Weekend Reading AASLD 2015 Key Abstracts and Treatment of HCV Genotype 3: Where are we now?

Weekend Reading AASLD 2015 Key Abstracts and Treatment of HCV Genotype 3: Where are we now?

Ready for Halloween? Around here the excitement builds, however once again the weather might not cooperate.  It may be a busy time around your house as well, but if you find yourself here in search of HCV information, I hope you consider it time well spent.

We start with a few headlines followed by key AASLD 2015 HCV Abstracts to be presented at the upcoming meeting, and last but not least the latest issue of Clinical Liver Disease.

In The News

Up to 4800 patients potentially exposed to hepatitis C at Ogden ...
OGDEN — Up to 4,800 people may have been exposed to hepatitis C by a now-fired nurse at McKay-Dee Hospital between June 2013 and November 2014, ...

CDC: Small portion of hepatitis C outbreaks occur in hospitals

Standard-Examiner - ‎9 hours ago‎
In the past eight years, 22 cases of healthcare-related hepatitis C were reported to the Centers for Disease Control and Prevention, according to the CDC's report detailing cases from 2008-2014.

Findings about WWII-Era Spread of Hepatitis C Could Inform Future Prevention Efforts
The breakneck pace of clinical research means that, by necessity, there is little time to assess the past. But research published earlier this year in the Journal of Virology on the origins of the Hepatitis C virus (HCV) shows that such examination is not a morbid trip down memory lane, but rather can deliver key insights into current prevention efforts

Study suggests unprecedented 3-week hepatitis C cure

Yet another stunning victory in the drug battle against the liver-damaging hepatitis C virus (HCV) may be in the offing: A small study suggests it may be possible to cure some people of their infections in as few as 3 weeks.

Tattoos drawing attention
The Dunedin City Council has been working with police and the Hepatitis C Resource Centre Otago to try to combat the problem, but hepatitis C health promoter Allison Beck said they were fighting an uphill battle.
''Anecdotally, yes I can say we have seen an increase in hepatitis C traced back to unsafe backyard tattooing jobs,'' she said.

Cherokee Nation gets $1.5 million grant to target hepatitis C

CATOOSA — The Cherokee Nation is getting some help to address the rate of hepatitis C in northeastern Oklahoma.

Merck CEO Says Drug-Price Debate Doesn't Account for R&D Risks
Bloomberg
Merck will probably introduce its own hepatitis C treatment next year. “If you didn't have a system that created an incentive for people like AbbVie or Merck to ...

Hepatitis C: Behind New Wonder Drugs Lies A Terrible Dilemma

There are 160m carriers of the hepatitis C virus across the world. Combined with the hepatitis B virus, which has 240m carriers, this causes 1.4m deaths every year.

Gilead Submits NDA to U.S. FDA for Fixed-Dose Combination of Sofosbuvir/Velpatasvir for Treatment of All Six Genotypes of Hepatitis C

-- If Approved, Combination Would Be First All-Oral, Pan-Genotypic Single-Tablet Regimen for Chronic HCV Infection --

Express Scripts to maintain availability of AbbVie's hep C drug

 Pharmacy benefit manager Express Scripts Holding Co said the potential risk of liver injury from AbbVie' hepatitis C treatments has not impacted the availability of the treatment for patients for whom it is safe and effective.

Statins Seem to Reduce Efficacy of Flu Vaccines
By Joe Elia
Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Two studies suggest that statins may lower the efficacy of flu vaccines, although commentators call the results "hypothesis generating" and not a reason to...

If you are living with Hepatitis C ask about a flu vaccination

The flu vaccine is provided free by the NHS to those living with serious health conditions as part of the NHS’s ‘Stay Well this Winter’ campaign. For most healthy people, flu is an unpleasant but usually self-limiting disease with recovery taking up to a week. People with flu are approximately 11 times more likely to die if they have an underlying health condition than if they don’t.

Research

HCV Guideline Update: Treat All Patients With New Drugs 

  An update has suggested that all patients, with the exception of patients with short life expectancies not related to HCV, should be treated with newer HCV medications.

Medscape Medical News, October 29, 2015 

Chronic Hep C is associated with increased risk of preterm birth 

The most recent issue of the Journal of Viral Hepatitis conducted a meta-analysis to investigate the association between HCV infection and preterm birth.

Special Issue: Managing Patients With Liver Disease
A special issue of Clinical Gastroenterology and Hepatology is dedicated to the clinical management of hepatic disorders, including nonalcoholic fatty liver disease (NAFLD), viral hepatitis, autoimmune hepatitis, and primary sclerosing cholangitis (PSC). The issue comprises 14 review articles that aim to present clinicians with evidence-based guidance and expert opinions on management of patients with liver

Read more

Hepatitis C Research Blog
Key AASLD 2015 HCV Abstracts: Dr. Lebovics
Posted on October 30, 2015

Hepatology, Creighton University, Phoenix, AZ

Click here for an overview of key HCV abstracts recommended by Dr. Lebovics to be presented at the upcoming liver meeting, including Gilead and Abbvie regimens.

Clinical Liver Disease© The American Association for the Study of Liver Diseases

Clinical Liver Disease (CLD) is the latest online learning resource of The American Association for the Study of Liver Diseases (AASLD.) CLD blends text, audio, video, webinars, and other interactive content into educational interventions launched every two months. These interventions are designed for any physician or healthcare provider caring for a patient with liver disease.

Volume 6, Issue 4 Pages 79 - 106, October 2015

Special Issue: New Treatments for CLD, Ethics and Liver Disease, Liver Transplantation & Non-Cirrhotic Portal Hypertension

New Treatments for CLD
Guest Edited by Nancy Reau, MD
Treatment of patients with hepatitis C virus genotype 3: Where are we now? (pages 79–81)
Carmen Landaverde, Jennifer T. Wells, Julio Gutierrez and Fred Poordad
Article first published online: 28 OCT 2015 | DOI: 10.1002/cld.506

Management of patients with hepatitis C virus resistance–associated variants to NS5A inhibitors: Where are we now? (pages 82–85)
Jennifer T. Wells, Carmen Landaverde, Julio Gutierrez and Eric Lawitz
Article first published online: 28 OCT 2015 | DOI: 10.1002/cld.507

Ethics and Liver Disease
Guest Edited by Andrew Aronsohn, MD
What Is the ethical (Not Legal) responsibility of a physician to treat minimal hepatic encephalopathy and advise patients not to drive? (pages 86–89)
Mette M. Lauridsen, James B. Wade and Jasmohan S. Bajaj
Article first published online: 28 OCT 2015 | DOI: 10.1002/cld.501

Transplant tourism versus proper travel for transplantation (pages 90–91)
John S. Gill and Francis L. Delmonico
Article first published online: 28 OCT 2015 | DOI: 10.1002/cld.503

What Is the moral responsibility of health care providers to report HBV or HCV status if they perform invasive procedures? (pages 92–95)
Jessica L. Mellinger
Article first published online: 28 OCT 2015 | DOI: 10.1002/cld.504

Liver Transplantation
Guest Edited by Paul Martin ' Kalyan Ram Bhamidimarri

Bone disease in cirrhosis (pages 96–99)
Nishita Patel and Santiago J. Muñoz
Article first published online: 28 OCT 2015 | DOI: 10.1002/cld.498

Criteria for liver transplantation in hepatocellular carcinoma (pages 100–102)
Laura Kulik
Article first published online: 28 OCT 2015 | DOI: 10.1002/cld.499

Non-Cirrhotic Portal Hypertension
Guest Edited by Theo Heller, MD, Ohad Etzion, MD, and Christopher Koh, MD

Systemic disease associated with noncirrhotic portal hypertension (pages 103–106)
David Semela
Article first published online: 28 OCT 2015 | DOI: 10.1002/cld.505

This too is can be a "HUGE" undertaking, although emerging data from clinical trials is promising, real world data, or HCV cure rates in real-life patients is lacking. So lets start with a few links with proven outcomes.

Just For Fun

Enjoy Halloween!
Tina

Gilead Submits NDA to U.S. FDA for Fixed-Dose Combination of Sofosbuvir/Velpatasvir for Treatment of All Six Genotypes of Hepatitis C

Gilead Submits New Drug Application to U.S. Food and Drug Administration for Fixed-Dose Combination of Sofosbuvir/Velpatasvir for Treatment of All Six Genotypes of Hepatitis C

Date(s): 28-Oct-2015 5:52 PM

For a complete listing of our news releases, please click here

-- If Approved, Combination Would Be First All-Oral, Pan-Genotypic Single-Tablet Regimen for Chronic HCV Infection --

-- Filing is Company's Third in Three Years for a New HCV Medicine --

FOSTER CITY, Calif.--(BUSINESS WIRE)--Oct. 28, 2015-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily fixed-dose combination of the nucleotide analog polymerase inhibitor sofosbuvir (SOF), approved as Sovaldi® in December 2013, and velpatasvir (VEL), an investigational pan-genotypic NS5A inhibitor, for the treatment of chronic genotype 1-6 hepatitis C virus (HCV) infection. The NDA is supported by clinical studies exploring the use of 12 weeks of SOF/VEL for patients with genotype 1-6 HCV infection, including patients with compensated cirrhosis and 12 weeks of SOF/VEL with ribavirin for patients with decompensated cirrhosis.

"As the first fixed-dose combination of two pan-genotypic, direct-acting antivirals, SOF/VEL represents an important step forward in the treatment of patients with hepatitis C," said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. "Genotype 1 is the most prevalent form of HCV in the United States, but worldwide, more than half of people living with HCV are infected with other genotypes. SOF/VEL complements our current HCV portfolio of Sovaldi and Harvoni, offering high cure rates and the potential to simplify treatment and eliminate the need for HCV genotype testing."

The FDA has assigned SOF/VEL a Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options. The NDA for SOF/VEL is supported by data from four Phase 3 ASTRAL trials, which evaluated the fixed-dose combination in hepatitis C genotypes 1-6. Of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 percent) achieved the primary efficacy endpoint of SVR12. The ASTRAL-4 study randomized 267 patients with decompensated cirrhosis (Child-Pugh class B) to receive 12 weeks of SOF/VEL with or without ribavirin (RBV), or 24 weeks of SOF/VEL. Those who received SOF/VEL plus RBV for 12 weeks achieved an SVR12 rate of 94 percent, while those who received SOF/VEL for 12 weeks and 24 weeks achieved SVR12 rates of 83 percent and 86 percent, respectively.

Patients treated with SOF/VEL for 12 weeks in ASTRAL-1, ASTRAL-2 and ASTRAL-3 had similar adverse events compared with placebo-treated patients in ASTRAL-1. The most common adverse events were headache, fatigue and nausea. The most common adverse events in ASTRAL-4 were fatigue, nausea and headache.

Gilead plans to submit a regulatory application for approval of SOF/VEL in the European Union by the end of the year.

The SOF/VEL fixed-dose combination is an investigational product and its safety and efficacy have not been established.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that FDA may not approve the SOF/VEL fixed-dose combination, and that any marketing approvals, if granted, may have significant limitations on its use. In addition, Gilead may be unable to file for regulatory approval of SOF/VEL in other geographies in the currently anticipated timelines. Further, additional clinical studies of SOF/VEL may produce unfavorable results. As a result, Gilead may not be able to successfully commercialize SOF/VEL. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2015, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full prescribing information for Sovaldi and Harvoni is available at www.gilead.com.

Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc. or its related companies.

For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Express Scripts to maintain availability of AbbVie's hep C drug

Express Scripts to maintain availability of AbbVie's hep C drug

Oct 28 (Reuters) - Pharmacy benefit manager Express Scripts Holding Co said the potential risk of liver injury from AbbVie' hepatitis C treatments has not impacted the availability of the treatment for patients for whom it is safe and effective.

The Food and Drug Administration said last week AbbVie Inc had identified cases of hepatic decompensation and liver failure in patients with liver cirrhosis who were taking the medicines.

Continue reading...

Related

Viekira Pak and Technivie - FDA warns of serious liver injury risk with hepatitis C treatments

Intercept Pharmaceuticals Announces Results of Phase 2 Trial of OCA in NASH Patients in Japan

Intercept's much-hyped NASH drug misses the mark in Phase II
Intercept Pharmaceuticals' ($ICPT) new drug for the pervasive liver disease NASH came up short in a Phase II trial in Japan, seeding some worries about an ongoing late-stage study designed to support future FDA approval.

Press Release
Intercept Pharmaceuticals Announces Results of Phase 2 Trial of OCA in NASH Patients in Japan

NEW YORK, Oct. 28, 2015 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept), a clinical stage biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat chronic underserved liver diseases, today announced the results of a 72-week Phase 2 dose ranging trial of obeticholic acid (OCA), Intercept's lead FXR agonist, in adult patients with nonalcoholic steatohepatitis (NASH) in Japan. The trial was conducted by Intercept's collaborator, Sumitomo Dainippon Pharma.

This trial is the first to evaluate the safety and efficacy of OCA in Japanese NASH patients. The primary efficacy analysis was conducted on an intention to treat (ITT) basis, testing the dose dependent effects of once daily OCA (10mg, 20mg and 40mg) versus placebo on the primary endpoint of a two point improvement in the NAFLD Activity Score (NAS) with no worsening of fibrosis. The ITT analysis included all randomized patients who received treatment (50 per group), and patients who discontinued or did not have a repeat biopsy were treated as non-responders. A pre-specified completer analysis was conducted on the patients who had biopsies at both baseline and 72 weeks (45, 44, 44 and 37 patients in the placebo, 10mg, 20mg and 40mg OCA groups, respectively).

The ITT results in the table below show a dose dependent increase in the percentage of OCA treated patients compared to placebo who achieved the primary endpoint (p=0.053, not significant). The 40mg OCA dose group achieved statistical significance on the primary endpoint compared to placebo (p=0.0496). Dose-dependent trends not reaching statistical significance were also observed for several other pre-specified histologic endpoints, including the proportion of patients with steatosis and inflammation improvement, ballooning resolution and NASH resolution. No difference was seen in fibrosis improvement in the OCA groups compared to placebo.



* Primary efficacy analysis is a stratified Cochran-Armitage test with multiple contrast coefficients. Statistical significance is based on a p-value < 0.05.

** The secondary efficacy analysis is a CMH (Cochran-Mantel-Haenszel) test stratified by baseline fibrosis stage for pairwise comparison of each OCA group vs. placebo group. The multiplicity was not adjusted.

In the completer analysis, similar dose dependent effects were observed, with 51% of patients in the 40mg dose group compared to 22% in the placebo group meeting the primary endpoint (p=0.0061).

With the exception of dose dependent pruritus, OCA appeared to be generally safe and well tolerated. The number of pruritus associated discontinuations were 0, 0, 2 and 5 patients in the placebo, 10mg, 20mg and 40mg OCA groups, respectively. Changes in lipid parameters, including LDL-C, HDL-C and triglycerides, appeared to be consistent with previously reported lipid changes in Western NASH patients. No other meaningful differences in the rate of adverse events between the OCA and placebo groups were noted.

"This study provides the first data on safety, efficacy and dose effects for OCA in Japanese NASH patients and we look forward to continuing to work with our partner Sumitomo Dainippon Pharma to understand the results further," said Mark Pruzanski, MD, Chief Executive Officer and President of Intercept. "There were distinct differences in baseline characteristics in this study population when compared to the Western patients in the previously conducted FLINT trial. We are currently actively enrolling our Phase 3 REGENERATE trial, which was designed based on the robust FLINT results to evaluate OCA's safety and efficacy in a similar Western patient population."

Conference Call on October 28th at 8:00 am ET

Intercept will hold a conference and webcast on Wednesday, October 28th at 8:00 am ET to discuss the results. The live event will be available on the investor page of Intercept's website at http://ir.interceptpharma.com or by calling (855) 232-3919 (toll-free domestic) or (315) 625-6894 (international) five minutes prior to the start time (no passcode is required). A replay of the call will be available on Intercept's website approximately two hours after the completion of the call and will be archived for two weeks.

About the Phase 2 NASH Trial Conducted by Sumitomo Dainippon Pharma

In this dose-ranging study, 202 Japanese biopsy-proven NASH patients (NAS 5-8) were randomized into one of four arms to receive either a 10mg, 20mg or 40mg dose of OCA, or placebo, and 200 of these patients - 50 per group - initiated treatment for a 72-week double-blind treatment phase, followed by a 24-week off treatment phase which is still ongoing. The primary endpoint was histologic improvement defined as at least a two point improvement in NAFLD activity score (NAS) with no worsening of fibrosis. The primary efficacy analysis tested the dose dependent effects of OCA versus placebo on the primary endpoint.

About the Phase 2b FLINT Trial

The FLINT trial was sponsored by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) and the results were published online inThe Lancet in November 2014. FLINT enrolled 283 adult biopsy proven NASH patients at eight U.S. centers comprising the NIDDK's NASH clinical research network (CRN). Patients were randomized to receive either a 25mg dose of OCA or placebo for 72 weeks. FLINT was stopped early primarily due to the demonstrated efficacy of OCA in a pre-planned interim analysis based on achieving the primary endpoint of at least a two point improvement in NAFLD Activity Score (NAS) with no worsening of fibrosis (p=0.0024 vs placebo). OCA treatment for 72 weeks also resulted in the improvement of fibrosis by at least one stage and resolution of NASH (among those with definite NASH at baseline) in a significant proportion of patients versus placebo. OCA treatment was associated with serum lipid changes, including average increases in total cholesterol and LDL-C and an average decrease in HDL-C, that developed within 12 weeks of treatment initiation, then began reversing through the end of treatment and returned to baseline during the 24-week post-treatment follow-up phase. OCA was generally well tolerated in the FLINT trial. Adverse events were generally mild to moderate in severity and the incidence in the OCA and placebo treatment groups was similar for all symptoms except pruritus. Pruritus in the OCA treatment group occurred more frequently (23% versus 6%, p < 0.0001), at a higher grade (predominantly moderate pruritus) but resulted in only one patient discontinuation.

About the Phase 3 REGENERATE Trial

In September 2015, Intercept initiated its international Phase 3 trial studying OCA in NASH. The trial, known as REGENERATE, is expected to enroll approximately 2,000 NASH patients with advanced liver fibrosis at up to 300 qualified centers worldwide. OCA is the first investigative therapy in NASH to have shown reversal of liver fibrosis with a significantly greater therapeutic response versus placebo in patients at higher risk of progression to cirrhosis. The U.S. Food and Drug Administration (FDA) has designated OCA as a breakthrough therapy in NASH patients with fibrosis and REGENERATE was designed in accordance with advice from the FDA and European Medicines Agency (EMA).

About Nonalcoholic Steatohepatitis

NASH is a serious chronic liver disease caused by excessive fat accumulation in the liver that induces chronic inflammation, resulting in progressive fibrosis (scarring) that can lead to cirrhosis, eventual liver failure, cancer and death. There are currently no drug therapies approved for the treatment of NASH. Patients with early disease but with risk factors such as diabetes, obesity or elevated ALT are at increased risk of progression to cirrhosis. The proportion of liver transplants attributable to NASH has increased rapidly in past years and by 2020 the disease is projected to become the leading indication for liver transplant ahead of chronic hepatitis C and alcoholic liver disease.

About Intercept

Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat chronic underserved liver diseases. The Company's lead product candidate, obeticholic acid (OCA), is a nuclear receptor agonist of the farnesoid X receptor (FXR). OCA is being developed for a variety of chronic liver diseases, including primary biliary cirrhosis (PBC), nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC) and biliary atresia. The FDA has granted OCA breakthrough therapy designation for the treatment of NASH with liver fibrosis and granted OCA fast track designation for the treatment of patients with PBC. OCA has also received orphan drug designation in both the United States and Europe for the treatment of PBC and PSC. Intercept owns worldwide rights to OCA outside of Japan, China and Korea, where it has out-licensed the product candidate to Sumitomo Dainippon Pharma. For more information about Intercept, please visit the Company's website at: www.interceptpharma.com.

Drug Pricing: Public Health Implications | The Forum at HSPH

Drug Pricing: Public Health Implications | The Forum at HSPH
Harvard University

Published on Oct 27, 2015

A full course of treatment with the blockbuster Hepatitis C drug Sovaldi costs $84,000 in the United States. A year on the new injectable cholesterol drugs Repatha and Praluent tops $14,000. The price of new cancer drugs now averages $10,000 per month, according to one estimate. Straining under the pressure, doctors, patients, and insurers are raising alarms over skyrocketing prices. Earlier this year, the American Society of Clinical Oncology released a new “value framework” for drugs that considers health benefit and price to help guide doctor-patient conversations around treatment options. For their part, pharmaceutical companies and some economists argue that the high cost of drug development justifies the price. This Forum explored the factors driving the high cost of new drugs. What policy changes, from the drug approval process to patent law, could change the equation? Are some of these drugs worth the cost? And what can be done to make sure that patients can afford the medications that they need?

Part of The Dr. Lawrence H. and Roberta Cohn Forums, this webcast was presented October 23, 2015 in Collaboration with Reuters and in Association with Harvard Health Publications.

Watch the entire series from The Forum at Harvard T.H. Chan School of Public Health at www.ForumHSPH.org.

Scientists track hepatitis C roots in Scotland

Scientists track hepatitis C roots in Scotland
SHÂN ROSS

The roots of hepatitis C virus (HCV) in Scotland can be traced back to the Second World War, according to new research from the University of Glasgow.

The researchers showed that HCV entered Scotland during the 1930s and 1940s while also spreading to other countries throughout the world, probably through the mass treatment of soldiers in field hospitals.

In the study published in the Journal of Virology, scientists from the MRC-University of Glasgow centre for virus research and NHS virus diagnostics labs describe how they examined the spread of HCV across Scotland by comparing the sequence of virus strains in infected individuals across various geographical areas.

Read more...

Viekira Pak and Technivie - FDA warns of serious liver injury risk with hepatitis C treatments

After patient deaths, FDA warns about liver damage risk of hepatitis C medications
The Food and Drug Administration said it had received numerous reports of patients who either died or had to undergo liver transplantation after receiving the treatments, known as Viekira Pak and Technivie. The agency said it had identified at least 26 such cases likely related to the drugs since late 2014, and that additional cases likely exist. The liver damage usually took place within four weeks of the start of treatment, and the patients involved already had cirrhosis of the liver, the agency said.

Source

Viekira Pak, Technivie May Up Serious Liver Injury Risk: FDA
"[T]he labels now state a [contraindication] in patients with moderate to severe hepatic impairment (Child-Pugh B and C). The label previously did not recommend Viekira Pak in Child-Pugh B and was contraindicated in Child-Pugh C," according to an AbbVie statement.

AbbVie's Hepatitis C Drugs Label Changed After Patient Deaths

Seven patients on AbbVie Inc.’s drugs for hepatitis C died after liver failure, prompting U.S. regulators to change their advice on how the medicine should be administered.
Doctors should monitor patients using Viekira Pak for signs of worsening liver disease, the U.S. Food and Drug Administration said in a statement Thursday..... 

Source

FDA warns of serious liver injury risk with AbbVie hep C drugs

The Food and Drug Administration said AbbVie had identified cases of hepatic decompensation and liver failure in patients with liver cirrhosis who were taking these medicines.
"Some of these events resulted in liver transplantation or death," the agency said in a posting on its website.
The FDA said it is requiring AbbVie to include warnings about the risk of serious liver injury in the labels of its combination hepatitis C treatments...

Source

Oct 22 2015

Safety Announcement
FDA Drug Safety Communication: FDA warns of serious liver injury risk with hepatitis C treatments Viekira Pak and Technivie

The U.S. Food and Drug Administration (FDA) is warning that hepatitis C treatments Viekira Pak and Technivie can cause serious liver injury mostly in patients with underlying advanced liver disease. As a result, we are requiring the manufacturer to add new information about this safety risk to the drug labels.

Patients taking these medicines should contact their health care professional immediately if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, as these may be signs of liver injury. Patients should not stop taking these medicines without first talking to their health care professionals. Stopping treatment early could result in drug resistance to other hepatitis C medicines. Health care professionals should closely monitor for signs and symptoms of worsening liver disease, such as ascites, hepatic encephalopathy, variceal hemorrhage, and/or increases in direct bilirubin in the blood.

Viekira Pak and Technivie are used to treat chronic hepatitis C, a viral infection that can last a lifetime and lead to serious liver and other health problems, including cirrhosis, liver cancer, and death. These medicines reduce the amount of hepatitis C virus in the body by preventing it from multiplying and may slow down the disease.

Our review of adverse events reported to the FDA Adverse Event Reporting System (FAERS) database and to the manufacturer of these medicines, AbbVie, identified cases of hepatic decompensation and liver failure in patients with underlying liver cirrhosis who were taking these medicines. Some of these events resulted in liver transplantation or death. These serious outcomes were reported mostly in patients taking Viekira Pak who had evidence of advanced cirrhosis even before starting treatment with it.

Since the approvals of Viekira Pak in December 2014 and Technivie in July 2015, at least 26 worldwide cases submitted to FAERS were considered to be possibly or probably related to Viekira Pak or Technivie. In most of the cases, liver injury occurred within 1 to 4 weeks of starting treatment. Some of the cases occurred in patients for whom these medicines were contraindicated or not recommended (see Data Summary). FAERS includes only reports submitted to FDA, so there are likely additional cases about which we are unaware.

We are requiring AbbVie to include information about serious liver injury adverse events to theContraindications, Warnings and Precautions, Postmarketing Experience, and Hepatic Impairment sections of the Viekira Pak and Technivie drug labels.

We urge health care professionals and patients to report side effects involving Viekira Pak or Technivie to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page...

Source =  http://www.fda.gov/Drugs/DrugSafety/ucm468634.htm

OCT/NOV 2015 American Liver Foundation Newsletter: Focus on liver cancer

Welcome to the October/November 2015 edition of the Liver Lowdown. Click on the links below and check out our featured stories for the month!

FEATURE- LIVER CANCER AWARENESS

This issue of Liver Lowdown focuses on liver cancer. Two top specialists answer your questions about liver cancer, a courageous patient tells how he turned down a liver transplant to save another; and American Liver Cancer launches a Liver Cancer Awareness Campaign with advertising on taxi tops and on buses.
READ MORE

BASIC LIVER CANCER Q&A
Are there different types of liver cancer? Find out the answer to this and other questions.
READ MORE

LIVER CANCER RISK FACTORS Q&A
Should you be screened for liver cancer? Learn the facts.
READ MORE

LIVER CANCER TREATMENT Q&A
What options exist for Liver Cancer Treatment? Get current information.
READ MORE

UNLEASH YOUR CREATIVITY FOR A GOOD CAUSE
Giving Tuesday is just around the corner. Get involved.
READ MORE

PATIENT STORY
Art Clark risked his life to save another.
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

In case you missed this months collection of Hepatitis Newsletters, please click here to view all October publications.

Diabetes, Hypertension Raise Risk for Liver Cancer

Medscape Medical News > Conference News 

Diabetes, Hypertension Raise Risk for Liver Cancer

Neil Osterweil | October 21, 2015
HONOLULU — Diabetes and hypertension are both independent risk factors for hepatocellular carcinoma, even in the absence of cirrhosis or the common causes of cirrhosis, according to a retrospective study.

Does this mean we should "screen patients with diabetes mellitus and hypertension for hepatocellular carcinoma in the absence of cirrhosis, and will this be cost-effective?" asked Allison Kasmari, MD, a gastroenterology resident at Penn State Hershey Medical Center in Pennsylvania.

Previous studies have suggested that diabetes increases the risk for hepatocellular carcinoma, prompting Dr Kasmari and her colleagues to investigate whether other components of the metabolic syndrome — such as hypertension and hyperlipidemia — increase risk.

She presented the results here at the American College of Gastroenterology (ACG) 2015 Annual Meeting.

The team retrospectively identified 17,446 patients of hepatocellular carcinoma diagnosed from 2008 to 2012 in the MarketScan Health Claims database.

The final study cohort consisted of 7473 patients, after the exclusion of those with possible confounders, such as cirrhosis, hepatitis B, alcoholic liver damage, nonalcoholic fatty liver disease, and some autoimmune and hereditary conditions.

The 22,110-person control group provided about three age- and sex- matched subjects for each patient with hepatocellular carcinoma.

Hepatitis C Link

The researchers found that diabetes is associated with the development of hepatocellular carcinoma (odds ratio [OR], 1.353), as are hypertension (OR, 1.229) and hepatitis C (OR, 2.102).

In contrast, hyperlipidemia appears to be protective against hepatocellular carcinoma (OR, 0.885).

There was a significant association between some diabetes medications, such as insulin, and an increased risk for hepatocellular carcinoma (OR, 1.640). But for other diabetes medications, such as metformin, there was a significant decreased risk (OR, 0.706).

In subanalyses, the researchers found a fourfold increase in the risk for hepatocellular carcinoma in patients with the combination of diabetes, hypertension, and hepatitis C (OR, 4.580). The risk was also elevated in patients with just diabetes and hypertension (OR, 3.399).

Risks were also elevated in patients with diabetes, hyperlipidemia, and hepatitis C (OR, 2.319), and in patients with diabetes and hyperlipidemia (OR, 2.395).

Dr Kasmari acknowledged that the patient population in this study is relatively young (range, 16 to 64 years), and that insurance claims data, compared with data from other sources, could have led to underestimates of some conditions.

In addition, the team was unable to look at obesity as a variable in their analysis, because obesity is not commonly coded as a diagnosis, she reported.

The finding that some diabetes medications are detrimental and some are protective is intriguing, said John Saltzman, MD, from Brigham and Women's Hospital in Boston, who is chair of the ACG educational affairs committee and who selected the abstract for presentation.

"Diabetes and hypertension were predictive of hepatocellular carcinoma, but I'm not sure I understand the mechanism of hypertension [in the disease]," he told Medscape Medical News.

"Are these modifiable risks?" he asked. "If you have a patient who has these things and you treat them, can you reduce those risks?"

The study funding source was not disclosed. Dr Kasmari and Dr Saltzman have disclosed no relevant financial relationships.

American College of Gastroenterology (ACG) 2015 Annual Meeting: Abstract 1. Presented October 19, 2015.

AASLD - Benitec To Present Interim Data of TT-034 Phase I/IIa Study At Liver Meeting

Benitec Biopharma's Abstract Accepted for Presentation at the AASLD Liver Meeting 2015

SYDNEY, Oct. 22, 2015 /PRNewswire/ -- Benitec Biopharma Limited (NASDAQ: BNTC; NASDAQ: BNTCW; ASX: BLT) is pleased to announce that clinical data on its Phase I/IIa study of TT-034 for hepatitis C will be presented in the 'late-breaking poster' session at The Liver Meeting® 2015, the 66th Annual Meeting of the American Association for the Study of Liver Disease (AASLD) being held in San Francisco on November 13-17, 2015.

The abstract, which has been published on the conference website, details interim results from patients in the first three cohorts in Benitec's Phase I/IIa study of TT-034, a DNA-directed RNA interference agent (ddRNAi). 

The primary endpoint that this study is monitoring is safety of this first-in-man gene therapy-based gene silencing drug. Key findings include:
The three doses of TT-034 administered to date have been well tolerated in human subjects infected with the hepatitis C virus (HCV) and there have been no reported serious adverse events related to administration of the study drug;

The initial dose (4E10 vg/kg) resulted in very low levels of transduction as expected.
The second dose (1.25E11 vg/kg) resulted in the detection of substantially higher levels of TT-034 in the hepatocytes, the predominant cell type in the liver, yielding 0.48, 3.65 and 10.44 copies of TT-034 

DNA per cell in the three patients respectively;
The first subject administered with the third dose (4.00E11 vg/kg) had 17.74 copies of TT-034 per cell, indicating that a significant portion of their hepatocytes may have been transduced, and expression of anti-HCV shRNAs was clearly detected in the transduced hepatocytes.

Benitec's Chief Scientific Officer, Dr David Suhy said, "We are pleased to be given the opportunity to present this interim data at the AASLD Liver Meeting next month. The results show that a single infusion of TT-034 is reaching the liver and that it has a very favourable safety profile at the doses tested to date. In the patient that has received the highest dose to date, we are able to detect that anti-HCV shRNAs have been expressed in the liver without any drug-related serious adverse effects, indicating that so far the trial is achieving its primary outcome. We are pleased with the progress of the trial to date."

To read the full abstract, please visit: http://www.aasld.org/sites/default/files/TLM-2015-LakeBreakingAbstracts.pdf

This announcement has been prepared for publication in Australia and may not be released in the United States. This announcement does not constitute an offer to sell, or a solicitation of an offer to buy, securities in the United States or any other jurisdiction.

For further information regarding Benitec and its activities, please contact the persons below, or visit the Benitec website at www.benitec.com.

AbbVie's HOLKIRA PAK Now Reimbursed in all Four Atlantic Provinces

AbbVie's HOLKIRA PAK Now Reimbursed in all Four Atlantic Provinces

HOLKIRA PAK now reimbursed in Nova Scotia, New Brunswick and Newfoundland and Labrador for patients with genotype 1 hepatitis C virus infection

Prince Edward Island was the first province in Canada to reimburse HOLKIRA PAK

In Phase 3 clinical trials, HOLKIRA PAK (with or without ribavirin) cured an overall 97 percent of genotype 1 HCV patients; additionally, 98 percent of patients completed treatment

MONTREAL, Oct. 21, 2015 /CNW/ - AbbVie's HOLKIRA PAK (ombitasvir/paritaprevir/ritonavir film-coated tablets; dasabuvir film-coated tablets) will now be reimbursed in Nova Scotia, New Brunswick and Newfoundland and Labrador. HOLKIRA PAK is an all-oral, short-course (12 weeks for the majority of patients), interferon-free treatment, with or without ribavirin (RBV), for the treatment of patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, including those with compensated cirrhosis.

"With the hepatitis C treatment revolution over the last few years, there is an amazing shift in how we approach our patients. We can now offer them options and hope," explains Dr. Lisa Barrett, Clinician Scientist, Division of Infectious Diseases, Nova Scotia Health Authority and Dalhousie Medical School. "Now, we want to eliminate HCV by treating and curing everyone, in order to prevent the devastating long-term effects the disease has on the liver. I am excited that providers have another tool to treat hepatitis C. In the long-term, this benefits not only people living with this disease, but also our health care system as a whole."

In the Atlantic Provinces, HOLKIRA PAK will be reimbursed for treatment-naïve and treatment-experienced adult patients with chronic hepatitis C genotype 1 infection, with compensated liver disease, (including compensated cirrhosis) according to specific criteria. Prince Edward Island's HCV strategy, including access to HOLKIRA PAK, was announced on February 121. HOLKIRA PAK was listed on theNewfoundland and Labrador Prescription Drug Program2, effective August 1. The listing by Nova Scotia Pharmacare3 was announced on August 13 but became effective on Tuesday, September 1.

"It is wonderful to see the new hepatitis C treatments, such as HOLKIRA PAK, become available in Nova Scotia. This treatment, that has an extremely high cure rate, manageable side effects, and short treatment course, offers hope to many Nova Scotians who have been living with hepatitis for years as well as those who are newly diagnosed. This is what we have been waiting for; it's a life saver," says Carla Densmore MS, executive director, Hepatitis Outreach Society of Nova Scotia.

In New Brunswick4, the listing on the Drug Plans Formulary became effective onOctober 14. "It is a truly exciting time to have well tolerated and curative treatments for a disease that is a leading cause of liver failure and liver cancer in New Brunswick. With these drugs New Brunswick physicians are dramatically improving models of care for patients living with this disease," states Dr. Daniel Smyth, assistant professor, Dalhousie University, Division of Infectious Diseases. "Research programs initiated in New Brunswick will show that using these drugs correctly saves money in the long term by preventing new infections and preventing costly complications of untreated disease. I recommend that all persons born between the years 1945 and 1975 be screened for hepatitis C infection, as well as others who may have been exposed through high risk activities including injecting drugs and self-tattooing. Please ask your family physician about hepatitis C testing, and referral if needed."

HOLKIRA PAK combines three direct-acting antivirals to attack the virus at three separate stages of its replication process. In Phase 3 clinical trials, HOLKIRA PAK (with or without ribavirin) cured an overall 97 percent of GT1 HCV patients, and 98 percent of patients completed treatment.

"Since the launch of HOLKIRA PAK in December 2014, we committed to a collaborative approach with governments, medical and patient organizations to bring our best-in-class treatment to Canadians living with genotype 1 hepatitis C. Today, we are proud to say that we made good on our promise because HOLKIRA PAK is now reimbursed across Canada," says Stéphane Lassignardie, general manager, AbbVie Canada. "And with HOLKIRA PAK, AbbVie is offering its support program AbbVie Care, designed to provide a wide range of customized services throughout the treatment and beyond."

HOLKIRA PAK was approved by Health Canada on December 22, 2014. The approval of HOLKIRA PAK was supported by a robust clinical development program that was designed to study the safety and efficacy of the regimen in six pivotal Phase 3 studies with more than 2,300 patients across 25 countries, including one trial exclusively in subjects with cirrhosis.

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October Update- Upcoming and Recruiting Hepatitis C Clinical Trials

Upcoming and Recruiting Hepatitis C Clinical Trials

The HCV clinical trials in this post are not a complete list; to learn more about Hepatitis C virus clinical trials or to find out if a study is enrolling patients in your area, please click here.

For a quick reference guide of drugs under development and FDA approved medications please visit:

HCV Advocate

Detailed Reference Guide

FDA Approved Medications

Phase II Clinical Trials

Phase III Clinical Trials

Hepatitis C Treatments in Current Clinical Development

Of Interest

The 66th Liver Meeting of the American Association for the Study of Liver Diseases will take place in San Francisco, California between 13th and 17th November 2015, view late breaking abstracts, here. get updates of the meeting on twitter, here, or follow AASLD tweets, here.

This study is currently recruiting participants

A Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With or Without Ribavirin in US Veterans With Genotype 1 Chronic Hepatitis C Virus Infection
ClinicalTrials.gov Identifier:
NCT02442284
Conditions: Chronic Hepatitis C; Cirrhosis; Hepatitis C Virus
Interventions: Drug: Ombitasvir; Drug: Paritaprevir; Drug: Ritonavir; Drug: Dasabuvir; Drug: Ribavirin
Sponsor: AbbVie

Verified October 2015 by AbbVie

This study is currently recruiting participants.

Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C - An Observational Study in Austria (REAL) 

ClinicalTrials.gov Identifier:
NCT02582658
‎Yesterday, ‎October ‎20, ‎2015, ‏‎12:00:00 PM
Condition: Chronic Hepatitis C
Intervention:
Sponsor: AbbVie
Recruiting - verified October 2015

New

This study is currently recruiting participants

Effectiveness of Paritaprevir/Ritonavir - Ombitasvir, +/- Dasabuvir, +/- Ribavirin in Patients With Chronic Hepatitis C - An Observational Study in Belgium
ClinicalTrials.gov Identifier:
NCT02581163

‎Monday, ‎October ‎19, ‎2015, ‏‎12:00:00 PM
Condition: Chronic Hepatitis C, Genotype 1 or 4
Intervention:
Sponsor: AbbVie
Recruiting - verified October 2015 

This study is currently recruiting participants.

Ombitasvir/ABT-450/Ritonavir (Ombitasvir/ABT-450/r) and Dasabuvir Therapy With Low Dose Ribavirin (RBV), Full Dose RBV or RBV Add-On in Treatment Naive Genotype 1a Hepatitis C Virus Infected Adults

United States, New York, France

ClinicalTrials.gov Identifier:
NCT02493855

Conditions: Chronic Hepatitis C; Hepatitis C (HCV); Hepatitis C Genotype 1a
Interventions: Drug: ombitasvir/ABT-450/ritonavir; Drug: dasabuvir; Drug: ribavirin
Verified October 2015 by AbbVie

This study is currently recruiting participants.

China

Sofosbuvir Containing Regimens for the Treatment of Chronic HCV GT3 Infected Patients
ClinicalTrials.gov Identifier:
NCT02576314

‎Monday, ‎October ‎12, ‎2015, ‏‎12:00:00 PM
Condition: Chronic Hepatitis C Infection
Interventions: Drug: SOF+DCV; Drug: LDV/SOF
Sponsors: Humanity & Healthy GI and Liver Centre; Beijing 302 Hospital
Recruiting - verified October 2015 

This study is currently recruiting participants

India

Safety and Efficacy of Sofosbuvir Based Antiviral Regimen for Treating Hepatitis C in Patients With Moderate to Advanced Chronic Kidney Disease and Patients Receiving Renal Replacement Therapy
ClinicalTrials.gov Identifier:
NCT02563665‎

Saturday, ‎September ‎26, ‎2015, ‏‎12:00:00 PM
Condition: CKD With Hepatitis C
Intervention:
Sponsor: Institute of Liver and Biliary Sciences, India
Recruiting - verified September 2015 

This study is currently recruiting participants

A Study to Evaluate the Efficacy and Safety of Three Experimental Drugs in Adults With Hepatitis C Virus Infection, Who Are Either Treatment-naive or Treatment-experienced in Brazil
ClinicalTrials.gov Identifier:
NCT02442271
Condition: Chronic Hepatitis C Infection
Interventions: Drug: Ombitasvir/Paritaprevir/Ritonavir; Drug: Dasabuvir; Drug: Ribavirin
Sponsor: AbbVie
Verified October 2015 by AbbVie

This study is currently recruiting participants

Canada, Belgium
A Study to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir, and Ledipasvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection

ClinicalTrials.gov Identifier:
NCT02421211
Condition: Hepatitis C, Chronic
Interventions: Drug: Simeprevir (SMV); Drug: Ledipasvir (LDV); Drug: Sofosbuvir (SOF)
Sponsor: Janssen Sciences Ireland UC

Verified September 2015

This study is currently recruiting participants

A Two Part, Open-label Study to Evaluate the Safety and Effectiveness of ABT-450/r/ABT-267 or ABT-450/r/ABT-267 and ABT-333 Given With or Without a Drug Called Ribavirin in People With Both Hepatitis C Virus Genotype 1 or 4 Infection and Human Immunodeficiency Virus, Type 1 Infection

ClinicalTrials.gov Identifier:
NCT01939197

Conditions: Hepatitis C Virus Infection; Human Immunodeficiency Virus Infection; Chronic Hepatitis C; Compensated Cirrhosis and Non-cirrhotics
Interventions: Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: Ribavirin (RBV)

Verified October 2015 by AbbVie

This study is currently recruiting participants

New Treatment Response in People With and Without Cirrhosis From Chronic Hepatitis C
United States, Maryland
ClinicalTrials.gov Identifier:
NCT01888900

Verified February 2015 by National Institutes of Health Clinical Center (CC)

Drug: Asunaprevir and Daclatsvir
Drug: Asunaprevir, daclatsvir, peginterferon, ribavirin

This study is not yet open for participant recruitment

A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, ACH-3102, and Simeprevir
ClinicalTrials.gov Identifier:
NCT02569710‎

Thursday, ‎October ‎01, ‎2015, ‏‎12:00:00 PM
Condition: Chronic Hepatitis C
Interventions: Drug: AL-335; Drug: ACH-3102; Drug: Simeprevir
Sponsor: Alios Biopharma Inc.
Not yet recruiting - verified October 2015 

This study is not yet open for participant recruitment

A Study to Evaluate Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir in Treatment-Naïve Hepatitis C Virus Genotype 1b-Infected Adults
‎Yesterday, ‎October ‎20, ‎2015, ‏‎12:00:00 PM

ClinicalTrials.gov Identifier:
NCT02582632

Conditions: Hepatitis C Infection; Hepatitis C Virus
Interventions: Drug: Ombitasvir/Paritaprevir/Ritonavir; Drug: dasabuvir
Sponsor: AbbVie
Not yet recruiting - verified October 2015 

New

This study is not yet open for participant recruitment

The Effectiveness of ABT-450/r - Ombitasvir, + Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C -An Observational Study in Ireland
ClinicalTrials.gov Identifier:
NCT02582671‎

Yesterday, ‎October ‎20, ‎2015, ‏‎12:00:00 PM
Condition: Chronic Hepatitis C
Intervention:
Sponsor: AbbVie
Not yet recruiting - verified October 2015 

This study is not yet open for participant recruitment
The Durability of Response and Persistence of Resistance to AbbVie's 2 Direct-acting Antiviral Agent (2D) Therapy in Japanese Subjects 

ClinicalTrials.gov Identifier:
NCT02581020
‎Monday, ‎October ‎19, ‎2015, ‏‎12:00:00 PM
Condition: Hepatitis C Virus
Intervention:
Sponsor: AbbVie
Not yet recruiting - verified October 2015 

This study is not yet open for participant recruitment

The Safety and Efficacy of Daclatasvir and Asunaprevir With Chronic HCV Genotype 1b Infection and Chronic Renal Failure
ClinicalTrials.gov Identifier:
NCT02580474‎

Friday, ‎October ‎16, ‎2015, ‏‎12:00:00 PM
Condition: Hepatitis C
Intervention: Drug: Daclatasvir plus Asunaprevir
Sponsors: Myeong Jun Song; Bristol-Myers Squibb; Soonchunhyang University Hospital; Dankook University; Chungnam National University Hospital; Konyang University Hospital; Eulji University Hospital; Saint Vincent's Hospital, Korea; Konkuk University Hospital; Cheongju St. Mary's Hospital, Cheongju, Korea; Severance Hospital; Korea University Guro Hospital; Eulji General Hospital
Not yet recruiting - verified October 2015 

This study is not yet open for participant recruitment

A Drug-drug Interaction Study Between Daclatasvir and Metformin
ClinicalTrials.gov Identifier:
NCT02565862

‎Wednesday, ‎September ‎30, ‎2015, ‏‎12:00:00 PM
Conditions: Hepatitis C; Diabetes Mellitus; Insulin Resistance
Interventions: Drug: Daclatasvir; Drug: Metformin
Sponsor: Radboud University
Not yet recruiting - verified September 2015 

This study is not yet open for participant recruitment
A Drug-drug Interaction Study Between Daclatasvir and Atazanavir/Ritonavir or Atazanavir/Cobicistat
ClinicalTrials.gov Identifier:
NCT02565888‎

Wednesday, ‎September ‎30, ‎2015, ‏‎12:00:00 PM
Conditions: Hepatitis C; HIV
Interventions: Drug: Daclatasvir; Drug: Atazanavir; Drug: Ritonavir; Drug: Cobicistat
Sponsor: Radboud University
Not yet recruiting - verified September 2015 

This study is not yet open for participant recruitment
Use-Results Surveillance Study of Sovaldi® Plus Rebetol® in Japanese Patients With Chronic Genotype 2 Hepatitis C Virus Infection
ClinicalTrials.gov Identifier:
NCT02562742

‎Monday, ‎September ‎28, ‎2015, ‏‎12:00:00 PM
Condition: Hepatitis C
Interventions: Drug: SOF; Drug: REB
Sponsors: Gilead Sciences; Merck Sharp & Dohme Corp. Japan
Not yet recruiting - verified September 2015 

This study is not yet open for participant recruitment

A Phase 2b Evaluation of Daclatasvir/Sofosbuvir in Non-Cirrhotic Treatment Naive Subjects With Genotype 1, 2, 3 and 4 Chronic Hepatitis C Virus Coinfected With Human Immunodeficiency Virus (HIV-1)
ClinicalTrials.gov Identifier:
NCT02556086

‎Tuesday, ‎September ‎15, ‎2015, ‏‎12:00:00 PM
Condition: Hepatitis C
Interventions: Drug: Daclatasvir; Drug: Sofosbuvir
Sponsor: Bristol-Myers Squibb
Not yet recruiting - verified October 2015 

This study is not yet open for participant recruitment

A Randomized, Open-Label Study of Daclatasvir and Sofosbuvir With or Without Ribavirin for 8 Weeks in Treatment-Naïve, Non-cirrhotic Subjects Infected With Chronic Hepatitis C Virus (HCV) Genotype 3
ClinicalTrials.gov Identifier:
NCT02551861‎

Tuesday, ‎September ‎15, ‎2015, ‏‎12:00:00 PM
Condition: Hepatitis C
Interventions: Drug: Daclatasvir; Drug: Sofosbuvir; Drug: Ribavirin
Sponsor: Bristol-Myers Squibb
Not yet recruiting - verified September 2015

AASLD: Bristol-Myers To Present Data From Multiple Studies Of Difficult-To-Treat Chronic Hepatitis C Patients

Bristol-Myers Squibb (BMY) To Present Data From Multiple Studies Of Difficult-To-Treat Chronic Hepatitis C Patients At American Association for Study of Liver Diseases

Real-world use of Daklinza-based regimens complements clinical findings across various HCV patient populations

Results of ALLY-3+ trial in genotype 3 HCV patients with cirrhosis to provide new insights into treating this patient population

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today that 17 abstracts have been accepted for presentation at The Liver Meeting® 2015, the annual meeting of The American Association for the Study of Liver Diseases (AASLD) 2015, taking place in San Francisco, CA., from November 13 – 17.

“The data to be presented at this year’s AASLD conference reinforces Bristol-Myers Squibb’s ongoing commitment to investigating Daklinza-based treatments that could address the still-challenging needs of many patients living with chronic viral hepatitis C”

Highlights include:
Real-world data in chronic hepatitis C (HCV) populations, including genotype 3 patients, post-liver transplant patients, patients with advanced liver disease (including decompensated cirrhosis) and those coinfected with HIV.
Late-breaking data from the ALLY-3+ clinical trial, a study of Daklinza (daclatasvir) and sofosbuvir with ribavirin in genotype 3 HCV patients with cirrhosis.

“The data to be presented at this year’s AASLD conference reinforces Bristol-Myers Squibb’s ongoing commitment to investigating Daklinza-based treatments that could address the still-challenging needs of many patients living with chronic viral hepatitis C,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “We are aiming to ultimately help a diverse range of hepatitis C patient populations.”

The complete list of Bristol-Myers Squibb data presentations follows. More information is available at http://www.aasld.org/.

Title			Date/Time
Oral Presentation: All-Oral Treatment With Daclatasvir (DCV) Plus Sofosbuvir (SOF) Plus Ribavirin (RBV) for 12 or 16 Weeks in HCV Genotype (GT) 3-Infected Patients With Advanced Fibrosis or Cirrhosis: The ALLY-3+ Phase 3 Study			Session: Late-breaking Abstract Session Date: November 16, 2015 Session Time: 3:00 – 4:30 p.m. Publication Number: LB-3
Oral Presentation: Safety and efficacy of daclatasvir plus sofosbuvir with or without ribavirin for the treatment of chronic HCV genotype 3 infection: Interim results of a multicenter European compassionate use program			Session: Parallel 5: Hepatitis C: Pre-Approval Clinical  Studies I Date: November 15, 2015 Session Time: 3:00 - 4:30 p.m. Presentation Time: 3:00 - 3:15 p.m. Location: General Session/3000 (Moscone Center) Publication Number: 37
Oral Presentation: Daclatasvir plus sofosbuvir with or without ribavirin in genotype 3 patients from a large French multicenter compassionate use program			Session: Viral Hepatitis Plenary Date: November 17, 2015 Session Time: 8:00 - 9:30 a.m. Presentation Time: 8:15 - 8:30 a.m. Location: Room 3000 (Moscone Center) Publication Number: 206
Oral Presentation: Daclatasvir and Sofosbuvir in Patients with Recurrent HCV Following Liver Transplantation and Advanced Fibrosis or Cirrhosis: United States Multicenter Treatment Protocol			Session: Parallel 32: Clinical Aspects of HCV Virology, Pathogenesis, and Immunology Date: November 17, 2015 Session Time: 11:15 a.m. -12:45 p.m. Presentation Time: 12:00 -12:15 p.m.* Location: Room 3014 (Moscone Center) Publication Number: 217 * Presentation time expected to change, TBC
Oral Presentation: Daclatasvir in combination with sofosbuvir with or without ribavirin is safe and efficacious in liver transplant recipients with HCV recurrence: Interim results of a multicenter compassionate use program			Session: Parallel 37: Hepatitis C: Pre-Approval Clinical Studies II Date: November 17, 2015 Session Time: 11:15 a.m. - 12:45 p.m. Presentation Time: 12:30 - 12:45 p.m. Location: General Session/3000 (Moscone Center) Publication Number: 252
Presidential Poster of Distinction:702 Short-duration therapy with daclatasvir/asunaprevir/beclabuvir fixed-dose combination plus sofosbuvir in patients with chronic hepatitis C genotype 1 (FOURward Study)			Session: Therapeutics: New Agents (not approved, Phase 2-3) Date: November 14, 2015 Presentation Time: 2:00 – 7:30 p.m. Location: Poster Hall Publication Number: 702
Presidential Poster of Distinction:Daclatasvir plus sofosbuvir with or without ribavirin for the treatment of chronic HCV in patients coinfected with HIV: Interim results of a multicenter compassionate use program			Session: Hepatitis C: Therapeutics /Approved Agents Date: November 15, 2015 Presentation Time: 8:00 a.m. – 5:30 p.m. Location: Poster Hall Publication Number: 1058
Poster: Improvement in liver disease parameters following treatment with daclatasvir + sofosbuvir and ribavirin in patients with chronic HCV infection and advanced cirrhosis			Session: Therapeutics: New Agents  (not approved, Phase 2-3) Date: November 14, 2015 Presentation Time: 2:00 – 7:30 p.m. Location: Poster Hall Publication Number: 706
Poster: Baseline HCV NS5A resistance-associated variants do not impact SVR12 rates in non-cirrhotic and post-liver transplant patients with genotype 1 infection treated with daclatasvir and sofosbuvir with or without ribavirin for 12 weeks: An integrated analysis			Session: Therapeutics: New Agents  (not approved, Phase 2-3) Date: November 14, 2015 Presentation Time: 2:00 – 7:30 p.m. Location: Poster Hall Publication Number: 709
Poster: Comparative Efficacy and Tolerability of Daclatasvir + Sofosbuvir versus Sofosbuvir + Ribavirin in Patients with Chronic Hepatitis C Coinfected with HIV: A Matching-Adjusted Indirect Comparison			Session: Therapeutics: New Agents (not approved, Phase 2-3) Date: November 14, 2015 Presentation Time: 2:00 – 7:30 p.m. Location: Poster Hall Publication Number: 711
Poster: An integrated safety analysis of daclatasvir + sofosbuvir, with or without ribavirin, in patients with chronic HCV infection			Session: Therapeutics: New Agents  (not approved, Phase 2-3) Date: November 14, 2015 Presentation Time: 2:00 – 7:30 p.m. Location: Poster Hall Publication Number: 716
Poster: Daclatasvir exposure does not explain lower sustained virologic response rates in cirrhotic patients with HCV genotype 3 following 12 weeks of daclatasvir plus sofosbuvir treatment			Session: Therapeutics: New Agents  (not approved, Phase 2-3) Date: November 14, 2015 Presentation Time: 2:30 – 7:00 p.m. Location: Poster Hall Publication Number: 720
Poster: Integrated Safety Analysis of Daclatasvir Plus Sofosbuvir, With or Without Ribavirin, in Patients With HCV Genotype 3 Infection			Session: Therapeutics: New Agents (not approved, Phase 2-3) Date: November 14, 2015 Presentation Time: 2:00 – 7:30 p.m. Location: Poster Hall Publication Number: 726
Poster: Daclatasvir exposure alone does not explain HCV relapse in HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir with ritonavir-boosted darunavir in the ALLY-2 study			Session: Therapeutics: New Agents  (not approved, Phase 2-3) Date: November 14, 2015 Presentation Time: 2:00 – 7:30 p.m. Location: Poster Hall Publication Number: 728
Poster: Daclatasvir and asunaprevir in non-Japanese Asian patients with chronic HCV genotype 1b infection who are ineligible for or intolerant to interferon-alfa therapies with or without ribavirin: Phase 3 SVR12 interim results			Session: Late-breaking Poster Session Date: November 16, 2015 Session Time: 8:00 a.m. – 5:30 p.m. Presenters available: 12:30 – 2:00 p.m. Location: Poster Hall Publication Number: LB-18
Poster: Impact of Daclatasvir-Sofosbuvir Combination Treatment on Medical Events and Costs in Patients Infected with Genotype 3 Hepatitis C Virus			Session: Cost-Effectiveness and Economics of Care Date: November 16, 2015 Presentation Time: 8:00 a.m. – 5:30 p.m. Location: Poster Hall Publication Number: 1456
Poster: Cost-effectiveness of Daclatasvir in Combination with Sofosbuvir for the Treatment of Subjects with Genotype 3 Chronic Hepatitis C Infection in the United States			Session: Cost-Effectiveness and Economics of Care Date: November 16, 2015 Presentation Time: 8:00 a.m. – 5:30 p.m. Location: Poster Hall Publication Number: 1461

About Bristol-Myers Squibb in HCV

Bristol-Myers Squibb’s research efforts are focused on advancing compounds to deliver the most value to HCV patients with high unmet needs. At the core of our portfolio isDaklinza, a NS5A complex inhibitor which continues to be investigated in multiple treatment regimens and in patients with high disease burden.

In July 2014, Japan became the first country in the world to approve the use of aDaklinza-based regimen for the treatment of chronic HCV. Since then, Daklinza-based regimens have been approved in more than 50 countries, including the United States, across Europe, and in numerous other countries in Central and South America, the Middle East and the Asia-Pacific region.

Indication and Important Safety Information - Daklinza™ (daclatasvir)

INDICATION

Daklinza™ (daclatasvir) is indicated for use with sofosbuvir for the treatment of patients with chronic hepatitis C virus (HCV) genotype 3 infection.

Limitations of Use:
Sustained virologic response (SVR) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving Daklinza in combination with sofosbuvir for 12 weeks.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
Drugs Contraindicated with Daklinza: strong inducers of CYP3A that may lead to loss of efficacy of Daklinza include, but are not limited to:
Phenytoin, carbamazepine, rifampin, St. John’s wort (Hypericum perforatum).

WARNINGS and PRECAUTIONS

-- Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: Coadministration of Daklinza and other drugs may result in known or potentially significant drug interactions. Interactions may include the loss of therapeutic effect of Daklinza and possible development of resistance, dosage adjustments for other agents or Daklinza, possible clinically significant adverse events from greater exposure for the other agents or Daklinza.
Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone: Post-marketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with another direct-acting antiviral, including Daklinza. A fatal cardiac arrest was reported with ledipasvir/sofosbuvir.
Coadministration of amiodarone with Daklinza in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no alternative treatment options, patients should undergo cardiac monitoring, as outlined in Section 5.2 of the prescribing information.
Bradycardia generally resolved after discontinuation of HCV treatment.
Patients also taking beta blockers or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone.

ADVERSE REACTIONS
The most common adverse reactions were (≥ 5%): headache (14%), fatigue (14%), nausea (8%), and diarrhea (5%).

DRUG INTERACTIONS
CYP3A: Daklinza is a substrate. Moderate or strong inducers may decrease plasma levels and effect of Daklinza. Strong inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir) may increase plasma levels of Daklinza.
P-gp, OATP 1B1 and 1B3, and BCRP: Daklinza is an inhibitor, and may increase exposure to substrates, potentially increasing or prolonging their adverse effect.
See Section 7 of the Full Prescribing Information for additional established and other potentially significant drug interactions and related dose modification recommendations.

Daklinza in Pregnancy: No data with Daklinza in pregnant women are available to inform a drug-associated risk. Animal studies of Daklinza at exposure above the recommended human dose have shown maternal and embryofetal toxicity. Consider the benefits and risks of Daklinza when prescribing Daklinza to a pregnant woman.

Nursing Mothers: Daklinza was excreted into the milk of lactating rats; it is not known if Daklinza is excreted into human milk. Consider the benefits and risks to the mother and infant when breastfeeding.

Please click here for the Daklinza full prescribing information

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