New All Oral Phase II Trial Coming

[curiouslady1]

PSI-7977 Polymerase Inhibitor  PSI-938 Polymerase Inhibitor  Pharmasset Aug 23, 2011
Comments:

Phase 1 combination study to evaluate once daily doses of PSI-7977 and PSI-938 (both dosed QD) in 30 patients with HCV who have not been treated previously. The antiviral properties of the drugs (alone and in combination) will be observed for 14 days.

EASL 2011: In the patients who received the PSI-7977 and PSI-938—92% were HCV RNA negative at day 14. The side effects were considered mild with no treatment discontinuations in the PSI containing arms.

A new study (QUANTUM) with PSI-938 and PSI-7977 (without interferon) is expected to begin in the third quarter of 2011.

[Bill200]

Sounds almost too good to be true!  But I like what I read!

[dointime]

Very interesting, thanks for posting.

Whew, staying abreast of these new combos is getting to be a full time job.  :)
DT

[MagTX]

Phase II, great news!  
Can anyone take a guess at when they will begin phase III trials for prior relapsers and non responders?

Thank you for posting.

M

[Bill200]

It sounds like they've pretty much got the virus in the crosshairs.  Like it's only a matter of time.  I'm guessing Phase III would be late next year at the earliest.  All you people who aren't in bad shape, should be able to get to the cure ok.

[meakea]

Makes me smile.  :)

[almawe]

What about those of us that are already DAA resistant..as in failed teleprevir trial?

[katla]

Just curious why I couldn't find this on cliniclatrials.gov. I was curious if my doctor was involved in this. Any ideas?

[curiouslady1]

kat_rvk:  It is not on clinicaltrials.gov yet.  I looked on Pharmasset's web site and I think it said they were not as yet recruiting.  

almawe:  Trials at Phase II often want treatment naive patients.  That is why those who have little or no fibrosis as of yet may want to "stay a virgin" in the event these opportunities come up.  However, the DAAs on the market are from different classes of drugs than the ones which are being tried now.  I was told that, if I failed my trial, I could go to the currently FDA approved triple and try that without a worry.  

meakea:  Me too.  I smile also at how easy my younger sisters and brothers had it growing up compared to me.

MagTX:  Keep clamoring.  It's gotta happen.  

Bill200:  There are all oral trials which are in process already.  This one hasn't begun yet.  Let's hope for the best.

Dointime:  You betcha!

[willbb]

I was told that, if I failed my trial, I could go to the currently FDA approved triple and try that without a worry.  
-----------------------------------------------------------------------------------------------------------------------------
Whoever told you this   should have injected the word "possibly" as there still is no definitive prove that cross resistance is not an issue.

There is much reasearch going on presently  but the full data is not clear yet...

Will

[curiouslady1]

Will, both research doctors told me this at a reputable University research site.   These are all different classes of drugs.  

Also, here is the link for anyone interested in studying up more on interferon free regimens.

http://hepatitiscnewdrugresearch.com/interferon-free-combinations.html

[willbb]

I understand fully these are different classes of drugs...however there is still no definitive clinical end point data that says there is no possibility of cross res.  

If these folk presented you with studies,,that say the problem has been solved   definitely....would you please posts these..

Will

[Willy50]

Most of these potent DDA's will produce a good viral decline initially.

The question is if they can provide a sustained viral decline, take it to undetectable and maintain it.  What *can* happen is resistant mutations can develop if the virus is not eradicated and suppressed long enough.

For instance....

Vertex had a trial last year in which 2 DDA's were used (no riba and no IFN) but the 2 trial arms were closed due to viral breakthrough.  This implies that; some trial participants were able to clear with just the 2 agents, but that they were unable to maintain that status.

Vertex, in the same trial (with Telaprevir and VX-222) in a 5th & 6th trial arm is now trying the 2 DDa's with ribaviren.
---------------------------------------------------------------------------------------
http://investors.vrtx.com/releasedetail.cfm?ReleaseID=593939
Two additional treatment arms (E and F) were added to the study to evaluate a three-drug, all-oral, interferon-free regimen of VX-222 (400 mg), INCIVEK and ribavirin. Enrollment in these treatment arms is expected to be complete by the end of the third quarter of 2011. Arm E will evaluate people with genotype 1b chronic hepatitis C and Arm F will evaluate people with genotype 1a chronic hepatitis C. Vertex expects to report data from the all-oral treatment arms in the first half of 2012.
====================================================

willy

[curiouslady1]

Will,  The issue of resistance was among the first questions I asked.  Both researchers independently confirmed the cross resistance was not an issue in my trial.  The study was designed to address resistances through the use of two drugs from two classes, one with a low tendency to create resistant virons and the other with a higher one paired in such a way to foil the process.  The principal researcher indicated that this was the "beauty" of the regimen.  I do not consider myself a fellow researcher but a patient and I normally do not demand that doctors "prove it" to me when I am very well aware how brutal their schedules are coming from a family of physicians.  I simply trust that researchers now know that resistance is a major issue and have addressed it. The way the resistance issue in my trial was discussed with me convinced me enough to proceed. Sometimes such confounds can be worked out in the lab.  My major concern is getting relevant lab results in a timely way in a research lab that has about 440 ongoing research studies.  Nor do I feel the need to "prove it" in this forum.  People here can make their own decisions from the information at hand.  You've got to trust someone sometime.  

[willbb]

Nor do I feel the need to "prove it"
---------------------------------------------------------
When you say  :

"I was told that, if I failed my trial, I could go to the currently FDA approved triple and try that without a worry.  

Folks here may read that to mean .."you can treat definitely with a Daa  and switch without any worries about cross... This is just not factually the case     not    "just yet."

.. They are still working on this and  again there is yet to be any end point  conclusive data

Actually it is even less clear treating with  just polys  (or in my case  a (Ns5A)  the cross issuse.

My best to you and your success

Will

[Willy50]

The protease inhibitors (boceprevir and telaprevir, for instance) ARE more prone to resistant mutations, and so other DDA combinations will possibly..... or more likely have less resistance issues.  My post was not intended to assert these trials won't work w/ just 2 agents, just to say that one cannot predict based upon the first 2 weeks of data.

Some of these initial pairings of DDA's will be more successful that others.  There it is thought that resistance issues will be less with DDA's that target different receptors.  The ultimate proof will be the trials.  This is one reason that early trial arms are kept small.

Believe me, everyone is cheering for the prospects of success.  PSI-7977 really looks like it could be one of the best in class.

willy

[willbb]

The ultimate proof will be the trials.
-------------------------------------------------------------
This was my point exactly...thx for stating better than I did  :)

And yes...we are l certainly all cheering on these  all orals....however I still believe any doctor just yet who ...says to a patient  "don"t worry if you fail this experiment ..you  can just switch Daa"s        without the end point data(that hofpully will be coming down the line)  or at least adding the word  "possibly " to a trial participant is  irresponsible.

Will

[kate82662]

what genotype is quanto=um getting a 90% clear rate?

[curiouslady1]

  If you treated with a NS5A Will then, no, it would not be true for you.  It would be true for me.  I am treatment naive and the two drugs that are in my trial are an NS5b (first, this particular drug has a very low tendency to create resistant mutations) and an NS5a (added later to "mop up" the several hundred per ml virons left).  If I fail then I would go to the SOC plus the protease inhibitor if I so chose . . . which I wouldn't because I have no intention of using interferon.  I will give more information on my trial later.  I am sorry you think my doctors are "irresponsible".  They are not the ones who hurt you.  

[curiouslady1]

Kate I believe I read that 2 and 3 are getting 100% with interferon added.  I don't know the rest.  I would just check the web site or the Pharmasset web site or google Quantum over the next few weeks.  

[willbb]

You aren"t treatment naive now.....you are treating with 2 polys...and again.  for the fourth time..there is no conclusive data that there is not cross.   They are still working on this aspect of Daa treatment..

I never mentioned anything about anyone hurting anyone....No one  has hurt me in the least.  I do know tho,,,in order to treat again(like anyone in a failed trial with a Daa..regardless of the mechanism) the resistance profiles will need more clarification to be able to treat again...that includes you also if you happen to fail (very much hoping you don"t)...      also no-one said your doctors were irresponsible...I said ..that any doctor that states categorically " if you fail in this experiment ..you can just swith to a Protease.. ...without the word "possibly inserted  when the data is not yet finished .."is irresponsible"   and   it is....if he showed you  any studies on cross on polys  please post them for others  to look over

Best to you...
Will
Will

[willbb]

You aren"t treatment naive now.....you are treating with 2 polys...

meant to say  you are now treating with a poly and an NS5A

[appleboy]

I have had Hep C for 28 years. The last few years have been a rough time for me not b/c of the disease (I am very lucky and it seems to never want to be an every-day issue with my liver) but because of PIs coming  and going when they get to near the line where they have to cross before they can be released.This last one sounds like a miracle with no Tx side effects (although none they mention). Maybe we do get favours from God now and again.  

[willbb]

The PSi 7977 / BMS 790052 combo looks very promising ... hopefully they will be on the market  as an INF.free therapy  sooner rather than later. Most in the field believe it could still be from 3 to 5 years away .
best to you.

Will