Researchers say method to detect drug resistant hepatitis C virus mutants has been developed

The new detection method for a key drug resistant hepatitis C virus mutation

A rapid, sensitive, and accurate method to detect drug resistant hepatitis C virus (HCV) mutants has been developed. Researchers at Hiroshima University established a system to rapidly and accurately measure the presence of HCV Y93H drug resistant mutant strains, and evaluate the proportion of patients harboring this mutation prior to treatment. Even in serum samples with low HCV titers, 

Y93H drug resistant mutation could be successfully detected in more than half of the samples. This new system for detecting mutant strains may provide important pre-treatment information valuable not only for treatment decisions but also for prediction of disease progression in HCV genotype 1b patients.

HCV is a major cause of chronic liver disease, liver cirrhosis, and hepatocellular carcinoma, affecting up to 180 million people worldwide. HCV often acquires resistance against direct acting antiviral agents. Presence of the Y93H mutation prior to treatment has been reported as an important predictor of virologic failure. Direct sequencing is a commonly used method to detect this mutation. However, it is only capable of detecting viral subpopulations with frequencies of at least 10% to 20%. Next generation sequencing has recently been applied as a more sensitive method to analyze viral mutations, but it is still complex to perform and expensive for widespread clinical use.

By combining nested PCR and the Invader assay with well-designed primers and probes, the Y93H drug resistant mutation can be detected with a high success rate of 98.9% among a total of 702 Japanese HCV genotype 1b patients.

"Our assay system also showed a much lower detection limit for Y93H than using direct sequencing, and Y93H frequencies obtained by this method correlated well with those of deep-sequencing analysis." Professor Kazuaki Chayama, the principle investigator of this study at Hiroshima University, explained.

The proportion of the patients with the Y93H mutant strain estimated by this system was 23.6%, and this rate is comparable with that assayed by real-time PCR and ranked between those of deep sequencing and direct sequencing reported in the Japanese population, presumably reflecting the lower detection limit of Y93H.

This new system attained a high assay success rate and was more sensitive in detecting Y93H than direct sequencing. The evaluation of Y93H strain may provide important information for prediction of disease progression in HCV genotype 1b patients.

Schematic flow diagram representing a method of nested-PCR followed by Invader: (A) The initial PCR was performed to amplify a fragment containing a part of the mutant region from HCV-RNA which was extracted from the serum of a patient. (B) An aliquot of the inital PCR product was used for the second PCR to amplify a fragment. (C) Invader oligonucleotide and allele-specific probes anneal with target to form one base overlap. (D) Three types of standard nucleotide (Std-YY, Std-YH, and Std-HH) were prepared, which includes binary target sequences, corresponding to wild (Y) or mutant (H) variants, and annealing sites with the internal primers at each end. (E) The Invader assay for each standard was also performed in triplicate.

More information: "Rapid, Sensitive, and Accurate Evaluation of Drug Resistant Mutant (NS5A-Y93H) Strain Frequency in Genotype 1b HCV by Invader Assay." 

DOI: 10.1371/journal.pone.0130022

Weekend Reading - Natural history of hepatitis C: An Updated Look at the Rate of Progression to Cirrhosis and the Incidence of Decompensation

Weekend Reading: Natural history of hepatitis C

On most weekends this blog offers up a bit of easy "Weekend Reading" on the topic of HCV.

After receiving a hepatitis C diagnosis, the first task at hand is understanding how the virus damages the liver. A good place to start is with the Natural History Of Hepatitis C. 

To date the natural history of hepatitis C remains controversial. Among HCV-infected individuals progression to advanced liver disease generally requires decades but is influenced by several host factors, the following offers an update on the natural history of hepatitis C using information found online at Medscape, NATAP, and the interactive website Hepatitis C Online.

The Natural History of Chronic Hepatitis C. An Updated Look at the Rate of Progression to Cirrhosis and the Incidence of Decompensation in a Large U.S. Health Maintenance Organization

We begin with a commentary  titled, "Hepatitis C: 25 Years Old, and Fading," written by William F. Balistreri, MD., recently published over at Medscape. The good doctor writes about a study presented last month at "Digestive Disease Week," which suggested the rate of developing cirrhosis and decompensation in people with HCV is higher than previously thought. An excerpt follows with a link to corresponding slides provided this week by Jules Levin @ NATAP.  In addition stroll over to "Hepatitis C Online" or download "Natural History of Hepatitis C Infection" for a quick review of related studies including; spontaneous clearance versus chronic infection and factors that may impact the rate of fibrosis,

Links

Excerpt; Hepatitis C: 25 Years Old, and Fading

Cirrhosis and the Incidence of Decompensation

The projected public health burden of HCV is based on old natural history studies. One presentation[6] suggested a need to reexamine the natural history of HCV because the current patient cohort is older and confounded by a higher prevalence of obesity, and other comorbid conditions that may affect the outcome of the disease. Therefore, investigators conducted a retrospective cohort study at Kaiser Permanente Southern California.

From 2002-2013, 60,338 adults had an HCV diagnosis code or a positive HCV RNA lab test. Of these, 33,124 HCV cases met inclusion criteria and were matched with 164,221 controls. Mean age of the HCV cases and non-HCV controls was 54 years. Among case-patients, 41% were white and 27% were Hispanic; among controls, the respective proportions were 46% and 28%.

Prevalent cirrhosis was found in 19% of the HCV-infected cohort and 1.4% of the non-HCV controls. The incident decompensation rate among previously compensated HCV patients with cirrhosis was 47%, which was almost twice the incident decompensation rate among non-HCV cirrhotic controls. Of note, 23% of HCV cases were diagnosed with cirrhosis after a median follow-up of 2 years, which indicates that the rates of development of HCV-related cirrhosis and decompensation are higher than previously reported. The authors attributed this to aging of the HCV cohort and associated comorbidities, such as obesity. Multivariable analyses to explore the relationship between baseline comorbid conditions and the incidence of cirrhosis and decompensation are ongoing.

1. Nyberg LM, Li X, Chiang K, et al. The natural history of chronic hepatitis C. An updated look at the rate of progression to cirrhosis and the incidence of decompensation in a large U.S. health maintenance organization. Program and abstracts of Digestive Disease Week; May 16-19, 2015; Washington, DC. Abstract 809.

Read it here....

View All Slides@ NATAP

The Natural History of Chronic Hepatitis C. An Updated Look at the Rate of Progression to Cirrhosis and the Incidence of Decompensation in a Large U.S. Health Maintenance Organization

Begin here....

About Hepatitis C Online
Hepatitis C Online is a free educational web site from the University of Washington.

The site is a comprehensive resource that addresses the diagnosis, monitoring, and management of hepatitis C virus infection. 

Hepatitis C Online

PDF (Quick Review):  Natural History of Hepatitis C Infection 

Website Site:

Module 2: Evaluation, Staging, and Monitoring of Chronic Hepatitis C 

Website:

Lesson 2: Natural History of Hepatitis C InfectionContents: 

Spontaneous Clearance versus Chronic Infection 

Variable Outcomes of Chronic Infection 

Factors Impacting Rate of Progression of Fibrosis 

Summary Points 

Download PDF...

HCV TGIF Rewind - Peak body, Gilead welcome hepatitis report

HCV TGIF Rewind 

Welcome to TGIF rewind, a weekly digest of news, research and a look at today's headlines.

Wednesday AbbVie announced clinical trial results from TURQUOISE-III which showed 100% of genotype 1b patients with compensated liver cirrhosis reached a sustained virologic response at 12 weeks post-treatment after therapy with Viekirax and Exviera, here is the press release, a summary available online @ Healio.  

The June issue of "Clinical Liver Disease" is up folks, the journal is an official digital educational resource from the American Association for the Study of Liver Diseases. Visitors can read full text articles or sit back and watch either an author interview, or a presentation of each article, begin here.

In 2014 The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) with the International Antiviral Society developed a living document with ever evolving guidelines to treat HCV.

 
The "guidelines" have a complex algorithm for practitioners around the country to follow and see whats the right right treatment, for the right patients, for the right about of time. Yesterday the AASLD announced updates for the use of hepatitis C drugs with a summary published in the AASLD journal, Hepatology.

VA In The Headlines

Excerpt;

VA to outsource care for 180000 vets with hepatitis C

"The VA had set aside nearly $700 million this year for HCV antiviral drugs. In documents and a written statement, department officials confirmed soaring patient loads and medication expenses have nearly wiped out that budget with several months to go in the federal fiscal year that ends Sept. 30. That's an estimated $400 million shortfall with more dramatic costs expected, beginning in October."

VA to outsource care for 180000 vets with hepatitis C

The Department of Veterans Affairs is moving to outsource care nationwide for up to 180,000 veterans who have hepatitis C, a serious blood and liver condition treated with expensive new drugs that are costing the government billions of dollars.

July 25

Wonder Drugs Blow a $1 Billion Hole in VA's Budget

Senior official at the Department of Veterans Affairs testified on Thursday that his agency is not rationing costly new drugs for veterans suffering from the potentially deadly Hepatitis C virus, as some have suspected, but acknowledged that the VA is reeling from the skyrocketing costs of providing the miracle drugs.

High Cost Of Specialty Drugs

June 26

Peak body, Gilead welcome hepatitis report
Australian Journal of Pharmacy
The report by the House of Representatives Standing Committee on Health, The Silent Disease – Inquiry into Hepatitis C in Australia has been welcomed by the peak body representing more than 230,000 Australians living with hepatitis C.

June 25

Skyrocketing specialty drug cost hurts wallets

The rising cost of specialty drugs to treat complex, chronic or life-threatening conditions has the potential to break the pocket books of businesses, consumers, insurance companies and the state, according to Milam Ford of Blue Cross and Blue Shield of Louisiana.

Ford is the vice president of pharmacy services for Blue Cross and Blue Shield of Louisiana. He spoke with The News-Star Thursday about the rising cost of specialty drugs, which are used for cases of hepatitis C, cancer, rheumatoid arthritis, multiple sclerosis and more.

Related; June Updates

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, Harvoni (ledipasvir/sofosbuvir) and AbbVie Viekira Pak.

June 24

Community outreach program cures Pearland resident of Hepatitis-C
When Pearland resident John Rocks went into the hospital in 2012, the last thing he expected was to be diagnosed with Hepatitis-C(HEP-C) [an inflammation of the liver due to virus or bacteria], yet that's exactly what the doctor told him. “I had a ...

June 23

China rejects patent linked to Gilead hepatitis C drug

China has rejected a Gilead Sciences Inc patent application related to its costly hepatitis C drug, a U.S. advocacy group said, adding the move may lead to other countries to consider rejecting patents for the controversial treatment.

Research 

June 26

World Journal of Gastroenterology

Hepatitis C treatment in the elderly: New possibilities and controversies towards interferon-free regimens

World Journal of Gastroenterology 2015 June 28

Hepatitis C virus (HCV) infection is a significant threat to the health of elderly patients, in whom liver disease progresses very rapidly and extrahepatic complications affect the quality of life. Till now, treatment attempts have been substantially limited by the side effects of interferon (IFN). Here we discuss how the availability of IFN-free regimens should prompt us to change our mind when assessing treatment indication and to consider a significantly larger number of possible candidates among elderly patients. Drug-drug interactions and assessment of liver disease-dependent vs comorbidities-dependent life expectancy, rather than anagraphic age, are likely to guide the choice of the aged HCV patients to be treated in the next future.

June 25

Clinical Care Options

Special Populations and Areas of Unmet Need in HCV Infection

Date Posted: 6/25/2015

In this downloadable slideset, Paul Y. Kwo, MD, reviews strategies for managing HCV infection in challenging patient populations, including an overview of data on the safety and efficacy of current regimens as well as potential future options.

June 23

MedPage Today

Cannabinoid Offers Modest Relief From Pain, Spasticity

by Sarah Wickline Wallan
Various cannabinoid compounds did not improve nausea, vomiting, or appetite, and only slightly improved chronic pain and spasticity, in patients with various long-term health conditions, a review of randomized clinical trials found.

The greatest reductions in chronic pain were reported by patients who smoked tetrahydrocannabinol (THC) in eight of the trials, but the majority of the 79 trials in the meta-analysis demonstrated cannabinoids had little effect on HIV/AIDS patients with low-appetite and actually worsened chemotherapy-related nausea and vomiting, Penny F. Whiting, PhD, of University Hospitals Bristol NHS in England, and colleagues reported in the Journal of the American Medical Association.

Big Pharma
June 26
BMS TO DROP ANTIVIRAL RESEARCH IN SHAKE-UP OF R&D
BMS is stopping early-stage discovery work in virology as part of a reshuffle in its R&D operations, pmlive.com reports.

The company stressed that the decision will not affect projects that have already reached the clinical development stage, which include beclabuvir for hepatitis C virus (HCV) in phase III and two HIV drugs in phase II, or indeed its marketed antiviral drugs including new HCV therapy Daklinza (daclatasvir).

The decision will mainly affect early programmes in hepatitis B and HIV, said the company, which said around 100 positions will be lost as a result. It will organisation will continue to focus on research in immuno-oncology as well as heart failure, fibrosis, genetically defined diseases and immunoscience.

Meanwhile, structural changes caused by the reshuffle include the opening of a facility in Cambridge, Massachusetts, due to open in 2018, as well as a the closure of its sites in Wallingford, Connecticut, and Waltham, Massachusetts, in 2018.

Around 200 workers from the two closing units and BMS’ New Jersey operations will relocate to the new unit, which will focus on discovery efforts in genetic diseases, molecular discovery technologies and discovery platform chemistry, said the company.
26 Jun 2015 | PharmaBusiness Daily

Blog Updates

June 26
The Top-Selling Drugs in America
NerdWallet (blog)-32 minutes ago
Sovaldi was first approved for most types of hepatitis C in 2013 and quickly skyrocketed to the top earnings spot in 2014. There are six genotypes of hepatitis C, ...

Greg Jefferys
My Hep C Travel Diary, Hepatitis C Advocate
Last Entry: Hepatitis C Musings (2015-06-25 15:03:51)
Tomorrow I should get my hepatitis C viral load results back.

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Matt Starr
Hepatitis, Liver Disease Support Coach
Last Entry: Hepatitis C and Treatment - The Long Haul (2015-06-25 06:24:05)
Regardless of one's personal situation, what does it mean to hunker down for the long haul? Can we deal with liver disease and hepatitis, get serious and be open to a wide range of possible treatments, while still maintaining our love for life and what is all around us?

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Karen Hoyt
Hepatitis C Advocate
Last Entry: Going Back to Bed after Liver Transplant Surgery(2015-06-24 06:40:27)
After the surgery, my transplant coordinators, friends, and family all conspired to make me rest. Then they got me all jacked up on steroids which made it totally impossible for me to sit still. It was quite a conundrum.

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Rick Nash
Hepatitis C Advocate
Last Entry: Road Tips (2015-06-23 14:11:01)
On my road trip to from San Diego to San Francisco, I took a critical look and what i did well, and where i could've improved and made a new road trip tip list for people living with the complications of Liver Disease.

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Kim Bossley
Hepatitis C Advocate and Co-Founder, The Bonnie Morgan Foundation
Last Entry: Everyday Life (2015-06-22 12:21:29)
I am not what I used to be but I am happy, I am a fighter wanting to survive.

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Lucinda K. Porter, RN
Author, Hepatitis C Advocate, Health Educator
Last Entry: When Hepatitis C Treatment is Hard and Scary (2015-06-22 06:07:58)
What if hepatitis C treatment isn't a cakewalk for you?

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Enjoy the weekend!

Tina

AASLD updates guidance for use of hepatitis C drugs

AASLD updates guidance for use of hepatitis C drugs

The American Association for the Study of Liver Diseases (AASLD), in partnership with the Infectious Diseases Society of America (IDSA) and in collaboration with the International Antiviral Society-USA (IAS-USA), created online Recommendations for Testing, Managing, and Treating Hepatitis C in 2014 to aid practitioners treating patients infected with hepatitis C virus (HCV). Now an update to the Guidance, with a summary of recommendations regarding treatment with direct-acting antiviral drugs, is published in the AASLD journal, Hepatology.

HCV is a blood-borne virus that infects the liver and may lead to cirrhosis or liver cancer (hepatocellular carcinoma). In the past 25 years HCV has gone from an undiagnosed disease to an epidemic level, with the World Health Organization (WHO) estimating that up to 150 million people worldwide live with chronic disease.

In the U.S., close to 30,000 new acute cases were reported in 2013 and 2.7 million Americans have chronic HCV according to the Centers for Disease Control and Prevention (CDC). "The good news is that HCV is now on the cusp of being a curable disease for the millions of Americans, many of whom are undiagnosed," says Dr. Gary Davis, President of MedLogician Consulting and co-chair of the AASLD/IDSA HCV Guidance writing panel. "The web-based Guidance document is an easy-to-use resource for practitioners treating HCV patients with novel antivirals."

A panel of 26 hepatologists and infectious diseases specialists and a patient advocate developed the original consensus recommendations that include:

HCV testing details and linkage to care
Recommendations for initial treatment of HCV infection in patients starting treatment
Retreatment information in persons in whom prior therapy has failed
Unique patient populations data

"The Guidance is a living document that will continually be updated with evidence-based advice about how to best use the next generation of direct-acting antivirals and other treatment options," comments Dr. Keith Lindor from the Arizona State University and President-elect of AASLD. "Our role as associations of researchers and clinicians is to provide key information in the appropriate format to patients and those who care for them."

Practitioners involved with treating patients with liver disease may access the Guidance, including new updates, at http://www.HCVGuidelines.org.

This guidance is published in Hepatology. Media wishing to receive a PDF of this article may contact sciencenewsroom@wiley.com.

Full citation: "Hepatitis C Guidance: AASLD-IDSA Recommendations for Testing, Managing, and Treating Adults Infected with Hepatitis C Virus." Authors on behalf of the Hepatitis C Guidance Panel (see AASLD/IDSA HCV Guidance panel members and authors). Hepatology; Published Online: June 25, 2015, (DOI: 10.1002/hep.27950).

URL: http://doi.wiley.com/10.1002/hep.27950

About the Journal
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published by Wiley on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://wileyonlinelibrary.com/journal/hep.

Researchers develop gel that could reduce jabs for Hepatitis C patients

The IBN behind the drug-delivering hydrogel. (from right) Dr Motoichi Kurisawa, Dr Ki Hyun Bae, Dr Keming Xu and Mr Fan Lee. Photo courtesy of the Institue of Bioengineering and Nanotechnology

Researchers develop gel that could reduce jabs for Hepatitis C patients
NEO CHAI CHIN
chaichin@mediacorp.com.sg
PUBLISHED: 6:09 PM, JUNE 25, 2015

SINGAPORE — Instead of weekly doses of discomfort, Hepatitis C patients could reduce the need for jabs by up to eight times if a drug-delivering hydrogel developed by researchers here reaches the market.

The gel works through a compound — called polyethylene glycol (PEG) — that serves as microscopic reservoirs for drugs typically used to treat chronic Hep C patients. The compound prevents premature leakage of the drugs, which also diffuse slowly as they flow in and out of the many “reservoirs” in the gel before being released out to the body.

It was previously impossible to use hydrogels to deliver drugs with long-term efficacy due to the difficulty in controlling the drug-release rate, said the Institute of Bioengineering and Nanotechnology (IBN), of the Agency for Science, Technology and Research, in a media release today (June 25).

The gel extends by up to 10 times the time taken for the amount of Hep C drugs in the body to be reduced by half, said Dr Motoichi Kurisawa, principal research scientist and IBN team leader. It reduces the need for frequent injections, he added.

Once the drugs are fully released, the gel degrades naturally and is passed out of the body.

The researchers’ findings were recently published in a journal called Biomaterials. But the new product could be several years from the market. The researchers are seeking a healthcare partner to conduct clinical trials, after studies conducted on animals.

Hep C, which affects about 0.2 per cent of the population here, is a liver disease that kills about half a million people worldwide yearly. Chronic Hep C patients typically undergo weekly injections of a protein drug called PEGylated interferon.

The gel is also being tested for the treatment of chronic diseases besides Hep C, said Dr Kurisawa.

http://www.todayonline.com/daily-focus/health/researchers-develop-gel-could-reduce-jabs-hepatitis-c-patients

The Future in Liver Medicine:Training the next generation of hepatologist: What will they need to know?

The Future in Liver Medicine, Liver and the Microbiome, & Liver Transplantation 

Hello folks, the June issue of Clinical Liver Disease is available online, here.

This journal is an official digital educational resource from the American Association for the Study of Liver Diseases. Along with full text access, each article includes a video presentation and author interview.

Clinical Liver Disease© The American Association for the Study of Liver Diseases
Volume 5, Issue 6 The Future in Liver Medicine, Liver and the Microbiome, & Liver Transplantation Pages 127 - 153, June 2015

The latest issue of Clinical Liver Disease is available on Wiley Online Library

The Future in Liver Medicine
Guest Edited by Meena Bansal, MD

The future of hepatology: Embrace change (pages 127–128)
Scott L. Friedman and Yael L. Friedman
Article first published online: 24 JUN 2015 | DOI: 10.1002/cld.473

Training the next generation of hepatologist: What will they need to know? (pages 129–131)
Dina L. Halegoua-De Marzio and Steven K. Herrine
Article first published online: 24 JUN 2015 | DOI: 10.1002/cld.461

Personalized management of hepatocellular carcinoma based on molecular information: Future prospects (pages 132–135)
Nicolas Goossens and Yujin Hoshida
Article first published online: 24 JUN 2015 | DOI: 10.1002/cld.483

Increasing impact of drug-induced liver injury (pages 136–138)
Paul H. Hayashi and Naga P. Chalasani
Article first published online: 24 JUN 2015 | DOI: 10.1002/cld.469

Future watch: Evolving trends in the management of nonalcoholic steatohepatitis (pages 139–141)
Arun J. Sanyal
Article first published online: 24 JUN 2015 | DOI: 10.1002/cld.477

Liver and the Microbiome
Guest Edited by Eamonn Quigley, MD

Host-microbiome interactions in health and disease (pages 142–144)
Liam O'Mahony
Article first published online: 24 JUN 2015 | DOI: 10.1002/cld.484

Liver Transplantation
Guest Edited by Paul Martin, MD
Hepatitis C treatment in liver transplant setting (pages 145–149)
Adam Peyton and Kalyan Ram Bhamidimarri
Article first published online: 24 JUN 2015 | DOI: 10.1002/cld.475

Renal dysfunction in cirrhosis (pages 150–153)
Chong Y. Parke, Paul Martin and Suphamai Bunnapradist
Article first published online: 24 JUN 2015 | DOI: 10.1002/cld.485

Viekira Pak - AbbVie hepatitis C cocktail succeeds in late-stage study

AbbVie hepatitis C cocktail succeeds in late-stage study

AbbVie Inc said on Wednesday that its hepatitis C cocktail Viekira Pak was effective whether or not it was used in combination with the compound ribavirin against the most common form of the disease, according to data from a late-stage study.

Viekira Pak, a combination of the drugs Viekirax and Exviera, was approved in December for use as both a standalone treatment and in tandem with ribavirin, a broad-spectrum antiviral approved in 1998.

All the patients in the study showed a sustained response to Viekira Pak as a standalone treatment after 12 weeks of treatment, AbbVie said.

The late-stage study on which the U.S. Food and Drug Administration based its decision to approve Viekira Pak in December showed it cured 91-100 percent of all patients with the infection.

Viekira Pak is one of three treatments for the liver-scarring disease fighting to corner the lion's share of the multi-billion dollar market and competes with Gilead Sciences Inc's Sovaldi and Harvoni, and Johnson & Johnson's Olysio.

(Reporting by Vidya L Nathan in Bengaluru, Editing by Simon Jennings)

http://www.reuters.com/article/2015/06/24/us-abbvie-study-idUSKBN0P413320150624

AbbVie Announces New Phase 3b Results in Genotype 1b Chronic Hepatitis C Patients with Compensated Liver Cirrhosis

- 100 percent SVR(12) rate achieved with VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA® (dasabuvir tablets) without ribavirin(1)

NORTH CHICAGO, Ill., June 24, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced TURQUOISE-III study results demonstrating 100 percent (n=60/60) sustained virologic response at 12 weeks post-treatment (SVR12) in genotype 1b (GT1b) chronic hepatitis C virus (HCV) infected adult patients with compensated liver cirrhosis.1 Patients received 12 weeks of VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA® (dasabuvir tablets) without ribavirin (RBV). These new results from AbbVie's Phase 3b study will be presented at the 15th Annual International Symposium on Viral Hepatitis and Liver Diseases in Berlin, Germany.

Approximately 160 million people worldwide are infected with HCV.2 Genotype 1 is the most common type of HCV genotype, accounting for 60 percent of cases worldwide3 and in Europe, the most prevalent genotype is 1b (47 percent).4 Over time, chronic HCV may lead to liver complications, including compensated cirrhosis, in about 10-20 percent of people infected.2

"Genotype 1b represents a large portion of HCV patients globally, as it is the most prevalent sub-genotype, and there is a need to continue to explore additional treatment regimens," said Jordan J. Feld, M.D., MPH, research director and clinician scientist, Toronto Center for Liver Disease, Toronto, Canada. "The results of TURQUOISE-III are promising, demonstrating that genotype 1b HCV patients with compensated liver cirrhosis have the potential to achieve high response rates with an interferon and ribavirin-free treatment in 12 weeks."

Patients in TURQUOISE-III were either treatment-naïve or treatment-experienced (failed previous therapy with pegylated interferon and RBV). No patients discontinued treatment due to adverse events.1 The most commonly reported adverse events (>10 percent) were fatigue (22 percent), diarrhea (20 percent) and headache (18 percent).1

"In the TURQUOISE-III study, GT1b patients with compensated liver cirrhosis achieved a 100 percent cure rate with VIEKIRAX + EXVIERA without ribavirin," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "TURQUOISE-III is part of our Phase 3b program, which aims to further enhance our understanding of AbbVie's regimen in HCV populations seen in clinical practice, and supports our commitment to continued investigation in this field."

About TURQUOISE-III Study
TURQUOISE-III is a multi-center, open-label Phase 3b study to evaluate the safety and efficacy of 12 weeks of treatment with VIEKIRAX® + EXVIERA® without ribavirin (RBV) in adult patients (n=60) with genotype 1b chronic hepatitis C virus infection and compensated liver cirrhosis who were treatment-naïve or treatment-experienced (failed previous therapy with pegylated interferon and RBV). The primary endpoint is the rate of sustained virologic response 12 weeks after treatment (SVR12).1

No patients experienced virologic failure during treatment and no patients experienced virologic relapse following the end of treatment.1

About VIEKIRAX® + EXVIERA®
VIEKIRAX + EXVIERA is approved in the European Union for the treatment of genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, including patients with compensated cirrhosis. VIEKIRAX is approved in the European Union for the treatment of genotype 4 (GT4) chronic HCV infection.

VIEKIRAX tablets consist of the fixed-dose combination of paritaprevir 150mg (NS3/4A protease inhibitor) and ritonavir 100mg with ombitasvir 25mg (NS5A inhibitor), dosed once daily. EXVIERA tablets consist of dasabuvir 250mg (non-nucleoside NS5B polymerase inhibitor) dosed twice daily. VIEKIRAX + EXVIERA are taken with or without ribavirin (RBV), dosed twice daily based on patient type. VIEKIRAX + EXVIERA is taken for 12 weeks with or without RBV, except in genotype 1a and GT4 patients with compensated cirrhosis, who should take it for 24 weeks with RBV.

Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for hepatitis C protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of chronic hepatitis C.

Additional information about AbbVie's hepatitis C development program can be found on www.clinicaltrials.gov.

About AbbVie's HCV Clinical Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating interferon-free, all-oral treatments with or without ribavirin with the goal of achieving high sustained virologic response rates in as many patients as possible. AbbVie's global Phase 3b program plans to include more than 2,800 genotype 1 patients in over 200 study centers worldwide, including the U.S., Canada, Europe, Russia and Brazil.

Additional information about AbbVie's hepatitis C development program can be found on www.clinicaltrials.gov.

VIEKIRAX® + EXVIERA® EU Indication
VIEKIRAX is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults. EXVIERA is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults.

Important EU Safety Information
Contraindications:
VIEKIRAX + EXVIERA are contraindicated in patients with severe hepatic impairment (Child-Pugh C). Patients taking ethinyl estradiol-containing medicinal products must discontinue them and switch to an alternative method of contraception prior to initiating VIEKIRAX + EXVIERA. Do not give VIEKIRAX with certain drugs that are sensitive CYP3A substrates or strong inhibitors of CYP3A. Do not give VIEKIRAX and EXVIERA with strong or moderate enzyme inducers. Do not give EXVIERA with certain drugs that are strong inhibitors of CYP2C8.

Special warnings and precautions for use:
VIEKIRAX and EXVIERA are not recommended as monotherapy and should be used in combination with other medicinal products for the treatment of hepatitis C infection.

Pregnancy and concomitant use with ribavirin
When VIEKIRAX + EXVIERA are used in combination with ribavirin, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and 6 months after the treatment. Refer to the Summary of Product Characteristics for ribavirin for additional information.

ALT elevations
Transient elevations of ALT to >5x ULN without concomitant elevations of bilirubin occurred in clinical trials with VIEKIRAX + EXVIERA and were more frequent in a subgroup who were using ethinyl estradiol-containing contraceptives.

Use with concomitant medicinal products
Use caution when administering VIEKIRAX with fluticasone or other glucocorticoids that are metabolized by CYP3A4. A reduction in colchicine dosage or interruption in colchicine is recommended in patients with normal renal or hepatic function. VIEKIRAX with or without EXVIERA is expected to increase exposure of statins so certain statins need to be discontinued or dosages reduced. Low dose ritonavir, which is part of VIEKIRAX, may select for PI resistance in HIV co-infected patients without ongoing antiretroviral therapy. HIV co-infected patients without suppressive antiretroviral therapy should not be treated with VIEKIRAX.

Adverse Reactions
Most common (>20 percent) adverse reactions for VIEKIRAX + EXVIERA with RBV were fatigue and nausea.

Full summary of product characteristics is available at www.ema.europa.eu

Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

1 Feld J, et al. TURQUOISE-III: Safety and Efficacy of 12-week Ribavirin-free Treatment for Patients with HCV Genotype 1b and Cirrhosis. Presented at the 15th Annual International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD) in Berlin, Germany, June 26-28, 2015
2 Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15
3 Global Alert and Response (GAR): Hepatitis C. World Health Organisation Web site.http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index2.html#HCV.
Published 2003. Accessed November, 2013
4 O'Leary JG, Davis GL. Hepatitis C. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 9th ed, Vol 1. Philadelphia, PA: Saunders Elsevier. 2010:1313-1335

To view the original version on PR Newswire, visit:
http://www.prnewswire.com/news-releases/abbvie-announces-new-phase-3b-results-in-genotype-1b-chronic-hepatitis-c-patients-with-compensated-liver-cirrhosis-300103829.html

SOURCE AbbVie 

Burman's Specialty Pharmacy shows hepatitis C cure possible while cutting a third of the drug costs

Burman's Specialty Pharmacy study shows hepatitis C cure possible while cutting a third of the drug costs

MEDIA, Pa., June 23, 2015 /PRNewswire/ -- Burman's Specialty Pharmacy, a Diplomat company, announced a study showing that more than a quarter of hepatitis C patients may be treated with an eight-week therapy, four weeks shorter than the drug manufacturers originally expected. This represents potential for a huge cost savings in a health care ecosystem where hepatitis C treatments have posed a looming problem for payor organizations.

According to the study – reported in 'Specialty Pharmacy News' June edition – among 1,093 genotype 1a and 1b patients who have completed treatment over the last six months, 385, or 35%, had a clinical profile that qualified them for eight weeks, instead of 12 weeks, of Harvoni® therapy. "We worked with physicians on prescribing the shortened therapy for 284, or 74%, of those patients," said Paul Urick, president of Managed Markets and Industry Relations. The indicated population is treatment-naive and noncirrhotic, with an initial viral load of less than 6 million.

"An eight-week treatment cycle's wholesale acquisition costs average $63,000, a savings of $31,500 versus a 12-week treatment cycle," Urick added. "This is a great opportunity to make a difference to patients, and it's great for payors as well."

For Burman's qualifying patients:
A 12-week regimen of Harvoni® would have cost $26,923,050.
An eight-week regimen of Harvoni® totaled $17,948,700.
Savings amounted to $8,974,350 in Harvoni® costs alone.

"We know that not all physicians will be willing to prescribe eight weeks of treatment at all times," Urick said, "especially since each patient may have extenuating circumstances beyond prior treatment status and cirrhotic status, among other factors. It's at physicians' discretion as to how long they want to treat patients. Still, nearly 75% of patients who qualified did achieve a cure with 8-weeks of treatment for their Hepatitis C disease."

Burman's adds to this cost savings with enhanced therapy management. Burman's proprietary software platform HealthTrac is specifically designed to navigate the complexities of hepatitis C therapy and allow pharmacists and providers to collaborate on patient care.

"Our approach to hepatitis C therapy is based on collaboration between all parties in a patient's treatment continuum," said Steve Burman, president and CEO of Burman's. "Our goal is to maintain the high-touch treatment experience that drives a cure for our patients while driving down the costs that too often prevent care. Ultimately, we would like to affect real policy change that improves access to cures."

To learn more about Burman's Specialty Pharmacy, visit www.burmansmedical.com.

FORWARD-LOOKING STATEMENTS This press release contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements give current expectations or forecasts of future events or our future financial or operating performance, and in this press release include the potential for an eight-week hepatitis C therapy with significant cost savings and Diplomat's distribution of the drug(s) set forth above (and any implied financial impact). The forward-looking statements contained in this press release are based on management's good-faith belief and reasonable judgment based on current information, and these statements are qualified by important risks and uncertainties, many of which are beyond our control, that could cause our actual results to differ materially from those forecasted or indicated by such forward-looking statements. These risks include sampling size and other risks related to conducting drug studies, the number of patients prescribed such drug(s) currently and in the future, patient's adherence to such drug(s), the number of distributors on panel and our relative distribution share, the timing of drug sales, the cost of such drug(s) and reimbursement rates by payors, drug competition, and the factors set forth in "Risk Factors" in Diplomat's Annual Report on Form 10-K for the year ended December 31, 2014 and in subsequent reports filed with or furnished to the Securities and Exchange Commission. Except as may be required by any applicable laws, Diplomat assumes no obligation to publicly update such forward-looking statements, which are made as of the date hereof or the earlier date specified herein, whether as a result of new information, future developments or otherwise.

About Burman's Specialty Pharmacy

Burman's is a leader in disease-specific treatment programs and has been in business for more than 50 years. Burman's comprehensive services and patient-first approach help patients and physicians navigate the complex waters of a variety of challenging health conditions, all while achieving improved results. Burman's offers individualized pharmaceutical care for a variety of challenging health conditions and complex drug therapies. To learn more, visit www.burmansmedical.com.