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News on the Tarvacin Trials

In September I posted that my husband would start the Tarvacin trials this month. Actually, he was supposed to receive his med administration this past Monday. We went to his evaluation visit on 10/31. Unfortunately, some prior blood work indicated an elevated AFP (alpha feto protein), and he had a CT scan. The scan indicated a significant number of enlarged lymph nodes along his gastric vein. Under the Peregrin guidelines, he was disqualified until we could identify the problem. The concern was that he may have lymphoma. Thankfully a biospsy for cancer was negative and my husband has been placed back on the trial list for December.

Has anyone heard from anyone else in the Tarvacin trials? Positive results??
41 Responses
Avatar universal
To this point, no results have been issued by the company that I know of, and I do check multiple news sources each day just for HCV.
Avatar universal
???i wondered if i could inturrupt for a note to goofy...thanks, sorry for the inturrupt florida...the post below was closed...

hey goof, i understand your thinking on the risk factor i talk about....but the only thing your not considering in your post below, is that it is "significant" that one gets the right tx for the right amount of time and the right doses while they are still TREATMENT NIAVE...

if you notice in all the tx trials of new meds for hep c, they test with treatment niave people...this way they know they are getting a pure specimin so to speak...i think the scientists know thier results could be a skew if they start using folks that have been on and off tx...just a though here for ya...

so when we stop tx for whatever reason there is thinking that it can give the virus a "foot up" on the situation...don't forget about quasispecies and breakthroughs and all the weird stuff this virus sets itself up to do...there is just not enough info out there to feel safe experimenting with this virus...

my thinking is hit it hard the first time, the right way, and you have your best shot right there...

...i thought i'd give you my thinking on it anyway...hope ya don't mind...

have a nice night goofy,

sandi
Avatar universal
That seems quite right sandi, and VRTX said as much today. WT (wild type, which I never heard of before today) was an issue in the dose groups that didn't work as well, but not in the best dose group. If you hit it hard and fast, then variants (mutations) should not be an issue.
92903 tn?1309908311
I hear you. I've always felt the desire for treatment niave pts for trials was because, being niave, they had not demonstrated a propensity to failing at treatment - not because the virus had mutated into a less-treatable quasispecies. But who knows?

I haven't seen data that suggests viral mutation into more virulent - less treatable - quasispecies after attempted tx, but I'd appreciate the chance to read it if it's out there. I have seen data that suggests a 12 week treatment makes one no more difficult to retreat than a niave patient, but bringing up studies and numbers doesn't further this discussion for anybody's benefit.

Thanks for your response Sandi. This is obviously an issue with room for many points of view.
Avatar universal
glad to be able to go back and forth on the issue...it is a very interesting subject to talk about...

most of what i said above was not based on reading a particular study...but just my own thinking, on what makes sense to me...after reading about all this stuff for years...

i agree with you that the primary reason to use a tx niave patient would be to get someone who hasn't already shown a propensity for failure to tx...but to me it also makes sense to prefer a more "pure" group...i mean if i were the scientist with this virus that's what i'd also be thinking...

thanks goofy for getting back to me on that...perhaps someone else can help us take a look at this...it's very interesting to me...that has been the main reason i went on to treat after the breakthrough WITHOUT A STOP...because i didn't want the virus to get a leg up at all...

sandi
Avatar universal
From what I gathered today from the VRTX call, if you don't knock it down fast, viral variants do occur. The ones that occured in their trial were not at full strength, if I interpreted the science correctly. VRTX said they are the first company they know of to examine this issue like this. The problem with those who have failed treatment IMO is that WT viruses, and variants have likely formed. The longer it takes to knock it out, the more potential for variants, and that did show up in their sub-optimal groups. Because it wasn't knocked out fast, resistance did have a chance to form.
They gave a reason before for wanting to do treatment naive for this one, and I don't remember what it was-maybe it was resistance.
In the prior trial, 23 of 30 were in treatment failures, and 950 as a monotherapy still did a tremendous job of knocking it down.
Remember, with food, 950 is about 2 times more active than the suspension used in the prior trial. It will be interesting to see if this enhances efficacy at all.
92903 tn?1309908311
Sandi - Thanks again for your thoughts. One more thing to consider is that there are proabable differences between the mechanisms that cause breakthroughs and those that cause relapses in short term tx'ers. I'm not sure it's applicable to apply the theory behind quasispecies-mutation tiggered breakthroughs to relaspses in short term tx'ers. Just my opinion, of course. Hope your having a good weekend.  


Mind saying how you changed the protocol after your breakthrough? I'm sure you posted it before, but I miss things and get befuddled.
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CTOAN - Thanks for your insights.

92903 tn?1309908311
Something that I thought was obvious in its absence in the analysts questions was what could happen to derail the drug? What are the unknowns that have yet to be cleared? Obviously it could be no-SVR or viral rebound, health issues such as heart or kidney probs, or the growth of big purple elephants on patients foreheads. Some of these are more likely outcomes than others. Which of these are things VX is concerned about and why?
Avatar universal
I get the impression that they are doing 1 riba arm based on recommendations from the medical community. I really hope they don't need it, and I think they don't expect it to be part of the future of treatment including their drug.
On the CC there were many questions about the viral variants, and it did seem at times that those asking needed to be reminded it was in dose groups that will not likely be used in future trials. It goes back to the popular thought, that if you knock it out fast enough, it isn't an issue.
Avatar universal
First sentence, third paragraph should have read:

"...of a 1-3 *month* Hep C knock-out punch..."
Avatar universal
In the original webcast, a caller did question the growth of big purple elephants on patients foreheads, but the caller was later outed a Roache representative. The comments were then deleted from later broadcasts.

But seriously, unless some significant sides occur as in the case of BILN,  with both a mono, dual and possibly triple-therapy arm, they are covering enough bases for FDA approval regardless of how the drug performs by itself. Remember, the standard for FDA approval is low -- it only has to perform as well as a non-peg interferon by itself.

The only other thing that could knock it off course is poorer than predicted trial results resulting in investor abandonement, especially if other drugs start showing more promise.

-- Jim

Avatar universal
What if the so called variants were not a bad thing after all, for some individuals? Were are assuming a bacteria-like "behavior" where a resistance  built against the medications used is what's occuring with hcv. And it would seem so, with folks that had to stop tx early and did not respond to later tx, or those who respond less and less with each subsequent try.  But, then there are those like TonyZ, who treated more than once, and finally beat it on the third try. Can it be that each tx brought about a weaker variant that finally responded to tx? Some do it on their second try or 4th... It could be that had they gone longer the first tx it would have taken care of all variants.

Seing so many different scenarios happen with HCV and tx, I would err on the side of going longer on tx, rather than going a second time, even if RVR.  I would not want to be the minor percentage that relapsed because of stopping sooner. More than one tx is not something to look forward to, if you can help it.
Avatar universal
Important to reinterate that the variant virus only showed up in the monotherapy sub-optimal dosing group, and therefore not believed to be a factor moving forward, as higher doses were tolerated almost as well as the placebo group with very minor sides. A new formulation is also in the works using an oral tablet to be taken with food to increase Vertex absorbtion.  Also, later in the conference call, it was suggested that in the combo therapy trials (Vertex and Peg) variants would be a non-issue becase of the action of the Peg.

It appears that the SVR data we're all looking for will be available early next year, probably on a 12-week tx course using the optimal dose of Vertex and Peg.

Later, will follow Vertex monotherapy data. Later still, the possiblity of triple therapy using ribavirin, but I'm guessing they only have this on the back burner in case they don't get the SVR numbers they're looking for with either dual or monotherapy.

Lastly, talk of a protease "cocktail" using other protease inhibitors, still unexplored and therefore unnamed. Very exciting stuff going on. A lot of people are keeping their fingers crossed.

-- Jim

-- Jim
Avatar universal
They are definitely covering their bases, including with the medical community, which makes sense since they are a public company.

It was interesting to note the very low standard needed for what I believed was FDA approval --  which is for Vertex to work as well non-pegalayted interferon.

So, on one hand, they are forging ahead with almost mystical (but realistic) expectations of a 1-3 Hep C knock-out punch with almost no side effects (WOW) but at the same time they're not ruling out using Vertex in some lesser,  companion capacity should the trial data come out differently. That's partly why they keep hedging their expectations. But with SVR data coming out early next year, the wait for results really isn't that long.

-- Jim
Avatar universal
The Idenix  NM283 Phase IIb trial is exclusively for Genotype 1 non-responders.  

rudy
92903 tn?1309908311
Another thing I think I heard in the variant discussion was that they attributed the build-up of variants as simply some variants stacking up because they weren't being killed off as quickly. This was found in the sub-optimally dosed 'Plateau' group and was attibuted to lower vx-950 sensitivety in certain variant strains. I don't think I heard them say tx was spawns any increases in variant production or viral mutation - but I should listen again - next time while I'm awake.
Avatar universal
i wish they would have said a bit more about the pill burden in the vertex Q/A... i found two pictures of the pill.  one looks like the size of a tylenol, and the other looks quite a bit larger - like a rounded TMP/Sulfa tablet which are BIG.  taking 15 or so of those a day along with everything else would not be fun.
Avatar universal
I have seen the pill and wondered too, but they have said it isn't that big. If this helps, it has an extremely high drug load of 75%, meaning most of the pill is active drug. Also, if it is a 750mg pill, which I don't think they have stated, it would be no more than 3 times per day, maybe less if future trials would support it.
Avatar universal
if i were guessing, it sounds like a 150mg pill.  makes for easier dose titration.  unlikely that it is 750mg.  i have heard 9-18 pills per day in the study.  if in the  750mg tid arm, looking at 5 pills tid.  i am at the conference and maybe someone will shed some light..... vx seems more willing to share than others.
Avatar universal
I am not too sure about that, I would like them to address it. I do know it has a 75% drug load which is very high, which should mean smaller/fewer pills to get dosage. Looking at the tylenol 500 mg gel caps, they are about the size that the pill looked on the slides. It is quite possible that the pills are 375 mgs.

I would rather not speculate but wait for hard facts on this. Also, it would be in their best interest to do it in as few pills as possible. The therapy cost as they say has been established, and to fit into to similar pricing, fewer pills should equal larger margin.
Avatar universal
i am going back to the meeting in a minute but about the mg strength - since they have a 450 tid arm, that would rule out 375mg tablet.  i am hoping that they will say something... of course i am about as optimistic as they come... so we'll see.  you have interesting insights, BTW.
Avatar universal
also - thank you also for listing the abstracts in one of your previous notes...
Avatar universal
They have 400 million in the bank, so the residents should worry about more important things. They did a secondary offering in June at under 14 and it was very well received. If they need cash, they will get it, that will be the least of the worries.

As far as no comparitor arms, remember they have had extensive discussions with the FDA, and I don't think they would do trials without knowing what they would want.
92903 tn?1309908311
Setting aside the pill size,  listening to the webcast last night I wondered about compliance on 3x/day with food regime. Getting decent food down at 8 hour intervals is going to challenge some folks. That's a meal at 10PM, 6AM, and 2PM - or 8-4-12 - (hmmm that's Dr Pepper time). I mean, it's a small price to pay for SVR, but still, I would expect to see a lot of late dosing with that regime.

--------------------------------------------------

Another thought on the viral variant issue we discused earlier - I think I heard them say this variant spawning activity is normal in replicating viruses, and not unique to HCV or treatment.

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CTOAN - I think you maybe covered this before - but let's say FDA approval were to come tomorrow. The stock should shoot up, I would think. What risks are removed by FDA approval that creates the boost in stock price - or it simply a matter of shortened time to a meaningful revenue stream?

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