Failed hcv tx

[foxgirl1]

3 mos. of  weekly inteferon tx, viral load stayed up;  now 2 mos of daily infergen and viral load still staying up.  What other treatment is available?  

[willing]

I had assumed the clinicaltrials.gov information re the boceprevir phase III trial (NCT00705432) was correct - apparently it's not.  It claims that trial is no longer recruiting and would have final data a year from now. Assuming Schering files at that time, and FDA final review runs a year or less, I was hoping Drs could start prescribing the stuff in 1st quarter of 11 - but that may  be wishful thinking.

At this point I'm leaning more towards waiting for approval (and the ability to mix a cocktail along the lines above). In part, this is due to a stubborn desire to limit the ifn damage to 6 months (likely more wishful thinking..)

[frijole]

More info provided by ejoli on the trial-- if you are not clear at week 12 (hopefully by a sensitive test)and have been on the placebo,  you can roll into a new trial with the Boceprevir immediately.  You have to do another 12 weeks so that extends the total time to 60 weeks.  She also said 2/3 of the patients in the trial get the BOC, 1/3 the placebo.  Any trial sites around you?
frijole

[frijole]

as far as timing with the phase III - If Schering is just now recruiting for the trial, all the slots won't be filled for at least a couple of months.  Ejoli is taking her second shot of the same trial tonight.  Kansas City only filled 4 slots and couldn't even find another 4 to fill their 8.  Can you believe that?  Ejoli said you get knocked out if you don't have a 12 week PCR -- things like that.  Ok, back to my train of thoughts  - lets say 4 more weeks to fill the slots,  48 weeks for the trial and another 24 week for the 6 month post results = 76 weeks - 1 1/2 years. So maybe early 2011.  If the FDA does take a year, that puts it to late 2011.  I really don't know.

Yes, it is the NCT00845065 trial and  you are right about it being Pegasys - Peginterferon Alfa 2a -- I  hadn't even keyed in on that.  I just assumed it was another Pegintron (alpha 2b) and was wondering why they were even doing this one.  I guess that is why - to prove it is effective with Pegasys.  I don't see anything about a roll-over for the placebo group on the clinical trial website.  It is a question you can be sure I will ask.
frijole

[willing]

interesting, I hadn't thought about the cost aspect.. but who knows what  insurance/medicare coverage will be? It's a safe bet Schering/Vertex won't make it cheap. All the best on your interview (and on getting into the right arm!)  I assume this is the BC/Pegasys trial (NCT00845065), will they offer roll-over if you're in the PO group?

and btw, why late 2011? I was already packing my suitcase.. Phase  3 data for both trials will be complete a year from now. I figured they'll make a big splash at DDW and AASLD10, give the FDA 6 months to look over the results and maybe get approval at the start of the year. If the phase III turns up problems, it'll be much longer.

[frijole]

Didn't mean to ignore you.  I don't post that often and when I see my friends posting , I try to catch them.

I didn't see you biopsy results so I wonder if you had one.  Given your track record with interferon and infergen, unless your biopsy is a 3/3 or so, I would not continue with the current protocol.  If I were you, I would look for a trial - but you have to be off current treatment for some time in order to qualify.  Do you live by a big city?

frijole

[frijole]

Actually I am trying to get into a Boceprevir trial right now.  It is not that I cannot wait - still probably a grade 1, stage 1-2 but rather I have concerns about the state of health care that may be changing.  Specifically, what will Medicaid cover.  Will it only pay for standard SOC or will it be on board for the new PI's.  I am still about 3 1/2 years away from that (Medicare) but it is a definite concern.  OR, and I think this is a real possibility, will the (possibly socialized) plan - Medicare or whatever -- even let me treat - or will they think I am "not that bad off?"  

In any event, I put a call into the Liver Institute in Dallas at a most opportune time.  It seems that they have the drug company interview (In order to determine that they are a suitable clinic to host their trial) on June 2 and the person I spoke with is to send me a packet and told me to call on June 4.  So we will see.  I will let you know.

best to you, frijole

[willing]

thanks for the free-access link; it's a good paper, might be of interest to many who are waiting for  BC/TV approval to re-tx (eg frijole,susan,magnum,dointime and others). Unless something changes significantly over the next year it's probably going to be my next bet. I can't wait four more years and the ability to mix a cocktail of this sort is one of the reasons to wait out the phase III trials.

As for ntz, there's some insight from recent easld'09 presentations:
Abstract 311 showed respectable improvement in EVR/cEVR among g1s:
http://www.kenes.com/easl2009/Posters/Abstract311.htm

However abstracts 321 (courtesy of CS) and 853
http://www.kenes.com/easl2009/Posters/Abstract321.htm
http://www.kenes.com/easl2009/Posters/Abstract853.htm
showed more modest improvement among NRs. As noted in the text, if ntz's mechanism of action is stimulation of PKR, an interferon-induced gene, then one would expect less effect among ifn nrs.

The extent to which this can be remedied by adding SAMe to rescue ifn expression
(eg abstract 491, also courtesy of CS)
http://www.kenes.com/easl2009/Posters/Abstract491.htm
remains unclear.

[jmjm530]

Full-text here for free. Didn't read it all, but interesting per your previous statment that they favored pre-dosing statins over Alinia.

http://www.jhep-elsevier.com/article/S0168-8278(08)00767-8/fulltext

[willing]

congratulations on surviving two nasty-sounding rounds of tx and sorry the results aren't more encouraging. It clearly seems you're not responding to the daily infergen; whether you were responding to the 1st round of peg ifn isn't clear. What dosages of ifn and rbv were you on?

The results are disappointing, but there are a number of other promising options, depending on how much liver-time you have left - ie on your fibrosis stage.

The best new tx options are cocktails that simultaneously go after the virus in different ways. As an example, a good recent review,
( not free-access, unfortunately )
http://www.ncbi.nlm.nih.gov/pubmed/19070928
recommends combining the following approaches to overcoming interferon resistance

1) an NS3A PI (boceprevir or telaprevir in ~18 months)
2) SAMe to restore IFN expression pathways blocked by the virus
3) high dose (15.2mg/kg or better) rbv
4)  exercise/weight-control to lessen insulin resistance
5) statins to inhibit host lipid biosynthesis that assist/support viral replication (or wait for debio-025, currently in phase IIb)

to which it would be reasonable to add alinia/ntz to augment the effect of PKR-induced ifn.All of the above except (1) are available now.

On the other hand, if you have enough time, you might be able to afford to wait for a polymerase/protease combo (eg R7128/Boceprevir, about 4 more years) which will likely require no/minimal ifn. A well-informed Dr. should be able to help you navigate a good plan.
All the best.

[newleaf09]

The interferon is the current key to successful treatment of the virus.  Unfortunately there are people with certain genotypes of the virus that do not respond to the interferon; the addition of extra interferon to the system does NOT throw the immune system into overdrive to kill the virus.  The ribivirin operates like lighter fluid to keep the response going.  I believe the view is that if one does not respond to this major weapon in the treatment arsenal, one never will.

The good news is that there are another group of drugs that operate in a completely different way than interferon, the protease inhibitors.  They interfere with viral reproduction.  They are in phase 3 testing now and it will still take another year or 2 to get them approved by the FDA and onto the market for all to use.  There is even another generation or specialized antivirals coming behind the protease inhibitors.  All of the new experimental drugs are looking very positive for overcoming the lack of a response to interferon.

Sorry you had to suffer through unsuccessful treatment but there is currently no other way to evaluate if a patient will respond except just trying it.  Take heart.  Take good care of your liver.  Something better is definitely coming.

[Bill1954]

Here’s a link to some of the lingo used in here:

http://www.medhelp.org/health_pages/Hepatitis/Common-Hepatitis-C-Acronyms/show/3?cid=64

You can also find this link on this page in a box titled ‘most viewed health pages’ in the lower right hand margin. This will help you through the gibberish used in here :o)

Bill

[Bill1954]

Your response to medication is typical of what is known as ‘null responder’ unfortunately. Were you fully compliant with the meds, with no gaps in treatment or anything? I understand your frustration… I had to treat twice, after becoming undetectable for virus, then relapsing thirty days after completion of treatment.

A good reference website for HCV is Janis and Friends:

http://janis7hepc.com/

Although some of the info is slightly dated, it can answer most of the basic questions we have about this disease. You might begin by opening ‘newly diagnosed’ near the top of the page, or by clicking on ‘other HCV information’ located in the right-hand margin.

Continue to ask questions in here as well as other places; there are a lot of genuinely capable and kind folks in here that can help guide you through the maze we call treatment.

Hopefully others will chime in with their experiences as well, and can provide other options for you to consider.

Welcome to the discussion group, and hang in there,

Bill

[portann]

Did you change something in your meds between November  and December?

According to these numbers, you had more than a two log drop within four weeks of starting treatment but then went up significantly.

Is 48,000 the correct November result?

[foxgirl1]

I really cannot respond about the two log drop, because I really do not understand it.  This website has given me information that I probably should have sought a long time ago.  

I have never been ill and now this hep c diagnoses that I can't seem to get rid of is taking a toll on me.  I've tried both tx and still I am in the same boat as before.  If it will help to know my viral load here it is..
       Weekly tx
Oct 08 = 6,700,600
Nov 08 = 48,000 -    down
Dec 08 = 578,000 -    up
Jan 09 = 1,030,000 - up
Mar 09 = 1,190,000 - up
      Daily tx
Apr 09 = 377,000 -   down
May 09 = 754,000   - up

[foxgirl1]

Tks for the info. will look into it.  This is so frustrating for me.  

[Bill1954]

Depending on the status of your liver damage, you might opt to wait for the new class of HCV drugs currently in late stage clinical trials. Boceprevir and Teleprevir are both in phase three trial now, and it appears they will be released to the public in 2011 or so. They will be added as an adjunct to the current standard of care for HCV; the preliminary news is that they will shorten the duration of treatment for genotype 1 patients from 48 weeks to 24 weeks, and with greater efficacy. We have members in here that were also null responders to IFN/ribavirin who went on to clear the virus with these new medications. If you want to research these further, Google HCV protease inhibitors, STAT-C therapy, or of course by name.

Best of luck to you,

Bill

[JennyPenny]

There are no other treatments available except those being tested in clinical trials. You might want to wait until one of the protease or polymerase inhibitors become available sometime in 2010 - 2011. They will be added to interferon and ribavirin and the trials are looking good for some previous non-responders.

Did you have a two log drop by 12 weeks? Relapsers and people with a 2 log drop have the best success adding one of these new drugs.