Telaprevir plus Pegylated Interferon Is Effective against Both Wild-type and Drug-resistant HCV Strains

[JRenquist]

Did you see this?  It was posted on the Vertex message board. http://www.hivandhepatitis.com/hep_c/news/2007/081707_a.html

[debnevada]

Forgive me for pulling you back to HCV101 but i have wild type genotype 4.  How does that differ?

Deb

[mremeet]

Yeah I saw it. The headline on this news update is just a wee bit disengenous on Vertex's behalf.  They say: “In patients given telaprevir alone, viral rebound can result from the selection of variants with greater fitness. However, the combination of telaprevir and pegylated interferon alpha-2a inhibited both wild-type and resistant variants.”

Ummm, yeah. Maybe that's technically true during the earliest phase of clearance, but from what we've seen of every single patient who frequents this forum and only received Telaprevir+IFN, effectively it isn't true. All patients that received Telaprevir+IFN here alone (i.e. without ribavirin) eventually rebounded/relapsed. Every one, although I think travelmom's daughter might be bucking that trend (hopefully). When telaprevir is dosed as monotherapy, like most PI's it kicks butt for about 2 weeks and then the virus rebounds with a vengeance right back to baseline values after that. When IFN is added to the mix, the typical profile is (1) strong initial viral decay, (2) UND levels are either approached or achieved by ~4 weeks, (3) then the initial strong antiviral effectiveness of the two drugs starts to peter out and the VL is seen to flutter around low detectable and UND levels, and finally (4) there's either a clear rebound prior to stopping therapy or there's a relapse after stopping the drugs. This is the response profile from all of the "Provers" I know of that did not receive ribavirin. So for vertex to try and color/report/represent their results in a manner to suggest or imply there's any real hope, optimism or utility in using telaprevir with IFN alone is pretty much absurd. (notice how the abstract says nothing whatsoever about what actually happened to the ribaless patients)

Clearly, the VX loses its oomph within a month after taking it with IFN alone. Clearly, there are telaprevir resistant variants alive and well in those who only received IFN+telaprevir. Clearly, those people will be saddled with some vestige of telaprevir resistant variants after taking IFN+VX for a few weeks or months (after relapsing/rebounding and stopping). So for this report to imply that telaprevir still handles "drug resistant" variants when dosed with IFN alone, or to imply this may be a fruitful treatment option for those who cannot tolerate ribavirin is, effectively speaking, BS.

[JRenquist]

I was mainly looking at the last paragraph, as I have genotype 1.

In the present study, they noted, “every patient who began pegylated interferon alpha-2a and ribavirin after the 14-day [telaprevir] dosing period had undetectable HCV RNA levels at 24 weeks, indicating that telaprevir-resistant variants are sensitive to pegylated interferon alpha-2a and ribavirin.”


But- what I think they are saying is that most of the virus is done away with by a certain type of drugs  (for instance ,the interferons) but  the virus also pretty easily mutates and the mutations are resistant to that same type of drugs. The mutation, though,  is not resistant to a different type of drug (for instance , a PI like Telepevir)  and the other type of drug can get rid of the mutations.  With the triple therapy, an antiviral (like ribavirin) could go in and mop up the few that escaped.  I'm not sure if that's right or that it would hold for genotype 4 as well - maybe someone here can explain it- but I think that's the gist of it.  

I just liked the "every patient " bit.  Yaaay.

[JRenquist]

Yeah, they do dance around the points you bring up, but it does say the successful results were for those who had the triple therapy. It really sucks for anyone who had just interferon and teleprevir though - seems like they are left with just the resistant viruses? Don't burst my bubble too badly - please?

[JRenquist]

Sorry - it took me so long to write my comment that you already had gotten the answer before I posted mine.  S.

[mremeet]

I wasn't trying to burst your bubble. Why would the knowledge that IFN+telaprevir alone is largely ineffective in most patients? The same isn't true at all as long as ribavirin is in the mix. Were hoping this report was suggestive that effective antiviral therapy is possible with only telaprevir and IFN? Are you intolerant to ribavirin? Is that it? If so, sorry to hear it. I know travelmom and others have the same problem. Personally I cant stand what riba did to me, but I love what it did for me.

[JRenquist]

No - I've done the ribavirin and interferon a few years ago - didn't work.  Ribavirin is just so disgusting- horrible rash  and they had to keep changing the dose because of anemia.  I guess now you can get procrit so the anemia isn't so bad.  Now that I've mostly forgotten what an awful year it was, I'd be willing to try about anything that would work. Be nice if it wasn't something that completely debilitated me, though.  I've just started reading here- it's very inspirational how some of the people here cope with therapy.  I had to take a leave from my job last time. Maybe because you all have each other? S.

[ladywhy]

I'm into (I think) 25th week of tx. It certainly hasn't been easy. This forum has made it tolerable for me though. It's helpful to know that others understand what you're going through and that you're not alone....
i hope you have an easier time of it on the 2nd go 'round and this time you reach "UND".
Y

[mremeet]

Well, with any luck the next time you do treatment you'll have access to both telaprevir and procrit/neupogen. If you do, the good news is that the treatment duration should be cut in half with a much improved chance of treatment success. Especially if you maintain full dosage of all drugs during treatment (which should last about 24 weeks, instead of the dreaded 48 or more). And yes this forum is very helpful to anyone going through treatment, especially through clinical trials (which I just wrapped up a few months ago). Best of luck on your next go around, whenever that may be.

[mary55]

We can't jump to conclusuions yet. As you know I'm in the "C" arm of the study. I have been off the Telaprevir for 6 weeks now and all indications are that I may be clear. I'm still going back for bloodwork. I was told if  you have a viral breakthrough then you are done. Not so in my case. I may have only done 12 weeks but who knows.....in the mean time I will remain calm and wait till the 1st of Oct to get all the anticipated paper work.

Mary

[JRenquist]

Thanks - did the trial work for you?

[mremeet]

jr - I don't know if the trial worked for me just yet. I was in an early VX950 (or "telaprevir") trial and experienced a bad rash that forced me to stop the drug early (continued on with IFN+riba though). I have remained UND since late August of last year. My last PCR was at 6 weeks post tx and remained UND. Odds are that I've made it to SVR, but that wont be conclusive until my 6 month post tx. I go in next Friday for my 12 week post tx PCR. If that one's still UND, I'll start feeling real confident the treatment worked. Physically and emotionally I'm feeling great since stopping the drugs. I don't want to count my chickens yet, but I'm thinking there is light at the end of the tunnel. Even though I got a bad rash, I'm very grateful to have had access to telaprevir when I did.

mary - I'm not trying to jump to conclusions concerning ribaless performance of the test participants we've seen here. Simply reporting what we've been seeing, that's all. I've also heard that Vertex reps have been conceding that the treatment requires ribavirin and is not feasible (under most circumstances) without it. I'm sorry I don't recally offhand what group C is...is that the ribaless group? If so, I wasn't trying to be disparaging or discouraging to folks like you. But da facts is da facts, and the facts right now very strongly suggest that ribavirin is required for any real chance of getting rid of the bug. Also, remember that IFN alone has the capacity to cure about 1 in 5 patients (depending on what stat you want to use). And I know you experienced the god awful VX rash like I did, which implies a strong immune reaction. It is my opinion that those with allergies, pre-existing autoimmune conditions and those who react with very strong immune responses when confronted with IFN/riba and possibly a protease inhibitor (like telaprevir) are generally more likely to wipe the virus out in a much shorter period of time. I don't have proof of that, but I still believe it is likely to be true. Anyway, hoping the best for you whether you received ribavirin during your abbreviated treatment cycle or not.

[mary55]

I'm so puzzled by the whole experience. No offence taken. I was not receiving any riba in my study. It all sounds too good to be true. In my heart I don't think I cleared, but on the other hand my nurse and Dr are optimistic. I can't believe how calm I have been......I'm just going to wait it out until Oct and if I'm clear........BONUS!!!

[VXman]

I like your attitude!

[susan400]

Mary,

I, too, was in Group C.   My Dr.'s at Mayo told me that I'd had viral breakthrough.  I, have had to come back to the clinic, but just for the follow-up (normal trial protocol), lab blood work.  They've never implied to me that there was any chance that I've cleared.  I was told quite simply at week 5, "stop the treatment, you've had viral breakthrough", end of my hope for the clearance, as far as I've been told.  Your case may be a totally different situation, but this is what happened with me.  Also, since I was in group C, I was told that there isn't any 'rollover' option.  I am not sure really, if different clinic are told different things by Vertex, or if the different clinics have their own interpretation of what Vertex has told them.  After being off the trial now for over 5 weeks, I've had a chance to look back at my experience.  I've pretty much decided that I don't want to do the VX again.  I didn't like the whole rash experience at all.  It was worse for me than anything I've ever had to experience with the Interferons or the Ribavirin.  I am now contemplating either maintenance or Albuferon, ....I think.  Not real sure about that even.  I'm sort of discouraged about it all.   I know I'll probably get over it and I'll probably, knowing me, try again with something.  Good luck to you in whatever decision you make.

Susan

[mary55]

I was told there is no roll over for the C group as well. I did 12 weeks but was taken off due to severe rashes covering my whole body. When it traveled into my mouth I knew I was done. I'm still on Prednisone. Out of 4 treatments this was the worst but nothing comared to what you have been through. This whole ordeal is quite puzzeling to me because I really don't know if I am clear. I have been told that if I had a viral breakthrough then I would not be going back for more bloodwork. One thing we do know is that the drugs did work on me, I just cant take them! I won't second guess at this point and will be patient and wait for the results in Oct. Now that I'm feeling better I ready for round 5. Lets get this done! One thing for sure is that if I do this treatment again I will only do it if I am offered  all three drugs.