Hepatitis C Research: What’s a Phase and How Can We Get through it Faster?

Hepatitis C:  Current Research Drugs

Picture your liver at the center of the Milky Way. Now, the swirling stars are treatments, some closer than others.  Drug studies are in orbit like this.  Work with me here.

Your Liver = Center of your universe.

Illustration of the Milky Way by Dianna Marquee

Illustration of the Milky Way by Dianna Marquee

Filed = Closest stars, drugs waiting on FDA approval.  The red tape wheels grind on.

Phase III = Next out, drugs being tested large-scale for safety and efficacy.  Will the virus die before you do?

Phase II = Further away from your liver, drugs shown not to kill  people when tested on a small group of sick patients. Cohort is the word.  This was me during round two of treatment.  Kind of risky here.

Phase I =  Compounds (drugs) that don’t kill healthy people crazy enough to volunteer (broke students and new parolees)

Preclinical =A blur of solar dust = test tube, computer chemical structuring, animal studies. Yep, animal testing.

When I was first diagnosed in 1991 with Hepatitis C, there was only one binary star, Interferon and Ribavirin.  Finally in 2011  came Telaprevir  and Boceprevir. That’s a long time between hits, 20 years.  Now the Hep C universe is almost getting crowded, but not yet.  The issue is safety and timelines.  The barbaric days of Interferon could be phased out (pun intended).

Phases of  Current Drug Research:  Thanks go to Dr Paul Kwo for this slide

Paul Y. Kwo, MD, is Associate Professor of Medicine and Medical Director of Liver Transplantation in the Gastroenterology/Hepatology Division of Indiana University School of Medicine in Indianapolis

Paul Y. Kwo, MD, is Associate Professor of Medicine and Medical Director of Liver Transplantation in the Gastroenterology/Hepatology Division of Indiana University School of Medicine in Indianapolis

So, this slide represents current studies, phases  and the mechanism of action (MOA).  Remember that we want at least two drugs with different MOAs in our bodies to avoid virus mutation and resistance.  The good news is that there are multiple drug candidates in each category.  For further information on any study, go to www.clinicaltrials.gov and enter the drug/compound name.  This site will also tell you if the study is enrolling patients and if there is a location close to you.  This website rocks.  Thank you federal government.

The US research system is business-based, where competition for the patent drives the process.  I’m not completely opposed to this system.  But it does have drawbacks.

Remember when AIDS researchers were competing to isolate the culprit?  France and the US,  it was crazy.  The two groups still argue about whom was first with what.

The HBO movie And The Band Played On documents government and cultural barriers to a disease connected with a cohort that isn’t mainstream, i.e. HIV and homosexual men.  I’m glad the barriers came down a bit faster with Hep C.  Initially the cohort was alcoholics and drug addicts.  But then the target audience became baby boomers.  This was 1. More acceptable and 2. A bigger pool of patients and potential profit.

Obviously the slide above is the star of this blog.    Drug companies race to be first with a new drug(s).  So why am I speaking of other things?  Because I think the days of working in a research vacuum are limited.  American drug companies say this is bad.  They claim without financial incentive, research will dry up.

But, wouldn’t it be great if companies worked together and combined research efforts?  I know, that is a big but.  I like big buts…There are novel initiatives include partnering between governmental organizations and industry. The world’s largest such initiative is the Innovative Medicines Initiative (IMI), and examples of major national initiatives are Top Institute Pharma in the Netherlands and Biopeople in Denmark.  In the USA it could be the National Institutes of Health (NIH).  We used to joke that NIH meant “Not Investigated Here”  meaning that the USA insists on its own research.  Only science types would joke about such topics. No wonder we have a reputation.

Paul Y. Kwo, MD, is Associate Professor of Medicine

Paul Y. Kwo, MD, is Associate Professor of Medicine

Now picture these studies sharing data.  Think of all the time and patient suffering saved by quickly identifying drug-drug and drug-disease interactions.  Think about how the winners would rise to the top.  I don’t care about the political/social overtones.  I am just thinking about patients. This is already happening with cancer research.

I have worked on this blog for a week and still can’t get it right.

http://en.wikipedia.org/wiki/Virus

http://www.chronicliverdisease.org/COEE/index.cfm?id=PKwo

http://en.wikipedia.org/wiki/Drug_development

http://voices.yahoo.com/a-summary-film-band-played-on-127287.html

Hepatitis C: Does “No Detectable Virus” Equal Cure Or Is It Smoke?

Am I cured or is it just smoke?

Hepatitis C cure?

 If my hepatitis C virus test shows non-detectable virus 6 months after the end of treatment, am I negative?  Will I  stay negative?  Am I cured?  In the recent past only “non-detectable virus” was declared. Now doctors are adding “cure” to the jargon.  This is with the addition of Incivek and Victrelis, and depending on the discussion.  No two clinical trials are alike and so Hepatitis C researchers use (they say utilize) sustained viralogical response (SVR) to compare outcomes.  Most trial design is by the company developing the drug.  One goal is to ask the study questions just right to get scientific and marketable answers.  “GodZillapravir had a non-detectable  SVR at weeks 12 and 24 in 85% of patients including those with mild to moderate cirrhosis”. “KingKongViracide cleared Hepatitis C virus in 94% of patients at 24 weeks including children 12 to 18 years of age”.  Which is the better drug?  You can’t tell by the claims because two different patient populations and time lines .  But they have  SVR in common.  That is why researchers use SVR.  BTW I made up the examples.  Now don’t get down on industry just yet.  Academics are accountable to department heads and medical journals.  That can be as powerful as a stockholder.

Industry is different: Stock holders in towers

When it comes to patients , the word “Cure” has emerged because research shows that if you have no detectable virus after six months, the chances of Hep C returning is about 1-2%.  And the argument is that it was never cleared, just so low that it was undetectable.

So with Hepatitis what does this mean?

Successful treatment for Hepatitis C hasn’t been available for long, so doctors are just starting to understand the long-term outcomes.  Do cancer survivors say cured?  I think they say  cancer-free for 2 years, 5 years, etc.  Am I a Hepatitis C survivor or am I cured?  Is it still a pre-existing condition?   A research site, not insurance, paid for my treatments.  But my medical records say Hepatitis C.

So at 24 weeks can I tell the insurance company that I no longer have Hepatitis C?  I can’t find the answer to that question without talking to them directly. I will wait until 2014 (I think that is the year) when they cannot cancel me for pre-existing conditions.  Insurance politics are so confusing, I am not clear if that stipulation is on the potential chopping block.  In speaking with my mental  Dr, I realize that I do not have confidence in my treatment and I am waiting for it to come back.  I am at 4 1/2 months post treatment.   I have been Hep C positive for so long, I don’t know how to have a future in which chronic debilitating illness isn’t a key player.  What is the world like with only mild hypertension and chronic but manageable depression?

Below is a good article for defining end-of-treatment terms, although it is a bit dated.  Newer drugs are not addressed but the terms are the same.

 Hepatitis C: What Is a Sustained Virologic Response or “SVR”? (From Charles  Daniel, former About.com GuideSVR) 

SVR is the closest you’ll get to “a cure” for hepatitis C.
 Sustained virologic response, or SVR, is the goal of hepatitis C treatment.  Conventional treatment (a combination of interferon and ribavirin) doesn’t  necessarily eliminate the hepatitis C virus from your liver. It can, however,  suppress the virus to undetectable levels for an extended period of time. In clinical language, this is called a “sustained virologic response,” or sustained  response. It means that during the six months after you complete treatment,  there is no detectable hepatitis C virus in your blood.                                         SVR is a good thing.
Studies have shown that with a six-month SVR (which means no detectable virus in your blood for six months after finishing treatment), relapse occurred in only 1-2% of patients. So, for every 100 people who finished treatment and attained SVR, the virus will return in only 2 of them. However, for these people, the
virus never really left. The medicine was able to eliminate most of the virus (so much that medical tests couldn’t detect it), but after treatment ended, for whatever reason the virus was able to continue replicating itself.

Early SVR is beneficial
Since the liver has incredible regenerative ability, achieving SVR
 as quickly as possible is important. This is important because some liver damage can be reversed if the cause of the damage is removed. After SVR is reached and depending on the degree of damage from the virus, the risk of hepatocellular cancer is reduced and about 25% of people see an improvement in fibrosis.

SVR compares one treatment to another. For those in treatment, SVR is the goal. However, for physicians and scientists researching new hepatitis treatments, SVR is also used to evaluate new medicines and compare them with proven therapies.
 For example, depending on the genotype, treatment with interferon alone usually achieves SVR in 15% of the patients. When interferon is combined with ribavirin in the same genotype, SVR is increased to 70% in some people.

Jana L. Lee, R.N., CCRC Clinical Research Nurse St. Luke’s Episcopal Hospital Advanced Liver Therapies, my practical answer source and demon fighter.

http://www.hepcadvocacy.org/factsheets/HepatitisC.pdf

http://hepatitis.about.com/bio/Charles-Daniel-37713.htm

The Hepatitis C Screen Door Swings Two Ways

My father-in-law wanted Viagra.  He wouldn’t shut up about it.  My mother-in-law finally said “Then what?  You’re not getting on me”  eewww, the visual for me….

So we screen for Hepatitis C, then what?

Attention Baby Boomers: The Centers For Disease Control (CDC), the group that tracks bird and swine flu, is thinking about screening you for Hepatitis C.

Hepatitis C is particularly dangerous because it is a silent killer. It can live for decades in a person’s body, slowly destroying the liver, while causing few symptoms,” said Dr. John Ward, director of the CDC’s division of viral hepatitis.

The new guidelines are expected to identify more than 800,000 infections, prevent 100,000 cases of cirrhosis, prevent more than 50,000 cases of liver cancer, and save more than 120,000 lives. Hepatitis C is the leading cause of liver transplants in the United States.

The relatively inexpensive blood test is “a small investment now for a big benefit later,” Ward said.

The CDC believes routine blood tests will address the largely preventable consequences of the disease, especially in light of newly available therapies that can cure around 75 percent of infections.

The field has attracted broad interest with two new hepatitis C drugs, Incivek from Vertex Pharmaceuticals Inc and Merck & Co’s Victrelis, reaching the U.S. market in the past year.

Sorry about the blur, link at bottom if you are interested

Should we screen for Hepatitis C in patients over 50?  There is no vaccine, the standard treatment of Interferon/Ribavirin is about  $60,000 and the eradication rate about 40-50% in the most common genotype (1).  Adding  Boceprevir (Victrelis) is $1,000 a week (x 24 weeks = $24,000). Telaprevir (Incivik) is $4,100 per week (x 24 weeks = $98,000).  So treatment =  $80,000 to $158,000.  They must be really proud of Telaprevir.  At that price they may have to keep it.  All of this assumes 24 week treatment but it is common practice for those on Interferon/Ribavirin to go 48 weeks ($120,000 for dual therapy)

 

These are all rounded numbers and this does not include anything but the drug.  Side effects are horrible.  A few are nausea/vomiting/diarrhea/depression/suicidal and homicidal thoughts/hair loss/anemia/insomnia . The new drugs add full body rash, rectal itching and/or rectal bleeding.  (This reminds me of the old treatments for syphilis: mercury and arsenic).   Many patients cannot hang and drop out. Jobs are lost, families strained and the patients overwhelmed. And then there is that pesky liver transplant for those beyond pharmacologic help (drugs).

But there are currently over 4 million people infected in the US and the largest group are over 50 with long-term damage.  And there are new tests and treatments.  For instance, researchers recently identified a specific DNA sequence in the gene that codes an immune response regulator, called IL28b. Different IL28b sequences predict whether treatment will successfully clear the virus.

With that in mind Goldhaber-Fiebert and Liu of Stanford created a computer model looking for the line at where it makes sense to go through treatment.  Remember that these people think in terms of how many patients out of 1,00 people, not what YOU should do.

After intense statistical and simulation analysis, the model showed that the new triple therapies were indeed cost-effective for chronic hepatitis C patients with advanced liver disease. Despite the large price tag and side effects, the new treatments help these patients avoid costly cancers and liver transplants — as well as allowing them to live longer, higher-quality lives.

For those patients with mild disease, the model indicated that determining their IL-28B genotype is the best next step, before prescribing a treatment.  The closer the threat of severe disease, the more justified treatment costs and risks become, said Goldhaber-Fiebert. “That would be the bottom line.”

Though these new drugs may offer relatively desirable options now, both Goldhaber-Fiebert and Liu noted that additional, and perhaps more effective, drugs are already in clinical trials.”

So in the “State-The-Obvious” department  they conclude: “As more and better treatments become available, the decision will continue to evolve, requiring further analysis, patients and health systems could also benefit from price competition with multiple treatment options available. But ultimately, treatment decisions will remain a private conversation between a doctor and a patient. “

A bit chicken shit but common in the academic world.  All studies end in “Further research is needed”.  Which is academic speak for “See you at the next medical conference where I will have more data”.  Note the reference to “health systems”.  This includes the insurance company.

Now, as a taxpayer, I wonder where the money is coming from. You can see one reason a clinical trial is an attractive option.  I didn’t pay a nickel.  In fact they paid my gas and parking.  BTW my results from 12 week post treatment just came back “No detectable virus”.  So why do I have a trace of cynicism about drug companies pushing for testing?

My mom used to yell, “close the screen door, you are letting the flies out”.  I always thought that was funny. Regarding screening and insurance that may be true but not so funny.

http://www.nlm.nih.gov/medlineplus/news/fullstory_125350.html

http://health.yahoo.net/news/s/nm/all-baby-boomers-should-get-tested-for-hepatitis-c-cdc

http://med.stanford.edu/ism/2012/february/hepatitis.html

We are in the Hepatitis C Virus Killing Business and Business is Good.

This fellow’s photo is here to encourage you to stick around to read the stuff below.

My Mamaw took Bufferin for  her “sick headaches”.  In looking back I realize she had migraines.  One day after coming out of the darkened bedroom, fixing her bun, she said  “How do it know where to go?”.  This is a woman who gave birth to 11 kids at home.

Mamaw Ora Mae Morris. I loved that woman. She smelled like biscuits.

The main reason to endure treatment is to kill the virus and get on with life.  With the addition of Bocephevir (Victrelis)  and Telaprevir (Incivek) , chances of clearing the virus have improved.  But, even if this isn’t achieved, there are other benefits:

  •  slow down the disease,
  • reduce or reverse liver damage
  • , reduce risk of liver cirrhosis/cancer,
  •  reduce need for liver transplant.

So how do we know the Hep C drugs are killing the virus?  “How do it know where to go?”

 Your blood is checked at the milestones listed above.  If the drugs are working, the viral load will go down.

Resist the urge to glaze over the terms below. Insist that someone on the treatment team explain the lingo to you. If that person can’t explain it, they shouldn’t be there. This is the language of your doctor when talking of your Hep C treatment results.

VL = Baseline Viral Load:  Amount of virus in your blood before treatment

RVR = Rapid Viral Response: The faster the response the better the chance of getting to cure.  This is assessed at 4 weeks

EVR = Early Viral Response: How you respond after 12 weeks of treatment.

SVR = Sustained Viral Response: No detectable virus 6 months after completion of treatment.  This is my next hurdle.

Resources:
  • Jana Lee, RN, CCRN, Advanced Liver Therapies, Houston