HCV Advocate Logo HCV Advocate Logo
Contact Us Site Map Resources en Espanol
For living Positivley. Being Well
About Hepatitis
News Updates
News Review
Conference Reports
News Articles
HCV Advocate Newsletter
Sign up for Email Updates
Community & Support
Resource Library
About Hcsp
 
 
HCV Advocate Newsletter

Back to Newsletters Bookmark and Share

January 2014 HCV Advocate

Download printable version

 

In This Issue:

HCV Advocate's Top News of 2013
Alan Franciscus, Editor-in-Chief

HEALTHWISE: New Hepatitis C Drugs: Disappointment or Hope?
Lucinda K. Porter, RN


Snapshots
Lucinda K. Porter, RN


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

Back to top


HCV Advocate's Top News of 2013
—Alan Franciscus, Editor-in-Chief

It’s always difficult coming up with the top news items, but in the last few years it has been even more difficult because of the accelerated rate of HCV drug development and the increased attention given to hepatitis C in the news.  This translates to a lot of really good news.  The “Good News,” however was confined to the development of drugs, the Baby Boomer testing recommendation, the discovery of another HCV genotype and the development of a structural picture of an HCV protein that may be the key to the creation of an HCV vaccine.  There were also some news items about HCV outbreaks in 2013 and verdicts from trials of people who were accused of contributing to HCV outbreaks in the past.   

It is usually difficult to come up with the number 1 item and this year was no exception; so we decided that two different news items topped our list—the Food and Drug Administration’s (FDA) approval of sofosbuvir combination therapy to treat HCV genotypes 1,2,3, and 4  and the recommendation that the United States Preventive Services Task Force (USPSTF) made for a one-time test for everyone born from 1945 to 1965 for hepatitis C.

The News

USPSTF—The recommendation from the USPSTF for a one-time test for everyone born from 1945 to 1965 (based on the CDC recommendations) has the potential to save many thousands of lives by identifying over 800,000 people with hepatitis C and, hopefully, getting the people who are diagnosed into medical care and treatment.  Although the uptake on testing has been slow it will hopefully increase in 2014.  New York State took the USPSTF and CDC recommendations to heart and passed legislation that a one-time test had to be offered to baby boomers when seeing their primary care doctor or when receiving hospital inpatient and outpatient care.  Way to go New York!

Sovaldi (sofosbuvir)—In December Gilead’s blockbuster drug received FDA approval.  The combination of Sovaldi (once-a-day pill), pegylated interferon (weekly injection) and ribavirin (dosed twice-a-day based on body weight) was approved to treat HCV genotypes 1 and 4.  The cure rates of 89% for people with HCV genotype 1 and 96% for HCV genotype 4 were achieved after only 12 weeks treatment duration.  Furthermore, the FDA approved the first interferon-free therapy—Sovaldi plus ribavirin to treat HCV genotypes 2 and 3.  The cure rates for HCV genotype 2 were up to 93% for people who were treated for 12 weeks and 84% for HCV genotype 3 who were treated for 24 weeks.  The FDA also approved Sovaldi for the treatment of people who are coinfected with HIV/HCV and for people with kidney impairment.  Patients with liver cancer who are waiting for a liver transplant can be treated with Sovaldi plus ribavirin.  The FDA approved the treatment of Sovaldi plus ribavirin (without interferon) for people who are HCV genotype 1 interferon ineligible—the recommended treatment duration is 24 weeks.      

The side effects of the triple therapy (PEG/RBV and Sovaldi) was mostly from interferon—fatigue, headache, nausea, insomnia and anemia.  The side effects from Sovaldi plus ribavirin (no interferon) for genotype 2 and 3 therapy were fatigue and headache.   

Check out Lucinda’s HealthWise column in this issue about the pros and cons of Sovaldi treatment.  

Olysio (simeprevir)—In November, Janssen’s new protease inhibitor triple combination therapy was approved to treat HCV genotype 1.  Olysio, pegylated interferon plus ribavirin therapy cured up to 80% of treatment-naïve patients and 79% of prior relapsers.  Olysio is a once-a-day pill.

COSMOS—In a study of the combination of Sovaldi and Olysio with and without ribavirin results showed very high cure rates (in one group 100%) in HCV genotype 1 people with cirrhosis.  Although FDA approval of this combination therapy is highly unlikely, the off-label use may be an option for those who have no other treatment options.

Breakthrough Therapies

All of drugs awarded “Breakthrough Therapy” status by the FDA made our list this year—the award is for potential treatments for serious medical conditions for drugs that have been shown to provide a substantial improvement compared to drugs that are currently available. 

AbbVie — To date there have been two (out of six) Phase 3 study results released of AbbVie’s  interferon-free therapy.  The topline results in the first trial (631 treatment-naïve patients) reported cure rates of 95% in HCV genotype 1a  and 98% in HCV genotype 1b for patients who were treated for 12 weeks.  The second trial (394 treatment-experienced patients) reported cure rates of 96% for genotype 1a and 97% for genotype 1b.  Forty-nine percent of the patients in the second trial were prior null responders—the most difficult patient population to treat.  The medications in the studies included ABT-333 plus ribavirin (both dosed twice daily) plus a fixed dose of ABT-450/ritonavir co-formulated with ABT-267 (one pill of ABT-450/ritonavir plus ABT-257 taken once-daily). 

Gilead — has interferon-free studies in Phase 3 that included 1,952 HCV genotype 1 patients who received Sovaldi (sofosbuvir) plus ledipasvir without ribavirin, or sofosbuvir, ledipasvir with ribavirin and who were treated for 8, 12 or 24 weeks.  The results reported were from the 8 and 12-week treatment duration arms.  The cure rates were 93% to 99%. The study results from the 24-week treatment duration arm (434 patients) are not yet available.  The study included 1,512 treatment-naïve and 440 treatment-experienced patients; 224 patients had cirrhosis.   

BMS – there is a 3-drug combination being developed by BMS to treat hepatitis C currently in Phase 3 studies.  The combination of daclatasvir, asunaprevir and BMS-791325 in an early dose-ranging study of 166 patients: HCV genotype 1a (82%) and genotype 1b (18%). The cure rate was 92% in patients regardless of subtype.   

Merck – was recently awarded “Breakthrough Therapy” status for the combination of MK-5172, MK-8742 and ribavirin.  In a small phase 2 study that reported on 58 patients cure rates were 96 to 100% These drugs are currently in early studies.

Accelerated Assessment

Although not awarded ‘Breakthrough Therapy’ Boehringer Ingelheim’s faldaprevir has been granted accelerated assessment from the European Medicines Agency.  The Phase 3 studies of faldaprevir, BI 207127 and ribavirin were begun in November 2013.  In a small dose-ranging Phase 2 study cure rates of up to 47% in HCV genotype 1a and up to 75% in the HCV genotype 1b group were reported.  The study included different treatment durations and different dosing schedules. 

Genotype 7

It has been theorized for some time that there are more than the six genotypes of HCV we know about. This year, a seventh genotype was discovered—genotype 7.  In addition to the identification of another genotype the researchers also identified another 67 subtypes. 

E2 Protein

Scientists at the Scripps Research Institute developed a structural picture of the HCV protein known as E2 envelope glycoprotein.  It is believed that this protein may be the key to developing an effective vaccine to protect against hepatitis C.  It is estimated that 170 to 200 million people worldwide are infected with hepatitis C.  This discovery of a vaccine to prevent HCV and medications to cure HCV could potentially eradicate HCV.

Treatment & Disease Progression

A study released in 2013 (Long term survival of liver fibrosis after virological cure in patients with chronic hepatitis C: The avenue of the scars? by Thierry Poynard) found that, for some people who have liver damage, even successful treatment may not stop the disease progression.  The take home message from the study is that if damage is occurring then it may not be safe to wait since even those who achieve a viral cure can have on-going disease progression.  This also re-enforces the necessity of monitoring people even after they achieve a cure.  

Justice?

There was finally a verdict in the largest hepatitis C outbreak in the United States—64,000 people who had procedures at a Las Vegas, NV endoscopy center were exposed to blood borne pathogens.  Of those who were tested, 7 were diagnosed with HCV and, sadly, one person died.  Dr. Dipak Desai was found guilty of second-degree murder for the death of the patient—Rodolfo Meana.  He was also convicted on 26 criminal counts and convicted of insurance fraud.  Desai was sentenced to life in prison.  The anesthetist Ronald Lakeman was found guilty of 16 counts and sentenced to 8 to 21 years in prison.   

Another tragic outbreak—David Kwiatkowski, a traveling medical technician who infected at least 45 people with hepatitis C was found guilty of 16 federal charges of drug theft and tampering.  Kwiatkowski was caught switching out syringes filled with pain medication for the syringes he used when he injected himself with the stolen pain medication.  Kwiatkowski pleaded guilty and was sentenced to 39 years in prison. 

Was justice served?  I will leave it up to our readers to decide, but personally I’m not so sure. 

Waiting for Justice?

In 2013, unfortunately, another large outbreak of HCV occurred at a medical center.  The outbreak was at a dental practice in Tulsa, Oklahoma. Dr. Harrington exposed 7,000 people to hepatitis C, hepatitis B and HIV due to unsafe safety practices.  Of the 4,202 who have been tested so far, 89 tested positive for hepatitis C, 4 for HBV and 1 for HIV.   The investigation and testing continues.  Harrington has been charged with 17 criminal counts.  

This was the first documented outbreak that has occurred at a dental practice.  

In yet another large HCV outbreak, this time in a long-term care facility in Minot, North Dakota.  So far 500 people have been tested and of those 35 cases of HCV have been confirmed. The state health department and the CDC are investigating the outbreak, but have not yet found the cause of the exposure.   

Note:  It’s important to be clear about these outbreaks.  The exposures occurred because someone (or many someone’s) didn’t follow universal or safety precautions.

In Memoriam

On October 27, 2013 we lost a true pioneer in the music field—Lou Reed died of complications from hepatitis C.  Reed was a founding member of the avant-garde rock band, Velvet Underground, and later had a successful solo career.  One of his most popular songs and one that became an anthem for many was “Take a Walk on The Wild Side.”


Back to top


HEALTHWISE: New Hepatitis C Drugs: Disappointment or Hope?
—Lucinda K. Porter, RN

Last month the Food and Drug Administration (FDA) approved the newest hepatitis C drug. Sovaldi (sofosbuvir) is the first polymerase inhibitor approved for hepatitis C treatment.

Sovaldi combined with ribavirin became the first interferon-free hepatitis C treatment, but the all-oral application is for those with genotypes 2 or 3, and special cases. I’ll say more about that later. Sovaldi with peginterferon and ribavirin was approved for patients with genotypes 1 and 4.

After the FDA announced the approval, messages from upset patients arrived. “@*#! I have genotype 1 (or 4). I thought the FDA was going to approve all-oral treatments.” Tweets and facebook posts expressed similar sentiments.  One patient asked if the FDA had just signed his death warrant.

I understand this reaction. For more than 15 years, interferon was the basis of hepatitis C treatment. The drugs improved in that more people were cured, but this cure had a high price with even more side effects. Some patients couldn’t or wouldn’t take interferon, or ribavirin for that matter. Patients had to make a risky choice—hope they didn’t progress to cirrhosis or endure a potentially grueling treatment that might not even work.  Both are lousy options.

When clinical trial results showed high cure rates using interferon-free regimens, hepatitis C patients began to hope. The big question was—would these drugs be here soon enough? Well, one of the drugs is here, sort of.  Let’s review who Sovaldi can technically be prescribed for, if one’s medical provider stuck to the label.

Sovaldi in combination with ribavirin and/or peginterferon can be prescribed to nearly everyone with hepatitis C. It doesn’t matter if you are new to treatment or a prior treatment failed to work for you. The only restrictions are the usual one, such as children, nursing mothers, pregnant women, and men with pregnant partners. Also, there are the usual warnings about ribavirin and pegylated interferon. However, the FDA opened the door for all-oral treatment for genotype 1 patients who are “interferon ineligible.” 

Other special populations for whom Sovaldi may be used:

  • Patients with hepatocellular carcinoma (liver cancer) who are waiting for a liver transplant (all-oral using Sovaldi and ribavirin/up to 48 weeks or until liver transplantation)

  • Patients with cirrhosis (safety not established in patients with decompensated cirrhosis)

  • HCV/HIV-1 co-infected patients

  • Patients with renal impairment

  • Adults age 65 and over

Here is a brief summary of Sovaldi. I’ve provided the Sovaldi Prescribing Information for those who want to read more.

Sovaldi in combination with peginterferon and ribavirin for adults with genotype 1 or 4

Pros

  • Short 12-week treatment duration, with limited exposure to peginterferon and ribavirin, which translates into an easier to tolerate side effect profile

  • High cure rate at around 90% overall

    • Genotype 1, 89%; genotype 4, 96%

    • Cirrhosis 80%

    • Hardest to treat (genotype 1, cirrhosis, IL28B non-C/C, high viral load) 71%

  • Highest rate of response in Blacks 87% vs. Non-blacks at 91%

  • Low drug-resistance profile

  • Sovaldi is a once-a-day pill with no food requirements

  • Fewer known drug interactions than other direct-acting antivirals (Incivek, Victrelis, and Olysio)

Cons

  • Peginterferon and ribavirin side effects

  • Cost ($84,000 for 12 weeks of treatment just for Sovaldi; pegylated interferon and ribavirin costs are additional)

  • Too soon to know if insurance will cover it

  • Treatment not approved for genotypes 5 or 6 yet (although the FDA didn’t approve this application, some providers may use it anyway)

Sovaldi with ribavirin for the treatment of adults with genotypes 2 or 3

Pros

  • No peginterferon

  • Short 12-week treatment duration for genotype 2, with limited exposure to ribavirin (24 weeks of treatment for genotype 3 patients)

  • High cure rate at around 93-95% overall for genotype 2

    • Cirrhosis 60-94%

  • Improved cure rate at around 84% overall for genotype 3

    • Cirrhosis 60-92%

  • Easier to tolerate side effect profile

  • Highest rate of response in Blacks 87% vs. Non-blacks at 91%

  • Low drug-resistance profile

  • Sovaldi is a once-a-day pill with no food requirements

  • Fewer known drug interactions than other direct-acting antivirals (Incivek, Victrelis, and Olysio)

Cons

  • Ribavirin side effects

  • Cost ($84,000 for 12 weeks of treatment just for Sovaldi; ribavirin costs are additional)

  • Too soon to know if insurance will cover it

Treat or Wait

Despite this progress, genotype 1 patients are still saddled with big decisions. Should they:

  • Go with one of these new, shorter interferon-based treatments

  • Ask their medical provider to prescribe Sovaldi and ribavirin without pegylated interferon

  • Wait for all-oral, interferon-free hepatitis C treatments, which will likely be available in late 2014 or early 2015

  • Wait until ribavirin-free regimens are available

  • Discuss off-label options, such as combining Sovaldi and Olysio

  • Look for a clinical trial

Here is some information to help you make your decision. In a small study, 60 participants received sofosbuvir and ribavirin for 24 weeks. The highest response rate was 68%. The most common side effects were headache, anemia, fatigue, and nausea. (Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients with Unfavorable Treatment Characteristics: A Randomized Clinical Trial – A. Osinusi, et al. JAMA August 2013)  

As for off-label use of Sovaldi and Olysio, results of a small study (COSMOS) showed excellent preliminary results. Patients with advanced liver fibrosis or cirrhosis had 96% to 100% SVR4 rates after 12 weeks of simeprevir and sofosbuvir with or without ribavirin. Note that SVR4 rates are not as meaningful as SVR12 or SVR24. The most frequent complaints were fatigue, headache, nausea and insomnia.

The sticky problems of using off-label hepatitis C drugs are: a) finding a provider who will prescribe the two, and b) getting insurance to cover it.  Twelve weeks of Olysio and Sovaldi would cost more than $150,000. Insurance companies will likely want solid evidence about this treatment before forking over that kind of money. SVR12 data should be released in January.

If you are waiting, these words are for you

I am deeply concerned that patients are delaying hepatitis C treatment too long. A study presented at the 2013 Liver Meeting showing that a virological cure for patients who had previously developed significant fibrosis, could continue to be at risk for fibrosis/cirrhosis and liver cancer. In short, those that delay treatment may go through treatment, clear the virus, but still suffer some of the tragic consequences. (AASLD 2013: Long term survival of liver fibrosis after virological cure in patients with chronic hepatitis C: The avenue of the scars? by Thierry Poynard)

If you think you are immune to progressive liver disease because previous biopsies have been good, think again. Fibrosis often accelerates with age and duration of infection, and is not a linear progression. Additionally, those with hepatitis C have added risks of stroke, heart disease, diabetes, kidney problems, and cancer.

It’s a hard decision to make. Don’t let fear of side effects be the main reason for your delay. Although the current hepatitis C treatments are hard, they are doable. With support and good side effect management, twelve weeks will be over before you know it.

If you can’t or don’t want to take pegylated interferon and/or ribavirin, use this time to build your health. Commit to a plan of living the healthiest lifestyle you can.  Aim to be physically active, maintain a normal weight, don’t smoke, wear your seat belts, floss your teeth, and laugh a lot.

I’ve seen far too many people die from hepatitis C, and I am sick over it. We are on the brink of changing the future for those affected by hepatitis C. Hope is here, but without action, hope is just hope.

Lucinda K. Porter, RN, is a long-time contributor to the HCV Advocate and author of Free from Hepatitis C and Hepatitis C One Step at a Time. Her blog is www.LucindaPorterRN.com

Further Information:



Back to top

Sofosbuvir (Sovaldi): FDA Approved




Click Here




Click Here


Snapshots
—Lucinda K. Porter, RN

Article: Hepatitis C Virus Maintains Infectivity for Weeks after Drying on Inanimate Surfaces at Room Temperature: Implications for Risks of Transmission – Elijah Paintsil, et al.
   Source: Journal of Infectious Diseases published online November 23, 2013

This study sought to determine how long hepatitis C virus remains potentially infectious, and to evaluate the effectiveness of antiseptics.  Researchers tested hepatitis C under a variety of conditions, trying to mimic average circumstances that people may come in to contact with hepatitis C on surfaces.

The Bottom Line: Hepatitis C virus remains potentially infectious on surfaces for up to six weeks. Infectivity increased with high viral load, temperature, and humidity. Commercial antiseptics, such as bleach and alcohol reduce hepatitis C infectivity, but only if used as directed at full strength.

Editorial Comment: This research is disturbing, but may explain some of the hepatitis C infections in people with no known risk factors. The authors discuss patients whose only risk factors were hospital admissions (no procedures), opening the door for a broader explanation for how people may acquire hepatitis C.

Article: Impact of Interferon Free Regimens on Clinical and Cost Outcomes for Chronic Hepatitis C Genotype 1 Patients – Zobair M. Younossi, et al. (Blogged Dec 2, 2013)
    Source: Journal of Hepatology in press November 20, 2013

Using a decision analytic model, this study evaluated the cost effectiveness of treating patients with genotype-1 hepatitis C with an oral interferon-free (IFN-free) regimen versus triple therapy using IFN, ribavirin, and a hepatitis C protease inhibitor.

The Bottom Line: The oral IFN-free regimen was the most cost effective at $77,133 - $90,681; triple therapy was $93,981 - $106,554 (see Editorial Comment). Oral IFN-free treatment reduced the incidence of advanced liver disease, while increasing life expectancy. 

Editorial Comment: Drug prices for oral hepatitis C treatments were not available for this analysis. Here is how the researcher approached this: “The baseline cost of oral therapy was calibrated such that the average total treatment cost of oral therapy was equal to the average total treatment cost of triple therapy, despite the shorter duration of oral therapy. This resulted in a baseline cost of oral therapy of $5,800 per week. We also considered the scenario where this baseline cost was increased by 50% to $8,700 per week.”

The researchers were a bit optimistic in their cost guess. The wholesale acquisition cost of Gilead’s Sovaldi is $84,000 for 12 weeks. Add in the cost of ribavirin, medical appointments, labs, and so on, and my guess is that triple therapy will come out ahead IF you only consider price.

However, the real measurement is comparing costs of drugs that patients can and will use. If we made decisions solely based on the cost of treatment, then many people I know would prefer to take their chances with hepatitis C. The real bottom line is effective, tolerable, and affordable treatment for all hepatitis C patients. 

Article: Industrial, Not Fruit Fructose Intake Is Associated with the Severity of Liver Fibrosis in Genotype 1 Chronic Hepatitis C Patients – Salvatore Petta, et al.
   Source: Journal of Hepatology December 2013; Volume 59, Issue 6, Pages 1169-1176

The average diet may contain fructose from two sources—fruit and manufactured, such as high-fructose corn syrup (HFCS). This study evaluated the impact of fruit versus industrial fructose in the diets of 147 genotype 1 hepatitis C patients.

The Bottom Line: Severity of liver fibrosis was limited to industrial fructose in the diet, and not to fruit fructose. Industrial fructose is associated with obesity and other metabolic diseases.

Editorial Comment: Most nutritionists are concerned about sugar in the diet, particularly for those with liver disease. Industrial fructose has no known health benefits, and the list of reasons why it should be avoided is growing. If giving up or reducing sugar intake is a struggle for you, or something you don’t want to do, then at least consider abstaining from high-fructose corn syrup.   

Article: Hepatitis C Virus Infection and Risk of Stroke: A Systematic Review and Meta-Analysis – He Huang, et al. (Blogged December 2, 2013)
   Source: PLOS ONE November 2013; Volume 8, Issue 11

“Stroke is the second leading cause of death worldwide,” write the authors of this paper. Hepatitis C has been associated with increased risk of stroke, and these researchers performed a thorough meta-analysis of the data to gain further insight.

The Bottom Line: Hepatitis C infection was associated with a significant increased risk of stroke. The physiological reasons for this risk are unknown. Some theories for why hepatitis C may increase stroke risk are increased plague in the carotid arteries, chronic inflammation, and hepatitis C-related metabolic disorders, such as diabetes.

Editorial Comment: Although this analysis isn’t hard proof that hepatitis C can raise stroke risk, it adds validity to other research showing a disturbing trend that chronic hepatitis C infection is a serious disease that affects both quality and quantity of life.


Back to top


Newsletter Archive


About Hepatitis | News Updates | Community & Support | Resource Library | About HCSP | Contact Us | Site Map | Recursos en Español | Home

Hepatitis C Support Project

© 2014 Hepatitis C Support Project

Medical  Writers' Circle
Fact Sheets