Recently disclosed VX-950 side effect profile info...

[mremeet]

During my last doctor visit I was given a revised VX-950 (telaprevir) consent form to review and sign. In the new form they had included some new information in regards to the observed side effects of teleprevir. I’ll excerpt the new/salient stuff here:

Blood Sampling: “If you already had a rash or if you develop a rash while on this study, one of the blood samples that have been collected will be used to look at certain genes in your immune cells. The samples will be used to see if there are changes in the genes that determine how these cells function. Certain enzymes that are involved in breaking down the drug will also be looked at to see if they have changed. Differences in these genes and enzymes may cause some people to have a higher risk of developing a skin rash.”

Potential risks based on clinical studies: “Skin rash appears to be the most common side effect associated with telaprevir. About 34% of study subjects receiving telaprevir in combination with pegylated interferon and ribavirin for up to 3 months experienced rash. This is compared to about 15% of those who received pegylated interferon and ribavirin alone. Most rashes have been mild to moderate in intensity. Up to 3% of subjects have experienced severe rash. Some of the subjects with severe rash have also had swelling, swollen lymph nodes or fever. Many of the rashes have been associated with itching. The rashes have resolved following discontinuation of the study medications and treatments applied to the skin or taken orally.”
(cont…)

[mremeet]

"Other side effects that may have been associated with telaprevir given in combination with pegylated interferon and ribavirin include low red blood cell count (anemia) requiring discontinuation of the study medications, gastrointestinal problems (nausea 36%, diarrhea 23%, vomiting 12% and hemorrhoids 10%). Each of these events also occurred in subjects treated with pegylated interferon and ribavirin without telaprevir, but in about 10% fewer subjects. Most of the gastrointestinal events have been mild or moderate in intensity."

"Additional uncommon but serious side effects occurring in people taking telaprevir in combination with pegylated interferon and ribavirin included anxiety, mood disorder, itching skin, eye problems, heart attack and mass in a gland in the abdomen found on a CT scan."

"Additional side effects that were reported by more than 10% of subjects in the study included fatigue, flu-like illness, redness at the Peg-IFN injection site, fever, chills, general rain (ed note: “rain” probably means “pain”), dizziness, insomnia, joint pain and muscle aches."

Potential Risks Based on Non- Clinical Studies: "Studies to look at the safety of telaprevir have also been done in laboratory tests and in animals. Some of the lab tests on a type of mouse cells done using a mixture of telaprevir and related substances showed that damage to the genetic material of cells could occur. Pure telaprevir, the drug that is used for human studies has been re-tested in these same tests and has not shown genetic damages."

"In one study, rats in the higher dose groups, there were signs of damage to the testicles that included low sperm production and smaller and softer testicles. This was not seen in similar studies in dogs. Other tests showed that telaprevir may interfere with sex hormone receptors in rats but not in humans. Laboratory tests (inhibin B) to examine for changes in testicular function in humans have not shown adverse effects, but men in this study will continue to be studied."

[Tallahassee]

Thank you!!!

[friole]

Very kind of you to share that with us.  I have added it to the Vertex word file I am compiling in the event I treat with it at some later date.
frijole

[Imagine]

mremeet - Thanks for the information. It sounds like most of the sides are the same as "standard combo" with the exception of the rash which happens twice as much with the telaprevir added. It's not clear to me if the other sides are more intensified or not.

I do wish they would have listed either the number or percentage of "Additional uncommon but serious side effects occurring in people taking telaprevir in combination with pegylated interferon and ribavirin included anxiety, mood disorder, itching skin, eye problems, heart attack and mass in a gland in the abdomen found on a CT scan."

Some of these are associated with standard combo as well.
Was it one heart attack? What gland in the abdomen and what kind of mass? Was this only one case?

I know you don't have the answers but I am just curious. It's difficult to distinguish what sides are introduced by just the telaprevir.

frijole - I believe you and I are in similar situations. Are you going to try and get in on the phase3 trials?

[Imagine]

The gene study is another potential difference between the two treatments as well. It will be interesting to see what those findings are. It could possible lead to an alleviation of the rash sides.

[Imagine]

LOL, LOL, I have no idea where I came up with frijole!!!!!
I am so sorry :)

[chcnme]

Thanks so much for that.

Just thinking out loud - dont hve not much time - wanted to ask you (if you don't mind me asking)  what did you think about it?  You don't have to answer, of course.

I wonder if this rash (and their studying the genetics and immune system behind the rash, and their mention of "damage to the genetic material of cells"  in the nonclinical studies) is going to mean that they are going to try to identify those who will have severe reactions.  34% on the rash is pretty high.  

On the damage to genetic material of cells (in the nonclinical study) I was glad to see it was not seen with "pure" teleprevir in humans (bet you were,too :)

On the sperm count and sex hormone receptors, wow - gonna have to wait and see.

Very interesting.  Thanks a lot for sharing that.

Here's something I read on VX-950 last night

VERTEX NEARS HIT OR MISS
http://tinyurl.com/37upmh

[APKhaos]

Seems to me that Vertex have done the right thing here. They have included all the information gathered during the trial into the consent so that subjects are fully informed with the most recent verified information. It certainly paints a clearer picture of potential sides with combo SOC + VX950.

There is more in the revised consent that mre chose to ignore. This includes:

- Group D subject who discontinue early for reasons other than non-responding will be given RNA follow-up tests and viral sequencing after completing telaprevir dosing.

- Group C or D subjects who relapse after the study dosing and are given off-study SOC treatment will also have RNA testing provided by the study during the off-study SOC. [The trial pays for the SOC drugs AND the SOC RNA assay]

- In cases where rash is present, the study will include gene analysis designed to detect any changes in the genes associated with the immune cell genes, and enzyme analysis to detect any changes. They are looking for any sign of a patway that is causing a higher risk of rash.

These changes to the study appear designed to do two things:
- To identify and inform subjects of new iformation on sides gathered during the inital period of the trial
- To include additional lab analysis designed to indentify the source of the most significant sides, and to provide follow-up PCR free fo charge for subjects who quit before finishing the full treatment.

Just providing some balance to mre's Chicken Little cherry picking of the revised study design. Lets try to be objective, shall we?  

[Imagine]

Very interesting article chcnme. I found the following of special interest to me.

"Vertex believes that the data generated by PROVE 1 and its sister trial in Europe, if positive, will be enough to form the basis of an approval filing with the Food and Drug Administration in the middle of 2008. The company does plan on running a phase III trial, starting in the second half of 2007, to add to the drug's safety database.

If Vertex can hold to this aggressive time line, telaprevir could be on the market by early 2009."

It confirmed the phaseIII trial projection for the second half of 07. I was starting to think I had dreamed this.

I also wonder about the following statement in the aricle

" A higher-than-anticipated dropout rate due to toxicity was also a bit unexpected, raising concerns that telaprevir, despite its high efficacy, might have safety issues. Specifically, some anecdotal reports of severe skin rash in patients taking telaprevir raised alarm bells on Wall Street, although Vertex has vehemently denied that any such problems exist.

I don't think Vertex has denied this or have they?

[mremeet]

Hey ch, sure I can comment on what I think of the revised information. It's about what I expected, when pds's and my rash deal was in full flower, there was a lot of debate on this forum about what was causing it. Mostly because none of us really knew for sure what was causing it at first, especially because we were blinded and didn't even know if we were getting VX or placebo and because IFN/riba are also known for causing rash too. But as things evolved it became clearer and clearer the rash was being caused by the VX. There were a few folks here that just obstinately refused to acknowledge in any way that it was being caused by VX, some of which had mixed motives, including financial interests (i.e stock ticker=VRTX). APK was one of these "foo fooers", and as you can see my post disclosing this information has caused him to respond above with some sort of lame, illogical retort implying I've deliberately withheld positive information in order to make Vertex look bad (because I've got it out for vertex, you see). Meanwhile, APK had the cited information before I did (as he always does because of his "early" start date, right APK? ;-) And APK deliberately chose to withhold the side effect information I've posted above from ya'll for some strange reason (but I'll deal with his bogus post seperately later). As you can imagine those people really irritated me at the time, so in a way it's good to be vindicated by it finally coming out that VX does have a significant incidence of rash (and I had guessed about 1/3 would get a rash before; looks like that was a very good guesstimation).

But of course, none of those stupid arguments matter now and I think it's unfortunate that the incidence of rash is that high, I was really hoping it would be much lower than that and that PDS and myself would turn out to be "rash freaks" that just happened to be clustered at the same study center. And even though a 1/3 rash rate is still in the minority, when you're one of the ones in the minority the fact that the remaining 2/3 don't get the rash doesn't help you much (or alleviate your misery). Kinda like when people say the unemployment rate is only 4.5% and how great that is. Yeah it is great, unless you're one of the 4.5 "percenters" that's out of a job! ;-)

On the other hand, these rashes occurred while taking both IFN and ribavirin. I'm hoping that the rate/severity of the rash will diminish and/or the time to onset will be delayed if ribavirin can be eliminated. I was always suspicious the ribavirin was contributing to my VX rash, as I've retained sensitive, blotchy and itchy skin to this day (months after stopping VX). I've modulated my riba dose up and down, and there is no doubt it aggravates my skin all by its lonesome. Although there was already an Englishman here (dointime) that apparently had a VX rash while only taking IFN along with the VX (i.e. no riba). So we'll see what pans out of the non-riba arm later I suppose.

In general though, I remain convinced and very optimistic that VX950 can offer excellent utility for the vast majority of those who have geno 1 HCV (when dosed in combination with at least IFN). As they stated in the revised consent form, they're trying to isolate exactly what enzymes are indicative of a patient that may be vulnerable up front, or might develop a vulnerability to the rash during treatment (as occurred with me and pds). And presumably this could mean they can find out if you're vulnerable to the rash prior to starting treatment. And if you are, they can watch carefully for its onset and perhaps even have some idea of when its likely to occur; especially with ongoing blood monitoring while taking the VX/IFN/riba. If they were able to do this, both myself and PDS could have been spared our whole rash drama-fest. We could have simply discontinued the VX just as our rash was first developing, because we would know what it was ahead of time and that we were likely to get it in the first place. Furthermore, all of the nasty immunosuppressants (prednisone/solumedrol) could have been avoided as well, removing what would be strongly contraindicated drugs during antiviral therapy (thereby further increasing your odds of achieving SVR). If it had played out this way for both of us, we still would have derived an outstanding benefit from the VX950, because by that time it had long since caused the virus to become UND anyway. It had already done the heavy lifting by delivering us our RVR's. And all of this is very significant for everyone else in my view, because both me and pds were near worst case scenarios. I seriously doubt there were many people that were worse off than we were. So that means only a very small percentage are likely to be excluded from being able to use VX950 altogether. Most will be able to take it for 3 or more months, and of those that will get a rash, most of them can still get 1-2 months of use out of the drug prior to its onset. So that should make the drug very useful to almost everyone - which obviously is a great thing!

Lastly, as far as the "soft shrunken testicles" part? Umm, let's just say I'm just keeping a wary and watchful eye on that situation. ;-)

[mremeet]

I don't know if Vertex denied the "rash rumors" or not. They probably did in some capacity. I noticed that when I had my rash, as far as I could see my study nurse always recorded it as "moderate" in my side effect journal, even after it had gotten much worse. Lets just say I've been getting an education on what pds rightfully called "the soft underbelly" of clinical trials. And also, in case you're interested, the "anecdotal" reports that Wall Street were/are worried about came largely from yours truly (and others) on this very site. All sorts of financially interested parties from Vertex to a zillion stock trader websites are tracking how VX950 is doing based on what we say here. That's also why a few folks here were so intensely and persistently dismissive of my initial/early claims that VX was causing the rash.

[Humble1]

I missed that trial-too many people in line.
How often do you have to come into the office and what exactly do they do to you on each visit?

[mremeet]

I'm assuming after reading your post that you feel I've unfairly characterized the bulk of the revisions in the latest consent form? Or you feel I've deliberately left out salient contextual information that favorably demonstrates telaprevir's performance? Presumably because you feel I "have it out for vertex"? Is that it? Because if so, that's just silly and patently false, I've done no such thing. And I'll be happy to respond to every one of your "points" to handily demonstrate that fact right now.

First off, I didn't make up any of the newly provided information above. It's information that was disclosed to me (and you) directly from Vertex, it's not secret, it's not lies, and it simply provides an ongoing update to the observed side effects and risks. It has been quoted precisely verbatim straight from the consent form. And it's information that is both new and not available anywhere else (that I'm aware of). If you don't like this information, or don't want to read it, or don't want others to read it...well, that's just too bad, isn't it? You should take your objections up with Vertex and the FDA - maybe they can censor your next consent form for you so you don't have to read anymore about your "soft testicles"? Secondly, the information I posted is meaningful to the prospective patients on this forum who are watching telaprevir and are very interested in the likelihood that it may be able to help them in the near future (especially the non-responders/relapsers who have significant fibrosis). Obviously a person in that position would be very interested in the latest disclosed information concerning risks, observed side effects and what is being done to ameliorate/counter those side effects. These factors also help to define how likely the drug is to gain FDA approval, yet another critical factor of interest to everyone waiting on this drug. The selective excerpted text I provided above provides just that very information.

As to your post and what you imply/claim I left out in an attempt to claim "the sky is falling"? Well, lets see what you've said here:

"Seems to me that Vertex have done the right thing here. They have included all the information gathered during the trial into the consent so that subjects are fully informed with the most recent verified information."

Vertex has the done the right thing here, who said they haven't? Oh I get it, what you mean is that Vertex shared this information with us purely out of the goodness of their own heart and NOT because they're legally required to disclose this information as dictated by the FDA? Is that it??

"It certainly paints a clearer picture of potential sides with combo SOC + VX950."

It certainly does, and that's precisely why I posted it - and your point is??

"There is more in the revised consent that mre chose to ignore. This includes:

- Group D subject who discontinue early for reasons other than non-responding will be given RNA follow-up tests and viral sequencing after completing telaprevir dosing."

Yeah, I chose to ignore this part. I left it out because I didn't think it was meaningful in the slightest to prospective patients looking for the latest info on telaprevir's effectiveness and side effect profile. And the reason for that is because it has absolutely *nothing* to do with telaprevir's effectiveness, nor side effect profile, nor likelihood to meet with FDA approval. You DO see that, right? Oh, and I also left it out because I didn't feel like typing/transcribing anymore than necessary (hope you don't mind?). Especially something that amounts to superfluous ****. But I can certainly see where you would think of someone as being a "chicken little" for omitting this devastatingly positive/significant information that Vertex has decided to continue to PCR test a participant after stopping early. Wait...no, actually I can't see that.

And incidentally I notice you're not actually quoting the text from the consent form. You don't disclose that in your post. You've actually streamlined and condensed your "quoted" excerpts, and intermingled your own bolstering verbiage without identifying it as such. That's a no no, don't you know that? Always best to meticulously quote with " " marks and quote precisely so people know they're reading exactly what was said and can distinguish where the author's "supplemental" content begins and the cited text ends. (as demonstrated in my original post) They teach you stuff like this in college. You went to college, right?

"- Group C or D subjects who relapse after the study dosing and are given off-study SOC treatment will also have RNA testing provided by the study during the off-study SOC. [The trial pays for the SOC drugs AND the SOC RNA assay]"

So what? This is nothing new and has been discussed many times here on this forum before. Plus, yet again, it has nothing to do with the side effect profile, risks and likelihood of FDA approval. And aside from that, you make it sound as if Vertex is being exceptionally benevolent by providing "free" RNA assays. Doesn't Vertex benefit from this data? Doesn't Vertex stand to make billions from this data? Aren't we test participants risking our life and limb by being the first to take substantial quantities of this experimental drug? It's a two way street here kilroy, don't make it sound like it isn't. And incidentally, although I'm almost certain follow up SOC and testing is free, how do you KNOW the RNA assays are all free based on your "quoted" excerpt above? It doesn't say that in the consent form under the section you're referencing.

"- In cases where rash is present, the study will include gene analysis designed to detect any changes in the genes associated with the immune cell genes, and enzyme analysis to detect any changes. They are looking for any sign of a patway that is causing a higher risk of rash."

Are you suggesting I haven't included this part in my original post??? Try reading it again maestro, because I've quoted everything precisely verbatim concerning this "excerpt" of yours. And once again, you're not quoting the text verbatim, you've condensed it and included your own interpretation without disclosing what part that is. I've included the entire verbatim text in context above - so your point here is?? I'm a "chicken little" because??

"These changes to the study appear designed to do two things:
- To identify and inform subjects of new iformation on sides gathered during the inital period of the trial
- To include additional lab analysis designed to indentify the source of the most significant sides, and to provide follow-up PCR free fo charge for subjects who quit before finishing the full treatment."

Once again you're making it appear as if this is an excerpt from the revised consent form. It isn't, it's APK personal comments. Also, once again the "free of charge" PCR's are not acts of selfless benevolence (nor are pertinent to side effects/FDA approval etc). This change/edit was made in response to some of the discussions they have been monitoring here. Specifically, my posts discussing how absurd it would be for Vertex to not track participants who dropped out of the trial due to adverse sides prior to completing their full (scheduled) course. After reading that potential scenario here (cited by me), they realized they had left out that contingency in the consent form and have subsequently added it in for that reason. So you can thank me for that addition APK, and Vertex (I know you're reading this), you're welcome. ;-)

"Just providing some balance to mre's Chicken Little cherry picking of the revised study design. Lets try to be objective, shall we?"

Oh yeah, you've really cleared everything up for us APK, thanks for that. And I'm real sorry to "cherry pick" only the meaningful information that people are actually *interested in* AND quoted it perfectly and completely. The stuff you added about PCR testing after stopping treatment has certainly "balanced" this grave situation. And you're so right, we all should strive for maximum objectivity at all times - thank goodness we have you as an example of that, huh??

Speaking of which, considering you've been silently sitting on this revised consent form which has all these latest, greatest, juiciest details regarding the trial results - why didn't YOU mention it?? Why didn't you explain/cite/quote what this new information was to everyone? That's damned curious that you didn't, but you sure have a keen interest in it now though, don't you? Is that an example of the "balance" and "objectivity" that you refer to above?

And one more thing APK - what was your EOT date again? Have you decided which one you're going to use from now on? Just thought I'd ask so I can scratch out the dates you're no longer using.

C20,21,22 http://www.medhelp.org/forums/hepatitis/messages/44838.html

[mremeet]

You forgot to include the part about 34% rash and the 9% discontinuation rate within the first 12 weeks (i.e. triple that of SOC).

And you should be thanking me a$$. I went through the trouble of tediously transcribing this information for the specific benefit of someone just like you. You can't take IFN anymore, so you're critically dependent on the development of drugs just like this. I'm assuming someone like you would really like to know just what's going on with this drug and how long it might take to come to market. If I'm  wrong about that and you're actually not interested, then by all means feel free to exercise your right to SKIP IT.

[chcnme]

uh... I'm uh.... uh .... just sitting here after reading Fignavomik's dissertation (or maybe it's a dairy diary.

Mremeet.  Sincerely - thank you.  

Has anyone heard there's an audition going on for the new American Badas** ?

http://www.youtube.com/watch?v=1TLr3xqIsmI

Hi Vertex : )

[Humble1]

Hi:

I'm really not up for a bunch of fighting. Is anyone here in the vx-950 non-responder trial? Can someone tell me about how often the office visits are, what tests they run, and what a patient's responsibilities might be?

Thanks

[Humble1]

Why not post the whole form and let everyone make their own conclusions or educate everyone instead of having this closed forum.

If you are truly posting for the good of everyone and not just to one up each other then post it all!