for private coverage on the exchange.

With its rate increase proposal, Anthem contends it is attempting to strike a balance between being competitive price-wise and remaining solvent and financially stable.

Michael Bears, Anthem's vice president of actuary, spelled out a number of reasons for the proposed rate increase. The list included higher costs for medical services and pharmaceuticals, especially drugs for treating Hepatitis C, and fees levied by the federal government as part of the Affordable Care Act.

The hearing officer, Paul Lombardo, asked Bears to provide the agency with additional information to justify the proposed rate increase. A final decision on Anthem's rate filing will be made within 30 days after the record of Friday's proceeding is closed. The decision will be posted on the Department of Insurance website.

Besides concerns about the size of the proposed rate increase, some members of the public brought up issues with Anthem's handling of its policies sold on the state's health insurance exchange.

Arvind Shaw, CEO of the Generations Family Health Center in Willimantic, said Anthem has been slow in reimbursing for services. He said his agency is owed about $43,000 but has been paid about $290 to date. Additionally, Shaw said some of his clients' prescription drug claims were erroneously denied.

"I am very concerned for the safety and care of these patients," Shaw said.

Bloggers Corner

Hepatitis C and Vultures 
Lucinda Porter RN 

 Take action and support the Viral Hepatitis Testing Act. Fortify your liver with good food, sleep, exercise, and humor. Don’t drink. If you can’t stop, get help. Get support..
Continue reading...   

Healthy You

Liver Health News and Research
A collection of  latest research, news and health tips about viral hepatitis and liver health.

Enjoy the program, and this lovely weekend.

Always Tina

Friday, June 20, 2014

June Hepatitis C Newsletters: Two New Drugs Under FDA Review, Treatment Side Effects And So Much More....

June Hepatitis C Newsletters: Two New Drugs Under FDA Review, Treatment Side Effects And So Much More....

Each month this blog provides a link to Hepatitis Newsletters, published by advocacy groups devoted to increasing awareness and information about viral hepatitis. In addition, a rewind of hot topics, research and news is offered with a focus on HCV.

Hello folks, hope you are all enjoying your summer! We begin with this months issue of "HCV Next" recently published online over at Healio.com.

Designed as an in-depth specialty clinical information website, Healio.com features the industry’s best news reporting, dynamic multimedia, question-and-answer columns, CME and other educational activities in a variety of formats.

HCV Next will bridge the gap between cutting edge news and the patient with HCV, by seeking to provide physicians with peer context and perspective on the latest research developments. Topics that will be discussed regularly in HCV Next are diagnostics, drug/drug interaction, combination therapies, guidelines, practice management issues, regulatory aspects, coding, general economic issues and treatment of patients in special populations and those with comorbidities.

In This Months Issue



Managing Side Effects of HCV Treatment
Leah Molloy, PharmD

Patient Profile
The Next Wave: Noninvasive Alternatives to Assess Fibrosis


Editorial
Influx of Data Sets Pace for the Year Ahead


Ask the Experts
HCV Care Requires Collaborative Effort 


Feature
From A to C: 
A Brief History of the Discovery of HCV


The Take Home
The Take Home: International Liver Congress

HCV Rx
Solid Organ Transplantation: Little Research, Big Need for Patients with HCV

Hellen Chiao, MD; Catherine T. Frenette, MD

5 Questions
A Conversation with Paul Martin, MD


Trend Watch
Action Plan to Combat Hepatitis Renewed by Federal Health Officials


A Call for Improved Prevention, Control of Coinfection in Asia


Two New Drug Combinations Under FDA Review 


Staying Safe Intervention Reduced HCV, HIV Risk in Drug Users


Vietnam Vets May Not Be at Higher HCV Risk than Nonvets


Begin Here...

For Your Viewing Pleasure


Highlights from Hepatitis C Management State of the Art



The 25th Anniversary of the Discovery of the Hepatitis C Virus



June Newsletters

Liver Lowdown is the monthly general interest e-newsletter of the American Liver Foundation.

June 2014 Edition 

In This Issue
The American Liver Foundation is making national news on topics including liver wellness, disease prevention, screening and treatment. 
READ MORE

There is a lot going on at the American Liver Foundation and we invite you to join us in our many events. With our Liver Life Walks, Flavors, transplant reunions and webinars, there is a lot to be a part of. Here is what we have been up to during the last few weeks.  
READ MORE

Most people don't associate liver disease with children. Yet thousands are diagnosed with liver disease each year. Read about three kids who not only survived but thrived.
READ MORE

ALF hosts a number of events throughout the year to support liver disease awareness. Check our events calendar and find one to participate in.
READ MORE

RECIPE OF THE MONTH
Looking for a delicious recipe to try tonight? We have one for you! Have a recipe to share? We would love to hear from you.
READ MORE 

Check Us Out On Twitter and Facebook
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HepCBC’s MONTHLY NEWSLETTER
The hepc.bull, has been “Canada’s hepatitis C journal” since the late 1990′s and has been published nonstop since 2001. The monthly newsletter contains the latest research results, government policy changes, activities and campaigns you can get involved in, articles by patients and caregivers, and a list of support groups plus other useful links.

June Newsletter 

In This Issue:
HepCBC Roadshow / The Untold Story
New Drugs Now
BEVERLY JUNE ARSENAULT
September 17, 1950 – May 14, 2014  
UNTREATED HEP C IN CANADA

Stay Connected

 
The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community. 

NYC Viral Hepatitis Monthly E-Newsletter

June Issue 

Harlem Hep C Task Force Meeting Highlights
Meeting highlights available here, slides for the following presentations are here. 

Get Involved! African American Hep C Action Day: July 25th 

PREP-C Psychosocial Readiness & Preparation for Hep C Treatment:
Online assessment and guidance interactive tool. Now a shorter version for less complicated cases.

Subscribe to this Newsletter

Join Us

  
GI & Hepatology News is the official newspaper of the AGA Institute and provides the gastroenterologist with timely and relevant news and commentary about clinical developments and about the impact of health-care policy. The newspaper is led by an internationally renowned board of editors. 

View Current Issue (Vol. 8 No. 6 June 2014): PDF | Interactive Issue 

In This Issue
PEARL-II: Oral ‘3D’ effective in HCV with prior tx failure
The investigational “3D” combination of oral antiviral drugs achieved a cure rate that was amazing in the phase III PEARL-II trial involving noncirrhotic patients with hepatitis C virus genotype 1b who had previously failed pegylated interferon– based therapy.

Larazotide soothes in celiac trial
Larazotide acetate, a first-in-class oral medication developed specifically to treat celiac disease, reduced both gastrointestinal and non-GI symptoms in patients who were symptomatic despite being on a gluten-free diet in a 74-site, randomized, double-blind phase II study.

NAFLD mortality higher in normal-weight patients
Lean patients with nonalcoholic fatty liver disease had a higher overall mortality than did overweight or obese patients with NAFLD, according to a review of 1,090 biopsy-confirmed patients in the United States, Australia, Thailand, and Europe.

Stay connected



Hep C Connections - Website
Our mission is to educate the general public about hepatitis C and to provide resources and support for those affected by the virus. Hep C Connection offers a helpline to answer your questions regarding hepatitis C (HCV). You can expect respect, patience & understanding, in clear, jargon-free language from our staff & volunteers. Call 1-800-522-HEPC (4372) today!

June Newsletter 

In This Issue
Diversity is Needed in Clinical Trials
Featured HCV Clinical Trials  

South Denver Gastroenterology, PC is currently enrolling patients for:
A phase 3 trial to investigate the efficacy and safety of a 12 week regimen of simeprevir in combination with sofosbuvir in patients that have or have never gone through treatment, with chronic HCV genotype 1 infection, and that have cirrhosis...

Eight Colorado Organizations Offered Free Hepatitis C Testing to the Public

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http://www.hcvadvocate.org/index.asp

The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education. 

HCV Advocate News & Pipeline Blog
Click Here

HCV Advocate Newsletter
June Issue

In This Issue:

HCV Drugs
Alan Franciscus, Editor-in-Chief

Snapshots
Lucinda K. Porter, RN

HEALTHWISE: Hepatitis C & Liver Cancer (HCC)
Lucinda K. Porter, RN 

New At HCV Advocate

Affordable Care Act (ACA) – Special Enrollment Periods
Jacques Chambers, CLU,
Benefits Consultant
Posted June 16, 2014
When health insurance companies agreed to cover everyone that applies under the Affordable Care Act (ACA), regardless of their health or medical history, they wanted some arrangement so people couldn’t wait until they felt sick to buy insurance. That was resolved by limiting enrollment to certain Open Enrollment Periods....
Continue reading here.... 

First Steps with HCV — for the Newly Diagnosed
Offers suggestions for managing the early phases of living with an HCV diagnosis.

HCV Advocate Eblast
Stay informed on the latest news...click here to register for email alerts
 
Connect With HCV Advocate



The HCV Action network has launched a new website and issued an Action Update reviewing the fast track funding from NHS England for Sofosbuvir. 

The HCV Action network brings together health professionals from across the patient pathway, including GPs, specialist nurses, clinicians, drug action teams, public health practitioners, prison healthcare staff and commissioners. We provide resources for commissioners, medical and drug services professionals, promoting good practice in HCV care across the UK.

Welcome to the new HCV Action website, the home of the UK’s hepatitis C professional community. Browse our tailored resource libraries, view our case study map or find out more information here>

HCV Action Update:

HCV Action good practice case study: Addaction's Positive Support Project, Lanarkshire
This HCV Action good practice case study gives an overview of a successful 'Positive Support' service for hepatitis C patients. Run by Addaction and based in Motherwell, the service provides informed advice, active support and treatment to otherwise isolated people with hepatitis C living in Lanarkshire, Scotland. The case study gives a breakdown of the issues the project aims to address; how the project works, and its outputs and outcomes.
UK, Scotland Jun 2014 Case study PDF

View this infographic of @PHE_uk's study highlighting high costs of untreated hepatitis C: http://t.co/OO6PHMXfb4

Visit HCV Action Website here

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Hepatitis C news, is an online community for those living with hepatitis C. Join us for news, views and features about hep C, read the real-life experiences of our guest bloggers, and learn about living well with the condition. 

New In June @ Hepatitis C News

25 years on
This year marks the 25th anniversary of the identification of the hepatitis C virus.

 View all HEP C News Videos, here

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TRIO is an independent, not-for-profit, international organization committed to improving the quality of life of transplant candidates, recipients, their families and the families of organ and tissue donors.
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HepatitisWA (Inc) is a non-profit community-based organisation providing free services to the community. HepatitisWA aims to assist in obtaining the best possible care and support for people affected by hepatitis, reducing discrimination and stigma directed at people living with viral hepatitis and raising community awareness in relation to hepatitis. Visit our website to learn more about viral hepatitis.

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• C the person not the disease - Feature
• Is an $84,000 hepatitis treatment drug too expensive? - Feature
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ACP Internist provides news and information for internists about the practice of medicine and reports on the policies, products and activities of ACP

June Issue

Disclosing medical errors the right way
By Jessica Berthold
After a medical error, patients want an explicit statement that an error occurred, what happened, and the implications for their health. They want an outright apology, not a statement of regret. Work from global organizations is refining the right way to disclose errors.
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Did the Affordable Care Act make the grade?
By Robert B. Doherty
Four years since health care reform became law, there is finally enough information to grade how well enrollment is going. It will be many more years before the program can be judged an overall success, however.
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Get rid of GERD without unneeded costs, tests
By Stacey Butterfield
Gastroesophageal reflux disease can be diagnosed in the office, without the need for expensive tests such as endoscopy. Learn how to make the right diagnosis while avoiding confounding symptoms that might steer a patient toward the wrong specialist.
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by Brendie Kelly on June 21, 2014
Between 2001 and 2012, Ed continued to research the new and developing treatments for Hep C. Ed regularly had his blood drawn to determine the progress of the disease, and had a liver biopsy to determine the level of fibrosis in the liver and provide his physician an assessment of histology; both important factors to consider in the management and treatment of the disease. In 2012, Ed was placed on the then current treatment cocktail of interferon injections (once per week), Ribavirin (six capsules, three each twice a day), and Victrelis (two capsules, four times a day). Due to the various risk factors, his genotype and a compromised liver, it was determined that Ed would be on this treatment regimen for a total of 48 weeks, a month shy of a year.

Merck offers nearly $4B to buy hepatitis C treatment maker Idenix Pharmaceuticals
Merck is starting a tender offer today to buy all of the outstanding shares of hepatitis C treatment maker Idenix Pharmaceuticals.

Whitehouse Station-based Merck announced earlier this month that it would pay about $3.85 billion for the Cambridge, Mass.-based company. Merck is hoping that teaming Idenix's hepatitis C medicines with its experimental drugs will produce lucrative combo therapies that quickly cure most patients with the blood-borne virus afflicting tens of millions.

Hepatitis C has become one of the hottest categories in drug research as companies race to develop a combination therapy without injections and debilitating side effects. Some have had their promising candidates fail after extensive testing, due to dangerous side effects, but Gilead Sciences is already raking in billions of dollars from its groundbreaking new drug, Sovaldi.

Merck said Friday that once the tender offer closes, Idenix stockholders will receive $24.50 in cash for each Idenix share validly tendered and not withdrawn in the offer.
Idenix shares finished at $23.99 in Thursday.

The tender offer expires on Aug. 4, unless extended.

The boards of Merck and Idenix have approved the deal, which is expected to close in the third quarter. Idenix will become a Merck subsidiary.

A 4-week hep C cure? Bristol to test drugs with Gilead's Sovaldi
Reuters 
In the race to find a faster cure for hepatitis C, Bristol-Myers Squibb Co said it will test its experimental antiviral drug combination with Gilead Sciences Inc's blockbuster drug Sovaldi, hoping to cut treatment time to four weeks.

Boehringer Ingelheim exits hepatitis C field, pulls regulatory filings for faldaprevir 
By: Joe Barber
Boehringer Ingelheim on Friday announced that following a strategic review the company has decided against moving forward in the field of hepatitis C. As such, the drugmaker indicated that it will withdraw all regulatory filings for faldaprevir, which had been granted accelerated assessment by the European Medicines Agency, and will discontinue further development of the protease inhibitor.

The German pharmaceutical giant Boehringer Ingelheim is stopping development of faldaprevir, its hepatitis C virus drug.

All treatment-naive and previously treated participants using a combination pill containing Gilead Science's hepatitis C virus polymerase inhibitor sofosbuvir and NS5A inhibitor ledipasvir, without ribavirin, for 12 weeks achieved sustained virological response in a Phase 3 study in Japan, where most hepatitis C patients have HCV genotype 1b.

Also See: Gilead Announces Phase 3 Data Showing That the Fixed-Dose Combination of Ledipasvir/Sofosbuvir Achieved 100 Percent Sustained Virologic Response (SVR12) Among Patients with Chronic Hepatitis C in Japan 

Benefit of HCC screening uncertain for those with chronic liver disease 
June 18, 2014
It remains uncertain whether systematic screening for hepatocellular carcinoma leads to a survival advantage in patients with chronic liver disease,... 
June 18, 2014
Baby boomers accounted for the majority of patients with hepatitis C virus who received health care in the ED and in the outpatient and inpatient...
Editor's Note: The treatment for hepatitis C is evolving rapidly, and interferon-free options are now finally possible, with impressive sustained viral response (SVR) rates. Medscape spoke with Donald M. Jensen, MD, Professor of Medicine and Director of the Department of Hepatology at the University of Chicago, about the new and forthcoming treatment options for hepatitis C, some of which were presented at the recent Digestive Disease Week (DDW) meeting; the collaboration of care among providers in the treatment of patients; and an assessment of the cost now versus the prior standard of care.... 

The aim of this study was to evaluate efficacy of the direct-acting protein inhibitor sofosbuvir in combination with RBV in treatment-naive patients with HCV genotype 1. What were the findings?
Evidence-Based Medicine, June 2014

Consensus Guidelines -- Hepatitis C Management 
This consensus guideline provides expert opinion on the current best standard of care with available agents at this point in the rapid evolution of hepatitis C therapy.
Alimentary Pharmacology & Therapeutics, June 2014

Treatment of Chronic HCV in Children and Adolescents 
How well do children respond to treatment for chronic hepatitis C?
Archives of Disease in Childhood, June 2014

Expanding Primary Care Capacity to Treat HCV Infection 
This report outlines a care model which utilizes videoconferencing and case-based learning to enhance primary care provider capacity to treat HCV infection among underserved populations.
Morbidity & Mortality Weekly Report, June 2014

DDAs for Chronic HCV Infection in Liver Transplant Patients 
Direct acting antiviral agents provide new opportunities for treatment of HCV recurrence, but are there pitfalls?
American Journal of Transplantation, June 2014  

Provided By NATAP

FDA HCV Submissions / HCV Update - Click here

U.S. FDA Grants Priority Review to AbbVie for Investigational, All-Oral, Interferon-Free Therapy for the Treatment of Genotype 1 Chronic Hepatitis C 

Hispanics & Liver Disease/Fatty Liver, Liver Cancer & Mortality Rates Increasing Particularly Among Blacks & Hispanics 

A Multicenter Compassionate Use Protocol of Daclatasvir (BMS-790052) in Combination With Sofosbuvir With or Without Ribavirin for the Treatment of Subjects With Chronic Hepatitis C - Europe 

A Multicenter Treatment Protocol of Daclatasvir (BMS-790052) in Combination With Sofosbuvir for the Treatment of Post-Liver Transplant Subjects With Chronic Hepatitis C - USA Expanded Access Open

Provided By - Gastrohep.com

Patient-reported outcomes in HCV patients with cirrhosis treated with sofosbuvir-containing regimens 
Whether the presence of cirrhosis influences patient-reported outcomes (PROs), including health-related quality of life, during treatment with newly available anti-HCV (hepatitis C virus) regimens is unclear... 

Updated June 20, 2014
An index of articles pointing the reader to the current controversy over the high price of Solvadi
 
Bloggers Corner

Lucinda K. Porter, RN
Hepatitis C Treatment: A Gift
Hep C Warriors Friday Forum Support Group
Just post in the comment section below and be sure to check back to see replies to your comment.   Feel free to keep the conservation going and reply back.   This is how we communicate with each other on the forum.  We care about you and your thoughts.

Stay safe and healthy, until next time.

Always Tina

Tuesday, June 17, 2014

Hepatitis C Treatment: Hope on the Horizon

Medscape Medical News from Digestive Disease Week (DDW) 2014

This coverage is not sanctioned by, nor a part of, Digestive Disease Week.
Return to Article

Medscape Gastroenterology

Hepatitis C Treatment: Hope on the Horizon

Editor's Note: The treatment for hepatitis C is evolving rapidly, and interferon-free options are now finally possible, with impressive sustained viral response (SVR) rates. Medscape spoke with Donald M. Jensen, MD, Professor of Medicine and Director of the Department of Hepatology at the University of Chicago, about the new and forthcoming treatment options for hepatitis C, some of which were presented at the recent Digestive Disease Week (DDW) meeting; the collaboration of care among providers in the treatment of patients; and an assessment of the cost now versus the prior standard of care. 

Interferon-Free Options At Last

Medscape: The ION, SAPPHIRE, TURQUOISE, and PEARL studies were for hepatitis C genotype 1 and tested interferon-free regimens in specific patient populations (such as treatment-naive, treatment-experienced, and cirrhotic patients). The results of these studies have now been shared, some of which were presented at DDW. Could you briefly describe the highlights from each study? Let's start with ION-1 and ION-2.

Dr. Jensen: Historically, hepatitis C genotype 1 has been one of our more difficult-to-treat patient populations -- and 70% of the US population with hepatitis C has genotype 1 -- so most of the studies focused on interferon-free therapies for this genotype.

The ION studies use an interferon-free combination of sofosbuvir plus ledipasvir, with and without ribavirin. Sofosbuvir is a nucleotide inhibitor, and ledipasvir is an NS5A inhibitor. ION-1 and ION-2[1-2] compared 2 different regimens: ION-1 in treatment-naive patients, 16% of whom had cirrhosis, and ION-2 in treatment-experienced patients in whom a pegylated interferon and ribavirin-based therapy, with or without a protease inhibitor, had previously failed.

The regimens were similar in both of these ION studies. They compared 12 or 24 weeks of sofosbuvir and ledipasvir, with or without ribavirin. ION-1 had over 200 patients in each of the 4 arms, and ION-2 had over 100 patients in each of the 4 arms.

In ION-1, the SVR rate, or cure rate, for treatment-naive patients varied between 97% and 99%. These are truly remarkable cure rates in this patient population. In ION-2, patients in whom therapy had previously failed demonstrated SVR rates between 94% and 99%, which are almost as impressive as in ION-1.

ION-2 showed that it did not seem to matter whether patients had failed prior protease inhibitor treatment. Ribavirin really didn't add anything to the success of any of the arms in either of the 2 clinical trials.

The difference between 12 and 24 weeks was also not readily apparent. In the patients in ION-2, there was a slight numerical advantage at 24 weeks with 99%, but it was 94% and 96% in the 12-week arms.

A subanalysis of ION-2 examined treatment-experienced patients who had cirrhosis. Patients given sofosbuvir and ledipasvir with or without ribavirin for 12 weeks had a response rate of 82%-86%, whereas when they received it for 24 weeks, they did much better -- with an SVR of 100%. This will raise the issue of whether cirrhotic patients in whom previous therapy failed might do better with 24 weeks of treatment as opposed to just 12 weeks.

This was not a statistically significant difference, but certainly this point needs to be further assessed. The number of patients with cirrhosis in each of these arms is relatively small (only 22 patients in each arm), so maybe more robust numbers will give a better indication of whether a longer duration is needed in this patient population.

Medscape: What were some of the highlights from ION-3?

Dr. Jensen: ION-3[3] -- which was presented at this year's DDW meeting -- compared treatment durations of 8 weeks vs 12 weeks with a sofosbuvir and ledipasvir combination in treatment-naive, noncirrhotic patients with hepatitis C genotype 1. There were over 200 patients in each of the 3 arms: sofosbuvir and ledipasvir for 8 weeks; sofosbuvir, ledipasvir, and ribavirin for 8 weeks; and sofosbuvir and ledipasvir for 12 weeks. The SVR rate was between 93% and 95% in all of the arms. In the 8-week arms, it was 94% with sofosbuvir and ledipasvir and 93% with sofosbuvir, ledipasvir, and ribavirin; in the 12-week arm, it was 95% with sofosbuvir and ledipasvir.

This suggests that 8 weeks might be just as good as 12 weeks in treatment-naive patients with genotype 1. But a word of caution: There were no cirrhotic patients, and all were treatment-naive. There were no treatment-experienced participants.

So will 8 weeks become the standard, or is this an option only for some patients? Going forward, I think 8 weeks looks like it may be an option for treatment-naive patients with mild hepatitis C genotype 1, but it remains to be seen whether those with more complicated disease can benefit from a shorter treatment duration.

Medscape: Have shorter treatment durations, such as this one of 8 weeks, been looked at in other studies?

Dr. Jensen: An arm of the ELECTRON trial[4] investigated an even shorter duration -- 6 weeks of sofosbuvir and ledipasvir and ribavirin -- the thought being that if 8 weeks was as good as 12 weeks, what about 6 weeks? There were 25 patients in that arm, and they were treatment-naive and without cirrhosis. The SVR rate was only 68%.

So, it looks like you need more than 6 weeks, but 8 weeks looks like it's as good as 12 weeks. Eight weeks is probably the shortest duration that we can think about in treatment-naive patients with genotype 1 with this combination.

Medscape: Let's talk about some of the other studies. What are the highlights of SAPPHIRE and TURQUOISE?

Dr. Jensen: In SAPPHIRE and TURQUOISE, 3 direct-acting antiviral agents were combined with ribavirin. These agents were ABT450, which is a protease inhibitor and boosted with ritonavir; ABT267, which is an NS5A inhibitor now known as ombitasvir; and ABT333, which is a non-nucleoside inhibitor now known as dasabuvir.

SAPPHIRE I[5] included noncirrhotic patients with hepatitis C genotype 1 who had not been previously treated. They were treated with this so-called 3D combination plus ribavirin. An SVR rate of 96% was achieved in those treated for 12 weeks. So, again, this is very comparable to what we saw with the ION-1 study, but here there were no cirrhotic patients.

In SAPPHIRE II,[6] treatment-experienced noncirrhotic patients with hepatitis C genotype 1 were treated with 12 weeks of the 3D combination plus ribavirin, and they also achieved an SVR rate of 96%. There were 297 patients, which is a very robust number.

To answer the question of whether cirrhotic patients did differently, TURQUOISE II[7] was done in 380 patients with cirrhosis; both treatment-naive and treatment-experienced patients were included. One arm of 208 patients received 12 weeks of the 3D combination plus ribavirin, and in the other arm, 172 patients received 24 weeks of the 3D combination plus ribavirin. The SVR rate in the 12-week arm was 92%, and it was 96% in the 24-week arm. These are very good response rates in cirrhotic patients.

Medscape: Moving on to PEARL, these studies were undertaken to analyze genotype 1a and 1b separately. Could you share the highlights?

Dr. Jensen: There was a lingering question about whether genotype 1a and 1b respond similarly. Previous data from the SAPPHIRE studies had shown that genotype 1a responded a little less well than genotype 1b -- so, yes, the PEARL studies were undertaken to analyze genotype 1a and 1b separately.

PEARL III[8] included 419 patients with hepatitis C genotype 1b who were treatment-naive. They were given the 3D combination without ribavirin for 12 weeks, or the 3D combination with ribavirin for 12 weeks. It only studied a 12-week duration. The SVR rates were 99% in both arms, so it was extremely good in genotype 1b.

PEARL IV[8] examined genotype 1a, the subtype of genotype 1 that didn't respond quite as well as genotype 1b in prior studies. In this study, they had about 200 patients in the 3D combination without ribavirin and 100 patients in the 3D combination with ribavirin. The SVR rate was 90% in the 3D combination without ribavirin, and 97% in the 3D combination with ribavirin. So again, this is a high success rate -- a little less than PEARL III, but these were not head-to-head studies. What it suggests, however, is that patients do very well with this 3D combination with and without ribavirin. Genotype 1a may benefit a little more with ribavirin.

It's amazing that we're even saying that 90% is inferior, compared with where we were not that long ago. But this is where we're going with genotype 1, as you can see from all of the studies we discussed.


Medscape: In your opinion, what do these interferon-free treatment options mean for providers and also for patients with hepatitis C genotype 1?
 
Dr. Jensen: I think it gives a lot of hope and promise for patients with genotype 1 -- both for those who have been waiting for these new therapies, and also for those who haven't even touched therapy yet.
For patients in whom previous therapy has failed, it's even more promising. I think those patients have been the most worried. They've failed 1 or 2 courses of an interferon-based treatment, and they've been to hell and back with those therapies. They are worried that they will develop cirrhosis, that they will need a liver transplant, or that they will develop liver cancer.
I think having these high cure rates -- even in previously difficult-to-treat populations -- is really all about hope. As providers, we can offer our patients something both better and safer. 

Medscape: What's also striking about these treatment options is how well they are tolerated. What are your thoughts?
Dr. Jensen: I think that is one of the biggest things. The fact that virtually all of the patients were able to complete the trials, and very few dropped out due to side effects, is impressive. The only side effects of most of these new drugs were headache and nausea, but nothing like what was experienced with the interferon-based therapies in the past.

Getting rid of ribavirin would be another huge step forward, and it looks like that may be possible from many of these studies. Ribavirin is associated with anemia and does have some teratogenicity, so women of childbearing age have to be careful.

Besides the fact that these therapies are well tolerated, we also know that a shorter duration and less pill burden does improve patient compliance and adherence.

Options for Patients With Genotypes 2 and 3

Medscape: What's on the treatment horizon for patients with hepatitis C genotypes 2 and 3?
 
Dr. Jensen: In a study[9] presented at DDW, patients with hepatitis C genotype 2 or 3 in whom prior treatment with sofosbuvir and ribavirin had failed were successfully retreated with a sofosbuvir-containing regimen. These patients were treated with either 12 weeks of sofosbuvir plus pegylated interferon and ribavirin or 24 weeks of sofosbuvir plus ribavirin, and the SVR12 rates were then compared.
The 12-week treatment arm (sofosbuvir plus pegylated interferon and ribavirin) had 34 patients, and the 24-week treatment arm (sofosbuvir plus ribavirin) had 73 patients. This was an interim analysis, because only 26 of the 34 patients in the 12-week arm and 40 of the 73 patients in the 24-week arm completed therapy. The SVR12 rate for the 12-week arm was 92%, and in the 24-week sofosbuvir plus ribavirin arm, it was 63% (50% in genotype 2 and 63% in genotype 3). Because both genotypes 2 and 3 performed equally in the 24-week arm, it suggests that we probably need something more than just longer retreatment with sofosbuvir and ribavirin -- perhaps interferon is not totally dead.
So for patients in whom treatment has failed in previous 12-week studies of sofosbuvir and ribavirin, this suggests that if they were to be retreated, they probably would do better with 12 weeks of sofosbuvir, pegylated interferon, and ribavirin than with sofosbuvir and ribavirin for 24 weeks. This might change once we have NS5A inhibitors to combine with sofosbuvir, but for now, this may be an option for these patients going forward.

No More "Difficult to Treat" Populations

Medscape: Where are we at in the treatment of coinfected patients? Are these newer drugs effective in this patient population as well?
 
Dr. Jensen: There have been studies[10-13] in coinfected patients with several of the different combinations, such as sofosbuvir and ribavirin; sofosbuvir and ledipasvir; and simeprevir, pegylated interferon, and ribavirin. What has come out of these studies is that the response rates in coinfected patients (regardless of genotype) are very similar to that seen in similar studies of monoinfected patients.
I think the big news is that this previously "difficult to treat" patient population with HIV and HCV is probably not going to be so difficult to treat moving forward. If their HIV is under control, patients seem to respond just as well to these new direct-acting antiviral combinations as patients without HIV. I think that is terrific news.
The same can also be said for many patients with cirrhosis, in that it is probably not as difficult to treat anymore. They are responding reasonably well, though not quite as well as noncirrhotic patients.
So, we are learning that these previously difficult-to-treat populations are probably not going to be so difficult to treat with these new agents.

Challenges to Treatment May Still Remain

Medscape: There's a lot of good news now surrounding the treatment of hepatitis C. Let's talk about some of the challenges. What about patients in whom therapy with these new drugs fails? Where are we at with resistance and rescue strategies, or are those still to be determined?

Dr. Jensen: Earlier, we discussed the study that looked at the retreatment of patients with hepatitis C genotypes 2 and 3 in whom prior treatment with sofosbuvir and ribavirin had failed.

The LONESTAR-2 trial[14] also included patients with genotypes 2 and 3 in whom prior treatment with pegylated interferon and ribavirin had failed. They received sofosbuvir plus pegylated interferon and ribavirin. This suggests that pegylated interferon and ribavirin with sofosbuvir may play a role.
I think we are going to have more data in the next several months so we can analyze it better. In the short term, though, it looks like pegylated interferon and ribavirin, along with a direct-acting antiviral, may still be in play for some patients who have failed treatment.

The LONESTAR study[15] examined patients with hepatitis C genotype 1 who failed prior treatment with a protease-inhibitor regimen. They were given sofosbuvir and ledipasvir, with and without ribavirin. We will find out whether this combination works for these patients with treatment failure. My hunch is that it will.

There has been a lot of concern in the past several years about viral resistance, in part because of the protease inhibitors telaprevir and boceprevir. I think what we are finding now is resistance really isn't such an issue when you get to these high SVR rates. I think the jury is still out on patients in whom therapy fails, in terms of whether we should measure resistance or not. But clearly, it will be an issue with only a very few patients. With multiple classes of drugs, which should cover resistance to any one class of drugs, it shouldn't be a big issue.

What's Coming Down the Pipeline

Medscape: We've heard about more agents in the pipeline for hepatitis C. What additional approvals might we expect to come within the next 6-18 months?
Dr. Jensen: There are other agents in the pipeline, with a few approvals expected in late 2014 or early 2015. As we discussed earlier, there is the combination of sofosbuvir and ledipasvir, which has been submitted to the US Food and Drug Administration (FDA) for approval. Also submitted to the FDA for approval is the all-oral combination of ABT-450 and ritonavir coformulated with ombitasvir, plus dasabuvir with or without ribavirin.

The combination of daclatasvir, an NS5A replication complex inhibitor, and asunaprevir, a NS3 protease inhibitor, has also been recently submitted. This combination of daclatasvir and asunaprevir works better in hepatitis C genotype 1b than genotype 1a.

Daclatasvir is also being studied in combination with asunaprevir and BMS-791325 (a non-nucleoside inhibitor), which has shown good activity against both genotypes 1a and 1b. However, this regimen has not yet been submitted to the FDA.

A little further behind is a combination of MK-5172 (protease inhibitor) and MK-8742 (NS5A inhibitor), which is currently being studied with and without ribavirin in treatment-naive, noncirrhotic patients with hepatitis C genotype 1 in the C-WORTHy study. Although there are small numbers of patients in this phase 2 clinical trial, the interim results show very good sustained response rates of 89%-100%. This also has not yet been submitted to the FDA. 

Medscape: With these upcoming treatment options, would you advise providers to treat now or wait?
 
Dr. Jensen: The promise that these therapies will be available soon (last quarter of 2014 and early 2015) is certainly hopeful. Currently, the only approved treatments for hepatitis C genotype 1 include pegylated interferon and ribavirin; simeprevir plus pegylated interferon and ribavirin; and sofosbuvir plus pegylated interferon and ribavirin. So for a patient with hepatitis C genotype 1 and mild disease who can wait until later this year, we will probably have the option of an interferon-free treatment.
The American Association for the Study of Liver Diseases/Infectious Diseases Society of America practice guidelines[16] have recommended a combination of simeprevir and sofosbuvir without pegylated interferon and ribavirin for interferon-ineligible patients with genotype 1. This offers an alternate treatment option for patients with hepatitis C genotype 1; however, it is not approved by the FDA and would be considered an off-label combination.

For patients with hepatitis C genotypes 2 and 3, we have good options right now that are interferon-free. For genotype 2, 12 or 24 weeks of sofosbuvir and ribavirin is terrific. For genotype 3, 24 weeks of sofosbuvir and ribavirin looks very good. It's unlikely that sofosbuvir and ledipasvir will offer much in the way of an advantage for these 2 patient groups.

So I think waiting offers an advantage for patients with genotype 1, but probably not as much of an advantage for patients with genotype 2 or 3.

Collaboration of Care Between Primary Care Providers and Specialists 

Medscape: With the call for all baby boomers to be screened for hepatitis C, there will be an increased number of patients receiving diagnoses. Will the availability of these new drugs and treatment regimens make it easier for those outside of gastroenterology/hepatology to treat patients with hepatitis C?
 
Dr. Jensen: First, we have a lot of work to do in terms of screening patients. Only 50% have been tested for hepatitis C. It has been estimated that 2.7-3.2 million people in the United States, without including the homeless or incarcerated, have hepatitis C; if you include homeless and incarcerated persons, it puts this figure closer to 4-5 million people. Among patients diagnosed with hepatitis C, only 1-1.2 million were referred to care, and of those, only 600,000-700,000 have been HCV RNA tested.

Because 75% of hepatitis C patients are baby boomers born between 1945 and 1965, this birth cohort screening is a one-time test for hepatitis C that could identify a significant number. It has been estimated that over 800,000 people would be potential candidates for treatment if they had a one-time test for hepatitis C. So there is a huge need to just get people tested.

With therapies that are relatively -- or potentially -- easy, can a primary care physician or a first-line provider not only screen patients but also treat them? Personally, I think that is an option that not only is viable, but also is going to be necessary to have an impact on the downstream effects of hepatitis C.
Remember, the average age of a patient with hepatitis C is mid- to late 50s. If we delay screening and treatment, more people will develop cirrhosis; more will develop liver cancer; more will need liver transplants; more will die of end-stage liver disease; and more will die of complications, not necessarily due to hepatitis C but to indirect causes of morbidity and mortality down the road. So identifying and treating patients sooner rather than later is imperative.

This ties in to what we talked about earlier -- whether to treat now or wait. For patients with advanced fibrosis, they need to be treated now! We need to get on top of those. For patients with mild disease, can they wait a little bit? Sure; they can wait for perhaps better, cheaper therapies in the future, but not too long.

Medscape: About 25% of patients with hepatitis C have cirrhosis already. Even if we cure these patients, they will still need to be monitored, because their cirrhosis puts them at risk for liver cancer in the future. What role might primary care providers play in the care of these patients?

Dr. Jensen: That is the rub in all of this: Can we educate providers who want to treat patients with hepatitis C to do fibrosis testing, and to continue surveillance for hepatocellular carcinoma? Some have suggested that one could use a relatively simple decision point as to when to refer patients on to specialists (eg, hepatologists, gastroenterologists).

That decision point might be a platelet count. We know that patients who have a low platelet count are more likely to have advanced fibrosis, and it is something that a primary care provider could easily obtain in their patients. It could be as simple as a platelet count or an assessment of fibrosis by calculating the AST-to-platelet ratio index (APRI), which is a combination of the aspartate aminotransferase level and platelet count.

The rationale is to identify the patients with advanced fibrosis and to refer them to a specialist. We'll have to figure this out, because I don't think there are enough hepatologists to treat the 800,000 baby boomers who should be uncovered by this screening -- and to leave patients untreated would be a tragedy.

Medscape: How would you suggest simplifying the decision point in terms of when to refer a patient from a primary care provider to a specialist? 
 
Dr. Jensen: We know it can't be a complicated decision point. It's got to be simple, cheap, and reliable. The one question here is the reliability: How reliable is a low platelet count for identifying patients with advanced fibrosis? It doesn't catch everybody, but you could even make that cut-off point for the platelet count very conservative.

The normal platelet count is 150,000 platelets/µL; you could raise it up to 200,000 per µL. You could set it to where the sensitivity is good enough that patients with advanced fibrosis are referred and those with milder fibrosis are treated by primary care. It needs to be worked on, but we don't have much time to do a lot of long-term studies.

Fortunately, there are many good surrogate markers for fibrosis that don't require liver biopsy; FibroScan is one. There are blood tests: for example, FibroSURE, FibroTest, Fib 4, APRI, and FIBROSpect. Many are readily available and provide good sensitivity and specificity for identifying patients with advanced fibrosis.

The Cost Per Cure

Medscape: The high cost of these new drugs for hepatitis C has been well publicized. Could you talk about the cost, and how it compares with the cost of the prior standard of care?

Dr. Jensen: It's not just looking at the cost of the drugs, but assessing the cost per cure -- or the cost per SVR. The previous standard of triple therapy (pegylated interferon and ribavirin plus telaprevir or boceprevir) involved a lot of nursing visits and laboratory tests; many patients required blood transfusions, erythropoietin injections for anemia, and rash treatment. When you take all of the global costs associated with therapy -- not just the drug, but also the care costs -- and divide it by the success rate of that therapy, which was only 70%, you get a value that is anywhere between $172,000-$189,000 per successful treatment course. Remember, the treatments were longer too -- 24-48 weeks -- and more toxic. When you look at the cost per success, or the cost per SVR, those therapies are actually very expensive.

If you compare it with the most expensive treatment that we use today -- the off-label combination of sofosbuvir plus simeprevir, which is around $150,000 -- and even add in a couple of nursing visits and blood tests at baseline and 4, 12, and 24 weeks, it comes to about $164,000 per cure or per SVR. The success rate of this therapy is 93%. It is cheaper in terms of cost per cure than what we had before.

I'm not justifying the price of $84,000 for 12 weeks of the drug sofosbuvir by any stretch of the imagination, but I think it's short-sighted to think that these patients should instead be treated with telaprevir plus pegylated interferon and ribavirin because the cost of the drug is cheaper; I think that is a mistake. Do we need cheaper alternatives? Absolutely, we need cheaper alternatives, but we need to think about the end result as well.

Medscape: What advice can you give to providers when it comes to cost in counseling patients about their treatment options for hepatitis C? 
 
Dr. Jensen: I don't have direct advice, but I can tell you what I do for my patients -- we do discuss the cost of these medications. Every insurance provider is a little different. Patients need to check with their insurance provider (or have their specialty pharmacy check with their insurance provider) about what their obligation is in those costs.
We don't know whether the costs will get cheaper in the future; historically, with any new therapy, they have not. Further down the line, there could be cheaper alternatives, but it's probably not going to be tremendously cheaper and probably not soon. We have to have a strategy where patients with mild disease might wait and see whether there are cheaper alternatives. Many insurance providers are also reassessing their coverage for patients with mild disease, so it may be out of our hands about treating patients with mild disease anyway. I have less of a problem there.
The issue is patients with advanced disease. They need to be treated now, and I think we need to find a way to get them treated without waiting and without significant out-of-pocket expenses, but that is going to be the challenge.

Medscape: Speaking of advanced disease, what is the cost of care involved with these patients?
 
Dr. Jensen: The annual healthcare cost per patient with hepatitis C is around $20,000. Specifically, for a noncirrhotic patient with hepatitis C, the annual healthcare cost is about $17,000 per year; it's about $22,000 per year if they have compensated cirrhosis. If they develop complications, such as ascites, jaundice, or encephalopathy, it jumps up to $60,000 per year. A liver transplant is $577,000 just for the procedure itself, and then there is the added cost of the medications associated with it.
Letting these patients with advanced disease go untreated is not a cheap alternative. We need to come up with a strategy of how we are going to deal with these millions of patients with hepatitis C who haven't been identified or treated in order to avoid these downstream costs, which will be expensive.

Medscape: Is there anything else you'd like to share with Medscape's clinical audience about today's treatment of hepatitis C?
 
Dr. Jensen: It's an exciting time in the treatment of hepatitis C, and I think that is a big message. The therapy, particularly interferon-based therapy, has been so brutal in the past. There is huge hope for these new therapies in that they will be so tolerable yet effective, and that it will encourage all providers to test their patients for hepatitis C, knowing that they can be cured with a relatively easy therapy.

The recommended baby-boomer screening hasn't really been embraced yet. There are a lot of strategies being used to improve it; for example, when patients go in for their colonoscopy screening, it is suggested that they are also tested for hepatitis C.
My hunch is that by getting out the message of a new, relatively easy therapy for hepatitis C, it will increase awareness, and people will get screened and then linked to proper care. I hope that is going to be what happens.

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