Disappointed in VX-950

As one who will not do the SOC as it stands now, and hoping for better meds I was somewhat dissappointed in Vertex's latest web cast. They made it perfectly clear that they thought peg and riba were the lead drugs and vx-950 was just an add on.

                                                              Ron

[FlGuy]

Even if vx goes on to be part of the peg/riba combo but proves to either enhance svr chances or to shorten treatment duration, it's better than a stick in the eye.

[Upbeat]

Agreed.  Still after all the hoopla a few years ago with the mono info and the huge log drops I was hoping for better.

                                                                                                        Ron

[cigaso]

No, it's not the "magic bullet" we were all hoping for, but as Flguy says at least we can attain evr/rvr and a shorter tx schedule. Cutting tx from 48 weeks and longer to 24 weeks will be a giant step. Maybe the second generation of PI's will have the answers.

[Upbeat]

If is a big word.  Vertex seems to be the masters of hype.  The proof will be in the pudding.  As with all drug companys they tend to bend the data to suit their needs. The phase 3 trials next year will give a clearer picture as far as the 24 weeks are concerned.  Strange protocal with 12 weeks of vx-950 followed with 12 od soc.

                                                                                                 Ron

[Jakied]

What is 'soc?'

[miked]

I'm in the Prove 3 trial.  Obviously don't know which arm yet

Arm B of the Prove 3 trial is just what your described; 12 weeks of VX950+RBV+INF followed by 12 weeks of SOC.  I think this arm makes the most sense and will become the standard.  Reason is 1a's 1b's are going UND very early (some as soon as 4 days; 15-21 days seems to be the norm for Prove i and Prove 2),  Then kill off the remaining virus with SOC.

VX950 is not without it'sides which is why I think it makes sense to use it for three months, get RVR then follow-up with INF + RBV.   BTW, I don think that the Ribaviren is still a necessary component along with the INF.  A Prove 2 guy named Nick who did 12 weeks of VX950 + INF but no RBV relapsed which support this theory (much to Nick's dissapointment).

The D Arm which is 48 weeks of VX950+INF+RBV to me is overkill.   A full year of a trial drug sounds like a lot but we'll all see what the optimum doseage, time and combinations of drugs are.

[miked]

SOC = Standard of Care.  For HCV that means interferon and ribavirin.

[nygirl7]

I wouldn't mind doing the full 48 of 950/Inf/riba if the odds were very, very good then that I'd be getting SVR.

To me - it's not how QUICKLY we can get there, but how great the chances are of how well we achieve and how many get SVR.

So far all we know if that it has great results creating rapid responders but what we don't know what the SVR odds are.

I'd root for the SVR odds over ANYTHING else.

And yes upbeat - the tremendous hype around the drug is something I"ve long ago learned to avoid. IT's all about making money after all and It's not the first magic bullet hopeful nor will it be the last.

But anything that helps us get SVR - sounds good to me.

I hope I don't need to use it but if I do, I'm glad it might be there.

[friole]

I am still encouraged, not depressed.  Like others have said - anything that may shorten the treatment is a good drug to me.  I guess I have resigned myself to the fact that this is just another add on.  

[andiamo]

I believe arm b is 24 weeks of 950, inf and riba followed by 24 weeks of inf and riba.

Arm d is 12 weeks of 950, inf and riba followed by 12 weeks of inf and riba.

I agree with nygirl, any improvement over SOC either in time on drugs or percentages of SVR is a very good thing.  I am in this for the 8th treatment and I think I am going to achieve svr for the first time!

The CEO of Vertex said that Riba was an important part of the mix and added to the svr rate even when the dropouts due to sides from riba were subtracted.  For first generation inhibitors it looks like it will be part of the mix.

[andiamo]

I should add that I did not get the impression they thought inf and riba were the lead drugs.  I had the impression they thought this would be a major improvement in SOC, and the first step in series of new drugs. The impression I got is that each drug played a major role in the "cure".

While I am also dissapointed that it is not a silver bullet.  I am very optimistic that it will receive FDA approval and will be a major improvement in treatment.

[susan400]

Riba is not a cure all either.  Riba alone does nothing for anybody and will not clear the virus.  I double dosed Riba along with daily Infergen 15mcg on my last round of treatment and at 44 weeks still had not obtained viral clearance.  So much for Riba being the magic bullet.  There is still hope for one who is on just the VX and Interferon.  You obviously cannot put everybody into a particular category with this virus and the treatment therein.  If that was the case, I would have cleared this by now and I AM working on my 8th treatment, remember?  I've done EVERYTHING humanly possible to get any time of even one lab report showing an undetected.  The best I've done so far is have one viral load erradicated.  I used to be tested as 1A/1B and now I'm just a 1A.  But, this long list of drugs:  Peg-Intron (more than once and also at double doses on one occasion), Pegasys (this is the 2nd time in this trial I'm in), Infergen 3 different times, Actimmune+Infergen and Riba (was one of those treatments), I've used the Thymosin (Zadaxin) before in the past.   None of these things have gotten me a viral clearance.  This is why I'm giving Prove 3 a chance.  I feel that I have nothing to lose really.  I'm getting excellent follow-up with my clinic and free labs and free drugs, and this all adds up in my book to a benefit for me.  Also, they need us lab rats, or those of you that follow would not get to know what the possible side effects are to us guinea pigs.  It's by them experimenting on us that you that follow, will get to have the benefit of correct dosing amounts and length of treatment.  So, don't be so quick to bash the VX trial and it's protocol.  It's research.  It's that what we all really want, answers, cures, SVR's?

Susan

[Forseegood]

I tend to agree with you, any improvement is an improvement...if it helps cut treatment times in half, I'm all for it...there saying that the ultimate treatment will have the PI's along with the other one's I cant spell at the moment, shorten treatment times and add many percentage points to SVR rates (had only a few hours sleep...)

[andiamo]

Get some rest!  

I take my shot on Monday so Tuesday is always my worst day.  I take a lorazapam on Monday night, so I get some sleep, but feel goofy and emotional on Tuesday.

[sunspot]

When will they tell you your VL? I'll send you good vibes on a UND.

[Upbeat]

Prove 3 is still phase 2b trials.  Phase 3 will start next year and then it will be determined if FDA will approve.  
                                                                                                       Ron
                                                                                                    

[GrandOak]

I don't believe anyone is bashing VX-950, it sounds to me like more are coming to realize that it's not the magic bullet or holy grail.  It amazes me how many hype it and go unchallenged, but let someone speak up to point out the truth that it may not be all that's it being hyped as and they immediately seem to be rebuked.

Not only is it yet another mix in the cocktail, but keep in mind that as such it also brings it's own set of sx's to the party too, not the least to mention is the nasty rash which some here experienced during their time in the trials!

The verdict also seems to be out as to whether it truly shortens tx as well.

None of the Protease or Polymerase meds I see being studied are doing much to find an alternative tx and from what I've seen all of them are only effective for a short period during the beginning of tx.  Mainly it would seem because viral mutation renders them ineffective within a short time.

I would also be curious to know what adding it to the mix means for those who fail to attain SVR?  Are the elligible to try tx again? Does it result in a viral mutation which makes SOC meds ineffective?

Will a shorter period make tx more bearable, that is the real question which it seems many of these trials are attempting to find out and not an alternative to tx?

It seems to early to tell if they will make SVR more attainable, particularily for those for whom regular tx fails.  If this was a goal, then it would seem that they would be interested in truly seeing those of us for whom tx has failed us and left us in the cold as far as viral eradication is concerned.  But then as unfortunate as it is, we may simply be acceptable casualties as far as the medical profession is concerned since we are all simply chart numbers to begin with.

[susan400]

You are entitled to your viewpoint....

Susan

[VXman]

The following interesting information posted In a publication last week at www.hcvadvocate.org,  

HEPATITIS JOURNAL REVIEW:
A Bi-Monthly Publication of the Hepatitis Support Project

June 15 , 2007
Volume 4, Issue 11

Resistance to Telaprevir

"One such directly targeted agent is the HCV NS34A protease inhibitor telaprevir (VX-950). Telaprevir demonstrates strong antiviral activity, but can lead to the emergence of drug-resistant virus, especially when used as monotherapy. As described in the May 2007 issue of Gastroenterology, C. Sarrazin and colleagues used a highly sensitive sequencing method to assess mutations in the NS3 protease catalytic domain in genotype 1 patients receiving various doses of telaprevir for 14 days. They identified several mutations that conferred low-level resistance (V36A/M, T54A, R155K/T, A156S) and high-level resistance (A156V/T, 36+155, 36+156) to the drug. After telaprevir was discontinued, most resistant variants were replaced by wild-type virus within 3-7 months.

[Forseegood]

I guess the way I look at it, it's an expectation thing...at first I was hoping it was a magic bullet (who wasn't?) but then I guess....oftentimes there's a glass of cold water that comes with high expectations...but even so, I'll take any improvement on a theme that I can get, even if all it indicates is a great promise of higher SVR rates, and shorter treatment times...though it comes with the old soc...

maybe the way it's panning out, they'll only give it to you at the beginning of treatment, to help clear it up fast...like someone said, better then a stick in the eye...

[web52]

im in prove 1 (12 weeks vx/inf/riba followed by another 36 weeks soc). last shot will be july 6. needless to say, it's been a difficult year. but, if i have increased my odds of svr to 80%, which i'm convinced the vx will do, it will have been worth it to me. data from the 6 month group should be out some time in september. hopefully 12 months of tx won't be necessary anymore, which is my hunch. i also have a hunch that riba will need to be in the mix. to me vx has been about increasing my odds for a "cure", plain & simple.

[VXman]

Elaine,

I didn't see your original text regarding the possible exclusion of ribavirin. In the PROVE 3 trial, there is an arm of the trial which is not blinded. This is Group C which does not include ribavirin. Perhaps this or one of the other PROVE trials is where you derived that information.

In PROVE 3, the Arms are as follows:

Group A. -  Control Group - Placebo/Peg/Copeg for 24-weeks, then, Peg/Copeg for an additional 24-weeks

Group B - Telaprevir/Peg/Copeg for 24-weeks, then, Peg/Copeg for an additional 24-weeks.

Group C - Telaprevir/Peg for 24-weeks (not blinded)

Group D - Telaprevir/Peg/Copeg for 12-weeks, then, PlaceboPeg/Copeg for an additional 12-weeks.

Take care,
Steve

[Willy50]

Back when I was first diagnosed there was talk of a PI called Biln 2061 that was expected to be the next great thing......or so it was hoped.  In spite of some promising results the compound was pulled from trials.  Fast forward about 3 plus years.  We now have a compound in Phase 2 trials (Vertex TVR) with some very positive results so far.  To be sure it isn't perfect but look at what we may soon see;

1)  A treatment duration that is cut about in half.  That means 24 weeks LESS of interferon and ribiviren treatment for most of us (unless we are some treatment failures who are facing 72 weeks of TX now).

2)  A treatment which may come close to doubling the SVR rate.  Even if it were only a 60% compared to todays 40ish percent for genotype 1"s....would that be so bad particularly when coupled with a shorter treatment?

3)  New hope for people who have taken treatment over and over and who have failed over and over.  These folks may be on the threshold of clearing or staying clear.  Something a bit stronger or that helps them clear a bit faster may indeed be just enough to get them to SVR this time.  It could save many, many lives.  Just a few days ago another one of us died who could not be cured with conventional treatment as it now stands.  An improved treatment a few years ago might have been a silver bullet for them and how many other heppers who have since died?

4) The webcast mentioned that TVR and interferon alone (no ribiviren arm Prove 2) did a better job of clearing the virus than existing SOC.  That also suggests that some people who CAN'T do ribiviren may also have some new hope for being cured.  They may not yet be done fiddling with the ribiviren; there could come a time where one ceased or tapered off without needing 24 straight weeks of it

5)  We may at some point see the results of new viral kinetics which might allow doctors to sort people into groups that determine the type and duration of treatment they need.  For instance if they can sort out the super responders they may be able to treat some people for less time than the 24 weeks.  Already they proved in Prove 1 that nearly 40% of those that RVR'ed (cleared by week 4 and maintained that status) SVR'ed.  They did this without ANY "rescue drugs".  This was only in Phase II trials.  Might they be able to improve that?  (I think and hope so.  : ) )

A silver bullet or miracle drug?  Perhaps not, but whatever drug, compound, treatment or protocol that comes along and helps is surely to be appreciated.  We've seen little snippets and great results from this drug trial.  There's been a lot of speculation and there will be for a while yet but by fall I believe there's another liver conference around October we may get the Prove 1 and 2 trial results.  We should also soon see the shape of the FDA approved Phase III trials if all goes well.  

I know that this is a "Vertex" thread but any of the new drugs that may be added to the mix won't just be "another drug" added to SOC.  It may be another additional 5 or 10% SVR rate added to what could become a tolerably successful and short(er) treatment.

I myself, have great hopes for this and other new drugs in the pipeline.  

Willy

[cruelworld]

i still see it as a silver bullet. i dont expect it to save everyone but i think it will clean up many hard to treat cases. i do have the highest of respect for
the lab rats who have to endure dead arms and no rescue drugs. from what i understand, there are scientists cracking the real code to make a vaccine.
when this day arrives i guess that 99% of us will be saved and the disease will disappear! the drug companies have determined they can make a ton on money on this deal. from what i can see they are all working pretty hard on it. i would bet that
in some lab somewhere is already a better silver bullet but needs more time to develope. unfortunately HCV is hard to crack but i predict progress to be exponential as this snowball keeps rolling. in my opinion, we are not being ignored and will soon (5 years or less) see spectacular progress.



hey, i forgot one more thing, your car just got stolen.

[Forseegood]

compelling post...

[jmjm530]

Haven't seen the webcast, but unless something has changed, Telaprevir still has the potential to cut treatment time in half with the double the SVR rates -- and if Willy's information is correct, it is more effective without ribavirin than SOC. What's more, Telaprevir's ability to induce RVR, may be the key for many prior non-responders -- all of course, to be confirmed when more study data arrives. I don't remember anyone here -- or anywhere -- claiming Telaprevir a "miracle" drug or "silver bullet", but certainly it appears to potentially offer a vast improvement over SOC.

-- Jim

[miked]

This has been a good discussion.  But in a way I question why we are having it?  

I agree with Willy50 that VX950 may not be the "take one pill and you'll be cured in the morning" but as a geno 1b probably infected over 25 years ago with one failed INF+RBV tx behind me; I'm liking these odds of in the 80's for geno 1s.

My personally is totally Type A.  On my first tx I remember researching and doing more research about what my odds are..."Let's see I'm a 1b, 3M VL, had it 25+ years, minimal scarring and inflamation (inflammation), caucasian, in my late 40's and in good shape....OK so my odds on RBV + Peg-Intron were like 41% and on Pegasys like 39%...if I decided to totally torture myself with up to 72 weeks my odds jumped to about the flip a coin (50%).  Or if I decided to really, really torture myself and improve my odds into the 60%+ range I could go on high doseage induction Infergen which a guy her named Magmun did; this poor guy could barely stand.

I decided to do the trial because I like the odds of 80+% for people with the really hard 1b geno.  

Over time I believe that they will keep fine tuning this thing.  Speculation only.... some combination of Albuferon as the interferon plus VX950 plus NM283 (a polymerase inhibitor) plus Statins, etc.  Also there's some bright work being done on HCV vaccines.

My kid has Cystic Fibrosis(CF), a genetic disaese (disease) that affects the lungs and pancrease.  We've been dealing his diagnosis for over 11 years.  At first I was all "hurry, hurry and cure this thing".  Over time I've learned patience, decided to raise money to fund the foundation researching new therapies to correct specific problems; hopefully a cure.  We've made significant progress with CF over he past 25 years but the progress has come in steps not leaps.


VXMAN...I haven't see you post before.  I too am week 7 of the Prove 3.  Keep in touch.

[couldn't think of a nickname]

Hi all, hope all are hanging in there, and well.

Almost a week ago, I posted in a VX thread that had a number of major mis-statements in it, and I think I can tie together what I said there, with the discussion in here-bear with me.

In that thread, there was discussion about how there was rampant insider selling, that they were "pounding" the stock, etc. However, none of that was close to reality. The problem lies with how things are reported, and how many misunderstand it. Conclusions on that are extrapolated to the drug, which is understandable to a point.

It is well-known that VRTX has a compensation plan where some can exercise (BUY) and sell options at a profit. Whether those plans are good or not is a whole other discussion. MOST of the transactions that people were pointing to were those. I saw a number that there were over 200k shares net sold. Not true. The lesson is, you MUST READ THE FORM 4'S!
In what I described above, the net effect is ZERO-not including a few other minor transactions. They buy, say, 1000, sell 1000. In fact, in that thread that I posted in, I showed that due to options awards, many of those people had MORE shares today, than they did 6 months ago. Options AWARDS are NOT BUYS, so they won't show up as that either.
I have seen some know this and use it to spin, I have seen many just not understand this at all. That's why I am correcting it, because many use that to draw conclusions on the drug.

MSFT, others, have been doing this for years. That in itself is not important. It is CHANGES IN INSIDER BEHAVIOR.
That apparently has happened at VRTX with Josh Boger. He discontinued his pre-planned exercise and sale program this year.
This month, he has exercised AND BOUGHT ONLY, NOT SOLD AS WAS HIS PRIOR PATTERN 21,100 shares this month.
He expressed frustration in the web call that more didn't recognize that it was a big deal the safety database doubled, with no new sides.
Coincidence? Not likely IMHO. He probably feels that the data makes the stock worth more than it is.

I don't like that we have to wait for meetings for real data and news. That's why the stock suffers, and he should know that (maybe he does). But, the info that he did give didn't surprise me one bit. Whenever I called and asked them, they ALWAYS told me that riba was likely going to be part of phase 3. They are looking for the fastest path to market. Other combos take longer and more money, and probably won't be kicked into gear until after.

I still will not take riba. I still think it is possible that in some they can cure in 12 weeks (6 out of 9 in earlier prove trial). I am disappointed that it will be stretched out for some, and then SOC will continue afterwards. I am not even sure if anyone knows if the latter is necessary, or for how long. Remember, it took many years before it was realized that geno 2 and 3 didn't need 48 weeks. Still a lot of unanswered questions.

In any event, this is JMHO. I have had issues at times with how they communicate, or in this case, the lack of it. I do not believe they have "spun" data though. The numbers are numbers, and they cannot change them.
Now, I just want to see more numbers, period.

miked, good post, and also, VRTX has drugs in phase 2 for CF with fast track status, and might get orphan drug status. Keep an eye on VX-770.

[miked]

Yep, we're tracking Vertex VX 770 as it moves into Phase II human trials.    I've post befrore that wouldn't it be ironic if the same company cured my son's Cystic Fibrosis and my HCV?

[couldn't think of a nickname]

That would certainly be something, and I hope for the best. I don't understand the CF area that well, but I hope sometime soon there could be some better info released on it.
There are so many illnesses that need better treatments, not only the areas mentioned, but MS, ALS, cancer, etc. That's why I like to follow biotechs, it can be uplifting when advancements are made.

[miked]

The problem with Cystic Fibrosis is that it's an "orphan" disease, meaning only 30,000 kids in the US have it.  The numbers are too low for drug companies to profit from a cure so they won't invest,  We work with the Cystic Fibrosis Foundation who funds promising research with companies until a viable drug compound is discovered.  They have funded Vertex over the past five years to screen compounds, identify and develop VX770.  If it's successful Vertex will be able to make a profit because we've funded the basic research and compound development.

It's really different watching the resources pour at HCV because there's 275M people with it.  Versus CF with 30,000 kids.

[dmhrdh]

I am in week 8 of Prove 3.  
I just want to say that the reason I come here is because of threads like this one.  THis has been a very interesting read.  Thanks for sharing all the great thoughts and observations everyone!

[Upbeat]

All I can say is Thanks!!!    Great post and outlook.

                                                                                                        Ron

[GrandOak]

Good post!

One concern I would have is for those who see VX as something more than it truely is and setting their hopes too high based on all the hype they see for it. The potential for emotional and mental distress would seem to be very precarious.

The other is the effect that hype'ing one possible medication can have upon the others due to the impact it can have upon the companies.  It certainly would be a shame to see other viable alternatives laid aside because the company redirects it's focus elsewhere, which certainly is a possibility if the all the hyperbola impacts their net worth.  Who knows, a true wonder drug could possible go undiscovered for this very reason.  So it would seem prudent to keep everything in a proper perspective and not go overboard because a light of promise is seen.

Also, if I'm not mistaken, I believe the research which may be yielding a sign of a possible vaccine by gaining a better understanding is actually coming from HIV and not HCV research.  I guess who cares where it comes from if it is indeed isolated, but I wonder how dilligently it is being pursued if HCV is not the primary focus of the research which may be uncovering it.

[VXman]

I am a new comer to the MedHelp forum and have found it to be very interesting and quite informative. There's nothing like an exchange of ideas and personal experiences that galvanize people with common issues.

Ironically, I came across this forum as a result of a Google search. I was curious as to whether there were any postings from someone commenting about the taste of a telaprevir tablet. Sure enough, there was a hit associated with this forum. With the double blinded nature of the PROVE3 trial, the interpretation of information is sparsely revealing at best. The only thing I knew with certainty was that I was not in Group C. This group does not receive ribavirin and is the only group that is not blinded. Why Vertex didn't design a placebo tablet for the ribavirin tablet, I don't know. Having received my medications on Day 1, which included ribavirin, it was clear that I was either in Group A, B, or D. What I wanted to find out is whether I was receiving a placebo for the telaprevir or the real thing. One of the individuals in this forum indicated that the telaprevir had a metallic taste. I was able to relate to that description, and began to feel somewhat confident that I was taking telaprevir. Unless Vertex purposely created a specific texture and taste in the placebo to mock the real thing, I deduced that I was in either Group B or D. I would go a step further in the description of the tablet. When placed on your tongue, the tablet immediately dissolves in thin layers that are stripped away from the tablet . It is a uniquely strange sensation that I have not experienced with any other medication. It also has a tendency of numbing your taste buds, if not swallowed in a timely manner. This is perhaps much more information than any of you would want.

I'm convinced now that I am on telaprevir because of the favorable minimum 1-log drop that I received after 4-weeks on the trial. There's no way as a previous non-responder to SOC, that I would have met this level of EVR. I barely made a 1-log drop after 12-weeks on Peg/Copeg treatment. What is interesting is that I may have approached ND after 4-weeks in the PROVE3 trial. They only tell you: A. You're still in,  B. You're out, or,  C. We need to perform another viral load test on you. Prior to the results, I felt like I was in American Idol.

A little trivia question for anyone out there. Why is telaprevir not capitalized?

Best wishes to all of you that are fighting to get this monkey off your back.

Steve

[miked]

Many people in the Prove 1, 2, 3 trials are tentative about posting any detailed information here because of the consent form that prohibits disclosing proprietary information.   Paranoid that Vertex is watching?   Maybe.

I too understand that I'm not in Arm C because I also am taking Ribavirin.  I thought it strange that Vertex wouldn't come up with a Ribavirin palacebo to make the trial totally blind.

There's been several posts about the taste thing.  For me the VX950 (or placebo) pills are bitter as hell.  One night while driving home on an extended road trip with no gas station in sight I decided to brave it and dry swallow two VX950 (or placebo) pills.....wow was that an ugly experience that I won't do again!  Lot's of people have reported the bitter taste thing.

There's a Prove 1 woman here who posted that her pills tasted sweet but when they unblinded her she was getting the real VX950; so go figure.

Last time I tx'd was with Peg-Intron (versus Pegasys with the Prove 3 trial) and Ribavirin and started about the same time of year.  One thing that's different this time is that I itch alot and am taking antihistamines and rubbing Gold Bond on 2-3 times per day.  Ir's not the crazy rash that some VXs's have reported, thank God, just sensitive to the sun and itchy.

If you are on week 7 watch postings from WC Missy.  She started right at the same time.

Good luck and keep in touch.

[willows]

My hat off to you, it can be so frustrating to try to discuss the "facts" sometimes, but you did a dandy job.  

We are on a long and winding path with the PI combo, I, for one, am damn glad that we are on this path, glad there is finally a PI far enough along and after talking with my big brain doc, it is easy to "keep the faith", he does.  He's very excited about teleprevir, now I am too.

Keep up the good work, the good words, too many confusing, contrary words here lately.

Willow

[Forseegood]

very well thought out post, points I hadn't even considered, bravo!

[mremeet]

I wouldn't be disappointed, the information they released was pretty much to be expected. You seem to have been following the VX development cycle all along and appear to have a reasonable grasp on what VX is and what it is not - what did you expect?

In my opinion, I think telaprevir makes a dandy adjunct to existing treatment and we should be glad to have it in the running. And I'm one of the relatively rare ones that got the uber VX nasty rash - and even I think so. We can't get overly discouraged just because VX isn't a magic bullet all by itself, or because it won't allow everyone to just take a few pills for a few weeks and be cured with 90%+ certainty with minimal side effects. It doesn't work like that, and probably won't be working like that for many years to come. What telaprevir appears to be is another potent additive to the existing antiviral mix. Remember how ineffective non-pegylated interferon was all by itself? SVR rates in the 10-20% range with monotherapy. But that's all that was available back in the early-mid 90's (and nothing else before that). Then along came ribavirin, which all by itself does nothing to eliminate the virus, but adding it to non-peg interferon really ramped up the SVR rate. And then pegylated IFN was developed, which once again incrementally increased effectiveness while also simultaneously reducing the side effect profile (and possibly drug toxicity due to peg IFN's longer-flatter-gentler absorption cycle).

So the trend over the past 15 years or so is one incremental step after another towards increasing SVR rates. It's been a slow and steady process, and it's been more evolutionary then revolutionary (although pegIFN+riba was a pretty big step forward). I view the introduction of a PI like telaprevir as another one of these evolutionary steps. And if you look at what it appears to be capable of doing based on existing available data (limited as it is), I'd say its introduction is more significant than nearly any of the singular previous big developments (i.e. peg IFN or ribavirin). When added to existing SOC, it's looking to me at this point that geno1 treatment cycles will be HALVED for most whilst simultaneously increasing SVR rates to levels well above 50% (I'm guessing 75%+ for those who endure full dosage of all drugs for 12weeks followed by full dosage of SOC for 12 more weeks). If these numbers are close (and I think they are), that's a HUGE step forward. We should be grateful to have telaprevir at our disposal (assuming there are no serious long term side effects discovered later on...like the wang fall offage previously mentioned ;-)

As to the increased side effect profile, yes it's true the increased side effects are significant and they can be a REAL bummer. But again, speaking as someone who got the worst of it, even I think those sides could be successfully managed in most who get them. Looking back in hindsight on my treatment and how my rash evolved, matured and was treated, I can see now how I could have avoided most of that trouble by stopping the drug as soon as it was clear I was having a serious allergic reaction to it. If I had, my experiences with the rash would have been a mere vestige of what they turned out to be. Plus, I still would have derived the awesome antiviral performance of taking all three drugs for ~8 weeks, which still delivered the incredibly fast UND within the first 2 weeks. As many of us know/believe, it's this early blitzkrieged deep anniliation of the virus using multiple action drugs (IFN+riba+VX in this case) which really serves up the coup de grace to the virus and dramatically enhances SVR rates.

With any luck, Vertex has carefully documented the details concerning the rash onset and they have some sense on how to determine if patient X is developing a full blown VX rash of the worst variety, or if it's something of a lesser variety that can be ridden out using antihistimines (as many "Provers" have successfully done here). They've been carefully analyzing our bloodwork and according to our revised consent form they're trying to identify and understand what the mechanism of the rash is and how it might be identified early on in those vulnerable to it. If they do develop an understanding of this, they might be able to dose a patient with a vulnerability for serious rash only up to the point where that patient can tolerate it, and withdraw the drugs just prior to a "meltdown". The rash experiential database can also include images and descriptions of what the rash onset looks like to help doctors identify it(although they took no pictures of mine), and what corrective treatment/medication protocols are appropriate in the event things take a turn for the worse (like taking x amount fo prednisone for x amount of time, including provisions for solumedrol etc etc). These facts and experiences could be carefully documented and provided to treating doctors to help them manage these additional sides. Doing so should greatly minimize the significantly increased dropout rates associated with the addition of VX to SOC, which once again should bring more people closer to SVR with a shorter course of treatment.

Lastly, when evaluating what a PI like telaprevir may mean, try and look to the near future as well. There are several other protease and polymerase inhibitors being developed besides telaprevir (along with other anti-HCV drugs unrelated to inhibitors). Sooner or later they're going to start dosing 2 or more of these drugs together, and in some cases even without IFN and/or riba. Lets not forget about the folks who have intolerances to IFN and/or riba, and lets not forget about how many awful side effects these drugs can have on their own. There are desperate HCV+ people out there with advancing fibrosis/cirrhosis who have automimmune hepatitis - interferon is off the shelf for them, taking it could kill them. Plus the way autoimmune disorders are effectively managed is via prednisone (an immunosuppressant). But prednisone also increases the replication and activity rate of HCV, which increases fibrosis/disease progression; thereby really putting these people in the box - both literally and figuratively. And while right now we just don't know what might happen if we combine multiple anti-HCV PI's, we do have HIV patients to look at it.

HIV protease inhibitor cocktails have been used for years to effectively manage HIV/AIDS patients and to reduce their disease from a death sentence to a chronically managed disease (and is why people like Magic Johnson remain alive and healthy so many years after being infected). And although these anti-HIV PI cocktails do not cure HIV patients, that certainly doesn't mean that anti-HCV PI cocktails will not be capable of curing HCV patients. HCV can be cured (without quibbling about what "cured" means), HIV cannot be due to critical differences in the mechanisms of the two viruses. But in my view, if HIV PI cocktails can persistently reduce HIV viral loads to UND for prolonged periods of time (spanning years in most cases), then that bodes well for us HCV patients. Suppressing geno-1 HCV to UND levels for significantly more than 6 months generally starts delivering "cures" in the form of SVR's. I'm optimistic that unlike HIV, HCV can not only be persistently kept down using a PI cocktail, it can also be CURED using mutliple PI's. PI's as monotherapy can pack a powerful and unprecendented initial wallop on HCV. It's just they peter out after only a few weeks because they're dosed as a mono-single action therapy (quickly giving rise to drug resistant rebound). Two or three multiple acting PI's together could conceivably knock VL's down very quickly, and more importantly keep it down. And keep it down without IFN and ribavirin.

In the meantime lets keep our fingers crossed, and above all remain upbeat...dude. ;-)

[willing]

it all seems part of the lab rat's contract : yes you'll get early access, but we need to understand exactly what this molecule does and we can only do that by introducing one effect at a time. There's good reason to be cautious : both of the most publicized HCV-targeted drugs investigated recently, biln-2061 and vx750, exhibited unplanned sides, suggesting that "rational drug design" is not quite as rational as one might hope. I assume this is part of the delay in reporting results from "cocktail" therapies - you first have to, slowwwwly,  pin down the risk profile for each drug individually. But, to all the brave souls out there testing the tolerability of vx - thanks! - those who will follow your trail owe you gratitude.

[willing]

it all seems part of the lab rat's contract : yes you'll get early access, but we need to understand exactly what this molecule does and we can only do that by introducing one effect at a time. There's good reason to be cautious : both of the most publicized HCV-targeted drugs investigated recently, biln-2061 and vx750, exhibited unplanned sides, suggesting that "rational drug design" is not quite as rational as one might hope. I assume this is part of the delay in reporting results from "cocktail" therapies - you first have to, slowwwwly,  pin down the risk profile for each drug individually. But, to all the brave souls out there testing the tolerability of vx - thanks! - those who will follow your trail owe you gratitude.

[VXman]

Thank goodness for clinical trials. I suppose that you could compare the participants as pioneers: however, in reality, most of us are attempting to better our own situations. VX-950 (telaprevir), may not be the silver bullet that many had hoped for, but it is a strong candidate to make it to market, and it has all the potential of becoming the SOC.

There is a great deal of greed and financial gain to be made by pharmaceutical companies: however, the patient's interests are not overlooked. A little hiccup in the 10+ sessions that require blood tests is all that it takes for a patient to be discontinued in the trial. What we are dealing with is a Phase 11b trial, not a Phase 1.

I'd like to take credit as being a philanthropist or humanitarian, but quite honestly, I'm in the PROVE3 trial for myself and my family.