BMS-790052 (NEW DRUG) trial decision ???

[uncledudeness]

I have an opportunity to be included in the BMS-790052, Once-Daily NS5A Inhibitor (BMS-790052) Plus Peginterferon-Alpha-2A and Ribavirin Produces High Rates of Extended Rapid Virologic Response in Treatment-Naïve HCV-Genotype 1 Subjects: Phase 2B Trial

wow that was a mouthful. i have been trying to find out more info on this new drug, but i haven't been able to find much on it. i am new at this and i don't know if it's a good idea or not. there is a 20% chance of receiving a placebo. i guess if i get the SOC what do i have to loose?

it doesn't start until July 1, and i would have to pass the screening first.

any thoughts would be really helpful.

the propaganda website:

http://www.bms.com/research/investigational/hepatitis/Pages/BMS790052_easl.aspx

thanks.

[pedro007]

Hi again... I forgot... about week 8,  I had small water blisters all over my arms. that went way in a month, using cortisone cream. That could be remnants of PCT or maybe the trial drug???
                  
                    Pedro

[pedro007]

Hi... I'm at week 9 post tx. Finished Mar. 8th. 2011 at 24 weeks.  Trial A1444010. Phase 2b   BMS-790052.  Still UND.at week 4.   Male, 57 years old,  G 1a, Base line VL 400,000, Stage 2/3.

Dose...180 mcg INF weekly
    
           600mg x 2  Am and PM    = 1200 RBV daily  
              and
  
                                      Placebo or
                    
                        10 mg x 2 daily    =   20 mg. daily of BMS790052  or
                  
                         30 mg x2 daily    =      60 mg  BMS790052  
  
   The 10 mg. pills tasted like nothing. The 30 mg pills tasted putrid. I'm thinking I was taking the 30 mg BMS790052, but I don't know for sure yet. The trial nurse said I displayed the worst SX's., of her participants.
  
Side affects were:
1. very  woozy / fatigue most of Tx.
2. week 4, had the shakes and seemed cold all the time
3. muscle ache and joint pain, ate 300 + ibuprofen over Tx
4. week 8, had horrible dry skin / dandruff
5. week 12, had horrible nausea,  hard to eat much, lasted rest of Tx and beyond
6. lost 20 lbs
7. feeling much better now  
8. Still have a few souvenirs. slight nausea / joint pain / muscle ache, but nothing like      before.  

I would like to compare notes with other BMS 790052 users.    

                           Pedro

[philbert58]

I'm geno1, Stage 1 grd 2, non responder just starting bms790052 study with soc. I'm presently 3 weeks into study and feel pretty well. As I understand, my study involves either 10 or 30 mg blind. From everything I've read this seems to be a wonder drug allthough I'm starting to hear more about 790052 in combo with 650032 with soc. I hope I didn't "jump the gun". I feel pretty lucky to be in this study. I only wish I knew a little more about it.I was in bociprevir study in early 09 and was the only 1 of 10 in my group to get  soc."placebo," 8 of those that recieved bociprevir remain viral free today and the 1 that didn't respond dropped out at week 18 for work related reasons. My nurse said he would most likley have been cured had he stayed in program. What excites me is that my Doctor seems to feel 790052 if even better than bociprevir.On 8/17/10 you mentioned you  were waiting on lab results. Were they for BMS- 790052 study? Have you started? You seen very knowlegable and I am hopeing to find more people in this study to share experiances with. Good Luck and thanks for all the helpfull info.

[uncledudeness]

the only thing left now is to wait for the lab results of the pre-screening exam and blood work....it's only been 2 weeks since i had it done.....i am getting really good at waiting....

thank you to everyone that responded. i hope this drug will end the pain and misery for us all...

[willing]

thanks for the update - looks like a good trial, and large.  With r7128 that now makes two large Phase IIbs close on the heels of the two Phase IIIs that are just finishing . The future's so bright ya gotta wear shades. Good luck with your screening appt.

[uncledudeness]

The trial was just listed today on:  http://clinicaltrials.gov/ct2/show/NCT01125189


Study of BMS-790052 Add-On to Standard of Care in Treatment Naive Subjects (HEPCAT)

At least 1 dose of BMS-790052 combined with Standard of Care (pegylated interferon and ribavirin) can be identified which is safe, well tolerated, and demonstrates extended rapid virologic response rates at least 35% greater than placebo.

Official Title: A Phase 2b Study of BMS-790052 in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 1 and 4 Infection

[Trish77]

willing mentioned your thread and I thought I'd drop in.  I've read through the thread to catch up and some comments ...

I looked on clinicaltrials.gov and I don't see the Phase IIb posted there.  I agree with willing that I'm surprised they're using a 3mg dose when it's clearly shown to be less effective in the IIa trial than the higher dosages however in the IIb trial they may not.  It's got an astonishing 91% RVR rate at the 10mg dosage on a study of mostly men 50 years of age and 20% black persons - both harder to treat categories.  That's impressive.

For the R1626 trial, there were 7 arms and not many of them had full SOC dosages the way your arms do.  We had various dosages of the interferon but always full ribarivin dosages. You'll get no less than SOC P/R dosages plus the trial drug, excepting the placebo arm where you get SOC only.  

The only thing that concerned me was that, like willing, I couldn't find any ACTUAL details on the adverse events - they said they were comparable to those on P/R but didn't actually say what they were.  I would ask about that just so you're aware what they're talking about when they say adverse events and take them into consideration.

They did post the actual adverse events for the R1626 trial and their main adverse event was neutropenia - low white counts - and at the higher dosages.  They seemed to be backing off from that highest dosage for the trial and even though the dosages they were using were still at some risk for neutropenia, I decided to go ahead as the drug itself looked incredibly promising and was one of the more exciting ones coming on the scene at the time with regards to results.  The neutropenia ended up being worse than originally noted and it plunged our white counts to some dangerous levels.  The trial was pulled across the board - due to staggered start times at various trial centres around the world, everyone was at different phases of treatment.  I was at 34 weeks and others were almost done their 48 weeks.  I did manage to SVR though.  Some others on the trial with me were not so lucky.  HOWEVER, having said that, many of those people also suffered dosage reductions at various points in the trial and my one trial buddy felt his ribavirin dosage was insufficient from the start, that he was on that borderline between 1000mg and 1200mg and should have had the 1200mg but his doc wouldn't budge.  I did have dosage reductions but only later in the trial and I was able to use rescue drugs to keep my ribavirin dosage constant throughout, something I feel is very important.  By the time my doc agreed to a rescue drug for my white counts, the trial as a whole was then cancelled across the board.  My interferon had been half-dose for the first 12 weeks and then started at 3/4 dose at Week 25 and never really went up, however the risk with dosage reductions is much greater in the first 12 weeks in particular and lesser as you move through treatment.  Having said that...I suppose I had a 12 week dosage reduction in the interferon for the first 12 weeks being at half dose but still managed to SVR, which I attribute to having had the trial drug for the first 12 weeks of treatment.  We were supposed to have it for 24 weeks but they pulled the trial drug and then stopped the trial eventually when our white counts didn't recover.

On ANY trial, you want to talk to your trial co-ordinator/doctor about their policy around dosage reductions to manage adverse effects.  Find out if "rescue" drugs or "helper" drugs are allowed on this trial.  There is neupogen to bring up low white counts and epogen for red blood counts.  Find out if they'll allow rescue drugs and that you'd like them used before any dosage reductions take place.  There is a point below which they MUST reduce your dosage according to trial regulations and you can find out at what point that will happen.  Usually it's if your hemoglobin level drops below 10.0 and various levels for white counts.  You can ask these questions.

While a Phase IIb trial is riskier than a Phase III trial as the best dosage profile is still being worked out, you look at the specifics of THAT trial and see how it shakes out.  On my Phase IIb trial it had 7 arms and few of them full SOC but I proceeded because each of  them had full ribavirin dosages.  The Phase 2a trial for your drug had full SOC dosages across the board and 4 arms.  The Phase 2b trial should be comparable and even more defined.

I would go through the screening for this trial in the meantime.  You'll get SOC in all arms and you'll get the trial drug in other arms.  You can work out these questions as you go along.   A 91% RVR rate is pretty exciting and your trial looks better than my Phase 2b trial did.

Hope I didn't throw too many obscure details at you.  If anything is unclear, just ask.

Good luck with this.

Trish

[willing]

magnum makes a good point about  risks with IIb. The hcv new-drug graveyard includes a couple that got as far as IIb before issues surfaced : BILN-2061 I believe was one as was R1626.  There was some discussion of R1626 on another thread yesterday that got zapped, (probably my fault). Anyway you might want to ask Trish77 about her experience with that trial. Nothing about trials is without risk, though based on the IIa results 7900052 looks as good a bet as any. The reduction and resistance properties can be thoroughly tested in-vitro, so it's unknown AEs that remain a possibility. Good Luck!

susan: the trial the nurse had in mind may have been NCT01012895 "Study to Determine the Effectiveness of Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) Infected Patients Who Have Previously Failed Standard of Care" by BMS. It will combine two DAAs, 790052 targeting the NS5 protein and 650032 targeting the NS3/4A protease (like tela/boce)  *plus* SOC (but only in one arm). For any genuine non-responder  this may be the best prospect for a while. I believe it's the 1st time 2 DAAs + SOC have been tested (though this could have been started at least a year ago). Unfortunately, they're only taking about 50. I'll bet my MH stars the SVR rate in the 2 DAA+SOC arm is in the 90% range -  on null responders.

[susan400]

There's some trial coming out in the summer for non-responders.  However, I don't know the name of the drug yet, nor what the inclusion, exclusion criteria is.  The nurse at the clinic I go to mentioned it to me.  Doesn't yet know if they will take PI failures.  I'm only putting this out there for anybody else who is a non-responder.

Susan400

[WriteItDown]

Ah, so things are a bit different since you're a stage 3.... I understand that. My husband also did a Phase IIb trial which worked out very well for him. Hopefully in the Phase IIb they will have worked out some of the kinks and dropped the 3 mg dose.

BTW it makes 100% sense for them to "kick you out" if your viral load hasn't dropped 2 logs at 12 weeks -- everyone, whether on a clinical trial of not, should stop tx at 12 weeks if this doesn't occur, this is standard protocol and completely correct. It has nothing to do with them trying to make their numbers looks better. If you haven't had a 2 log drop by week 12 you're not responding adequately to the tx and you will be wasting your time and health continuing. I believe that soon they will be looking for even faster viral load drops to qualify to continue treating.

Good luck to you whatever you decide.

[Magnum]

I would wait if you can, until the upcoming PI's, because entering phase 2 is still not as secure as entering phase 3. In other words, if there are bugs in the drug, best to wait as long as you can rather than expose yourself to something not as proven as would be in phase 3. Just a thought..

Magnum

[uncledudeness]

thank you willing...I don't know what the clinical trial ID is. all i know is that it is the Phase 2b trial...i guess my head was spinning when he was describing it.

that makes sense to stop if it isn't lowering the VL at 12 weeks. I will find out if there is a roll over also.

thank you again for your help. i would be lost without people like you...thanks

[willing]

sounds like the right call. Do you have the clinical trial id for the PhaseIIb trial? Only the Phase IIa id (NCT01017575) seems to be listed. They may have pulled the 3mg arm from the IIb based on the Phase IIa data (all their other ongoing trials seem to use the 60mg dose) so only the placebo arm would remain as a risk and at stage 3/4  the prudent course would be to start soc in any event.

This is a relatively new drug but looks as promising as r7128.  The RVR rates look better than boce/tela, as does resistance,  and the sides seem minimal. Looks like Dr. Lin was one of the authors on the EASL2010 presentation which reported the Phase IIa data.

Getting kicked out if VL doesn't drop sufficiently is typical of these trials ('exit strategies'). It doesn't really help their stats, because  they have to report SVR rates as intent-to-treat (ie over all patients who intend to complete, regardless of whether they finish). The rationale seems to be to spare you from risk if it's not working.

Many trials offer 'roll-over' options, though you often have to  stop and start over - worth asking about since in your case you'd probably want the option of continuing the P&R.

[uncledudeness]

...sorry, it's the PHASE 2b trial i am waiting for.....my hepatologist was involved with the phase 2a trial and has published papers on it. (smart guy) Dr. Lim.

question: he told me if at 12 weeks i do not show a 2 log drop, i am out of the trial....hmmmm, i think they want only positive responders so they can window-dress the outcome...oh my, imagine that....

[uncledudeness]

thank you for the responses. I am at Stage 3 (possibly Stage 4), my VL is 964,000, Platelets are 96,000 and my geno is 1a. I do have insurance.

I don't think it's a good idea to wait much longer for Tela/Boce, as it might be more than a year before approval. The trial I am waiting on is the Phase 2a trial. It starts July 1. There will be 400 in the trial.

thanks again.

[WriteItDown]

I don't know, 50% chance of getting with SOC or the low-dose arm to me means that you'd be better off waiting for Telaprevir, if you are at a low stage and have insurance.

In fact, even if you don't have insurance, a 50% chance of those two less-than-desirable arms would lead me to seek other trials.  But YMMV.

[willing]

looks like Liz Highleyman put  together  an article on the Pol presentation at EASL:

http://hepatitiscnewdrugs.blogspot.com/2010/04/bms-790052-bristol-compound-potent.html

that page also includes a review of the  recent Nature article on 790052:

http://www.ncbi.nlm.nih.gov/pubmed/20410884

Not much additional usable information from a patient perspective, but the  resistance profile looks good:
"For genotype 1b, L31V and Y93H were identified as the major resistant variants whereas changes were observed at residues M28 and Q30 of genotype 1a in addition to substitutions at residues L31 and Y93. In general, substitutions in genotype 1b NS5A confer only modest effects on the potency of BMS-790052 whereas substitutions in genotype 1a NS5A are associated with much higher levels of resistance in the replicon system. The most resistant 1a variant, L31V, is inhibited in vitro with an EC50 of approximately 20 nM, a plasma concentration that we have shown is readily achievable in humans after oral dosing (see below), which indicates that single-point substitutions should be suppressed in vivo. Notably, many of these resistant variants display reduced fitness in vitro and none are recorded as major species in the HCV sequence database, which suggests that natural selection prevents them from having a dominant advantage in vivo."

so at higher dose, resistance should not be a problem (another reason to stay away from the 3mg)

Also, apparently no nasty hidden AEs:
"Headache was the most frequent adverse event, reported by four subjects after administration of BMS-790052."

and finally (surprise, surprise) it works much better when combined with another DAA:

"In combination studies, BMS-790052 displayed additive-to-synergistic effects with interferon-α/ribavirin, an inhibitor of NS3 protease (ITMN-191), and both nucleoside and allosteric inhibitors of NS5B polymerase, which is indicative of the potential of this molecule as a candidate for combination therapy with other HCV therapeutic agents"

looks good!

[willing]

it'll be harder to dig up information about this trial than some others. The drug targets the viral NS5 protein which is a relatively new target for a DAA drug - the main targets to date have been NS3/NS4A(tela/boce/itm-191) and ns5b(r7128).
The main data available for it is that press release, based on a small phase1, which matches information just presented at EASL 2010 (abstracts available online).

Overall, it looks  promising : 80-90% RVR rates which is generally a hallpass to SVR. However the phase I was only 12 patients so if you sign up you'll be part of the 1st wave checking for adverse effects in a larger trial. They don't tell you what the significant AEs were ( "Adverse events were consistent with those commonly observed with P/R."  so that's one concern to check into ) In previous candidates like R1626 the effects didn't show up until Phase II testing and were enough to kill the drug though some still successfully got to SVR.  The other concern is that it seems  they're still trying  a 3mg arm, though the results there are less impressive (42% RVR) and there's also an implied breakthrough at that dose "Confirmed viral breakthrough was not observed in the 10 mg and 60 mg BMS-790052 arms through Week 12.". - so getting 3mg might be another risk besides soc. and worth asking about.

At the higher (10/60) dosages it seems a better bet than waiting for tela/boce - and you save a year.

[WriteItDown]

Hi. There's another thread started about this entitled "Bristol-Myers Study" -- you might get some info there.

The study you named seems to be completed -- do you know the name or trial number of the study you would be in? Is it listed at the clinicaltrials.gov website? If we could see that it would help.

Especially since you are treatment-naive, my opinion is that you do have something to lose by picking the wrong trial, and perhaps it might be better to wait until Telaprevir is approved. Especially if you are at a low stage of liver damage and can afford to wait, you really want to try to hit it one time with your best shot. So, were I you, I'd examine all my options very closely before making a decision. At this point, I personally would not want to treat with SOC. But that's not to say this trial isn't a great opportunity -- I just don't know. And others could well disagree with me. So you have to read a lot and figure out where you stand on all this.

Other things to take into account are your situation regarding insurance, how anxious you are to treat, your other health problems if any, your state in your life personally, etc. Making the choice of when and how to treat is complex, so please give us more info about you and this trial if you can so we can better help.