Genotype 3: An Unmet Treatment Need for Some, by Alan Franciscus, Editor-in-Chief

 Originally Published June 15, 2015

 

While conducting a workshop in New England, I was asked a question about genotype 3 treatment for people who are treatment experienced and had cirrhosis—a question I am frequently asked.  At this time, we do not have an interferon-free treatment with high cure rates for this particular group of people with hepatitis C.  This is an unmet medical need for a large group of people in the United States and Worldwide.  I am asked this question at almost every workshop, which surprises me. 

There are many drugs in development that hold the promise to solve this problem.  In the meantime, there is a solution—the combination of Sovaldi, pegylated interferon and ribavirin.   When I bring up interferon, I get the cringe reaction.  It is a very understandable reaction. However, there are a couple of serious points to consider:

• Cirrhosis can be a life-threatening event.  You do not want to wait—If you have genotype 3 and cirrhosis you should consider taking action now
• Genotype 3 leads to the formation of steatosis (fatty liver)—successful treatment reduces or eliminates steatosis
• Steatosis can accelerate HCV disease progression—by itself steatosis can lead to cirrhosis
• People with genotype 3 are at increased the risk for liver disease progression and liver cancer
• Pegylated interferon and ribavirin can be difficult to tolerate, but the majority of side effects occur after 12 weeks
• The side effects of pegylated interferon and ribavirin can be managed successfully especially if the medical provider and patient are proactive

Interferon-Free Therapy
The current standard of care for genotype 3 is the combination of Sovaldi (sofosbuvir) plus ribavirin for 24 weeks.  The cure rates for treatment experienced patients without cirrhosis are 85%, but for treatment experienced patients with cirrhosis the cure rates are 60%.  Clearly, genotype 3 patients who are treatment experienced with cirrhosis are in need of better treatment options.  I have listed below two studies that include treatment of Sovaldi, pegylated interferon plus ribavirin.  Note:  I only included the information about the cure rates of the genotype 3 treatment experience patients with cirrhosis treated for 12 weeks.

Sovaldi/Peg/RBV
A recently published study in Hepatology “Sofosbuvir with Peginterferon-Ribavirin for 12 Weeks in Previously Treated Patients with Hepatitis C Genotype 2 or 3 and Cirrhosis,” –E Lawitz et al. showed very high cure rates. 

Note:  There were 47 genotype 2 and 3 patients included in the study.  Only genotype 3 results are listed below. 

There were a total of 24 genotype 3 patients with and without cirrhosis.  All were treated for 12 weeks with Sovaldi (sofosbuvir), pegylated interferon plus ribavirin. 

The cure rates were the same for those with cirrhosis 83% (10 of 12 pts) and without 83% (10 of 12 pts) in the genotype 3 patients. 

The second study was presented at EASL 2015 “Sofosbuvir Plus Peg-IFN/RBV for 12 Weeks vs Sofosbuvir/RBV for 16 or 24 Week in Genotype 3 HCV Infected Patients and Treatment-Experienced Cirrhotic Patients with Genotype 2 HCV:  The BOSON Study,” –R Graham et al. 

Note:  This study was a large study of 592 genotype 3 treatment naïve/experienced patients without and without cirrhosis.  I will only list the treatment experienced patients with cirrhosis who were treated for 12 weeks with Sovaldi (sofosbuvir), pegylated interferon plus ribavirin and the comparator arm of the treatment experienced patients with cirrhosis who received Sovaldi plus ribavirin without pegylated interferon. 

After 12 weeks of treatment the group of patients who were treated with Sovaldi, pegylated interferon plus ribavirin achieved a cure rate of 86% (30 of 35 pts) compared to a cure rate of 47% (17 of 36 pts) for those who received Sovaldi plus ribavirin but without pegylated interferon. 

The most common side effects were flu-like symptoms, fatigue, and anemia. 

 
Comments: The addition of pegylated interferon to Sovaldi and ribavirin almost doubled the cure rates for people with genotype 3 in both studies who had cirrhosis and who were treatment experience.  The best strategy is to talk with your medical provider and come up with a plan to get treated as soon as possible, seek a possible cure and stop hepatitis C in its tracks.

http://hcvadvocate.org/news/newsLetter/2015/advocate0615_mid.html#2

The Five: HCV Genotypes —Alan Franciscus, Editor-in-Chief

Originally Published June 15, 2015

This month’s column is about hepatitis C (HCV) genotypes.  I will discuss genotypes 1, 2, 3, 4, and 6.  You will notice that I am not discussing genotype 5 since it is discussed elsewhere in this issue. Genotype 7 is also not being discussed because only three people with genotype 7 have been identified—all found to be from the Democratic Republic of Congo.

According to the World Health Organization 130 – 150 million people worldwide have chronic hepatitis C and 350,000 – 500,000 die every year from complications of hepatitis C. 

As mentioned above there have been seven genotypes identified but there are likely more that have not yet been found or classified.  There is a 30 to 35% viral diversity or difference in the genetic make-up of the nucleotide sites of the virus that are used to classify them as different genotypes.  This viral diversity is what makes it so difficult to develop one drug to treat all of the genotypes.  There are new drugs called pan-genotypic that work on all of the genotypes that are being developed that might just produce high cure rates across all of the genotypes.  The viral diversity i.e. genotype is another reason why it is going to be difficult to develop a therapeutic or a protective vaccine.  There has been some early research that is encouraging.

All evidence points to that the hepatitis C virus originated in Africa and spread throughout Africa by various routes including the European colonization of Africa, unsafe medical practices to treat tropical diseases and various cultural practices.  HCV spread out of Africa occurred by way of the slave trade throughout the World, needle reuse, organ transplantation, unsafe medical practices, unscreened blood, and injection drug use, etc. 

Genotype 1
Genotype 1 is the most common genotype worldwide and accounts for approximately 46% of the total number of people with hepatitis C worldwide —83 million people.  The prevalence of genotype 1 expanded greatly during the 20th century due to unsafe blood product/organ transplantation, unsafe medical practices and injection drug use.

Countries with the highest prevalence include East Asia (32,082,000), South Asia (12,889,000), Southeast Asia (4,910,000), Western sub-Sahara Africa (4,427,000), Eastern Europe (4,023,000), Central Latin America (2,796,000), Central Asia (2,100,000)
 

Genotype 1 has two main subtypes 1a and 1b. Genotype 1a accounts for about 55% of those with genotype 1 in the U.S. and 45% of those with genotype 1b. HCV 1a is more difficult to treat than HCV genotype 1b.  The current standard of care for treating HCV genotype 1 can cure up to 90% to 100% of people who take the medications.  The current standard of care treatment is HARVONI and VIEKIRA PAK. 

Genotype 1 subtypes c through l have been identified but are uncommon

Genotype 2 
Genotype 2 is the 3rd most common genotype worldwide and is also the 3rd most common one in the United States.  The areas of highest prevalence of genotype 2 worldwide include central Latin America (754,000), high-income Asia Pacific (629,000), Southeast Asia (1,572,000), East Asia (8,444,000), Western sub-Saharan African (1,550,000) and western Europe (583,000). Genotype 2 accounts for more than 16.5 million people worldwide with hepatitis C. 

Genotype 2 spread through the slave trade from Africa to the Americas and through trade routes from the Africa, the America and Asia. 

The most common subtypes of genotype 2 are 2a, 2b, and 2c, so far there have been another 15 subtypes identified.

The standard of care for treating HCV genotype 2 is the combination of Sovaldi (sofosbuvir) plus ribavirin for a treatment duration of 12 weeks.  The cure rates are 88% to 97%. 

Genotype 3
Genotype 3 is the 2nd most common genotype in the United States and worldwide.  The areas with the highest prevalence of genotype 3 include Australasia (280,000), Central Asia (906,000), East Asia (5,762,000), Eastern Europe (1,881,000), High Income North America (492,000), and South Asia (39,706,000). The total number of people worldwide with genotype 3 is 54 million.

Genotype 3 has been found to exist for 200 years. Genotype 3 causes steatosis (fatty liver), insulin resistance (precursor of type 2 diabetes), and increases the risk of HCV disease progression and liver cancer.

So far there have been 10 genotype 3 subtypes identified—subtype 3a is the most common.

The current standard of care to treat genotype 3 is the combination of Sovaldi and ribavirin for a treatment period of 24 weeks.  The cure rates are up to 83%.   However, Sovaldi plus ribavirin doesn’t work as well in genotype 3 people with cirrhosis who are treatment experienced.  There are, however, very good treatment options (see article in this issue on Sovaldi, pegylated interferon and ribavirin) and many new drugs are being developed to treat genotype 3. 

Genotype 4
Genotype 4 is the 4th most common genotype worldwide and accounts for 90% (6,030,000) of the hepatitis C population in Egypt—The HCV population of Egypt is estimated at 6.7 million.  Africa and the Middle East account for the majority of genotype 4 infections.  Approximately 1% of the U.S. population has genotype 4.  Genotype 4 has many subtypes – a through o.

In Egypt the spread of hepatitis C genotype 4 was the result of a mass campaign in the 1960’s through the 1980’s to control schistosomiasis infection—a parasitic disease transferred by snails to humans wading in water while working in rice fields.  During the 1960’s through the 1980’s people infected with schistosomiasis were treated with drugs using unsterilized and re-used syringes.

The current standard of care for treating HCV genotype 4 is the combination of Sovaldi (sofosbuvir), pegylated interferon and ribavirin.  The treatment duration is 12 weeks and cure rates are up to 96%.  There are many drugs that have been developed to treat genotype 4—by AbbVie and Merck—that are likely to be approved in the near future.

Genotype 6
Genotype 6 is mostly seen in Southeast Asia.  The estimated number of people who are infected with genotype 6 is about 10,000,000—mostly in Asia. It is the most prevalent genotype in Laos and one of the most common genotypes in Vietnam.  Genotype 6 is seen in countries outside of Asia, but mainly in populations that have emigrated from Asian countries.

Genotype 6a is the most common, but there been 26 subtypes identified so far.

There is no standard of care to treat genotype 6.  In a study of 25 people who took Harvoni (sofosbuvir plus ledipasvir) for a treatment period of 12 weeks to treat genotype 6 resulted in a cure rate of 82%.   The study included people who had never been treated and people who had been treated but had not been cured.  There are many other drugs in development to treat genotype 6 including Merck’s combination of grazoprevir/elbasvir.

The future is bright for the treatment of hepatitis C with more awareness of all of the HCV genotypes worldwide.  There are many drugs under development to treat hepatitis C that are even more effective.  Many of the newer drugs in development are pan-genotypic—that is they work against all genotypes and have the potential to cure all genotypes—these drugs could provide cures worldwide if we could only identify and treat everyone.

http://hcvadvocate.org/news/newsLetter/2015/advocate0615_mid.html#1

Area veteran can't get treatment for Hepatitis C

GREENCASTLE : Adam Shaffer, a disabled veteran with two tours in Iraq, discovered that the Department of Veterans Affairs has a cure for one of the things that ails him.

Only thing is: He can't get it.

"With Hepatitis C, the government doesn't have enough money to give veterans the pills," said the 30-year-old Shaffer. "They put you on a waiting list, and it's long. You can't get any treatment. It will kill you."

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Port Aransas man with hep c fights insurance company

 "I want to live. I want to be healthy. I want my liver to be cured now, not when it's almost impossible to cure and then be put on the liver transplant list."

PORT ARANSAS -A Port Aransas man is literally fighting for his life.

Richard Titus, 56, has been duking it out with his health insurance company to cover a treatment that could save his life.

Titus recently discovered he has Hepatitis C, a liver infection caused by the Hepatitis C virus.

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Cost in the way of a cure for hepatitis C

Christopher Cummins, 42, believes he contracted hepatitis C through blood transfusions at birth. Last year, his insurance paid for a $100,000 treatment that eradicated the virus.

Dee’s liver is scarred, but just a bit too healthy for her insurance to foot the bill for the new medications that cure hepatitis C more than 90 percent of the time.

The Butler County resident, who suspects she got the virus getting a tattoo, was recently told by her doctor to come back in a year.

John, a retired small-business owner from Washington County who was given blood in the early 1990s, was also denied the antivirals. Now, as he watches a friend grow weak from liver cancer, he fears he’s glimpsing his future.

An appeal to a pharmaceutical company is Jennifer’s last shot at treatment after the insurance company denied her three times. The 34-year-old office manager – who said she gave up her heroin habit nine years ago – can barely make it through the workday because of fatigue. 

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I-MAK Exec Discuss Gilead Support Path Decision with HCV Advocate, by David Heitz

When Gilead decided this week to curtail access to lifesaving Hepatitis C drugs through its Support Path program, those living with the disease – and itching for a cure – had mixed reactions.

“I’m so glad I live in New Zealand and don’t have to go through all the bullshit some of you do!” said the member of one patient community.

“Insurance companies need to be covering these drugs,” said another. “Gilead is offering the patient assistant program on its dime. There is no obligation on it to maintain this program. We need to push insurers to start covering the treatments. We pay for insurance for a reason.”

In an interview with HCV Advocate, Priti Radhakrishnan of I-MAK (Initiative for Medicines, Access & Knowledge) took issue with the latter statement.

“I disagree with that point of view very strongly,” she said. “I don’t think the Gilead price point is anywhere near what the market can bear.”

I-MAK’s work centers around how and why Gilead has received a patent on sofosbuvir. Some countries were able to jockey in such a way that they have not had to pay outrageous sums based on a patent, like insurers in the United States must. Radhakrishnan explains this process very clearly in this opinion piece she wrote for CNN.

“In many countries across the world, they don’t have an insurance system,” she explained during the interview Sunday evening with HCV Advocate daily. “We need to look for companies to set more equitable pricing. But even here in the U.S., I disagree with that statement. Even as insurance companies take on exorbitant and overpriced drugs, the more the system has to bear that cost. And the cost ultimately is passed along to the consumer.”

You can read Gilead’s letter about curtailing the Support Path program here. Gilead did not respond to a telephone call and e-mail this morning by HCV Advocate.

In explaining its decision, Gilead makes the case that insurers need to begin paying for these drugs. It says it no longer will help patients whose insurers make restrictions based on low fibrosis scores.
So, to answer the questions so many ask: Correct, you can’t get these drugs unless you’re sick enough. And now it’s going to be even harder.

And if you’ve got mental or substance abuse problems and your insurer denies you? Gilead no longer will help in those cases either.

Carrie Yohe Johnson is a person with Hepatitis C in State College, Penn. She can’t get the drugs because her fibrosis score is 0. But her viral load is high.

She got the disease from her mother. Yohe has two children, both HCV-negative. She didn’t know she had the disease when she had the first child; she had a very low viral load when she had the second.
But she’d like to have a third child. Even though only 5 to 6 percent of mothers pass along Hepatitis C during childbirth, it’s still a risk most don’t care to take.

I'm a healthy person. I've never done drugs. I haven't drank alcohol since discovering my illness (not that I really ever was a drinker). I live a healthy life,” Yohe explained. “I've had one partner my whole life (my husband). I have young children and I teach preschool. I constantly worry about accidentally infecting others or whether or not my liver and body will last. Or if this disease will begin to attack my kidneys and heart as it has shown to do…before my insurance finally gives the meds. I don't think it's fair that I have to wait for a cure.”

So what can people like Yohe do? Lobby their members of Congress.

“Citizens can advocate by saying that we want to see transparence in the cost of drug development, and to mandate disclosures,” Radhakrishnan said. “The patient system is really broken, and the companies are way too powerful in terms of reforming laws in their favor. Their needs to be more citizen participation in the process to safeguard patient rights.”

Gilead Limits Enrollment in its Hep C Patient Program to Pressure Insurers

In a bid to push back against payers, Gilead Sciences GILD -0.71% is limiting enrollment to its patient assistance program for hepatitis C drugs, which helps people obtain the Sovaldi and Harvoni treatments when they lack sufficient insurance coverage or the financial wherewithal to get the medicines otherwise.

The drug maker is taking this step after finding that some payers, despite receiving discounts in recent months, have continued to restrict patient access to its hepatitis C medicines. As a result, Gilead has been picking up the cost of the medicines for more people it would like seeking patient assistance, according to a July 1 letter sent to patient groups and community health providers, among others.

A Gilead spokeswoman declined to say how many people are enrolled in its Support Path assistance program, how many may be affected by the change or provide actions taken by specific payers.

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