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

Hepatitis C Now Godzillaprevir and KingKongViracide: Yes but is Interferon Still in the Mix?

GodzillaPrevir

KingkongViracide

No matter how powerful add-on drugs are, if Interferon is still part of the mix, many patients will not be able to finish the treatment.  If I was in early stages of Hepatitis C with minimal liver scarring, I would wait 12-24 months for new treatments sans Interferon.  If my Hepatitis C were more advanced, I would go to www.clinicaltrials.gov and type in my disease and city. (Note disclaimer at end of blog)

Below are “press releases” from companies and are mostly targeted to investors, e.g. The market for treating hepatitis C has burgeoned  (My spellchecker doesn’t recognize this as a word) in the last year.

Always look at the source of medical information, if it is Kiss Your Assets Good-Bye or Liver Heard on the Street, run away. If it is the New England Journal of Medicine, or Gastroenterology proceed with caution and a jaundiced eye.  Oops a hepatitis pun.

Dec 1, 2011 – Novel Hep C Treatment Excludes Peginterferon Alfa By: DENISE NAPOLI, Internal Medicine News Digital Network Therapy with a novel

But then if I didn’t read the business news, I wouldn’t know about this for another couple of days:

Bristol-Myers Drops Hepatitis C Drug After Patient Death

Daniel Acker/Bloomberg

Bristol-Myers Squibb Co. has abandoned an experimental hepatitis C pill it bought for $2.5 billion earlier this year after one patient died and others were hospitalized while taking the drug in a study.

                    

Bristol-Myers will take a charge of $1.8 billion in the third quarter related to research and development of the therapy, the New York-based company said in a regulatory filing today. The drugmaker suspended testing the medicine, known as BMS-986094, on Aug. 1 after a patient developed heart failure.

Bristol-Myers said yesterday it has discontinued development of the drug, part of a class of medicines called nucleotide polymerase inhibitors, and was consulting with U.S. regulators to assess the treatment’s effects. Along with the death, eight patients suffered from heart and kidney toxicity, the company said in a statement.

“Bristol-Myers paid a fortune for a pearl that turns out to be fake,” said Erik Gordon, a University of Michigan businessprofessor who follows the health industry, in an e-mail today, referring to the company’s “string of pearls” name for its acquisition strategy. “The Inhibitex acquisition shows the dangers of paying huge premiums for late-stage drug candidates in hot areas. They still can fail.”

I love it:  The dangers of paying huge premiums…Not the dangers of participating in clinical trials. No disrespect to business people, just a different perspective.  I should know, I worked in Big Pharma for twenty-five years.  First make money for share holders, then do no harm to patients.

dictionary.reference.com/browse/inherent existing in someone or something as a permanent and inseparable element, quality, or attribute:

There is inherent risk for patients in clinical trials.  You can quote me on that.

In The Waiting Room With The Losers: They Don’t Look Like Losers, Do We?

Tuesday Girl

When in a clinical trial for hepatitis C, there is no place to hide in the waiting room.  We are all there with our livers and our coolers full of injectable poisons.  You can tell what trial each person is in by the cooler they carry.  And watching the progress of a person, you can evaluate the side effect profile of the drugs.  Sort of. Do they bother combing hair? Coloring lips? Putting on lace up shoes?   Is that insider trading?  No, studies are blinded.  But we are not.  Clinicians would learn a lot observing us before we go on stage with the white coats.

I’m a Tuesday girl, I come on Tuesdays.  I recognize the Tuesday people.

You can clearly see the transplant candidates.  They look like Cecil without a smile.  A  yellow-green snot color with a gaunt face and an ascitic belly.  The post transplants look less yellow but more waxy, and kinda more dead.   High doses of steroids and immunosuppressives  will do that.  I look around thinking “These are not my people”  but they are.  If I look beyond the medical realities, they show up in a shirt and tie, uniform, sweat suit. But they don’t look like, I don’t know, losers.

I want so badly to change the TV to CNBC or CNN. But I am too short to change channels and everyone is staring at Good Day Houston.  I want to scream.  I breathe in and try to focus on questions I have and remember to request a copy of my lab work.  Don’t forget, don’t forget, don’t forget (Brain Fog).

I am sitting where I can’t see the TV, and listening to a book on my phone.  But then I watch everyone watch Good Day Houston and try to guess their faces.  Ugh, the only thing worse than a national daytime talk show is a local daytime talk show.  I remember Girl Talk with Virginia Graham out of Cincinnati when I was a kid home ill. I’ d never seen anyone so made up in my life.  And at 9 AM.  She had her hair combed into cotton candy, and four shades of lip color.  I don’t know about her feet.  She motioned for guests to join her at the coffee table.  Her jewelry jingled but her hair never moved. .  She was not my people.

Virginia Graham (the early 60s) way before The View…
Woah!  I Googled Girl Talk and got something completely different.