best tx for geno 1?

As I started approaching the 24th shot mark, I returned to doing some research, in case I did not clear, to learn about options.
I have not logged into this site since spring, pre tx.  I decided on the pegasys option based on the input of this site, started tx in July, and went about dealing with the sx and doctor's opinions and misinformation.  
In my recent searches, I came accross sites that deal with hiv coinfection. I figured that hiv gets a lot of research money, so they must have the most updated info.  the hivandhepatitis.com site posted several of the 54th Annual meeting of the American Association for the Study of Liver Diseases.  The article on the Infergen trial in Germany reports undetectable rna at 48 wks  for geno 1 in the 70% range, that is considerably higher than what we are been offered here in the US.  Given this data, I would have opted for this option had it been available in the US.  Each drug company have their pet project and they are not looking for the most effective tx for us, mostly for an alternative that is comparable to  brand x so that they can get in the market to recover costs and make profits.  
Has anyone else read these articles?

[Marlies52]

I was just looking on the internet,(did a Google Search) and it looks like Infergen was approved for marketing by the FDA in 1997. I don't know why we don't hear more about it, if it has such a high SVR.  Does anyone know?

[ms.star]

My Dr. told me the same thing about a 2 log drop.  He gave me the exact 3% chance of SVR if there was not at least a 2 log drop.  However he did tell me he would let me decide to continue to the 24 week mark where he said that if there was not the 2 log or tenfold drop at that time him and the insurance co. would not allow me to continue tx.  I just took my 12 wk. bloodwork last Friday and I am still waiting for the results to come back.  What a wonderful x-mas to all of us if GOD would grant us ALL SVR this year.
Starla

[jonihs]

I've heard it alot on here but in my opinion, Blame the insurance companies!    Joni

[Indiana]

Infergen is not a pegylated interferon. That study used the a high dose DAILY shot. Those results were for geno 1's with a low load doing DAILY shots at a high dose. Results for geno 1's with any kind of a higher load were about the same as the pegylated interferons. The big advantage of Infergen is that it is a "consensus" interferon so it is a viable alternative for those who do not respond to the standard tx.
Personally, I don't think I would opt for 336 shots instead of 48.....unless I was desperate. Not to mention the sides that have to come with it. Being a kind of skinny guy I think I would run outa places to stick it..........
I lost my whole a$$ doing 50 weeks of Peg/Intron. I can't imagine what I might lose doing DAILY shots. I DO want to be able to have sex when it's all over with..........
Hahahahahahahaha

[Magnum]

I did daily shots for 4 months after two failed attempts at the traditional and then the Pegylated. I must be a very hard 1a case to cure because not only did the doctor have me on daily shots but also added Amantadine and I did not respond. However, that's me, and I don't want to discourage anyone because a friend of mine was 1a and responded to Pegasys. Look into the Protease Inhibitors, once the FDA approves it. It's supposed to be THE miracle cure...

Good luck, keep fighting...

Magnum

[giddyup]

I'm not sure but it seems what you  are saying is that the German study gives the response rate at 48 wks. After that there is still the hurdle of svr at 6 mo post tx the post 6 mo svr rate would be less then the 70% mentioned.Best wishes 4 svr.

[Galen]

What you are looking for at 12 weeks is a two log drop.  To figure this out, drop the last two digits from your starting viral load, ie, if you started at 2,000,000, you want to down to at least 20,000 or better yet, undetectable.  Statistic show that if at least a 2 log drop is no achieved by 12 weeks, chances of obtaining an SVR are at less than 3%.  There is a great presentation of this study at
http://www.medscape.com/viewprogram/2234
You will be required to sign up for a user name and password, but this only takes a couple of minutes and is well worth it.

[hph5477]

My doc will do a 12-wk PCR to see if I have a 2-log drop in my VL.  Started with a VL of 596,000.  If so, I continue tx for another 12 wks and my chances for SVR go up from 50% to 60%.  Doc will test again at 24-wks hoping I am undetectable at that time.  If so, I continue tx for another 24 wks (that makes 48 wks total) and my chances for SVR go up to 70%.  Then another test at either 3 or 6 months after tx to see if I remained undetectable.

Good luck with your tx.  I just did #9/48 this morning.

[OkieJim]

Hey what's up. Aren't you close to your 12 weeks??? How are you feeling. I hope all has been well. I'm still kickin'
Got my results back and I'm negative ATT. I pray you get the same. Merry Christmas and god bless.

[tikerberi]

This is a tad off the subject, but related to geno 1.

I'm geno 1b, and will be starting treatment next week when my meds come in.  I have to do the first injection at my docs office.  He told me that in my case (geno 1b, grade 1, stage 2, VL 272,000) that Pegasys+Copegus is the best, but that it will be planned initially for 12 weeks.  He said that after 12 weeks, there should be a dramatic drop in VL (I think he said a "tenfold" drop) after 12 weeks.  If there is, that is good, and then treatment will continue for the balance of the year to clear it up and keep it away.

However, he said that if there is no dramatic drop in VL after 12 weeks, we would not continue treatment.  He said it would be pointless, and other alternatives would have to be explored.

I've heard everyone on this forum talk about year long treatments, or multiple treatments.  But I haven't heard anyone mention the 12 week drop in VL as being a benchmark.

Is anyone familiar with this?

[Southernboy]

Hi there,

Infergen is the brand name for interferon alfacon-1.  It is produced by InterMune.  It is sometimes called consensus interferon because it is a combination of interferon alfa 2a (Roferon-A or Pegasys in the pegylated form) and interferon alfa-2b (Intron A or PEG-Intron in the pegylated form).  Infergen is not yet available in the pegylated form.  Some people respond better to 2a and some to 2b, so the theory is that a greater number will respond to Infergen as it is a combination.  Since it is not yet available in pegylated form the studies have been focusing on daily dosing.  The study you are refering to uses high dose daily dosing.  Some Dr's are looking at this, in combination with Riba and other drugs, as tx for relapsers or nonresponders.  I am on Infergen 3x/week, Riba 1200mg/day and Interferon gamma-1b 3x/week at the present time after being a nonresponder to Pegasys/Riba tx.  I would be glad to answer any questions you may have.

Best to everyone and hope you are all well,
Steve

[Sioux]

I'm a 1a on week 38/48 Peg-Intron and Rebetol. At start of tx I had a 10 million v/l at 12 weeks it dropped to less than 5.I am also stage 3 grade 2. Today is a major brain fog day. It has taken me about 10 min to just do this......<smile>

I hope everyone has a great holiday !!!!

[cuteus]

Thanks Steve for your input. It is good to hear from someone on the tx.  Are you in the US?  My hepatologist stated that daily doses of Infergen tx is only available in Germany, and you must take off from work for a year.  I would have tried the best available for my geno in order to get rid of this demon once and for all!  
My vl did not decrease by log 2 @ 12wks., but my GI kept me on anyway, (following the formula by Starla). He will wait for the 24th week (I'll do it at 25 wk :)) Then stop if not cleared.  I had a low vl to begin with (376,000), female, minimal damage, etc etc, but did not clear at 12. I still had hopes, but now I'm edgy.  Can I start the Infergen soon after the PEG?  Do you Know?

TY for your input

Ive

[Revenire]

According to Miles Keaton the 12 week predictor was suggested by Roche Pharmaceuticals, not approved by the FDA. Peginterferons have a antifibrotic effect, in many patients, WHETHER or not you get the 12 week 2 log drop or not.

Apparently more than a few doctors at the most recent AASLD meeting were not all in favor of taking people off of treatment just because they don't achieve this # by week 12. Some studies now suggest odds of a SVR can be predicted by as early as 1 week into treatment, based on the drop in viral load.

Keaton is going to take Infergen and then switch to Pegasys. Check his website out (you will have to read through a bit to get to the Infergen parts) or email him. He is also on the board of the Hepatitis C Association.

<a href="http://www.mkandrew.com/">Hepatitis C Blog - Miles Keaton Andrew</a>

I will quote from his site on Infergen induction therapy.

"So where was I? Oh yeah, Dr. Gish's induction treatment. I know, I know - every-f*cking-body says induction treatment doesn't work, okay? I say horseshit to that too. Fact is, induction treatment did not work at all with the non-pegylated interferons, and the reason is Duh City. Okay? I mean, back then, in the dinosaur days of therapy, induction therapy meant daily interferon for a week, then switching to three times a week. So of course it didn't work. I have no idea why anybody thought it would work, because you were going from a relatively high dose to major lag time between shots, so there was viral rebound in between shots. You were going from more interferon to less interferon.

"Here's the new thinking on induction therapy: Okay - the non-pegylated interferons, like Intron-A, Roferon, and Infergen, are super-fast acting, but they only stay in your body for 8 hours per shot. This gives the virus time to mutate and regroup. However, nothing takes down viral load like a normal interferon.

"The PEGs don't act so fast. In fact, most people don't even feel side effects from Pegasys until week 6 or so. However, the PEGs last longer, so this gives you the exposure time you need - exposure time is how long the virus is exposed to interferon.

"So anyway, you gotta have this big drop by week 12, and Roche was just assuming you were gonna do it with Pegasys, but why take a chance with a slow-acting interferon, especially if you are IFN-resistant? All that matters is EVR. It doesn't matter how you get there, so you might as well get there fast, with daily, normal interferon. Most doctors would probably agree that out of all of the un-pegs, nothing works like Infergen. Infergen is a designer alfa. It's been genetically engineered. They take out a couple amino acids here, and put a couple more in there, and bang, you've got Infergen - so you're fighting hcv with a molecule the virus has never encountered - it already knows all of the alfas you've got.

"So, you get your EVR by starting off with daily Infergen, then you switch to a PEG. Okay? You knock down that viral load, then you sustain it with nonstop exposure time - that's the theory. I hope it works."

[giddyup]

Hi Oakie, Congrats on the 12 week undetectable! Looks like my test is mia. They want to retest and let me know the result on the 23rd or 24th.Good news is my blood level are up to 10.8. Keep on keeping on Oakie!

[cuteus]

Ty for your post.  I checked his site and it is quite controversial at times. Whatever it takes. We are the ones living with this long tx that might not work, and then have to start on more long treatments all over, plus the long waits for svr in between.  I'll be on Medicare at that pace!  Some of these doctor's are so non-chalant in their approach,i.e. "I don't biopsy unless blood work is abnormal, I don't treat if no symptons, etc.) They don't have to live with the fear of infecting their child or mate!  Then there are the ones that want to show they know everything, i.e. "Tx for hcv has been out for a long time, we have long term effect data, anemia doesn't cause bleeding problems, Bextra doesn't cause GI problems, etc.")

You have to bite your tongue sometimes, because you need them for the rx and f/u. Anyway is a little PMS, I'm going thru maybe.
(Pre-midtest scare)

TY all

[Southernboy]

Hi again Ive,
I am in the US, Arizona actually, and at this time am receiving tx through a clinical study due to the use of interferon gamma which is not an approved drug for HCV.  Infergen is approved by the FDA for use in the United States.  In fact, it is the only interferon labeled for use for non-responding patients (www.intermune.com/wt/itmn/infergen).

I plan on keeping everyone here updated on my progress with this program because it might be an option for us "non-responders".  I hope you are not going to be included in this group, but if so, there are options available.

If you are looking to go the daily high dose infergen route (www.natap.org/2003/DDW/day6.htm) you would need to find a Dr who is willing to become educated and willing to "think outside the box".

I spent 28 weeks on Pegasys/Riba and did not clear although I had almost a 2 log drop.  Vl is also fairly low at 450,000 iu but liver damage is an early 4 leaving me very few options. Am male and geno is 1a.

I hope this info helps and if I can answer any other questions please let me know.

Best to you and I hope it turns out that all this is not necessary for you.
Steve

[nurse12hr]

My husband did Infergen a few years ago (3 times a week for a year) genotype 3a.  Relapsed by 6 months post tx.

[MichaelT]

2003 NOV 24 - (NewsRx.com & NewsRx.net) -- InterMune, Inc., (ITMN) announced the presentation of positive clinical data from an investigator-sponsored trial using Infergen (interferon alfacon-1), the company's bio-optimized type 1 interferon alpha, in combination with ribavirin for the treatment of patients suffering from hepatitis C who have failed to respond to other interferon and ribavirin combination treatments (nonresponders).

In addition, in vitro data were presented that showed potent synergistic antiviral effects of using Infergen and Actimmune (interferon gamma-1b) in an in vitro model predictive of antiviral activity against hepatitis C virus (HCV).

Stephan Kaiser, MD, head of the liver outpatient department and lecturer in hepatology at the University of Tuebingen, Germany, presented the clinical study entitled: "Retreatment of standard interferon/ribavirin nonresponder patients with chronic hepatitis C with daily consensus interferon and ribavirin yields high sustained response rates."

The study evaluated the efficacy of two induction dosing regimens of Infergen therapy followed by Infergen plus ribavirin combination therapy in 120 hepatitis C patients who had not responded to standard interferon plus ribavirin combination therapy. At time of enrollment, all patients had detectable levels of hepatitis C virus in their blood and the majority was infected with genotype 1, the most refractory form of the virus. Additionally, all patients showed biochemical evidence of liver damage and chronic liver inflammation. This was confirmed through liver biopsy and pathological examination.

"Approximately 50% of patients treated for hepatitis C virus do not respond to currently available treatments. This represents a significant and rapidly growing unmet medical need," said James E. Pennington, MD, executive vice president of medical and scientific affairs at InterMune. "Numerous published studies have shown that retreating hepatitis C nonresponders with pegylated interferon alpha plus ribavirin achieves very low sustained viral response rates in the 6-12% range."

He continued, "Dr Kaiser's presentation provides evidence for an approximately 3-fold higher sustained response rate measured 24 weeks after the end of treatment in the difficult to treat nonresponder population. Based on the data for daily use of Infergen plus ribavirin for HCV nonresponders, we plan to initiate a registration trial investigating the use of this combination therapy for the treatment of these patients."

In another session, Lawrence Blatt, PhD, vice president, applied research at InterMune, presented a study entitled: "Synergistic Effects of Type 1 (Infergen) and Type 2 (Actimmune) Interferons in preclinical models of HCV: Demonstration of potential efficacy." Scientists at InterMune and collaborators at Utah State University and Indiana University conducted this study. The researchers evaluated the antiviral effect of a combination of consensus interferon (Infergen) and interferon gamma-1b (Actimmune) in in vitro models of hepatitis C infection. This study was recognized as an American Association for the Study of Liver Diseases presidential "Poster of Distinction."

The clinical success of combination therapy using interferon-alpha plus ribavirin is believed to be due, in part, to the direct effect of the interferon-alpha combined with the ability of ribavirin to induce an immune cell response mediated by the release of molecules such as interferon gamma. Based upon this hypothesis, InterMune scientists and their collaborators employed in vitro models of HCV replication to analyze the possible synergistic antiviral properties of Infergen in combination with InterMune's proprietary recombinant form of interferon gamma-1b (Actimmune).

Studies of the direct antiviral effects of Infergen and Actimmune in these in vitro models of HCV replication, such as an infectious flavivirus system (West Nile virus), demonstrated very strong synergistic effects for a range of varying doses of combination therapy versus Infergen monotherapy. Analysis of gene expression showed that several genes involved in critical cellular processes that were not significantly upregulated by either drug alone were upregulated by the combination of Infergen and Actimmune. In addition, several known interferon stimulated genes were more significantly activated by the combination therapy versus Infergen monotherapy.

"There is a strong scientific rationale for the use of Infergen and Actimmune in combination for the treatment of hepatitis C," said Blatt. "These results provide intriguing evidence for a potentially synergistic antiviral effect and based upon this encouraging data, we are now evaluating a clinical program of this combination in HCV nonresponders."

[Southernboy]

Hi Michael,
Good to hear from you.  I hope your are well.  Thanks for the information.  This is exactly what I am participating in.  I will keep everybody up to date on the results as they come in.
Best to you and all,
Steve

[ms.star]

I wish you tons of God's grace to get you through the coming days of the wait and see game.  Afew weeks ago I was feeling so low and just out of the willingness to keep going on tx, because of all the sides.  However, I have had a few good days lately and I believe I'll make the same decision as you and continue tx to 24 wks regardless of the outcome of the 12 wk test.  The waiting is killing me though.  Good luck
Starla

[berlynn]

Steve,   I also live in AZ and I have a friend who was just dx with HEPC, she's a 2. Her dr. advised her to do the 24 week treatment of pegasys/copegus. Unfortunately my friend has lousy insurance and she would have to fork out about $1000.00 a mos. out of pocket to pay for tx. She can't afford it, but as I've told her, as she already has some liver damage,she can't afford not to tx.... before her liver worsens. Do you((or anybody))know of any studies or help she can get hooked up to...to offset this cost so that she can get the tx she needs?
Thanks, berlynn

[Bodie]

Have her try the drug companies. She may be able to get help there. Roche and Sherring have patient assistance programs. They may help with the co-pay. Or if she could get the insurance to deny her tx, they will kick in, I think. I'm on Medicare and no rx coverage, so I have to get everything through PAP's.
Good Luck.

[Indiana]

Here's a couple of links to clinical trials.
On the web md page scroll about 1/2 way down on the right and you will see the box for the links.

By the way Berlynn....I got your e-mail and will write you back tomorrow when I have more time.

[jonihs]

Janis7hepc.com  has alot of phone numbers for the drug company that make both peg-intron and pegasys. Look under financial and insurance aid. My best  ,  
joni

[Southernboy]

Hi berlynn,
Sorry it took so long to get back to you...a bit of a difficult day.

Please email me at ***@**** and I may be able to provide some information that can help your friend.

Also, I just wanted to thank so many of you for what you bring to this forum. Indiana and lately, ringading, your humor is most appreciated and brings a smile to my face on even the most difficult of days.  There are too many others to list by name, just want you all to know that your support, information and positive outlook are appreciated more then you will ever know.

Thank You,
Steve

[susan400]

I was on Infergen many years ago at the beginning of 1999.  It did not work on me any better than anything else I've tried, and I've been on them all.  Magnum, I can relate to your frustration in clearing.  I've been on daily doses of reg. Intron + Peg-Intron (twice a week for awhile, but then switched to once a week), for the past 10 mon. and I still have not cleared.  This is my 5th treatment try.  I don't know about you, but I get frustrated that other people seem to be able to clear 1st go.  Oh well, my time will come eventually.

Susan400

[txpartner]

Hubby had the insurance problem.  They didn't cover injectable drugs AT ALL.  The Patient Assistance Programs, look at the drugco's web site, were wonderful.  He got the PegIntron and Riba for FREE.  He also got Amgen to pay for the Neupogen (with would have been $4,000 for 10 shots!).  We had to pay for the Procrit ourselves...the most expensive part.  Having good coverage for labs is important because someone wants a gallon of your blood all the time.  And the work up was expensive for us...cardiac stress test, untra sound, liver biopsy.  He had such a high deductible, we pretty much paid for all that!  UGH.  The doc apts are generally covered in most plans, and you really only see the doc or pa once in a while during the tx.  Good luck to her.

[berlynn]

Thanks to all of you for your helpful info!  :) I'll pass this on to my friend. I have also encouraged her to check out this site. I think that she does peek in once in a while. Thanks again, berlynn

Southernboy, thanks, I'll drop you a line:) berlynn