How much longer ?

I know no one can actually give me a date when something, anything, other than INT +REB is available, but how about an estimate (what year ?) of when something should be available. My Hepatologist  has been telling me for 3 years now that PIs should be available 'next year'. I am a non responder to SOC and am tired of waiting (yes I know, 'be patient' seems to be what I hear a lot).

Anyone have an ideas. opinions etc. ?

Thanks and sorry if I sound a little desperate.

[Marc1955]

Most people on this board seem to be operating with 2011 as the year when effective new treatments will be approved. I don't know the month. Maybe someone else does.

*****, huh? It feels so weird to potentially have your life hinging on a race with new medical treatments. But it could be worse. There are many horrendous illnesses for which there is no effective treatment in the pipeline. Imagine you were 50 years old and were diagnosed with Parkinson's Disease. So I guess we should count our blessings that science is progressing as well as it is for us.

[applez]

I was looking at some  phase 3 results for telaprevir and non responders and it sounds like non reponders who have telaprevir added to int-reb have a 44% success rate. I'm not a real gambler but I dont like those #s. They're better that nothing, true, but still ! lol

If anyone has a somewhat rosier outlook I'm all ears !

[Rockerforlife]

It dont get much more rosier than this



patients who received the boceprevir P/R lead-in regimen and had rapid virologic response (RVR), defined as undetectable virus (HCV-RNA) in plasma after 4 weeks of boceprevir treatment, SVR was 94 percent in the 48 week regimen and 82 percent in the 28-week regimen. RVR has been shown to be a reliable predictor for achieving SVR. These final results are from the HCV SPRINT-1 study in 595 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1.


http://www.medicalnewstoday.com/articles/130622.php

[applez]

Anyone have any results or info for a non-responder ? (I had my VL go down only 1 log after 12 weeks)

[Isobella]

This may just be my docs opinion, but we were discussing my daughter starting tx this summer....she'd go 48 weeks.  And he said not to because by the time she was done, telaprevir would be on the market.  So he's thinking mid to late 2010.  

He also told me Roche has a phase 2 trial starting this summer that looks promising as well...R7128.

And, no....you don't sound desperate-you sound just like the rest of us, lol!!  Waiting for the next best thing to cure us.

Hang in there =)

[pjhep80]

It dont get much more rosier than this


patients who received the boceprevir P/R lead-in regimen and had rapid virologic response (RVR), defined as undetectable virus (HCV-RNA) in plasma after 4 weeks of boceprevir treatment, SVR was 94 percent in the 48 week regimen and 82 percent in the 28-week regimen. RVR has been shown to be a reliable predictor for achieving SVR. These final results are from the HCV SPRINT-1 study in 595 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1.



ya those are great stats for RVR people... but what about the rest of us, non/slow responders, what are the stats with the PI's for that???  only about 50-50 is what i hear...

[Rockerforlife]

i was a slow responder

[Rockerforlife]

in my first round of tx with SOC drugs i didnt get undetected untill somewhere between week 12 and week 24....this disease WILL be beaten

[Willy50]

2 possible routes;

Early approval for TVR for past TX failures; the FDA will be shown the final results for Prove 3 when they are all in and that should be about now.  Andiamo TX'ed as long as the SOC arm and so since he is post SVR the FDA has likely seen the data or will very soon.  They will then be in a position to evaluate the difference between SOC and triple therapy for past non responders.  I believe the average in the trials was 52%.  If Vertex can offer what no other form of TX can at a healthy margin the FDA could move to approve for past TX failures.  (I believe that the average success rate might be in the single digits merely retreating with standard SOC.  Results vary; based on whether one was a null responder vrs a relapser)

The other route is conventional approval.  I believe they just are finishing enrillment in the second TX niave trial.  That means that sine the longest arm will be one year (48 weeks) with a 6 month wait it will take at least 1.5 years.  Figure another 6 months for getting tests all in, compiling data; just round it to 2 years.  That puts it at early 2011 or thereabouts.  Hard to figure how it could be sooner.

Willy
-----------------------------------------------------------------------------------------

http://www.hivandhepatitis.com/hep_c/news/2008/061308_c.html
(preliminary Prove 3 tx-failures trial)

Vertex Reports 52% SVR 12 Rate for a 24-week Telaprevir-based Regimen in Genotype 1 Hepatitis C Patients Who Failed Prior Treatment

• 73% of prior relapsers achieved SVR12 with 24-week telaprevir-based treatment.

• 41% of prior non-responders achieved SVR12 with 24-week telaprevir-based regimen.

[HectorSF]

There seems to be some confusion about the term "non responders"...

Technically speaking viral patterns of nonresponse include BOTH "null response" and "partial response". So there are two very different sub groups of non responders.

A "Null response", defined as < 1 log10 IU/mL decline in serum HCV RNA after 12 weeks of treatment.

"Partial virologic response" patients have a ≥ 2 log10 IU/mL reduction in HCV RNA but never achieve undetectable HCV RNA.

"Null Response" Patients are poor candidates for retreatment. Such patients have no significant decline in HCV RNA during treatment and are essentially refractory to the effects of interferon. Studies have shown that retreatment of peginterferon and ribavirin null responders with another course of peginterferon and ribavirin is not beneficial and results in only a 3% to 10% SVR rate.

Patients with partial virologic response are excellent candidates for retreatment. If these patients are treated with higher doses of interferon or peginterferon alfa, they can potentially achieve a greater decline in HCV RNA, perhaps achieving undetectable values and, in some cases, SVR

Note: Persons who relapse are responders. They are not part of the non response group. A "relapse" is the reoccurance of HCV RNA in patients who achieved and maintained undetectable HCV RNA throughout the duration of treatment.

INT + REB will be around for the foreseeable future. New meds will be in addition to Int + Riba.

So we hope and wait.....

HectorSF

[Willy50]

I don't know if you've looked over the "107 study" from Vertex.  It is basically the partial results of the Prove 1 and 2 (SOC control arm) treatment failures.  They were allowed to enroll into a "rollover" trial and received triple therapy.  Due to the record keeping of Prove 1 and 2 they were able to track how past treatment failures responded to triple therapy.  This trial is not yet complete and so we may see early response rates but NOT SVR rates.  I don't think one can draw a conclusion but it appears that even null responders can respond to triple therapy if I'm reading this right.

http://www.natap.org/2008/EASL/EASL_06.htm

best,
Willy

[HectorSF]

Willy,

Thanks so much for that paper. I had never seen the chart data before. Excellent. I need to do some more research myself to see if there is any updates on this data. If I find some I will past it along.

My doctor at UCSF had mentioned that she may have a trial this coming winter that I may be able to join if the meds show that they work for null responders. So this is all good news.

Thanks again for the info!

HectorSF

[zazza]

Excellent definition of null responders in your link:

"null responders defined as non-response week 4 (<1 log drop in HCV RNA at week 4) or as non-response week 12 (<2 log drop in HCV RNA by week 12)"

[zazza]

"A Study of Telaprevir Combined with Peginterferon Alfa-2a and Ribavirin in Patients with Well-documented Non-response or Relapse After Previous Peginterferon Alfa-2a and Ribavirin Treatment: Interim Analysis"

Update on study 107 from AASLD, Oct 31-Nov 1 2008, San Francisco, CA

http://74.125.77.132/search?q=cache:hvX3IZdFDzUJ:www.natap.org/2008/AASLD/AASLD_39.htm+study+107+non+responder+Telaprevir+2008&hl=sv&ct=clnk&cd=1&gl=se

[zazza]

http://74.125.77.132/search?q=cache:hvX3IZdFDzUJ:www.natap.org/2008/AASLD/AASLD_39.htm+study+107+non+
responder+Telaprevir+2008&hl=sv&ct=clnk&cd=1&gl=se

[zazza]

http://www.natap.org/2008/AASLD/AASLD_39.htm

"A Study of Telaprevir Combined with Peginterferon Alfa-2a and Ribavirin in Patients with Well-documented Non-response or Relapse After Previous Peginterferon Alfa-2a and Ribavirin Treatment: Interim Analysis"

Update on study 107 from AASLD, Oct 31-Nov 1 2008, San Francisco, CA

This is the correct link. The other one was my search link. Sorry.

[HectorSF]

Got it!
Thanks so much!!!

HectorSF

[Willy50]

That was a tremendous link.  (well worth the wait.  ; ))  

I still don't think we have seen all that this compound will do.  I am awaiting the news on the predosing trials, the shorter course of triple therapy, etc.  The response rates of past null responders looks very encouraging.  If there were an adjunct that could be added or possibly the predosing strategy could also increase response rates further.

I have to wonder what we will see when they add a polymerase inhibitor to the mix.

Thanks for the link Zazza.  By the way.....I believe that the 107 study should be complete fairly soon.  We may then have some solid SVR rates reported, possibly in the spring EASL conference.

best,
Willy

[HectorSF]

Absolutely! This is the best news I have ever seen for null responders like myself. Actually it is the only retreatment for null responders that has a greater than single digit chance of SVR. Those viral curve graphs are stunning.

In summary -

At week 24
43% of null-responders (n=42) achieved undetectable HCV viral load
82% of partial responders did also (n=22)
71% of relapsers (n=7) did as well.

If these results correlate to SVR rates to any degree this will be a HUGE improvement for all non responders!!!
I've been in a good mood every since comprehending this data. ;- )

This at least gives us (cirrhotics) reasonable odds of SVR before the only remaining option, transplant.

Thanks again for making me aware of this data.
HectorSF

[Willy50]

Really fabulous study; great news, great write up and spectacular graphs.

Do you mind if I add the 4 and 12 week results?

Table 5. Week 4 HCV RNA by Prior Response to Control Peg-IFN + RBV Arm in the PROVE Studies (ITT Analysis).
From Jules: 75% of null-responders (36/48) had <25 IU/mL at week 4; 97% of partial responders ((32/33) had <25 IU/mL at week 4; 100% of relapsers (22/22) had undetectable at week 4.


Table 6. Week 12 HCV RNA by Prior Response to Control Peg-IFN + RBV arm in the PROVE Studies (ITT Analysis).
From Jules: 58% of null-responders (28/48) had <10 IU/ml (undetectable viral oad) at week 12 79% of partial responders had <10 Iu/mL at week 12; 73% of relapsers (16/22) had <10 Iu/mL at week 12.

--------------------------------------------------------------------
It was very interesting to see the representations on graphs; the lack of response on null responders in SOC trials, breakthroughs, the curious stall points in which many people hover either just above detection for a spell and then either breakthrough but more often clear.  The range of differentiation in slopes between null responders and past relapsers is also amazing as is the response rates between the 2 groups.  The 107 study provides a lot of hope.  It's comparing the exact same people; first on SOC and then giving them triple therapy.  

Thanks again zazza for the spendid link.  And here it is again;

http://www.natap.org/2008/AASLD/AASLD_39.htm

Willy