Decided on VX-950

As I posted a few days ago, I had to make a decision on the clinical trial treatment with VX-950 because of the distance and cost. There are still unanswered questions by both the Gastro and Hepatologist. I will have a Cat Scan next week because the Ultrasound of the abdomen was inconclusive.

Wednesday, I had a Varicose test of the esophagus. The nurse in the recovery room said that the test results were positive for varicose veins. However, I'm a singer and have already had two throat surgeries for removal of polyps. Could this also be the result of singing as opposed to Cirrhosis? This is what the doctors have to decide.

At any rate, why prolong the inevitable? I'm a 4-time non-responder and the Telepravir is my main hope at this point. No beating around the bush thinking this problem will go away by itself magically or by some Chinese herbal miracle. Face the music and dance one day at a time.

Living in Las Vegas, I'm a mild gambler, but I see the odds of me getting the VX-950 as opposed to a placebo as being 66%, I think that's decent odds. As for reading test results, one doctor sees this, the other doctor sees that and no one can seem to come to one conclusion. My conclusion is to have as much fun and enjoy life one day at a time while everyone else struggles over what is really going on with me.

I pray everyone here clears. We must go into battle and be victorious at all costs. Damn the torpedoes, full speed ahead. Take the bull by the horn, turn him around and kick his butt....

Magnum

[meki]

Rock on Mag... That's too awesome.

You live in one of my favorite places in the world --- BTW.

I love Vegas - especially if I'm winning.. LMAO!

Anyhow - good odds, if you've calculated correctly.

Much love and luck!

Keep us posted.

Meki

[Rockerforlife]

Good choice you made...looks good to me...this may be you ticket out....good luck my man...im getting butterflies thinkn bout kickn some *** myself...im scheuled to tx this July 25...all systems are a go....all ducks and geese are down for the count.

[mikesimon]

Good luck, Mike

[Trinity4]

Good Luck and I think you made a very wise choice.  It's time hit em with all you got!!!
Trin

[pigeonca]

I'm with the band on this one.  You made a good choice, and I'm betting on your winning.  In fact, I bought 100 shares of Vertex stock a week ago 'cause it sounds great.  Happy 4th.
pigeon

[Marcia2202]

I'm also happy to hear this, thinking you definitely made the right decision. I wish you all the best with treatment. May you slay this dragon once and forever!

Marcia

[dointime]

I'll be watching and hoping for success for you,

dointime

[HCA]

Good luck-look forward to updates.Hope you get the real pills.
I'm not far behind you in disease progression and will take tri-therapy as soon as it is licensed.

[comeagain]

You made up your mind, thinks that fine.
I like your spirit you wanna take the dragon down so do I.

Wish you the very best I´m covering your back with prayers.

May the good God bless and protect you.

ca

[fretboard]

Good luck with your tx plan, I hope all works out for you.  God Bless

[Bill200]

Mangum, I do it if I were you.  The good thing is you can quit the trial if it appears that the teleprefir is not working or if you somehow found out you're getting the placebo.  If I get a chance to do the teleprefir non-responder trial and, certainly if I haven't cleared by 12 weeks, I out.  No need to continue to put oneself through treatment hell to finish out the trial.  

Does the trial rule out those with cirrohsis or varices?  In your case, Is that still part of the consideration to treat or not?
regards, Bill

[Isobella]

Congratulations on your decision.  I am looking forward to hearing all your good news.  

I find out Thursday about the Vertex tx naive trial, so I will also be making a decision!  

All the best to you---keep us posted!

Isobella

[Willy50]

I read this a second or third time and caught something I hadn't noticed in your earlier posts.  You write that you are "I'm a 4-time non-responder".  If this is true and if you mean that you've never cleared the virus even for a while during your four treatments it could undermine your chances, even with Telaprevir.  I just want to be clear about the way that you describe your treatment failures.  There is some thought that some people have interferon resistant virii and that as long as interferon is part of the mix...part of the main attack that they will not clear.  I don't know the answer and the "final" results of the Prove 3 have not been revealed yet to the public but I want to mention it to you.  You may want a quick consult with the doctor and run through exactly how you failed your past treatments.  If you are a "classic non-responder" there are some people who will tell you that even with a PI you cannot succeed.  Interferon.....or your immune response with interferon would be thought to be the weak link in the chain.  Personally, I am hoping that the Prove 3 results may show that this isn't as clear cut as was once thought.  If I remember correctly you were connected to Dr. Gish, weren't you?  They would be able to provide you an answer.... the answer..... or an answer with some qualifications.

The preliminary results for past non-responders in Prove 3 was 41% SVR12.  That's as close as I can get to what you could expect from the trial if you had participated in Prove 3.  

I don't like throwing water on the idea but I would want to find out so you can have several plans in place and pick from the one that offers you the best odds.  Here is my thinking;

IF you have the resistance issue that I've described there is a possibility...even a strong possibility that triple therapy won't or can't work.  I am not the guy who can tell you that.  I will suggest that if you have the profile of a classic non-responder you have a much tougher road before you with lower odds.  IF that were the case....how would you line up a treatment so as to have the highest chances of clearing?  There could be a number of things that you could do which could raise your chances of clearing and maintaining.  You may need more control over your treatment than you could get in a trial.

I still think that the Vertex offers you a far better chance of clearing or getting an SVR than through double dosing.  The question could be.....IF you could wait until it is approved whether you could make some additions to your treatment which could raise it over the clear rate of the fall/winter trial (If you are to be accepted of course).

The weak points of the trial are;

You stand a 1 in 3 chance of getting into a SOC arm.
You may or may not be allowed rescue drugs at critical times. (I personally believe that they may allow them)
You will not be allowed some deviations in treating which could impact of success. (ex; double dose IFN in early weeks)
You would not be allowed other adjunct compounds or therapies in the trial (such as alinia)

Lets also assume that one of the two triple therapy arms is superior over the other.  For a proven responder it may not make that much difference...... but to a classic non-responder it COULD make a difference.  I don't know enough about the principle of interferon resistance but I think there are some who maintain that if you are have the interferon resistance it might not any difference.  The viri will win until a treatment comes up without interferon.  My point is that IF it is NOT so clear cut, a treatment that makes maximum use of all your options could make the difference.  This is a question which could be better answered by someone like Dr. Gish than by me.  

A final factor is that if you were to fail while using Telaprevir you may also face resistance with that treatment as well, or PI's in general.  So...in a nutshell.....if you figured that you only had one more chance at learning the virus..... how would you mount the attack?  The answer could be with "everything but the kitchen sink".  Waiting would allow you all these options.  It would also allow you the knowledge of what will work and what won't.  There are still many things which will come up in the upcoming 2 years which could assist in your clearing.

I don't want to discourage you on the trial idea.  I think the trial is your better option over double dosing.  I just want you to do a little more homework and really use the doctor's knowledge....and add in the data which will come right around trial start time.  It could make a difference and I want you to better understand the issues.  

best,
Willy

[susan400]

Yea, like me and my resistance to Telaprevir.  So far, I'm still on treatment.  Finished Debio-025 portion of trial and waiting for results from Part 1.  I was told that as long as I'm still dropping on my viral load, that I could continue on with Part 2 the (SOC).  Study nurse told me that they had 2 other patients who even though they had a slight viral rebound on Day 15 blood draw (this is because on this arm you get twice a day Debio+SOC during the first 7 days and on Day 8 switch to once a day Debio + SOC), that those patients viral loads stabilized and then, continued to drop by 2 more logs and by the time of the Day 29 blood work.  She said those same 2 patients cleared by week 12 and these were previous non-responder patients.  She told me all of this to encourage me and she told me that I was still in that same 'curve' as those other two patients.  So, for now, until I get my results back, I still have some hope.  I continue on with SOC.  I didn't get that many sides at all from the Debio-025 and had no rash (thank GOD)!  I'm having more sides from the SOC now that the Debio has stopped.  I was fine on Wed. when I had my 12 hr day appt on Day 29 and then, made the 3 hr drive home on Thurs. But, Fri., I crashed.  This was 2 days after Peg shot.  I have a pleurisy like pain in my back which is hurting alot and because I was resting alot from sides, now, my right knee is hurting.  So, it's just one of those FUN things that goes along with the whole TX party!  Tomorrow's another day and I could be fine by tomorrow.  I just pray to get through these hard days and rejoice in the good ones.  BTW I can get rescue drugs in this trial now that I'm on Part 2, whereas, I was NOT allowed any on the Prove 3 trial.  I don't know if they've changed that any, on this later phase.  Also, I was totally double blinded so I did not get any reports whatsoever, on what was happening with my viral load until I was kicked out of trial for rebound and even then, didn't get results until I was unblinded at week 24.  Remember, I was kicked out on week 5 and had to wait all the way up until week 24 to get results, even though I wasn't even in the trial any more.  I sure hope that they've improved some of their requirements.  What I like about Debio is that the are a fully funded company that is not a publicly traded company.  They are a Swiss company and not dependent on the stock holders.  I'm also making around $1,000.00 just to participate in this trial and everything is being paid for by them.  I got nothing out of Vertex.  No gas mileage reimbursement for the 3 hr drive, no $$$ for participating.   If I had cleared, it would have all been worth it to me, but since I got the rotten luck of Group C, I've kind of got a biased viewpoint on my experience.  I don't fault anybody for wanting to try anything that they need to, to clear this beast.  I mean, I did do it myself.  I'm happy for those that did the VX and had a good experience.  It just didn't work that way for me is all.


Susan400

[Willy50]

I know that it has to be a bitter pill to swallow.  It's one tough thing about trials.  There is a lot of uncertainty.  There are bound to be some failures.  Some of those failures may seem very apparent in retrospect.

I hope that your current treatment proves to be your success.  I don't know anyone who has tried as many times as you.  I still think that they will get this virus licked.  There will be many therapies, some of them will be used in combination with one another or sequentially like with HIV treatments.

Crossing my fingers for your success this time.  Wouldn't that be great finally!!!!

Best,
willy

[Andiamo1]

I think you made a wise choice.  Do you know if you were a non-responder, relapser, or breakthrough?

I did try 7 previous times and finally seem to have done it with Telaprevir.  I am undetectable 12 weeks post treatment and have hope for SVR.

I believe Vertex is trying something new in this trial and lengthening treatment based on the 4 week response.  They take many viral load tests. 4 the first day, one a week for the next four weeks, every two weeks for the next month and then monthly till end of treatment.

I believe the trial participants are not given the viral loads until EOT.

Best if luck to you and let me know if I can answer any of your questions.  I was in the  24 + 24 arm of prove 3.

Eric

[Willy50]

The answer is that some of this is yet unknown and is currently being discovered and proven.

The answer hinges in part on how one failed past treatments.  IF one never had much immune response and has never cleared that could point to having resistant mutations.

As the preliminary results suggest, if the past "non-responders" had a 41% 12 week SVR rate then some non-responders do indeed clear and maintain the viral response.

IF some people don't maintain either a full dose or complete compliance then they may not be considered classic non-responders since they didn't really do full recommended dosing. (ie; their failure could be more of a dosing consequence than a viral response issue)  I don't know how any of the successful Prove 3's failed in earlier treatments.  I'm not asserting this theory is true, simply passing on the general ideas involved.

We don't want to confuse a non-responder with other treatment failures.  Non-responders are considered to be the toughest to treat.  The past relapsers in the triple therapy arm fared much better; 72% 12 week SVR rate. (versus 41% past non-responders)

It appears that some past non-responders will achieve an official SVR in the Prove 3 trial.  Even if that is the case there could still be a sub-set of non-responders who truely are interferon resistant and who might not respond to interferon based therapy.  I don't know the answer to that one.  We do see from the results that I posted that at best 41% of past non-responders succeeded meaning that 59% failed the triple therapy.  Can that be improved on?  I think so.  I just wanted to make the point for Magnum to ponder or ask his doctor.  Some of his chances will bear on exactly how he failed in past treatments, at least that is the theory borne out by statistics.

best,
willy

[Marcia2202]

This just came out, i think it will be interesting for you to read.

Marcia


http://clinicaloptions.com/Hepatitis/Conference%20Coverage/Milan%202008/Tracks/Investigational%20HCV/Invest%20HCV.aspx

[Marcia2202]

Sorry, it won't copy the whole link. If you go to   http://clinicaloptions.com/Hepatitis   you can register and subscribe for hepc news. It's the mail I got today concerning the telaprevir trials.

Marcia

[w.c. missy]

as a 2 time non-responder, i cleared the virus with the telaprevir at 12 weeks.  i am currently in the 24+24 roll-over prove 3 study.  the telaprevir seemed to be the ticket.  i think you made an excellent decision, and i believe you will be very happy with the care you receive in los angeles.  just a thought, but if you know your lab dates ahead of time, and book in advance,  sometimes you can get a round trip ticket on southwest for a little over $100.00.  much cheaper then filling up that big truck...

best to you,
w.c. missy

[Magnum]

Thanks for your lengthy advice. I'm a positive thinker and have been through hell in 13 surgeries and still here to tell the tale. Let me say that during the 4 treatment attempts, the two different Gastros that treated me never allowed me to complete the entire 48 weeks because although I didn't develop serious side effects, I didn't drop below an acceptable point in my viral count.

What that means is that every time I treated, I went from several million count to once going down to 380,000, to the lowest at 6000. The 6000 count was with the near death double dosing with Infergen for four months.Had I been allowed to continue for the full 48 weeks, both doctors felt it would not have caused SVR.

I will have to have another biopsy before being allowed to enter the Telepravir trial for non-responders. I am on the list and will be called within the next three months.

One thing I want to advise everyone here on, is to keep complete records of ALL test results, biopsies, bloodwork, etc... Get copies EVERY time you are tested. Why? The trial director told me it was that, that put me on the list right away. Meaning that it saved THEM a lot of time requesting my records from test centers, making phone calls to my doctors, etc..

What I did, was to scan all my records I asked my doctors to give me copies of (going all the way back to 1994 when first diagnosed), and put them in JPEG files on a CD and sent it to Cedars-Sinai’s clinical trial center. This advice Im passing on to prospective entrants to the clinical trial, was what I was told propelled me into the line much faster than those who did NOT have these records to send right away.

As for Dr. Gish, he feels (as the Gastro also feels), that I should go for the VX-950. Dr. Gish's nurse said they have had good success in the double dosing of Pegasys with non-responders, while my Gastro feels the success rate will be 15-20% with double dosing. Again, this is two doctors with two different opinions.

I will do the trial because my Gastro said that if I get the placebo, he will put me on double dosing. Many things can happen before that point. Let's hope one of those many things will include SVR. It remains to be seen.....

Magnum  

[DragonSlayer45]

Willy,

I just recieved an email this morning and it covers this exact topic. From what I read the Telaprevir trial proved to be effective for previous interferon non- responders even though conventional wisdom thought it would be like taking monotherapy since they were resistant to interferon based therapy. The trial shot that theory down. Here is an excerpt from the publication:

An open-label trial conducted by Poordad and colleagues[8] (Capsule Summary) analyzed the response rates of 60 previous nonresponders to peginterferon alfa-2a plus ribavirin from the PROVE studies who received retreatment with triple therapy containing peginterferon alfa-2a 180 µg/week, ribavirin 1000-1200 mg/day, and telaprevir 750 mg 3 times daily for 12 weeks followed by 12 weeks of peginterferon/ribavirin. Since these patients were derived from a pool of treatment-naive patients who failed to clear the virus by Week 12 in clinical trials, their compliance and virologic response to previous peginterferon/ribavirin therapy was extremely well documented. Based on their previous response to known dosages of peginterferon and ribavirin, they were categorized as null responders (< 1 log10 IU/mL decline in HCV RNA at Week 4 or < 2 log10 IU/mL decline in HCV RNA by Week 12), partial responders (≥ 2 log10 IU/mL decline in HCV RNA by Week 24), relapsers, or breakthrough patients.

The investigators were able to demonstrate a very high RVR rate in these previous nonresponders; specifically, 70% or more of patients in each previous response group achieved HCV RNA < 25 IU/mL at Week 4 of retreatment. The highest RVR rates were seen in patients with previous breakthrough (100%) or relapse (100%), whereas the lowest RVR rates were seen in patients with previous null response (70% to 75%). These data are important because many clinicians believed that peginterferon/ribavirin nonresponders might not respond to triple therapy with peginterferon, ribavirin, and telaprevir because it might essentially equate to telaprevir monotherapy. However, these patients responded extremely well.

This was an interesting proof of concept study in a well-characterized cohort of patients. These data have heightened the interest in the current nonresponder study that is underway—the PROVE 3 study—which again is studying peginterferon alfa-2a, ribavirin, and telaprevir combination therapy. Furthermore, these results may impact future study designs since nonresponder trials with triple combinations have now been validated by this study.

Magnum,

Good luck with your decision but it sounds to me like you have already decided to go for it. I would too if I were you. God speed and kick some Dragon Arse my friend. I will pray you do not get in the placebo arm.

[susan400]

Just so that you know, I've always been in full compliance on all of my treatments.  I even dropped down to 200 copies from the millions on around 3 of my past treatments, but it was so late into the treatment and I still wasn't clear and the doctors would not allow me to continue any further.   On one of them, I had already treated for 52 weeks and still hadn't cleared but had dropped down to around 125 copies and I was stopped.  On Telaprevir, I dropped from 6,770,000 copies on screening to 195 copies by the end of week 1 (but had no Riba in the mix) and I had a huge rebound and did not clear it by week 4 (which was the requirement) and got kicked out of the trial on week 5.  So, my doctor told me that I was a 'partial responder' based on my past history of treaments.  I definitely drop quite a bit, but have never cleared and it's definitely not due to non-compliance on my end.  I have a lot of resistance I'm afraid.  I used to have 2 genotypes, 1A and 1B and now, I am only testing as having 1A.  I found out that I only had 1A left when I had the screeing done prior to using Telaprevir so I don't give the losing the 1B - credit - to Telaprevir, but to prior treatments.  I double dosed on a few different treatments.  Doubling the interferon on one of them and on another was on 1600mg of Riba which was way more than my weight based dosage.  

Susan400

[Andiamo1]

Wasn't it the breakthrough group that had the lowest probability of SVR?  Non responders did  better and with the new protocol, I think they will do even better.

I was a non responder for the first five trials.  I responded and relapsed during the next two and so far in Prove 3, I am still undetectable.  I think non response with SOC is a very complicated issue with many factors involved besides viral resistance being involved.

I think drug absorption and elimination play a strong role in keeping the trough levels of the drugs high enough to keep the virus from reproducing.  Our own immune system also plays a role.

I think I am living proof that repeated interferon treatments don't produce resistant virions.  Treatment with PIs do encourage resistant virions. There are conflicting opinions about how damaging that might be.

I think VX 500 will handle the 950 resistance, since it was developed using sequencing information gathered from the Prove trials.

Eric

[Trish77]

I'm excited for you for this opportunity to be in the Telaprevir trial.  I hope you will keep us all posted as you're able (both mentally and physically!).    I am also glad you have your "Plan B" in place in that your doc will double dose if it's clear you have placebo.

I'm wondering when you will get your first results, have they told you?  

I wish you a good journey, Magnum.  Here's to SVR for you.

Trish

[Willy50]

Magnum, I'm wasn't trying to suggest any course,  I'm just describing the terrain.  It's up to you to plot the course.  As I've posted, I was only just aware of the possible non-response issue and wanted to give you both some feedback on what some professionals thought, and why they think it.  I also took it as an opportunity to show that the preliminary results of Prove 3 are suggesting that what was previously thought doesn't match the trial results.  I have argued for a while that this might be the case but of course, I'm not a technician and always have a large reserve of self doubt.  

So far as the double dosing....it doesn't come close to what Telaprevir provided in Prove 3 (41% non responder, 72% relapser, 52% aggregate 12 week SVR).  You know what I think; numbers talk.  Could they wring higher SVR rates with the use of rescue drugs and improved rash control?  I think so.

In a way.....I'm sorry that I brought this up since I don't intend to worry people into thinking about resistant virii.  I think that the numbers prove that TVR IS working on groups that they hadn't expected much of a response.  That's a GOOD THING.  In that regard I am glad that I digressed a little with this mornings wanderings.

I was just trying to break it down so that Magnum could see his options and ramifications better.  I also wanted him to lay it out to his doctor so that if they had any issues that Magnum could have the full benefit of his advice.

Dragon Slayer; thanks for the great e-mail article.  This is one of those things that IF you were to post an article about what people thought a year or two ago it would fly in the face of what we are now seeing.  This is a better result than the pros expected, I think.  It's great to have some "INK" on the topic so people can read it from a creditable source.  It's much appreciated.

Eric, you are probably aware that I've had even overly optimistic expectations for this compound to the point of annoying people.  : )    I also thought of your experience with treatments as a sort of proof that this compound was going to do great things....and it did.   ; )

OK.... I'm going outside.   It's a beautiful summer night.     : )

Thanks to all for the comments, feedback and information and I hope that it helps people considering the trials.

Best,
Willy

[kickboxingmom]

Sending Prayers your way for you to Fight this with all you have...Positive thoughts=Positive Reactions !

[DragonSlayer45]

You are welcome. I just thought it was uncanny that I had just read the article then went online and one of the first posts I saw was talking about that. I also agree with your assessment of conventional wisdom on this disease. Since it is a realively new disease they are learning as they go along. Yesterdays thinking is being proven to be not as accurate as it used to be.

One more thing to keep in mind for everyone. Keep learning and sharing this kind of valuable information as we get it. Do not blindly follow any doctors or Nurses advice when treating or deciding to treat. In the trial I am in my trial coordinator was concerned with my cholesterol going up and mentioned it to the PA (Dr. was out of country). The PA told her that it is not a side effect of the treatment. When  the trial coordinator told me this, I politely told her the PA was mistaken and it is a side effect. I then went to work adn emailed her an article from the Journal of Gastroenterology and Hepatology that said exactly what I was talking about and how somepatients cholesterol has risen as high as 1000 while treating. All I can do is shake my head as this is a PA who works for one of the world renown hepatitis C dr's. this type of thing has happened to me before as well. My last Dr. I had has a PA who runs all of his trials and when I asked her about the telaprevir trial she said there is no such trial. I then sent her the link for it and she responded Oh we are participating in that trial. That is when I began looking for another Dr. Obviously people like us have a vested interest in all of this but I still find it disturbing that people do not know their job and can spout bogus information to patients. Like I said we all need to do our homework and don't be afraid to question things. The experts are not infallible and they are still learning as they go along.

[DragonSlayer45]

Correction the above post should have read "We are NOT participating in that trial" Sorry sometimes brain moves on before typing can catch up LOL

[Andiamo1]

I second Elaine's comment!

Eric

[Willy50]

The article that DragonSlayer posted is really about the best possible thing that you could expect.  The problem is that faulty data leads to faulty theories.  IF one doesn't know EXACTLY when people clear or rebound and the EXACT dosing that they've been doing one does not have a accurate model to draw conclusions from.

The data From Prove 1 and Prove 2 provided a group of people on SOC that had that EXACT information.  They had numerous PCR's and dosing diaries.  They had an excellent record of the people who failed SOC......and then they had the EXACT same people who failed in various ways (non-response, null-response, slow response, breakthrough, relapse), and then they put them on Telaprevir and recorded the response.  It can't have been fun failing TX and having to treat again, but these people who did so provided some cutting edge information...... that might have been as or more shocking than the response rates of the naives in Prove 1 and 2.  I mean, the naives were expected to respond with a decent SVR rate.  The treatment failures...... I don't think that this kind of response was expected.  Look at the group of relapsers who re-treated.......72% 12 week SVR rate!!!!  That is a higher rate than experienced by Prove 1 and Prove 2.  I think that you maybe able to infer that the Phase 3 trials may also see increased SVR rates due to improved rash and sides management.  Think what could happen if they also add rescue drugs.   In any case....the information provided from the trials has undercut conventional thought on response in past treatment failures.  That doesn't mean that IFN resistance doesn't exist, but it may be less of a factor than was previously thought when treating with Telaprevir.

Vertex is keeping pretty mum on VX500, but I would also hope that if they thought it prudent to advance the new compound that they must have even higher hopes for it.  Here's a happy thought; approval of telaprevir.  When VX-500 is going thru trials triple therapy will be the new SOC.  Even if you draw a control arm you'll be on a great arm in a trial (by todays standards).

Thanks for the kind words.  Just remember that I'm rather haltingly trying to describe the current state of what's going on. I could sure be incorrect in a few, more than a few areas, and that even some pros are only now getting up to speed on some of the ramifications of the response in this trial.  This is all an area where what is "known" is dynamic, and changing with every new bit of data that comes out.  I'd be greatly surprised if I'm right on the money about everything.  Overall though...things are looking better and better.

best,
Willy