Sunday, December 22, 2013

Hepatitis C: 2013 A Year In Review

  Welcome To Hepatitis C: 2013 A Year In Review 

The Big Story Of 2013?

The biggest story thus far is the FDA approval of Olysio (simeprevir) and Solvadi (sofosbuvir), two new oral drugs to treat hepatitis C, or is it?

In 2013 we found ourselves with a prolific HCV pipeline of direct-acting anti-viral agents which have improved: 1. Efficacy - overall 90% cure rates, 2. Tolerability - less side effects and 3. Convenience - shorter treatment duration, less pill burden. Wow. 

In this short 2013 review we count down twelve months of news, research and breakthroughs that made a significant difference in the lives of people living with hepatitis C.


BMS-986094 Lawsuit

We heard more on the lawsuit involving 15 patients who were tragically hurt - one died- during the company-sponsored clinical trials of the hepatitis C drug BMS-986094. The Wall Street Journal reported that Bristol-Myers Squibb agreed to pay $80 million to 15 patients who either died or were hospitalized while participating in the study.

The Canadian Liver Foundation (CLF) recommended hepatitis C screening among all persons born between 1945 and 1965

The Canadian Liver Foundation (CLF) urged general practitioners (GPs) to immediately begin recommending a one-time blood test for all adults born between 1945 and 1975.

2013-Guide to Clinical Trials for People with Hepatitis C

The Treatment Action Group (TAG) published an insightful second edition guide to hepatitis C clinical trials, written by Tracy Swan and Matt Sharp.

Pegylated interferon- Pegasys, PegIntron similarly effective for chronic HCV genotype 1

*Pegylated interferon alfa-2a (Pegasys) and alfa-2b (PegIntron)
A paper published in BMC suggested standard doses of pegylated interferon alfa-2a and alfa-2b, administered with ribavirin, were similarly effective in patients with chronic hepatitis C genotype 1.

Updated Practice Guideline: Treatment of Genotype 1 Chronic HCV Virus Infection

 In 2011 the American Association for the Study of Liver Diseases released "An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection" in January a new section was added to the guidelines entitled "Use and Interpretation of HCV RNA Results During Triple Therapy."


Sexual transmission of HCV rare among long-term, monogamous couples

(The HCV partners study)

Patients with chronic hepatitis C in long-term, monogamous relationships are at a very low risk for transferring the virus to their partner via sexual contact.

The study, published in Hepatology is available at NATAP, this past April Drs. Stephen A. Harrison and Norah A. Terrault discussed the article: Sexual transmission of hepatitis C virus among monogamous heterosexual couples: The HCV partners study, below in this podcast.

Idenix drops development of 2 hepatitis C drugs

The company has elected not to continue its clinical development program for IDX184, a nucleotide polymerase inhibitor in phase IIb testing for the treatment of hepatitis C virus (HCV) infection, or to continue its development of IDX19368, an HCV nucleotide polymerase inhibitor

The two Idenix drugs, IDX184 and IDX19368, as well as another drug from Bristol-Myers Squibb Co. called BMS-986094, work in similar ways. All three products are nucleotide inhibitors, meaning they are designed to prevent the hepatitis C virus from making copies of itself.

In August *2012 Bristol-Myers halted testing of BMS-986094 after one patient in the clinical trial died of heart failure following treatment. The drugmaker eventually abandoned development of the product.

 Idenix has said there are important differences between the drugs, but the Food and Drug Administration placed IDX184 on clinical hold Aug. 16. At the time, it was Idenix's most advanced experimental drug. The FDA also had placed a hold on IDX19368, which hadn't begun patient dosing.


Mortality risk greater among patients with HCV who moderately drank alcohol

For people with the chronic liver infection hepatitis C, heavy drinking is an obvious no-no, but a new study links even modest alcohol consumption with an increased risk of death - and not just from liver disease.

"What this study shows is... truly, even what might be considered a moderate and safe amount of alcohol use in people without hepatitis C is dangerous to your health if you have hepatitis C," said Rae Jean Proeschold-Bell, a hepatitis C researcher at Duke University in Durham, North Carolina, who was not involved in the study.

Of Interest
6 Booze-Free Ways to Toast the Holidays with Hepatitis C
If you have hepatitis C, your doctor probably told you, “No alcohol.” If you like to drink, this is hard news to bear, particularly around the holidays. Alcohol seems to be everywhere this time of year, even in grandma’s fruitcake. It may be alluring to the mouth, but it is like adding fertilizer to hepatitis C.........

April 2013

FDA Approves FibroScan for Noninvasive Liver Diagnosis

A painless alternative to liver biopsy for evaluating the stage of liver fibrosis.

video platformvideo managementvideo solutionsvideo player

The new machine called a fibroscan is a timely and welcome alternative to a needle biopsy as diseases of the liver increase.

EASL 2013

The International Liver Congress 2013 of the European Association for the Study of the Liver (EASL), took place April 24 to 28 in Amsterdam, The Netherlands.

EASL 2013 - Internet Symposium: Watch Advances in Chronic Hepatitis C Management and Treatment - Interferon  Free, All Oral Regimens Are Highlighted

Watch - Best of the EASL 2013 on hepatitis C - webcast with Dr Andrew Muir


Hepatologist Urges caution among clinicians in the administration of telaprevir

Dr. Maheshwari urges caution among clinicians in the administration of telaprevir, and stresses the need for rigorous side-effect management protocol and adequate long-term follow-up for patients with HCV receiving this treatment.

In December 2012 telaprevir included a “black box” warning that fatal and non-fatal serious skin reactions have been reported in patients taking INCIVEK

DDW 2013 - May 18-21, 2013 - Orlando, FL

Digestive Disease Week - The conference will showcase the latest advances in GI research, medicine and technology in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery
View Media and DDW Updates

DDW 2013 - Coverage @ GI & Hepatology News
Aug 12 2013 - DDW 2013 The AGA Report
Download PDF | Digital Edition


US Preventive Services Task Force recommended hepatitis C screening among all persons born between 1945 and 1965

In June 2013, the US Preventive Services Task Force updated recommendations to include hepatitis C screening among all persons born between 1945 and 1965.

The USPSTF had initially recommended a "C" rating for this birth cohort (1945 and 1965) in a draft proposal, conflicting with the CDC recommendation and creating confusion in the primary care community. The change from a "C" to a "B" rating gives primary care clinicians the absolute clarity of the hepatology community -- early detection of HCV allows for the drastically greater possibility of treatment success for patients. The new "B" rating allowed for testing without a copayment by  both Medicare and private insurers.

The recommendation statement was published online June 24 in the Annals of Internal Medicine.

A Science First: Japanese researchers grow human liver using stem cells

It could herald a giant leap forward for the field of human regenerative medicine.Japanese researchers say they have grown a tiny human liver, only five millimetres long,from reprogrammed human skin cells.


JAMA - Deaths from liver disease increased from 1990 to 2010

The most common causes of both cirrhosis and liver cancer are viral hepatitis, alcoholism, and obesity-related fatty liver disease. However, it is hepatitis C that is the most likely cause of the emergence of liver disease as a growing threat to American lives.

 According to a July 10, 2013 article published in the Journal of The American Medical Association – “The State of US Health, 1990-2010: Burden of Diseases, Injuries, and Risk Factors”  deaths from liver disease increased from 1990 to 2010. Liver disease also rose as a contributor to premature mortality.

Cirrhosis -- damaged liver tissue and the loss of liver function due to a variety of liver diseases -- has risen substantially from the 14(th) most frequent cause of death in 1990 to the 8(th) most frequent cause of death in 2010. In the same time period, liver cancer went from the 39(th) to the 30(th) most frequent cause of death in the US. The prognosis of liver cancer is particularly poor with the medical community's limited ability to treat patients with liver cancer, with death most often occurring within six months.


Documentary - Breaking the Silence: Voices of Chronic Hepatitis C

As once a hepatitis C patient myself, I was deeply touched while viewing this awe inspiring documentary from Janssen Therapeutics. For 17 minutes the viewer with hepatitis C is not alone, for 17 minutes normal people just like you and me share their story, diagnosis and family struggles. Support of family and friends is critical, but no matter how much our loved ones may empathize with us - connecting with other people living with the virus is invaluable.

**View the video or read the transcript here.

Diet And Liver Health

There isn't really a diet for people with hepatitis C, but research has shown people with HCV that are obese have a higher risk for developing fibrosis, scarring, and cirrhosis of the liver.

In the August issue of "Nutrition Journal" researchers suggest exercise, low-fat or low-calorie diets can improve fibrosis, steatosis and insulin resistance in people living with chronic hepatitis C.

For the hands on reader, in this September video Dr. Galati answers the common question about diet and liver health.

Additionally, a podcast on the effects of acetaminophen and alcohol on the liver is hosted by Dr. Galati, check out Part One and Part Two 


Surgeons at New York-Presbyterian/Columbia University Medical Center Report Successful Laparoscopic Living Donor Liver Retrieval for Adult Recipients

A team of surgeons at New York-Presbyterian/Columbia University Medical Center is the first in the country to report a fully laparoscopic hepatectomy — the removal of a portion of the liver — from a living adult donor for adult and teenage recipients. The procedure advances transplant surgery and offers hope for addressing the significant shortage of liver donors.


Hepatitis C Treatment One Step at a Time

Ms. Lucinda K. Porter the author of "Free from Hepatitis C" has graced the HCV community with a second book "Hepatitis C Treatment One Step at a Time".

The timing of the book couldn't be more perfect. With screening strategies in place by the CDC and Task Force which recommend all people born from 1945 through 1965 get tested one time for hepatitis C, and new drugs moving through the final stages of FDA approval - the need for a guide during HCV therapy is paramount.

This comprehensive book provides tips for people starting hepatitis C treatment while slowly dissipating the fear of the unknown.


OLYSIO™ Simeprevir FDA Approved 

OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C
Johnson & Johnson's protease inhibitor OLYSIO (Simeprevir) is approved for the treatment of HCV genotype 1, in combination with peginterferon alfa and ribavirin in adults with compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous interferon therapy (pegylated or non‑pegylated) with ribavirin.

OLYSIO™ (simeprevir) not effective in patients with HCV Q80K variant

OLYSIO improved tolerability, has a lower pill burden and appears to be slightly more effective than the standard of care, curing 80 percent of treatment-naïve patients, but there are some drawbacks. Before starting treatment patients with HCV genotype 1a need to be screened for Q80K polymorphism, alternative therapy should be considered for people with the mutation, according to simeprevir prescribing information

Healio; Screening available for HCV Q80K polymorphism

Hepatitis C: Boehringer Ingelheim's faldaprevir granted accelerated assessment from European Medicines Agency

“Faldaprevir* has been studied with pegylated interferon and ribavirin in a broad range of more than 3,300 patients typical of those that doctors see in every day clinical practice. Faldaprevir* has demonstrated strong efficacy and a robust safety profile while also offering the convenience of once-daily dosing and no food restrictions,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “The acceptance for accelerated assessment by the EMA supports our position that if approved, faldaprevir* will provide an important alternative to currently available hepatitis C treatments.”

For full results see the STARTVerso™ press release here.

The 64th Annual Meeting of the American Association for the Study of Liver Diseases

The meeting took place in Washington, DC; November 1-5, 2013, highlights include new data on FDA approved and experimental therapies for hepatitis C.

AASLD Coverage - Clinical Care Options CCO

AASLD In Review

In HCV Advocate's December newsletter, information on key breakthough therapies presented at this years AASLD is offered in an easy to digest summary. 

AASLD 2013 Internet Symposium

 AASLD 2013 Internet Symposium -ViralEd
The 1.5 hour symposium discussing key studies on current and HCV future drugs, featuring 4 well-known and recognized thought leaders in the HCV field; Fred Poordad, MD ( looking hot in his bow tie), K. Rajender Reddy, MD., Mark Sulkowski, MD., and Nezam H. Afdhal, MD.

Just Released

Best of HCV From AASLD 2013 @ Medscape 
Andrew Muir, MD; Michael P. Manns, MD
CME Released: 12/23/2013
Faculty will be discussing information about pharmaceutical agents that is outside of U.S. Food and Drug Administration approved labeling. The following off-label uses are discussed: simeprevir, sofosbuvir, daclatasvir, asunaprevir, ABT-450, ABT-267, MK-5172, MK-8742, faldaprevir, deleobuvir, PPI-668, and ledipasvir

Published December 27
Top 10 Highlights From The Liver Meeting - A Future Without Hepatitis C
A Future Without Hepatitis C
The successful development of targeted therapies for patients with chronic hepatitis C virus (HCV) was clearly evident. Several companies are jockeying to be the first to offer an all-oral, interferon (IFN)-free strategy. On the near horizon is the promise that a cocktail of agents, constructed on the basis of synergistic mechanisms of action, will be available for clinicians to wisely, effectively, and safely treat patients with HCV infection. A major advance, in my opinion, is the validation of regimens that are devoid of IFN and, in some cases, ribavirin.
Continue reading @ Medscape

Daclatasvir plus Asunaprevir HCV Regimen: No Interferon, No Ribavirin, No Problem

Patients who failed to respond to standard treatment for hepatitis C virus (HCV) infection achieved greater than 80% sustained virologic response at 24 weeks with an all-oral regimen that eschewed both interferon and ribavirin, researchers reported here.

Among 135 patients who were either ineligible for interferon therapy or who were intolerant of the treatment, 87.4% achieved a sustained virologic response -- basically a treatment cure, reported Kazuaki Chayama, MD, PhD, professor of medicine and director of Hiroshima University Hospital.

In his plenary session report at the annual meeting of the American Association for the Study of Liver Diseases, Chayama also reported that 80.5% of 87 previous non-responders or partial responders achieved a sustained virologic response at 24 weeks.

The two investigative agents attack the virus in different ways. Daclatasvir is a potent NS5A replication complex inhibitor with pan-genotypic antiviral activity. Asunaprevir is a potent NS3 protease inhibitor with antiviral activity against genotypes 1, 4, 5, and 6. Chayama said the phase III study he described follows successful phase II studies showing a strong impact on patients with genotype 1b.

The median age of the 222 participants in the trial was 62.5, about 35% were men, and about 10% were diagnosed with cirrhosis. Baseline factors, including male gender, advanced age, high baseline hepatitis C virus RNA, and cirrhosis, did not appear to have an impact on response rates, Chayama said.

The Japanese population mainly had genotype 1b infections, he said. Yet the success rate in achieving sustained virologic response was greater than 80%. "When I first started treating hepatitis C virus infection in the 1990s we were getting sustained virologic response rate in the 7% area, and to be getting response in the 80% to 90% levels we are seeing today is phenomenal."

He acknowledged that historically genotype 1 hepatitis C infection has been considered a more difficult disease to treat than genotypes 2 or 3, but in studies presented at The Liver Meeting 2013, "What has emerged is that genotype 3 is the new genotype 1. With these new drugs I think there has been a surprise that we get suboptimal results with genotype 3."

Read the article @ MedPage Today

Finally we make it to December


Gilead's Sovaldi (Sofosbuvir) Is FDA Approved

On December 6, 2013, Sovaldi, a polymerase inhibitor was approved to treat HCV genotypes 1 and 4 treatment-naïve adults in combination with PEG-IFN and ribavirin and the first approved interferon-free treatment regimen for people with HCV genotypes 2 and 3. Overall cure rates are at 80%, response rates and treatment duration varies, depending on genotype, viral and host factors.

Gilead states that Sovaldi in combination with ribavirin alone for 24 weeks can be considered for patients with genotype 1 infection who are interferon ineligible. Additionally, Sovaldi should be used in combination with ribavirin for treatment of HCV patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation to prevent post-transplant hepatitis C infection.

See PDF - For Full Prescribing Information.

The Cost?

High price for Hep C drug sparks controversy

Lynda Dee, co-chair of Fair Pricing Coalition, called Sovaldi a “very safe and highly effective drug” but noted that it must be used in combination with other drugs to treat different Genotypes, or strains, of Hepatitis C.

She said that although the other drugs – pegylated interferon and ribavirin – are not as expensive as Sovaldi, the price tag for combination therapy with Sovaldi comes to $93,000 and $168,000 for various treatment regimens for a single person living with Hepatitis C.

“Gilead has set the bar dangerously high as other companies determine prices for similar Hepatitis C drugs as they enter the market,” Dee said.

In a statement released at the time the U.S. Food and Drug Administration approved Sovaldi for patient use on Dec. 6, Gilead said it had put in place a patient assistance program to ensure that people with Hepatitis C have access to Sovaldi regardless of their ability to pay for it.

Continue reading.....

Sovaldi Website
PDF - FAQ about Sovaldi
Patient Information
Support And Patient Assistance Program
PDF - Full Prescribing Information

Best treatment options for HCV genotype 1: All of them contain sofosbuvir, all are expensive

Paul E. Sax, MD, Editor-in-Chief - HIV and ID Observations, wrote an article suggesting the best possible treatment opinion as of December 8, 2013, for genotype 1 patients, listing the PROS and CONS  (cost estimates approximate):

1. Simeprevir + sofosbuvir for 12 weeks.PROS: More than 90% cure rate in the COSMOS study.

Two pills once daily (it’s amazing even to write that.)

CONS: The COSMOS study was very small. Simeprevir can lead to photosensitivity and has many drug-drug interactions. The Q80K polymorphism may reduce response to simeprevir.

This regimen is not “FDA approved.” Cost = $145,000.

2. Sofosbuvir + ribavirin for 24 weeks.

PROS: Cured 76% of HIV/HCV co-infected patients in the PHOTON-1 study. May well do better in HCV mono-infected. Regimen is “FDA approved” for interferon-ineligible patients, which could help get insurance coverage.

CONS. Ribavirin, and all its side effects. 24 weeks seems long compared to 12 weeks. Response rate is lower than other options listed here, which would require re-treatment.

Cost (not including ribavirin) = $160,000.

3. Sofosbuvir + interferon + ribavirin for 12 weeks:

PROS: 90% cure rate in the NEUTRINO study. Only 12 weeks of interferon and ribavirin.

Cost = $90,000. CONS: Interferon. Ribavirin. Enough said.

All are a lot better than what we had just last week. All of them contain sofosbuvir. And all are expensive.

The Next Big Thing Is Sofosbuvir and Ledipasvir

Sofosbuvir and Ledipasvir Amazing Late-stage Hepatitis C Data 

The excitement builds with the one pill two trick pony. Can I say that? Well I did.

The buzzword is "nukes", the drug is Sovaldi, a nucleotide analog polymerase inhibitor that works by blocking an enzyme the hepatitis C virus needs to copy itself, the drug is potent and has antiviral activity against HCV genotypes 1-6. Ledipasvir, an NS5A inhibitor, has potency against genotypes 1a and 1b.

SVR12 Rates From Three Phase 3 Studies Evaluating a Once-Daily Fixed-Dose Combination of Sofosbuvir and Ledipasvir for Genotype 1 Hepatitis C Patients

Gilead tested its promising combination pill - consisting of both agents, Sovaldi and Ledipasvir in various treatment durations, with and without ribavirin. Physicians and patients were excited to see high cure rates without ribavirin. A drug that has side effects including rash, cough and anemia.  Here are those SVR rates;

In ION-1, which looked at 865 treatment-naïve patients, including 136 participants in the study with cirrhosis, after 12 weeks of therapy 97.7 percent  reached SVR- or 97.7 percent of patients were cured.

In ION 2 - the study included 440 treatment-experience or difficult to treat patients, these participants failed therapy in the past. Included in the trial were 88 people with cirrhosis - SVR rates were at 93.6 percent after 12 weeks of therapy - while the cure rate rose to 99.1 percent with 24 weeks of treatment.

Finally, in ION-3 - 647 treatment-naïve patients without cirrhosis were treated for 8 weeks, 94 percent achieved SVR. In patients who treated longer, for 12 weeks, SVR was a bit higher at 95.4 percent.

AbbVie Demonstrates 96 percent SVR(12) in its Phase III Study of Treatment-Experienced Patients with Genotype 1 Hepatitis C

Next up we have AbbVie, results of  phase III trials were recently released for a three drug regimen plus ribavirin which consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333.

In the 394-patient SAPPHIRE-II study 96 percent of genotype 1 patients with no evidence of liver cirrhosis who previously failed standard treatment, including approximately 49 percent prior null responders, achieved sustained virologic response (SVR12) with the 12-week regimen.

An important factor here is that the majority of patients were genotype 1a, which is considered a difficult-to-treat subtype. The SVR12 rate for genotype 1a and genotype 1b were at 96 percent and 97 percent, respectively. 

Virologic relapse or breakthrough was seen in 2 percent of patients receiving the regimen. In addition, the discontinuation rate due to adverse events was 1 percent.

In TURQUOISE-II naïve and experienced patients with compensated cirrhosis are included, those results are expected in January 2014.

Faldaprevir effective even in patients with HCV Q80K variant

Hepatitis C: Phase III data show Boehringer Ingelheim’s faldaprevir* is effective even in patients with common drug-resistant viral variant

Summary: Naturally occurring mutations in the hepatitis C virus (HCV) are common and many lead to reduced efficacy of antiviral treatments. Faldaprevir* has now been shown to be effective even in patients with the common HCV Q80K variant,1 which affects an estimated 700,0002,3,4 patients in the USA alone. Faldaprevir* is being studied in combinations both with and without interferon. The EMA recently granted accelerated assessment for faldaprevir* as part of an interferon-based regimen and a decision on marketing authorisation is anticipated next year.5,6
Read press release here....

'Serial Infector' Gets 39 Years

The FBI released a story this month describing the criminal investigation into the HCV outbreak at Exeter Hospital.
David M. Kwiatkowski, a former healthcare worker at Exeter Hospital stole syringes intended for hospital patients containing the narcotic Fentanyl. After injecting himself with the narcotic, he replaced the syringes of Fentanyl with saline to use on future patients, 45 people became infected because of the drug diversion tactic. Kwiatkowski pleaded guilty to diverting and obtaining the controlled substance fentanyl as well as to product tampering.  He was sentenced earlier this month to 39 years in prison.

Its Not The First Time Fentanyl Was Diverted By Healthcare Workers

Similar to the Exeter Hospital outbreak, from 2008-2010 three case scenarios of drug diversion took place at the following medical facilities: Rose Medical Center in Denver, Mayo Clinic in Florida and Riverside Regional in Virginia, a complete summary is available here on this blog.

At the three facilities employees admitted to stealing syringes filled with Fentanyl, injecting themselves with the drug and replacing the syringes with saline to be used on future unsuspecting patients. The employees, like Kwiatkowski, also traveled around taking jobs at various clinics and hospitals.

EASL - Revised clinical practice guidelines for management of hepatitis C 

Management of Hepatitis C: Revised Version December 2013
3.28 mb | Revised Edition
Based on a systematic review of existing literature, the CPGs provide best practice recommendations on a number of key areas:

Current standard of care and developing therapies;
Diagnosis of acute and chronic hepatitis C;
Goals and endpoints of HCV therapy;
Indications for treatment and who should be treated;
Treatment strategies for different viral genotypes;
Treatment monitoring including virological response-guided triple, and dual therapy;
Monitoring treatment safety; and
Treatment of special groups including HIV co-infection, hepatitis B co-infection and patients with other co-morbidities such as severe liver disease

Learn More?

An interactive course on hepatitis C was launched online this year which offers newly diagnosed patients an opportunity to learn more about the management of HCV, to take part in the learning activity, begin here.

*The project is brought to you from the University of Washington and includes a collaboration with the International Antiviral Society-USA (IAS-USA). Funded by a grant from the Centers for Disease Control and Prevention

Well, that's all folks

Wishing You All A Very Merry Christmas And A Safe New Year !

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