Vertex

[pln]

My speakers are not working, please tell me if this is good news . Thanks Pam   http://publish.vx.roo.com/thestreet/portal/?clipId=1373_10331778&channel=Exec+Interviews&puc=yahoo

[mremeet]

Jim, "cure" is what happens when Jesus puts his hand upon your shoulder. And would Jesus leave a low level viral presence able to be identified using highly sensitive reverse transcription-polymerase chain reaction (RT-PCR)-nucleic acid hybridization assays?

No. I don't think Jesus would, now would he? ;-)

http://www.hivandhepatitis.com/hep_c/news/2005/010305_b.html

[jmjm530]

For those interested, Dr. Jen's dissertation on HCV and "cure" can be found at the Clinical Options Website in the video module "Doc Eye for the Hep Guy". As Mre has pointed out, others in the medical community may have a different take, but I found Jen's take very moderate and reasonable given current evidence. In the end, "cure" is simply a word, the important thing IMO is how the word is defined in terms of HCV and treatment.

(Free registration required to view video module)
http://www.clinicaloptions.com/Hepatitis.aspx

[jmjm530]

I'm pretty sure that Dr. Jen..., on Clinical Options web site, was specifically addressing the newer studies when he differtiated with  phrases such as "clinical cure" and "microbiological cure". You may not think this differentiation holds water (or maybe blood), but many do -- including myself and I will do so until something substantive shows that the so-called persistent virus has clinical implications -- which to date none of the persistent virus studies have. Also, I can't believe Boger has claimed to have cured Hep C,  but merely I imagine that he said something like he *hopes* to cure Hep C soon. Something tells me you don't like Boger :)

As to releasing study data on the 12 week arm of VX plus peg plus riba --  if I remember correctly that group should be having their 3-month post treatment PCRs right about now, and I would expect that data to be released fairly soon or I also would be disappointed. The only reason I can think of why they might not release it immediately is because of the effect a negative result might have on the 12-week arms in Europe. Without commenting on the ethics of that, from what I've been led to believe, this is pretty common in the trial process where they don't want to release data from one arm that might cause others in similar arms to drop out in the case of negative results, or conversely to shorten treatment in other arms because of positive results that may or may not be consistent with SOC durability per  this newer type of therapy.. Make no mistake, you all are guinea pigs with certain advantages/priviledges over the rest of us, and also with certain downsides due to the trial process itself. Knowing myself, I also would be looking for answers quickly -- very quickly -- and for that reason probably would not make a very good trial participant.

-- Jim

Of course, what we're all hoping for is that tomorrow that data will be released with an astonishing 3-month preliminary SVR rate that will give added hope to all the other arms.

[mremeet]

jimquote: "Many doctors, including my own, use the word "Cure". In fact, the word is used by Dr. Jen... at his teaching module over at the Clinical Options site. He uses and makes a case that Hep C can be "cured" in the clinical sense. I am not as studied as you and Mre as to the context of how Boger uses the word "cure" but why hold him to a higher standard than many of our top Hep C clinicians?"

It's true that many doctors use the word cure, or at least they certainly have in the recent past before the low level persistence findings were published (which are yet to be widely/universally accepted). However, I've noticed a shift in how some doctors now parse their words concerning this subject, *especially* if confronted with these studies on the spot. You'll get at least some hemming and hawing, I can promise you that. More and more frequently I've seen the word cure avoided, or at least conditionalized. I think based on the current controversy it's appropriate to clearly state that we don't know if the current treatment is truly curative, or that it permanently and *completely* eradicates the virus once and for all. In doing so in no way diminishes the clear and compelling case for the excellent durability and ongoing benefits of achieving an SVR. And seeing that Boger's company (and new drug) is on the cutting edge of treatment therapy, if we don't even know for certain if IFN/riba is truly curative (after all these years of using it), than how can he so liberally use the "cure" word with unambiguous and repetitious zeal? Especially within the context of very substantially abbreviated treatment cycles? (i.e. *one fourth* the duration of current treatment). That's quite an optimistic forecast without providing some proof, wouldn't you say?  I think he should stick to the facts as best we know them at this point. And if he has "private facts" that are prodding him to believe that VX *does* cure, especially in such a short timeframe, then let's hear about them. Speaking of which, where are the followup results of the trial participants who underwent 4 weeks of VX+SOC + 44 weeks of SOC? (beyond the 12 week followup reported months ago) And how about a prelim look at the 12 week VX+SOC participants? Most of them are more than 3 months post treatment by now.

Carl Sagan once commented on those who claimed that the Earth was being frequented by aliens from outer space - paraphrasing him from memory, he said: "Bold claims should come accompanied with bold proof." I think Sagan was right about the UFO's, and I think I'm right about Boger's usage of the word "cure" for the same reason.

"While it's true, the microbiological aspects of SVR are being investigated and debated, clinically "cure" seems as good a word as any."

Not for me. In my view, "cure" has a very special meaning. Cure means complete eradication, with *zero* chance of relapse and/or *any* further complications or parasitic maladies. I think most ordinary people would perceive it this way too if asked within the context of a viral or bacterial infection. And if it were explained that the virus may be persistently hiding out at low levels, in a "seemingly" benign way (necroinflammatory activity notwithstanding), then clearly most people would classify that as "sustained remission", or equivalent.

"So if "cure" is being used within the medical community, wouldn't Boger qualifying it to the shareholders (and others) be more misleading/confusing than helpful? How many shareholders do you think understand what "persistent" virus is verus "occult" virus, for example? How many doctors do for that matter :)"

So since shareholders might become confused about all this complicated and messy viral persistence gobbly gook, he should just *streamline* his message down to simple terms that "we can all understand?"  Nah, I don't think that's appropriate. The flat and somewhat ambiguous truth as we currently know it is what's appropriate, even if it takes Boger a minute or two to tediously disclaim what he means by cure. That's not so hard is it? And stockholders in many cases are sophisticated people, some of which even have HCV. So are many prospective patients, and of course so are the doctors watching these reports. Boger is speaking to a very large audience and he's on the hook both legally and ethically to be totally honest. He's not wearing a plaid leisure suit, he's not selling a '73 Chevrolet Caprice, and he should hold himself to a higher standard than that.

[prettydamscared]

I sometimes get the impression Boger is a bit too much of a "cheerleader" for his current drug in development and certainly agree with you that the word "cure" should not be bandied about as if the meaning were a widely accepted medical term applying to this disease.  I find it, imho, to be a bit irresponsible especially since he's not backing it up in any real meaningful way at this point.

[susan400]

My idea of the word "cure":

Cure = ongoing persistent SVR.  W/O SVR = no cure.  Also, I did not get any reversal on biopsy from all the treatments I've had, so in my case, I do not see myself as having obtained a cure.  It's still a possibility on the horizon.

Susan

[jmjm530]

Many doctors, including my own, use the word "Cure". In fact, the word is used by Dr. Jen... at his teaching module over at the Clinical Options site. He uses and makes a case that Hep C can be "cured" in the clinical sense. I am not as studied as you and Mre as to the context of how Boger uses the word "cure" but why hold him to a higher standard than many of our top Hep C clinicians?
While it's true, the microbiological aspects of SVR are being investigated and debated, clinically "cure" seems as good a word as any.

So if "cure" is being used within the medical community, wouldn't Boger qualifying it to the shareholders (and others) be more misleading/confusing than helpful? How many shareholders do you think understand what "persistent" virus is verus "occult" virus, for example? How many doctors do for that matter :)

As to the clinical ramifications of either, no one really understands. Lastly, Boger isn't supposed to be 100% objective. He's the president of a company that is trying to get a drug approved by the FDA. I think it understandable that he would slant things in a favorable way within the rules of accurate reporting. Maybe if I heard him speak in public -- full text and intonation -- I'd have a different take on him. Bottom line to me will be the trial results, the rest is fluff.

BTW if I were in the VX trials I might be picking apart things more, just like the two of you. Hats off to anyone who takes the leap of faith and plunges into a trial situation. But one of the reason they call them trials is because they are trying things out on you and full disclosure has never been part of the game both for scientific and other reasons.

All the best,

-- Jim

[jmjm530]

"...You can't always get what you want
You can't always get what you want
You can't always get what you want
But if you try sometimes you might find
You get what you need..."

-- Rolling Stones
-----------------------
Chris,

At least at my advancing age, SVR is more than what I need, regardless of what may (or may not) be lurking under the covers.

While academically interesting, the so-called persistent virus is very far down my rung of concerns; way below for example my family history of heart disease, as well as other health and non health related concerns.

They say "choose your battles" in life. For some of us, HCV is worth battling, and SVR is definitely the victory many of us need.

Be well,

-- Jim

[jmjm530]

Oh, yeah, what I WANT is Aishwarya Rai, but that Bachchan fellow beat me to her. Oh well :)  http://tinyurl.com/27sxbx

[ChrisDDD]

pln,

First, thanks for posting that link.  I just listened to the presentation and think it sounds very good.  Also, thank you, Jim, for your positive outlook.  I need that right now, whether it's true or not!  Let's all hope it is!  I hope all Vertex trial participants will be posting their PCR results and side effects so we know what to expect, if I ever get the chance to try it!

[mremeet]

Jim I agree with your characterization of the benefits of an SVR. If I manage to achieve one, I'll feel very good about what it means in terms of preserving my liver, probably extending my lifespan and improving overall QOL, especially as I get older. But considering the small but growing body of evidence in regards to persistent low level viral presence, I think we have to grudgingly reserve our full judgement on the situation until more is known. Offhand from memory, I believe the low level viral persistence studies did mention that necro-inflammatory activity was still observed in a significant portion of the SVR patients surveyed. I don't know if that activity is latent/unhealed residue from the active infection, or if it might be caused by other risk factors like alcohol/drugs/etc, or if may be "maintained" or even directly caused by the (apparent) ongoing low level viral infection. I don't think anyone can say that with certainty at this point, it's not fully understood at all yet. And again, I'm not suggesting this possibility would make me overly worried at all if I manage to SVR. Nevertheless, in my view it is something to consider regarding the understanding and use of the *very* special word "cure".

And speaking of the word "cure", I think the use of that term should be cautiously applied depending on context. In the case of Mr. Boger and his presentation, I think a person in his position should be held (and should hold himself) to the very highest standards of honesty. He should choose his words very carefully, he's a medical/pharmaceutical corporate official who is providing critical public information to *millions* of stockholders, patients and professional clinicians alike. All of these people have huge gains/losses at stake, be they financial and/or healthcare related. And they're depending on an inscrutably honest, forthright and complete dissertation of the facts from him regarding his product currently under development. So to breezily, repeatedly and emphatically elicit the completely and totally unqualified usage of the word "cure", I think is perhaps a bit reckless in lieu of developing information (which he's certain to be aware of). I think a brief verbal caveat concerning the ambiguities surrounding this issue would have been appropriate. Or simply stick to references to "SVR", instead of cure.

I also think this is important, as suggested above, because I think most people interpret the word "cure" not necessarily solely as defined from a particular dictionary, but as it's commonly understood amongst the masses. When using and interpreting the meaning of words in the English language (as in all languages), common usage wins. And I'd say most folks commonly think of "cure" in regards to a viral or bacterial infection as being "eradicative". "Cure" does not imply an ongoing persistent low level viral infection; that smacks of "remission". To many (including myself), "cure" implies a *complete* resolution of the problem or disease processes. It implies the total elimination of foreign and harmful agents. It implies the health problem has been permanently and irrevocably eliminated. If this isn't the case, then "cure" should at the very least be conditionalized or put into proper context. And it might even be appropriate to use another term like "sustained remission", should the SVR viral persistence theory become fully vetted in the future.

Take care...

[nick m]

I can live with those definitions. and thanks to that last for extrapolating the key statement i'd missed in my initial panic - "liver damage improved in all but 2...". Naturally, the body has its own fossil record. nick m

[jmjm530]

As I said in another thread, until they demonstrate that the so-called persistent virus both exists AND IS HARMFUL, then there is nothing further to cure. Even should they prove both, the benefits of eradicating the persistent virus would still have to be weighed against the risks of whatever drug concoction might eradicate it, if any. Too much and too far ahead for this peg and riba ravaged mind to spend much time worrying about.

-- Jim

[Skepsis]

Thank you, Jim, this is the best summary for the everyday use of all the dispute of viral clearance with SVR.

Skepsis

[Imagine]

I would agree with Jim, that's my view as well. I would add this, see above post by Miked entitiled "Will VX-950 and other Protease Inhibitors stop viral replication in our livers" The positive sentence I took from it was "-Liver damage improved in all but 2 patients" .

[jmjm530]

The dictionary defines cure as "a means of healing or restoring to health; remedy.". It does not define cure as some abracadabra on a microbiological level to eradicate something whose existence is still disputed, and whose consequences hasn't been proven to be anything at this point but benign.

In this sense, SVR is indeed a cure since it halts viral progression in the serum, often stops and reverses liver damage, and is associated with lower rates of HCC, and offers the individual (so I've been told) the same projected life span as if they never had HCV. In other words it "heals and restores to health". Certainly sounds like a cure to me at least on a clincial level.

As to what is going on microbiologically, I wouldn't be surprised that if you dig deep enough, you'll probably find remants of many diseases and conditions (including cancer) somewhere in the tissues/lymphatic systems of those who have been afflicted at one point.  Doesn't mean these people haven't been cured or that they should start injecting new drugs into their system to eradicate something that hasn't been proven to be harmful. Just means that under the microscope the body is a very complex organism that still holds more mysteries than answers.

-- Jim

[w.s.]

i might of misread what you said-but did you nsay that ait will be available in a couple of months- probably wrong-let me know-w.s. walt

[susan400]

I have a somewhat negative leaning opinion on "cure" with regard to a drug so new on the market.  I've heard that, TOO many times to count from the various times that I've tried all the different regimens.  Oh, I heard that Infergen would probably be my "cure".  I heard that when Ribavirin first came out on the market as a secondary drug to Interferon.  I heard that with the added Gamma into the mix of Alpha and Interferon, that it would have this huge percentage rate of "cure" for those trying it.  I'm just road weary of hearing that word with regard to newer drugs.  I'm not saying that it isn't a possibility some day for some of you, so please, don't misunderstand me.  I'm happy for those of you who have obtained SVR.  It's just hard for me to get too excited about it, until I see what happens with some time behind it and when/if I decided to give it a try, what happened in MY own case.  

But, yes, thank-you for transcribing that.  That was very nice of you.

Susan

[DoubleDose]

Use of the word CURE is only as good as the exact definition of CURE by the person using it.  It is a word that has many shadings of meaning and interpretation.  Don't get too excited by its use in this case, because the type of cure that is being referred to is most likely the same CURE that is referred to by many doctors today using the standard inf/riba therapy.

  Basically it boils down to SVR, or getting the virus to undetectable levels, by PCR blood testing after 6 months post-tx.  I do not think that the person using the word CURE is presenting this as something that counters or eliminates the current issue of minute, persistent amounts of replicating HCV in other compartments long after SVR.  I have seen no indication that any of the next generation drugs will address this controversial issue.  I think that the new cure will be the same as the old cure, with the little *asterisk, by the researchers, that SVR's will probably carry 'persistent, replicating HCV RNA' in barely-detectable amounts possibly in the liver, PBMC, lymphatic system, etc.

The upside is that the new 'cure' will hopefully only take a few months to obtain!  Now that is really good news, and if the new drugs eliminate the need for interferon at some point....even GREATER news.  Less long term after-effects, less provoking of depression, autoimmune problems, etc.

In summary, cure is a relative term, but it is the current goal, whatever it entails, and... it provides many benefits...even if not the full 100% enchalada quite yet.  Someday we will be able to eradicate ALL of the HCV.....and all of the symptoms accompanying the disease and the treatment.  It may just take a good while.

DoubleDose

[couldn't think of a nickname]

Mre,

The 3 month treatment estimate is based on HCV models. They have talked about it a while back, and I have asked about it.
All companies developing drugs use these models to come up with time estimates. I believe it is based on the amount of time it takes to go undetectable.
I believe SGP has mentioned that type of model also, in the past when they talked about trial design.

They do use the word cure, and I have asked about the new studies, I think most, if not all companies are working off of consensus opinion.

[chcnme]

lol - you're all welcome.  Only I could read what I first typed,  but I could read it :) Any info I can get to anyone who doesn't have speakers, I'm more than glad to.

[pln]

Thanks alot!! :)

[Imagine]

Nice play by play! :)

[Forseegood]

hey, thanks for transcribing that...