Welcome to HCV Advocate’s hepatitis blog. The intent of this blog is to keep our website audience up-to-date on information about hepatitis and to answer some of our web site and training audience questions. People are encouraged to submit questions and post comments.

For more information on how to use this blog
click here, the HCV drug pipeline click here, and for more information on HCV clinical trials click here

Be sure to check out our other blogs: The HBV Advocate Blog and Hepatitis & Tattoos.

Alan Franciscus
Editor-in-Chief
HCV Advocate
HBV Advocate

Drugs in Development / Clinical Trials—Updated August 19, 2014

Wednesday, August 27, 2014

European Commission Approves Bristol-Myers Squibb’s Daklinza (daclatasvir) Across Multiple Genotypes for the Treatment of Chronic Hepatitis C Infection

Daklinza, when used in combination with sofosbuvir, is an all-oral, once daily regimen that yields cure rates of up to 100%
Daklinza + sofosbuvir offers potential cure for a broad range of EU HCV patients, including those with advanced liver disease, genotype 3 and protease inhibitor failures


Wednesday, August 27, 2014 5:00 am EDT
 
"The eradication of HCV is in sight, and with today’s approval, Daklinza, in combination with other agents, will be an important option to achieve cure across many HCV genotypes and patient types for those in the EU who are in dire need of new treatment choices"

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced that the European Commission has approved Daklinza (daclatasvir), a potent, pan-genotypic NS5A replication complex inhibitor (in vitro), for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Daklinza, when used in combination with sofosbuvir, is an all-oral, interferon-free regimen that provided cure rates of up to 100% in clinical trials, including patients with advanced liver disease, genotype 3 and those who have previously failed treatment with protease inhibitors. Daklinza is the first NS5A complex inhibitor approved in the European Union (EU) and will be available for use in combination with other medicinal products, providing a shorter treatment duration (12 or 24 weeks) compared to 48 weeks of treatment with interferon- and ribavirin-based regimens.

Today’s approval allows for the marketing of Daklinza in all 28 Member States of the EU. The marketing authorization for Daklinza follows an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP), a designation that is granted to new medicines of major public health interest.

“HCV is a challenging virus to overcome, requiring multiple modes of attack. With the approval of Daklinza, we have a new class of drug that disrupts the virus in two ways - by inhibiting both viral replication and assembly - and when combined with other compounds often results in cure among even the hardest-to-treat patients,” said Michael P. Manns, MD, Professor and Chairman, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
Of the estimated nine million people living with HCV in the EU, genotype 1 is the most common genotype, though distribution varies across the region. The burden of liver disease and other morbidities from HCV infection is significant in Europe, where HCV accounts for 63% of liver transplants among patients with virus-related liver disease. Patient populations with high unmet needs include those with advanced liver disease, protease inhibitor failure, genotype 3, HIV co-infected patients and those who have undergone liver transplant.

“The eradication of HCV is in sight, and with today’s approval, Daklinza, in combination with other agents, will be an important option to achieve cure across many HCV genotypes and patient types for those in the EU who are in dire need of new treatment choices,” said Emmanuel Blin, Head of Worldwide Commercialization, Bristol-Myers Squibb. “We are proud to have discovered, developed and now brought to market this first-in-class NS5A replication complex inhibitor. We look forward to our continued work with EU health authorities to ensure Daklinza-based regimens are available to patients as quickly as possible.”

The approval of Daklinza is supported by data from multiple studies, including an open-label, randomized study of Daklinza with sofosbuvir in genotypes 1, 2, and 3, including patients with no response to prior therapy with telaprevir or boceprevir and patients with fibrosis. Results showed that a regimen of Daklinza with sofosbuvir achieved SVR12 (sustained virologic response 12 weeks after the end of treatment; a functional cure) in 99% of treatment-naïve patients with HCV genotype 1, 100% of patients with genotype 1 who had failed treatment with either telaprevir or boceprevir, 96% of those with genotype 2 and 89% of those with genotype 3.

In addition, the regimen resulted in low rates of discontinuation (<1%) due to adverse events (AEs). The rate of serious adverse events (SAEs) was low (4.7%). The most common adverse events were fatigue, headache and nausea. Across clinical studies, Daklinza-based regimens have been generally well tolerated with low rates of discontinuation across a range of patients. Ongoing and completed Daklinza studies have included more than 5,500 patients in a variety of all-oral regimens and with the current interferon-based standard of care.

The safety of Daklinza for the treatment of hepatitis C has been demonstrated in diverse patient populations that include elderly patients, patients with advanced liver disease, post-liver transplant recipients and patients co-infected with HIV. No unique safety concerns have been identified in patients who were treated with Daklinza across clinical studies and in the early access program. Several of these studies are ongoing.

Recommended regimens and treatment duration for Daklinza combination therapy include:
 
HCV genotype and patient population     Treatment     Duration
Genotype 1 or 4 without cirrhosis    
Daklinza + sofosbuvir
    12 weeks
Consider prolongation of treatment to 24 weeks for patients with prior treatment including a NS3/4A protease inhibitor (see sections 4.4 and 5.1).
Genotype 1 or 4 with compensated cirrhosis     Daklinza + sofosbuvir     24 weeks
Shortening treatment to 12 weeks may be considered for previously untreated patients with cirrhosis and positive prognostic factors such as IL28B CC genotype and/or low baseline viral load.
Consider adding ribavirin for patients with very advanced liver disease or with other negative prognostic factors such as prior treatment experience.
Genotype 3 with compensated cirrhosis and/or treatment experienced     Daklinza + sofosbuvir + ribavirin     24 weeks
Genotype 4     Daklinza + peginterferon alfa + ribavirin     24 weeks of Daklinza in combination with 24-48 weeks of peginterferon alfa and ribavirin.
If the patient has HCV RNA undetectable at both treatment weeks 4 and 12, all 3 components of the regimen should be continued for a total duration of 24 weeks. If the patient achieves HCV RNA undetectable, but not at both treatment weeks 4 and 12, Daklinza should be discontinued at 24 weeks and peginterferon alfa and ribavirin continued for a total duration of 48 weeks.
 
Daklinza monotherapy is not recommended. The Summary of Product Characteristics will be available at www.ema.europa.eu. Commercial availability of Daklinza in the EU will be determined by individual Member States.
 
About Hepatitis C
Globally, there are 150 million people infected with HCV and of that, an estimated 9 million people are living with hepatitis C in the European Union (EU). Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, 20 percent of people with chronic hepatitis C will develop cirrhosis and, of those, about 5 to 7 percent of patients may ultimately die of the consequences of infection.
 
About Bristol-Myers Squibb’s HCV Portfolio
Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, a potent pan-genotypic NS5A complex inhibitor (in vitro), which continues to be investigated in multiple treatment regimens and in people with co-morbidities.
Daklinza was recently approved in Japan in combination with Sunvepra (asunaprevir), a NS3/4A protease inhibitor. The Daklinza+Sunvepra Dual Regimen is Japan’s first all-oral, interferon- and ribavirin-free treatment regimen for patients with genotype 1 chronic HCV infection, including those with compensated cirrhosis.

Applications for the daclatasvir Dual Regimen are also under review by the U.S. Food and Drug Administration (FDA), which granted priority review status and set a target review date under the Prescription Drug User Fee Act (PDUFA) of November 30, 2014.
In 2014, the FDA granted Bristol-Myers Squibb’s investigational daclatasvir Dual Regimen (daclatasvir + asunaprevir) Breakthrough Therapy Designation for use as a combination therapy in the treatment of genotype 1b HCV infection.

In 2013, Bristol-Myers Squibb’s investigational all-oral 3DAA Regimen (daclatasvir/asunaprevir/BMS-791325) also received Breakthrough Therapy Designation in the U.S., which helped to expedite the start of the ongoing Phase 3 UNITY Program. Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. The daclatasvir 3DAA Regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.
Additional studies with daclatasvir in combination with sofosbuvir are being conducted in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV co-infected patients and patients with genotype 3 as part of the ongoing Phase 3 ALLY Program.
 
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

StoryCorps Chicago: Hepatitis C survivors bond over advocacy work

After contracting Hepatitis C through a blood transfusion, Lucinda Porter became a nurse and advocate for people living with the disease. In this week's StoryCorps she speaks with friend and fellow Hepatitis C survivor Alan Franciscus.

Listen to their stories here

StoryCorps is one of the largest oral history projects of its kind. Since 2003, StoryCorps has collected and archived more than 50,000 interviews from more than 80,000 participants. Each conversation is recorded on a free CD to share, and is preserved at the American Folklife Center at the Library of Congress. Millions listen to our weekly broadcasts on NPR’s Morning Edition and on StoryCorps’ Listen Page. Learn more about StoryCorps here.

Tuesday, August 26, 2014

Commentary: Public Health Initiatives Needed to Combat Hepatitis C

The United States could eradicate the hepatitis C virus, but significant strides in public health have to be taken to achieve that goal, say researchers at Weill Cornell Medical College and National Development and Research Institutes.

Written for a symposium on hepatitis C in Antiviral Research, the commentary outlines a comprehensive approach to eliminating the disease. While new HCV treatments are now approved for wide use, they will not end the epidemic by themselves, according to the authors. Instead, they write, public health practitioners must work with policymakers, physicians, scientists and advocates to wipe out the infection, a serious illness that attacks the liver and often leads to cirrhosis or cancer.

“There is no question that the disease could be eliminated, but there is also no question that it’s going to require effort, resources and commitment,” said lead author Dr. Brian Edlin, an associate professor of medicine at Weill Cornell. “I think it’s clear that we’re entering an area where morbidity and mortality will begin to respond to our efforts. But without a balanced, full approach to the problem there’s a risk that it will continue to linger and disparities between advantaged and disadvantaged communities will sharpen.”

Read more...

Monday, August 25, 2014

Fundraiser for musician suffering from Hepatitis C: Linda Nash Stevenson

A jazz concert is being held at the Palladium Theater in St. Petersburg on Monday to raise money for local musician Linda Nash Stevenson, who's suffering from a chronic liver condition and needs about $100,000 to pay for life saving medicine.

"If I don't get the medicine I will die," Stevenson said.

The jazz benefit is scheduled to begin at 7 p.m. at the Palladium Theater, located at 253 5th Avenue North, in St. Petersburg. Musicians Jun Bustamante, La Lucha, Nate Najar, John Lamb, Stolen Idols and Ray Biscoglia will be performing. The suggested donation at the door is $20.

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UPDATE—Patients First: The Right to Be Treated and Cured, by Alan Franciscus

 
  —Alan Franciscus, Editor-in-Chief


AASLD/IDSA recently released hepatitis C treatment guidelines that limit treatment of hepatitis C to those who are considered the most seriously ill. In this respect, people with debilitating fatigue are recommended as the “highest” in need of treatment along with those with advanced disease, other conditions or diseases in addition to having HCV, and HCV populations who are at high risk for transmitting HCV.

One of the most important strategies that people can do is to make sure that all of their symptoms are reported to their medical providers and documented as part of their medical records. 

The article below provides tips to help people report and document their symptoms. 

                                                                                                                       -Alan



Very soon there will be treatments that will cure almost everyone of hepatitis C. These new treatments will have:
  • Minimal side effects, especially compared to the therapies that came before them
  • Cure rates that will be approaching up to 100%
  • Treatment periods that will be limited to  12 weeks—at least for some treatments
Hurray!  Good news for everyone with hepatitis C.

But of course there is a downside – the price of the new medications.  We don’t know yet what the price for the next generation of interferon-free medications will be, but generally once a price has been set there is little chance that medications that come along later will be priced lower—I really, really hope that I am wrong.  But even if they are somewhat lower they are still going to be expensive. 

The problem of the high cost of current medications is already impeding access to treatment.  Insurance companies, government payers (Medicare, Veterans Healthcare, etc.) are trying to come to terms with the expense of the medications when the great number of people who need to be treated is factored into the equation.  There have already been denials of coverage because people are not deemed ‘sick enough’ to qualify for treatment.   Plain and simple: It is unethical to deny people a medication because they are deemed to be ‘not sick enough.’  Another sore point—being ‘sick enough’ is being narrowly defined as having severe liver scarring without any consideration for other (extrahepatic) symptoms and side effects that many people with hepatitis C experience.  

Everyone with hepatitis C should have access to these life-saving medications.  In response the HCV Advocate will be publishing a series of articles, fact sheets and tools to help patients navigate through the medical care maze and help them to self-advocate. 

Topics will include:
  • Medical appointments: 
    • How to maximize your medical appointments, questions to ask, reporting symptoms, how to dress, being respectful and respected, what to do if you disagree, working with the gatekeeper (the nurse), and many more strategies to make the transition from a passive to an assertive patient.   How to talk to your doctor about treatment.
  • Medical insurance – what, when and how.  How to fight rejection letters.  Open enrollment and what that means for your drug coverage.  Questions you should ask yourself about your coverage.
  • Patient Assistance Programs – getting started before you start treatment.  Knowing your options, and what services are offered. 
  • Finances – what to expect if you are on treatment. 
  • Getting support
We are going to be adding more educational tools as we hear more from people about some of the obstacles they are facing.  But please check out our fact sheets and guides—we already have many resources that can help people access services and treatment. 

Symptoms of Hepatitis C
As I mentioned before, some insurance companies are basing approval of the medications on the degree of liver damage.  People living with chronic hepatitis C have many other symptoms and conditions that are not necessarily related to the scarring of the liver.  This is why it is so important to make sure that all of the conditions and symptoms of hepatitis C are recorded in your medical records. It is also important to record how the symptoms and conditions affect your daily activities. 

The symptoms of hepatitis C range from mild to moderate to severe.  Personally, I believe that everyone with hepatitis C has symptoms, but they come on so gradually and over such a long period of time that most people don’t notice them or believe that they are part of the aging process.  The list below contains some of the more common symptoms reported by people with hepatitis C, but the list is not all inclusive.  If you have symptoms that are not listed here be sure to mention them to your medical provider.
  • Fatigue is the most common symptom reported by people with hepatitis C.  It can range from mild to moderate to severe.  Again, some people may not even realize how fatigued they are if the fatigue falls somewhere within the mild to moderate range.  A good way of measuring it is to talk with friends who are healthy to find out what their fatigue level is. Another good way is to talk to others with hepatitis C and try to gauge how your fatigue measures up with their fatigue.  Finally, try to figure out how fatigue affects your daily life.  How does the fatigue affect your work, recreation and interaction with family and friends. 
  • “Brain Fog” is a common symptom of hepatitis C which is usually defined as low-level cognitive impairment.  Typical symptoms include fuzzy thinking, memory problems, and lack of concentration.
  • Muscle and Joint Pain  – low level aches and pains throughout the body.
  • Insomnia – inability to sleep or sleep that is not restful.
  • Headaches – pain or pressure on one or both sides of the head.
  • Fevers and Night Sweats – generally light fevers and waking up with clothes and/or bedding wet.
  • Depression and anxiety – feeling down and nervous.
  • Loss of Appetite or weight loss.
  • Nausea and vomiting  - feeling sick to your stomach or vomiting.
  • Abdominal Pain or pain in the general area of the stomach and intestines.
  • Liver Pain in the upper right side, right behind the rib cage.
In addition, ask your medical provider to test you for extrahepatic manifestations—these are conditions outside of the liver.  There are many conditions that are either directly caused by hepatitis C or that are more commonly seen in people with hepatitis C.  See our fact sheet on extrahepatic manifestations.  Ask to see a specialist who understands and can diagnose extrahepatic manifestations. 

Symptoms of Cirrhosis
Cirrhosis is a potentially life-threatening condition.  There are two types of cirrhosis—compensated and decompensated.  Compensated cirrhosis is defined as a liver that is heavily scarred but can still perform most of the important chemical functions that keep the body running smoothly.  When the liver is decompensated this means that the liver is severely scarred and damaged and normal function is impaired.  In addition to the symptoms listed above, other symptoms that need to be diagnosed by a medical provider are: 
  • Fluid retention and swelling in the legs and hands
  • Frequent urination
  • Bleeding and excessive bruising
  • Pruritus – excessive itching
  • Jaundice – yellowing of the skin and eyes
  • Menstrual irregularities
  • Nail changes
There are other symptoms that need to be diagnosed and managed by a medical provider including:
  • Encephalopathy – mental confusion, changes in sleep patterns, loss of memory, coma
  • Varices – stretched and bleeding blood vessels of the esophagus and stomach
  • Malnutrition – this happens when the liver isn’t able to process nutrients
  • Portal hypertension – the liver is so scarred that blood can’t get through it
  • Ascites – fluid retention in the abdominal region
Measuring Symptoms
A good way to measure the symptoms is by the 1 to 10 method with 10 being the worst. For example, if you could not get out of bed one day because you were so tired, rate that fatigue as a 10.  If you were tired so that you decided that you would just watch TV that night it might be a 4 or 5.  It might be a good idea to start a symptom log or journal.  A copy could be inserted into your medical chart.
Don’t be afraid to tell your doctor or nurse what symptoms you are having—most doctors and nurses welcome patient involvement in their medical care.

Remember everyone has the right to be treated and cured.

Get Tested. Get Treated. Get Cured.

Saturday, August 23, 2014

The battle against hepatitis in Japan

TOKYO —The numbers are startling: more than 3 million people in Japan suffer from chronic hepatitis B or C, many over the age of 60. About 50% are unaware they have the diseases, not having been screened. Globally, viral hepatitis kills about 1.5 million people each year, as many as does HIV/AIDS.

The World Health Assembly of the World Health Organization (WHO) recently passed a resolution aimed at getting countries to develop plans for the screening, diagnosis and treatment of viral hepatitis. EURObiZ Editor-in-chief Mike de Jong spoke with World Hepatitis Alliance president Charles Gore and infectious disease control and prevention specialist Dr Junko Tanaka of Hiroshima University about the screening and treatment in Japan.

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Friday, August 22, 2014

Study shows variations in distribution of hepatitis C inside Egypt

A new study by researchers at Weill Cornell Medical College in Qatar (WCMC-Q) shows that there is a large geographic variation in the distribution of the hepatitis C virus (HCV) in Egypt.

Egypt has the highest infection level of the disease in the world, with 14.7% of the population carrying HCV, but it is still not clear why this is so.

Treatment campaigns for bilharzia – a disease caused by parasitic worms - during the 1960s and 1970s, using parenteral antischistosomal therapy (PAT), contributed to the epidemic through wide-scale sharing of needles and syringes. However, these campaigns can explain only about 10% of HCV infections in the country. It is probable that most HCV infections in Egypt are linked to exposures in medical care settings.

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