Aa
Trials vs SOC
Hi guys,
I had my appointment with hepatologist yesterday, and he advised me to go ahead and start treatment. He offered me the choice of SOC or trial with BMS-650032 trial (ClinicalTrials.gov Identifier: NCT01030432). I looked at the trial information and it did not look very appealing to me with possibility of getting SOC with Riba dose at 500-600mg.
I was looking into other trials around the area where I live and found one with BMS-790052 that looked promissing (not sure if I still have time to get in).
So, I wanted to get your opinion on what is the best way to attack/and get rid of this virus:
a) SOC
b) BMS-650032 trial (ClinicalTrials.gov Identifier: NCT01030432).
http://clinicaltrials.gov/ct2/show/NCT01030432?term=hepatitis+c%2C+alabama&rank=2
c)BMS-790052 trial (ClinicalTrials.gov Identifier: NCT01125189).
http://clinicaltrials.gov/ct2/show/NCT01125189?term=hepatitis+c%2C+alabama&rank=20
Again, I'm just looking for your opinion and fully aware that the final decision is totally my responsibility.Your response will be greatly appreciated.
I had my appointment with hepatologist yesterday, and he advised me to go ahead and start treatment. He offered me the choice of SOC or trial with BMS-650032 trial (ClinicalTrials.gov Identifier: NCT01030432). I looked at the trial information and it did not look very appealing to me with possibility of getting SOC with Riba dose at 500-600mg.
I was looking into other trials around the area where I live and found one with BMS-790052 that looked promissing (not sure if I still have time to get in).
So, I wanted to get your opinion on what is the best way to attack/and get rid of this virus:
a) SOC
b) BMS-650032 trial (ClinicalTrials.gov Identifier: NCT01030432).
http://clinicaltrials.gov/ct2/show/NCT01030432?term=hepatitis+c%2C+alabama&rank=2
c)BMS-790052 trial (ClinicalTrials.gov Identifier: NCT01125189).
http://clinicaltrials.gov/ct2/show/NCT01125189?term=hepatitis+c%2C+alabama&rank=20
Again, I'm just looking for your opinion and fully aware that the final decision is totally my responsibility.Your response will be greatly appreciated.
http://www.bms.com/research/investigational/hepatitis/Pages/BMS790052_easl.aspx
Efficacy Results: The proportion of patients in each dosing arm that achieved eRVR at weeks 4 and 12 (primary endpoint), RVR at week 4 and cEVR at week 12 was:
BMS-790052 3 mg: 42% , 42% and 58%, respectively
BMS-790052 10 mg: 83%, 92% and 83%, respectively
BMS-790052 60 mg: 75%, 83% and 83%, respectively
Placebo: 8%, 8% and 42%, respectively
Efficacy Results: The proportion of patients in each dosing arm that achieved eRVR at weeks 4 and 12 (primary endpoint), RVR at week 4 and cEVR at week 12 was:
BMS-790052 3 mg: 42% , 42% and 58%, respectively
BMS-790052 10 mg: 83%, 92% and 83%, respectively
BMS-790052 60 mg: 75%, 83% and 83%, respectively
Placebo: 8%, 8% and 42%, respectively
http://pubs.acs.org/cen/coverstory/88/8818cover.html
"Improved protease and polymerase inhibitors aside, EASL attendees say the most-talked-about compound at the conference last month was part of a new class of drugs. Bristol-Myers Squibb’s lead candidate, BMS-790052, is a potent inhibitor of NS5A, a protein that seems to play a role in HCV replication.
The discovery of BMS-790052 was made possible by the development of cell-based assays that allowed researchers to probe for inhibitors of every protein potentially involved in viral replication, explains Nicholas Meanwell, executive director of virology chemistry at BMS. Using a chemical genetics approach and three assays, BMS screened more than 1 million compounds simultaneously to come up with an NS5A inhibitor.
The compound, BMS-858, is an imino thi azo lidio none that is a highly specific—albeit weakly potent—inhibitor of HCV RNA replication. Through a medicinal chemistry campaign to improve the compound’s potency and pharmacokinetics, the company gained insights into its structure-activity relationship. By plucking out the parts of the molecule responsible for its activity, BMS came up with a symmetrical structure that appears key to its ability to shut down the virus. “It was an awful lot of work to make the leads into a druglike molecule,” Meanwell says.
Despite its promise as a drug target, NS5A is still a bit of a mystery. It is clearly important to the survival of HCV, but its role in the life cycle of the virus is not fully understood. Regardless, NS5A has been a boon for BMS. In a recent letter in Nature, BMS said BMS-790052 is the most potent in vitro blocker of HCV replication reported to date (Nature, DOI: 10.1038/nature08960). It seems equally powerful in patients: In a Phase II trial involving people with HCV who had never been treated, adding the drug to interferon and ribavirin shut the virus down in four weeks, with no viral breakthroughs even after 12 weeks in 83% of those given higher doses of the drug."
"Improved protease and polymerase inhibitors aside, EASL attendees say the most-talked-about compound at the conference last month was part of a new class of drugs. Bristol-Myers Squibb’s lead candidate, BMS-790052, is a potent inhibitor of NS5A, a protein that seems to play a role in HCV replication.
The discovery of BMS-790052 was made possible by the development of cell-based assays that allowed researchers to probe for inhibitors of every protein potentially involved in viral replication, explains Nicholas Meanwell, executive director of virology chemistry at BMS. Using a chemical genetics approach and three assays, BMS screened more than 1 million compounds simultaneously to come up with an NS5A inhibitor.
The compound, BMS-858, is an imino thi azo lidio none that is a highly specific—albeit weakly potent—inhibitor of HCV RNA replication. Through a medicinal chemistry campaign to improve the compound’s potency and pharmacokinetics, the company gained insights into its structure-activity relationship. By plucking out the parts of the molecule responsible for its activity, BMS came up with a symmetrical structure that appears key to its ability to shut down the virus. “It was an awful lot of work to make the leads into a druglike molecule,” Meanwell says.
Despite its promise as a drug target, NS5A is still a bit of a mystery. It is clearly important to the survival of HCV, but its role in the life cycle of the virus is not fully understood. Regardless, NS5A has been a boon for BMS. In a recent letter in Nature, BMS said BMS-790052 is the most potent in vitro blocker of HCV replication reported to date (Nature, DOI: 10.1038/nature08960). It seems equally powerful in patients: In a Phase II trial involving people with HCV who had never been treated, adding the drug to interferon and ribavirin shut the virus down in four weeks, with no viral breakthroughs even after 12 weeks in 83% of those given higher doses of the drug."
Hi Alex-
I think you should try getting in the trial if you feel good about it. There is really no commitment by the way. The trial agreement will tell you that you can stop any time you choose. it happens all the time. I would contact them asap.
Dave
I think you should try getting in the trial if you feel good about it. There is really no commitment by the way. The trial agreement will tell you that you can stop any time you choose. it happens all the time. I would contact them asap.
Dave
Is there a site one can use to find more information such as trial protocol about a particular trial, or does one has to call the trial coordinator to get that info?
Dave, If that is the case---it is a great opportunity and I would most likely try it. The problem is that I think I'm running out of time for this trial.
Dave, If that is the case---it is a great opportunity and I would most likely try it. The problem is that I think I'm running out of time for this trial.
According to RobertbeWell the BMS-790052 is not randomized as 1/3 for each arm.
You will have an 80% chance of 790052 being included.
The tela/vx222 trial looks excellent. vx222 is a polymerase inhibitor which does not have the mutation issues of the protease inhibitors and should work well in combo with telaprevir and hopefully. I would hope to have soc included in the trial at this point personally.
You will have an 80% chance of 790052 being included.
The tela/vx222 trial looks excellent. vx222 is a polymerase inhibitor which does not have the mutation issues of the protease inhibitors and should work well in combo with telaprevir and hopefully. I would hope to have soc included in the trial at this point personally.
I think an attractive trial that comes along should be given a serious look. I'm geno 1A, stage 1, grade 1, and I want to get rid of the virus asap. Looks like I'm going to get into Vertex's newest trial with riba, Peg, Telaprevir, and VX222. Expectations are extremely high as people who were on VX222 alone for only three days had up to 3 and 4 log drops in viral load. I weighed the risk of mutations, and feel they are low. If I don't succeed on this trial, we feel another go with SOC and Telaprevir upon release would be viable. Good luck. One thing I've learned is that this message board is a HUGE source of information. And information is your greatest weapon against this disease. Keep learning...
Another often overlooked point that has to be remembered is... some people, in addition to getting cured, may derive some satisfaction from the fact that they are blazing the way for others. I know for me it is anyhow. I get some enjoyment out of knowing that if I get in a trial, I may ease the road for someone else in the future.
i chose to do a boceprevir trial, a protease inhibitor which I am currently treating with, so I decided the risk of resistance was worth the gain considering my own hcv related health issues and liver damage.I am not sure what the right way to go is for anyone else.
I am not trying to create fear of these great new drugs that should save a lot of lives, I just think people should be informed when they make a choice. and consider the urgency of needing to treat based on their disease progression against the pros and cons of the drugs they are thinking of treating with. of course hopefully the decision about what to treat with will be made with the advice of a good hepatologist.
There should be two protease inhibitors available next year, telaprevir and boceprevir. probably telaprevir will be available first.
I am not trying to create fear of these great new drugs that should save a lot of lives, I just think people should be informed when they make a choice. and consider the urgency of needing to treat based on their disease progression against the pros and cons of the drugs they are thinking of treating with. of course hopefully the decision about what to treat with will be made with the advice of a good hepatologist.
There should be two protease inhibitors available next year, telaprevir and boceprevir. probably telaprevir will be available first.
It makes little sense to me personally to decide not to use a treatment with a much higher success rate out of fear of creating resistant variants. You can always stop triple therapy as well as SOC if you were not UND by 4 weeks.
My feeling is that triple therapy works for pretty much all the people who would SVR with SOC alone; and also for many of those who wouldn't. Maybe I'm wrong but I would be surprised to learn that the doubling of cure rate for triple therapy involves people who would have attained SVR on SOC alone.
The theory that one should try SOC first in order not to create resistant variants so that you would have a backup tx plan doesn't make sense to me, since generally speaking at this time the backup plan is triple therapy anyway.
Now, if you wanted to talk about waiting even longer until the protease inhibitors are available, that's another argument. But that, I fear, could well take quite a few more years.
So my opinion is, use the best drugs available now or in the near future. Just my 2 cents, YMMV!
My feeling is that triple therapy works for pretty much all the people who would SVR with SOC alone; and also for many of those who wouldn't. Maybe I'm wrong but I would be surprised to learn that the doubling of cure rate for triple therapy involves people who would have attained SVR on SOC alone.
The theory that one should try SOC first in order not to create resistant variants so that you would have a backup tx plan doesn't make sense to me, since generally speaking at this time the backup plan is triple therapy anyway.
Now, if you wanted to talk about waiting even longer until the protease inhibitors are available, that's another argument. But that, I fear, could well take quite a few more years.
So my opinion is, use the best drugs available now or in the near future. Just my 2 cents, YMMV!
Thank you for this information. I was not aware of the resistance issue. Could you, please, post some links where I could read more about it?
thanks guys for your opinions.
Dave, the situation with resistance mutation appears to be a double edged sword to me also. Important one too. Based on the mutation issue it almost makes sence to try SOC first (at least for the first 12 weeks). By chance do you have any info/studies on wether the any type of resistance to the drugs will be developed if SOC is used for 4-12 weeks?
I think I will wait for the 2nd opinion on the biopsy report (from UAB pathologist) before making any conclusions/decisions. Personally there is a big difference in chosing the best actions if my stage is 2, between 1 and 2, or 2 and 3 (I hope not:):). There is so many things to consider, but at least we have a choice.
Alex
Dave, the situation with resistance mutation appears to be a double edged sword to me also. Important one too. Based on the mutation issue it almost makes sence to try SOC first (at least for the first 12 weeks). By chance do you have any info/studies on wether the any type of resistance to the drugs will be developed if SOC is used for 4-12 weeks?
I think I will wait for the 2nd opinion on the biopsy report (from UAB pathologist) before making any conclusions/decisions. Personally there is a big difference in chosing the best actions if my stage is 2, between 1 and 2, or 2 and 3 (I hope not:):). There is so many things to consider, but at least we have a choice.
Alex
The current Pi's are a double edged sword. Although the success rate is 70-75 percent for geno 1 instead of 45 percent, if you don't succeed you may be stuck with dominant mutations that will be resistant to future treatment. In a couple of more years there will be combos of new drugs. Many pharmaceutical companies are already starting to test combos of protease and polymerase inhibitors that will likely reduce the chance of mutants becoming dominant.
The reason I mention the mutants is because it makes me think that treating with soc first until combos are available is not a bad idea. If you do not have a rapid viral response or early viral response you don't have to continue treatment and you will not have created long term resistance. Rapid viral responders (undetectable at 4 weeks) to soc have the highest success rate of svr.
Of course treatment decisions are bases on the extent of damage, previous non response or relapse and a person's own desire to treat or wait. there is really no correct answer. It sounds like you are doing a good job educating yourself, at least this way whatever you decide, you will have been informed of the gains and risks to expect.
good luck,
I wish you the best in eradicating this disease in the near future,
- Dave
The reason I mention the mutants is because it makes me think that treating with soc first until combos are available is not a bad idea. If you do not have a rapid viral response or early viral response you don't have to continue treatment and you will not have created long term resistance. Rapid viral responders (undetectable at 4 weeks) to soc have the highest success rate of svr.
Of course treatment decisions are bases on the extent of damage, previous non response or relapse and a person's own desire to treat or wait. there is really no correct answer. It sounds like you are doing a good job educating yourself, at least this way whatever you decide, you will have been informed of the gains and risks to expect.
good luck,
I wish you the best in eradicating this disease in the near future,
- Dave
I would wait, and I say this as someone whose husband did a clinical trial.
You want to hit it with your best shot the first time. You don't want to have to treat twice. In both trials you would have a 1/3 chance of getting placebo. Personally I would not want this big a chance of getting SOC with Telaprevir just around the corner -- and yes, I believe it will be available within the year even though of course it's not guaranteed.
However, if you're choosing between SOC or a trial I would do either of these trials over SOC -- I would research the results of their earlier trials and choose the one that looked better.
Best of luck whatever you choose.
You want to hit it with your best shot the first time. You don't want to have to treat twice. In both trials you would have a 1/3 chance of getting placebo. Personally I would not want this big a chance of getting SOC with Telaprevir just around the corner -- and yes, I believe it will be available within the year even though of course it's not guaranteed.
However, if you're choosing between SOC or a trial I would do either of these trials over SOC -- I would research the results of their earlier trials and choose the one that looked better.
Best of luck whatever you choose.
Alex, I recommend for you to wait until Telaprevir/Boceprevir get approved. There is no question that they will be approved. It is a certainty. In a few months, in a year, or in two years-it doesn't matter for you, because you can safely wait. I think it will happen sooner rather than later, because the results are good, and the companies of course see very profitable opportunity.
Many hepatologists right now advise genotype 1 patients to wait. This strategy was even discussed at some liver conferences. Your doctor might have a different opinion, but it is you who are in the driver's seat. It is good that you understand that the decision is yours and yours only. This is the way I think too.
The reason I dislike trials is because you can get into SOC/placebo arm. Often it means wasted time, suffering side effects needlessly, slow response, retreatment etc. I personally would like to know what exactly I take-and why.
Many hepatologists right now advise genotype 1 patients to wait. This strategy was even discussed at some liver conferences. Your doctor might have a different opinion, but it is you who are in the driver's seat. It is good that you understand that the decision is yours and yours only. This is the way I think too.
The reason I dislike trials is because you can get into SOC/placebo arm. Often it means wasted time, suffering side effects needlessly, slow response, retreatment etc. I personally would like to know what exactly I take-and why.
Dave (spectda) knows lots about the new drugs and trials. You can trust his opinion it comes from experience. Much more than I have.
Judy
Judy
Alex-
My understanding is that 790052 is as powerful as boceprevir or telaprevir and may create less resistance since it acts on a different part of the hcv molecule. You will be able to use all rescue drugs also, and of course there is little expense except the rescue drugs. If you do not rvr and you are in the soc arm, you could always stop.
- Good luck with whatever you decide,
Dave
My understanding is that 790052 is as powerful as boceprevir or telaprevir and may create less resistance since it acts on a different part of the hcv molecule. You will be able to use all rescue drugs also, and of course there is little expense except the rescue drugs. If you do not rvr and you are in the soc arm, you could always stop.
- Good luck with whatever you decide,
Dave
Dave,
thanks for your response. Yes low riba does not look good to me neither. The BIG question is will Telaprevir be available next year??? From reading this site it looked like people were expecting it 2-3 years ago. I will arrange to receive a second opinion on my biopsy slides, and then I will have to make a decision.
Judy,
Thank you for your response as well. First of all I would like to say that I was following your treatment progress as you were going through your 12 weeks of treatment. Please don't be discouraged by the SOC treatment outcome---that means the PI will finish this little virus off.
As for the trial with BMS 790052, I would like to consider this opportunity as it's the most attractive (in my opinion) trial in my area. Don't even know if it is still open---but will call on Monday. As I mention above the BIG point is that we don't know how long we will have to wait for Telaprevir and Boceprevir. At least we have a choice to wait (or I would like to think so).
Alex
thanks for your response. Yes low riba does not look good to me neither. The BIG question is will Telaprevir be available next year??? From reading this site it looked like people were expecting it 2-3 years ago. I will arrange to receive a second opinion on my biopsy slides, and then I will have to make a decision.
Judy,
Thank you for your response as well. First of all I would like to say that I was following your treatment progress as you were going through your 12 weeks of treatment. Please don't be discouraged by the SOC treatment outcome---that means the PI will finish this little virus off.
As for the trial with BMS 790052, I would like to consider this opportunity as it's the most attractive (in my opinion) trial in my area. Don't even know if it is still open---but will call on Monday. As I mention above the BIG point is that we don't know how long we will have to wait for Telaprevir and Boceprevir. At least we have a choice to wait (or I would like to think so).
Alex
If the new meds weren't so close to being on the market I'd say go for the trial. Too many possibilities on a trial. This medication regime is tough and tougher for some. You want to do this only once with the best possible outcome. Your liver can wait it seems. Some trials don't let you get all the helper drugs a private MD can provide. My opinion for geno 1 is wait if you can until next year.
Judy
Judy
I wouldn't go for the low dose riba personally. I directed a friend to the bms 790052 trial which looks very good to me especially if you are willing to treat with soc alone anyway.
At stage 2 you could easily wait until next year and treat with soc plus boceprevir or telaprevir without any trial contraints. If you get into SOC arm of the trial your chances are only around 45 percent of success. The good news is that you can still treat with a PI next years because SOC won't give you long term resistance. The bad news is that you may have to treat twice unnecessarily, but then again if you don't respond they will probably stop anyway.
They allow all rescue drugs on your insurance in the 790052 trial which is great. The only true downside I can see is the 24-48 week tx period based on response, is that true for geno 1 also?
I would personally go for the 790052 trial, the has a lot of potential from what I have read.
- Dave
At stage 2 you could easily wait until next year and treat with soc plus boceprevir or telaprevir without any trial contraints. If you get into SOC arm of the trial your chances are only around 45 percent of success. The good news is that you can still treat with a PI next years because SOC won't give you long term resistance. The bad news is that you may have to treat twice unnecessarily, but then again if you don't respond they will probably stop anyway.
They allow all rescue drugs on your insurance in the 790052 trial which is great. The only true downside I can see is the 24-48 week tx period based on response, is that true for geno 1 also?
I would personally go for the 790052 trial, the has a lot of potential from what I have read.
- Dave
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