Boceprevir Trial Results - high viral clearance and low skin problems

[mremeet]

Below is an excerpt from the recent Schering Plough Boceprevir (formerly SCH503034). For those not familiar with this formerly murky drug, it's a protease inhibitor that has been developed more or less in parallel to Teleprevir (formerly VX-950). It's a potent drug when dosed in conjunction with IFN+riba, with antiviral performance that appears similar to Teleprevir's. But something really interesting here is that it does NOT appear to have the skin rash problem that Teleprevir has. Take a look at what has been reported below. This is a large study too (over 800 people enrolled), it's not some small/statistically ambiguous sampling. And they come right out and say "No increase in skin adverse events (rash) beyond what was seen in the PEGINTRON and REBETOL control was observed." That's impressive! Although they do mention that "Gastrointestinal events were the most common adverse events leading to discontinuation in the boceprevir arms." But then Telaprevir also caused a decent amount of gastointestinal distress too, so hopefully it's no worse. Anyway, this could really be something here. And again, this is a large study with both treatment naive AND non-responders included in it, so the results have some heft to them. Take a gander at the link below. Things are really heating up with HCV treatments, I honestly think this disease is going to be on the run within just a few more years.

http://www.schering-plough.com/schering_plough/news/release.jsp?releaseID=1064540

[Mr Liver]

It's exciting to see all of the new drugs currently in trials. HCV infection rates have been plummeting in the US and most industrialized countries since the early nineties. Treatment for HCV will start dropping precipitously as well in concordance with the lower infection rates. This dropoff is projected to begin around the year 2016. From this projected date forward the treatment population will decline rapidly. The pie will just keep getting smaller and smaller as the market dries up here and abroad.

So, its no wonder there are so many trying to grab the big prize ($$$) before the treatment population starts to decline.

God Bless capitalism.

Mr Liver

[viaduk]

Thanks for posting this encouraging information.

[copyman]

i wish it said that the duration would be shorter like VX but from what i read it seems like you still have to do 48 weeks, unless i missed it?  the reason i'm really looking forward to VX is because of shorter tx. i believe most of the permanent damage is done during the 2nd half of tx (last 24 wks).

[JOHNWS]

I started with all three. SOC and Boceprevir. It is 28 weeks all three then stop all three at the same time. I have been on the compound the whole time 26 weeks so far. No rash so far just anemia as well as some GI issues that come and go.

[Upbeat]

The trial data that might surprise everone is  Alinia.  Can't wait for the info.  It wasen't that long ago most on this board thought this was a scam. Who knows could be part of a cocktail like they do with aids.  With all this possitive info and if the odds are raised to 80% after only 12 weeks I might even jump into treatment.

                                                                                                                                    Ron

[Willy50]

It has been for many of the folks in the Prove trials.  

The arm construction looks a little different than the Prove arms as well.  Did you start on Boceprevir or was it added?  How many weeks on the compound?  I think I stumbled across the arms earlier today but haven't got em copied yet.

I think you'll do fine; you may have been on triple therapy longer than some TVR trial participants.  The rough data so far suggests that they are roughly equivalent.  We'll get a better handle on it in the future...and maybe the very near future.

best,
Willy

[JOHNWS]

Still in treatment week 26 or 28. I started with SOC and the Boceprevir. I have been undetectable the whole way. Since week two. At week 28 I stop everything. As you near the end you hope it was long enough

[Willy50]

Thanks, our posts crossed.  I've thought about trying to get into a trial.  I was pretty locked into trying out for a Phase 3 TVR but have started considering that there may be more than just the one upcoming and that the response rates may continue to go up.

I know a few folks that nearly opted for the HCV796 trial.  Kinda scarey reading about that one.  Overall the performance was good...... but they had an unexpected and high liver toxicity issue.  It really gave one pause listening to the conference when they pulled it from trials.

I hadn't yet compared interferon dosage in trials....was it less than SOC?  Also I wonder why that for Boceprevir but not for Telaprevir?  More incongruent info to be filled in.

best,
Willy

[Susie2007]

Thanks Mre. I appreciate the URL also. I am a bit disappointed in the null responder response of 7-14%. Personally I wish it had been higher for people like myself and Susan400. I've had almost a 2 log drop before at 12 weeks, but that was when I added Zadaxin to Peg/Riba.

[Willy50]

I think that drug was set to be used with Boceprevir.  At the time I thought that was pretty shrewd of SGP to latch onto that one; it looked like a good compound. It was a polymearase inhibitor and (it is theorised) that they may be the next generation to be combined with the PI's like Boceprevir or Telaprevir.  They killed the study however when liver toxicity turned up.  Some of the issues also didn't resolve after weeks and so could have signaled longer term damage.  I sure hope not.

We may hear more about that at the AASLD also.  It should be a pretty interesting conference.  

So far as the relapse rate the 2 drugs seem pretty similar today.  For want of other information ya might as well assume the 10%.  Who knows?  It may be better if there isn't a mutation issue.  There are lots of ways these compounds can be compared and this is only the beginning of the comparisons.

Are you still treating then on SOC or are you done?  Which arm are you again?

[Mr Liver]

Those trials will be coming where boceprivir will be used as adjunct therapy with SCH, peg, riba.

"Schering-Plough also is exploring novel therapeutic approaches with PEGINTRON in combination with investigational antiviral agents to optimize treatment for patients with more difficult-to-treat forms of the disease, such as those with HCV genotype 1 and nonresponders to previous therapy.

Schering-Plough is undertaking a large, fully integrated clinical development program for its oral HCV protease inhibitor boceprevir (SCH 503034), with the goal of developing new strategies for improving treatment outcomes for patients with hepatitis C.

As part of this effort, Schering-Plough has collaborated with Wyeth/ViroPharma and Idenix/Novartis to conduct separate in vitro studies of boceprevir in combination with their respective investigational HCV polymerase inhibitors, HCV-796, a non-nucleoside polymerase inhibitor, and NM107 (the active moiety of NM283, valopicitabine), a nucleoside polymerase inhibitor. These in vitro experiments suggest that the combination of boceprevir and either one of these polymerase inhibitors achieves additive antiviral activity and a complementary resistance profile; the combination of two agents increases the barrier for developing resistance to either drug alone.

In addition, Schering-Plough has initiated the HCV SPRINT-1 study (HCV Serine Protease Inhibitor Therapy-1), a large Phase II study that is currently enrolling 400 HCV genotype 1, treatment-naAve patients in sites across the United States, Canada and Europe. The primary objective of the study is to evaluate the safety and efficacy of boceprevir 800 mg TID in combination with PEGINTRON and REBETOL in the treatment-naAve patient population.

Schering-Plough also is conducting a large Phase II study evaluating the safety and efficacy of boceprevir 800 mg TID in combination with PEGINTRON and REBETOL in patients chronically infected with HCV genotype 1 who were nonresponders to previous peginterferon and ribavirin combination therapy. The study involves approximately 350 patients at centers in the United States and Europe. All study participants have completed treatment and are in the follow-up phase. Sustained virological response data from this study will be available later in 2007, and will help guide future clinical development of boceprevir.

My doc has been telling me for quite some time that the SP products will allow for a much smaller dose of IFN. And of course a shorter tx period  just as with VX.

Regards,
Mr Liver

[JOHNWS]

No problem. They asked us not to post however with me towards the end it may help others to understand what it is like going through the trials. For me it appears to be as effective as the other PI however as more folks post and data is released we may get a better understanding of its true effectiveness. I wonder what the relapse rate will be with the SCH drug once thearpy stops. For Vertex is looked like a 10% relapse rate. I hope the numbers are similar. I do remember reading where SCH was looking to combine with another PI to eliminate all mutations, I have not heard any new news on that as of yet

[Willy50]

Thanks for posting John.  It's really great to have some input from people on the trial.  Even though we are kind of comparing the two drugs and interested in seeing which is best or worse in various ways the bottom line is that it looks like a double win of sorts for all of us.  

There was a recent drug (actually several this summer) that died in trials that showed great promise;HCV796.  Anytime one of these drugs hits a roadblock we all get hurt a little.  Right now it looks as if we have 2 potential winners coming up in trials.  I also wonder what would happen if any of the rebounders in a Vertex trial were given the Boceprevir? (or vica versa?)  I also wonder what the effects would be in combining them, or a final switch of dosing before ending a treatment.  Could one eliminate a few varients and increase the SVR rate?  Some time in the near future we may see other trials where these and other compounds get tested.

best,
Willy

[mremeet]

susan - Absolutely it means it might work for you. I don't recall your whole treatment history, other than you've treated many times before. But this drug coming along with Telaprevir and maybe Alinia as another possible contributor, is a good omen. We might end up with all kinds of mix and match possibilities with substantial antiviral wallop. Including maybe combining both PI's together, both with and without IFN and/or riba. Now THAT would be something to see, especially for those with AIH or other intolerances to interferon and/or riba.

3tx - Yeah I saw what appeared to be the relatively high discontinuation rate. I'm guessing this thing really gives people the sh*ts, I mean it has to considering the dropout rate (unless anemia was making people drop like flies before they allowed procrit).  Also as far as the PCR results, I don;t think the difference between 10 IU/ml and 15 IU/ml is all that meaningful. Plus it may be a misnomer, our Telaprevir PCR results were presented to us saying "<30 IU/ml No RNA detected". But what it really meant was that we were below <10 IU/ml. Also some of us got a test result of "29 IU/ml", but what this really meant is that we qualitatively tested positive between 10 IU/ml and 29 IU/ml. Anyway, it might be possible they have reported their PCR testing sensitivity in a similary confusing way. Like maybe they can quantify above 15 IU/ml, but they have a qualitative test between 5 IU/ml and 14 IU/ml. But either way, in the final analysis I don't think it makes that much of a diff. Have to read through th e rest of this in more detail later when I have more time, especially considering they don't exactly report their results in a very straightforward manner.

[JOHNWS]

Interesting reads, thanks for all the information. As I have mentioned earlier I am in the SCH trial week 26 of 28. I have asked the Hepatologist who is involved in both the Vertex trials and the SCH trials, the difference in effectiveness. He said no difference between the drugs except rash with Vertex and more Anemia with SCH. The SCH trial is not blinded as we know which trial we are in and get our blood results back the following week from a draw. Undetectable in the SCH trial is 30 not 15 not sure that makes much of a difference.

[Willy50]

the 12 week discontinuation rate for Telaprevir was;
• The treatment discontinuation rate due to adverse events through 12 weeks was 11% in telaprevir arms and 3% in the placebo arm.

However as the treatment continued think it went to 17%.

My understanding is that the full dose for the SGP drug was 12% but that the people on the drug may have also been on rescue drugs during treatment with the compound.  If so....the drop out rates could have been comparable or even higher.  It's too early to tell, not from the data.  IF it's true that SGP decided mid course to add rescue drugs one could say that they were "cooking" the outcomes as well as making it less possible to compare the 2 drugs.

The outcomes in terms of efficacy may both be comparable but if rescue drugs were permitted in one trial but not the other it is an apples to oranges comparison.  This may also hold true for the comparison of sides but it appears that they may also share a similar drop out rate.

IF anemia is the sole issue of Boceprevir it may be a more easily treated side effect.  It will be interesting to see how it shakes out.  SGP spokesmen are claiming that they can be selling this in 2010.  Some people think that Vertex has a year to 18 month lead on SGP.  The news just doesn't all quite line up.

best,
Willy

[jmjm530]

It's not that they are using different points of measurement, it's that they are using tests with different sensitivities. A small but important difference. In other words, it doesn't mean that someone taking boceprevir who shows 14 IU/ml is counted as UND. Again, just means the tests they use have a different sensitivity. As to the difference in sensititivies, they are so close that I don't see this as relevant,.In any event, the critical data will be the SVR data.

-- Jim

[3txsofar]

Also - I should mention a point of measurement.  Schering is counting und as under 15 IU/ml, while Vertex is using under 10.  Can anyone comment on the significance of that difference?

[3txsofar]

Small but critical point - the discontinuation rates are similar to telaprevir, but are taken at 12 weeks of treatment, while the most recent telaprevir data is taken at the end of 24 to 48 weeks of treatment.

So, the boceprevir discontinuation rates could very well worsen.

[susan400]

Hey, maybe, down the road when it's approved and w/rescue drugs, then, maybe that will work for me?   I will not give up hope, I will not.......     Susan

[nygirl7]

achieved a high rate of early virologic response, with up to 79 percent of patients having undetectable virus (HCV-RNA) at week 12 of boceprevir treatment compared to 34 percent of patients receiving PEGINTRON and REBETOL alone.


That surely is fantastic.

[nygirl7]

Wow Meet that is great news!  I think the biggest hurdle that Tele has to face with the FDA is the rash that wipes out way too many people - get rid of that problem and have something viable...that would be the TICKET.  Can't wait to read this!