Boceprevir FDA application

[frijole]

Merck, known as MSD outside the United States and Canada, announced today that regulatory applications for boceprevir, Merck's investigational oral hepatitis C virus (HCV) protease inhibitor, were submitted in 2010 and have been accepted for expedited review in both the U.S. and the European Union.
that offer major advances in treatment, or provide a treatment where no adequate therapy exists. FDA's goal for completing a Priority Review is six months.

The U.S. Food and Drug Administration (FDA) granted the New Drug Application (NDA) for boceprevir Priority
Review status, a designation given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. FDA's goal for completing a Priority Review is six months.

Additionally, the European Medicines Agency (EMA) accepted the Marketing Authorization Application (MAA) for boceprevir for accelerated assessment. Accelerated assessment is available for products that respond to unmet medical needs or represent a significant improvement over current treatment options within a major public health interest such as treatment of hepatitis C virus infection.

Data in the NDA and MAA have been provided in support of the proposed use of boceprevir for the treatment of chronic HCV genotype 1 infection, in combination with standard therapy, in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.

"We are pleased that the FDA and EMA have accepted boceprevir for expedited review. Our goal is to be able to bring forward a new treatment option for patients living with chronic hepatitis C, and we are now closer to that goal,” said Dr. Peter S. Kim, Ph.D., president, Merck Research Laboratories

[merryBe]

I know this will sound crazy, but since you are already treating, if one drug came out weeks or months before the other, I'd use it.

Look you could always switch PI's when they both arrived, assuming you preferred the stats on the latter release, but the sooner you get some sort of PI going the sooner you could be done with tx, so in your case it might be worth at least exploring the options.

I don't see what difference doing it this way would make in terms of your tx since you aren't in a trial. You can do whatever your doc will go along with.

As far as all the discussion about rescue drugs goes, perhaps one drug is more symbiotic with the riba, perhaps there are absorption differences there as well, as there are with riba as regards BBMV uptake. In any case, I'll have to keep an eye out for studies on PI absorption, ; )

mb

mb

[willing]

yup - since the clock is ticking I'll probably go with the first one available. If I hadn't had to drop the Alinia it might be more of an elective option.

[can-do-man]

Hi ya kit kat, your a wise person so you will make the right decision...... Really great new about ejoli, she still might need the TP but it looks as if she will be HCV free.

can

[frijole]

Since I did have anemia for most of treatment and I intend to work through treatment, and I don't have sensitive skin, it appearsTelaprevir would be the best for me. However, I like the successes I am seeing with hard cases on Boceprevir like Can do man and Ejoili to name a couple.

I would like to schedule a summer appointment with a hepatologist in Dallas and discuss it.  However the clinic where I consulted after relapse could never seem to get any of the R/R trials - only the treatment naive.  So whereas they have local data on that, I am not sure they are any more informed than me on responder/relapser results.  

So the jury is still out.  Are you still on line to add a PI to the mix as soon as they are out?

frijole

[willing]

so do you already know when/where you're going to put down your chips? I haven't seen much reason to make a clear call one way or the other. I don't trust my Drs (mostly because they can rarely be trusted to have had time to think about the  chart notes before making a  'decision') and I absolutely don't trust the drug cos or inscos, but I do trust my fellow lab rats and have been paying close attention to what Spectda is going through and the rash from h*** stories.

re ERISA I'm still hazy on the details and will  know more after I meet with the lawyer, but my understanding is that after the insco internal appeals of denials are complete it ends up in federal court under ERISA law as is the case for other employer-contributed benefits (401K, disability, COBRA). Different district courts have different precedent about whether judicial review is de-novo (all facts) or limited to procedural review, so the contents of the insco internal reviews submitted in  district court are critical. I'm in the 9th circuit which in principle allows a de-novo review.  

[miked]

Sorry, I reread the thread and your comment cracked me up.  Thanks.

About your reply to Willy...I wouldn't make a decision to go with whoever is first to the market.  Willy's been a patient "wait and watch" person for a long time and making an informed decision.  It's a slow moving disease.

[miked]

Hi Deb, always good to hear from you.  

Agreed that docs made their minds up during the trials.  As a former 1b, my research pointed to VX950 as my best option.

You doing OK?

Take care.

[miked]

Your comment cracked me up..."Hoping to be fainting or scratching by summer!".  I've been smiling about this all day.

I was in Vertex' Prove 3 trial and SVR'd after 24 weeks of tx.  Got the rash from he11 during tx.

Best of luck.

[nygirl7]

Hey Mike -- thats what I think :D

[miked]

This is a very interesting turn of events.  It's also interesting that Vertex stock is up today to $39.25.

I've been intentionally quiet about the topic but would appreciate more insights into what you guys think.

Take care,

miked

[frijole]

I really hope that this is a comparison thread for Boceprevir and Telaprevir.  We all need to make informed decisions this summer.

I do think there are a lot of folks who will take the first one out of the starting box.  But my thinking is that the FDA will approve both at the same time, allowing competative pricing.  

I have not heard as many comments about stomach problems with Telaprevir as with Boc.  I think we all have to look to our natural status.  If we are prone to stomach disorders we should not take Boceprevir.  If we have sensitive skin we should not take Telaprevir.  As far as the anemia, I think many of us will take epogen whichever we take.  It seems to me that the drop outs in the Telaprevir trials would probably be those who needed epogen (except for the rash drop outs).   The anemia is one issue that I (personally) would like the advice of a hepatologist on.  I would like to be able to show a doctor my chart on my hemoglobin counts and Procrit shots and have him recommend whether Boceprevir would be too much.  

Willing - what is the deal with ERISA?

frijole

[Trish77]

"I hope that they are both approved.  I believe that while they will be similar each one may have it's strong points for certain people. "

I think that's the key for me also.  Personally, I've favoured boceprevir more watching both of them for my own reasons, others would say telaprevir and isn't it great if patients had choice and more options.  So having both of them come to market is a good thing and hopefully insurance companies will not restrict to one or the other and treating docs for that matter and will take the one that suits their patient the best.  To me, key is to be able to be adherent and complete treatment and choosing the drug wisely from that perspective is important.  Adding a PI adds another layer of complexity to treatment - we haven't had to concern ourselves with resistance profiles until now and adherence will be more critical than ever with regards to resistance profiles as well.  Having a knowledgeable doctor becomes important who understands the extra variables that adding a PI brings.  Thankfully, one of those variables is significantly higher SVR rates.  Some things are worth the extra trouble.

[willing]

agreed that epo definitely will cost more than treating rash but until the relative cost of tela/boce is revealed it's hard to know if that's a big  factor.

The data above suggests most (61% and 54% of the two tela arms) will deal with rash - not the other way around, though hopefully for most it won't be as hellish as it was for susan, mremeet and dointime (and they were not alone given the posts in the archives)  Let's hope!

Personally I think for those hoping/planning to be early in line there's very little that will surface between now and July other than cost and manufacturing availability. In terms of making a choice, the phase III data is in (even if not in complete detail), and the brave pioneering fellow lab rats have shared their sx stories and results.    

[Willy50]

discontinuation rates SOC

http://www.hivandhepatitis.com/hep_c/news/2011/0107_2010_b.html

(end of 4th paragraph)

"Although the first DAAs still require concomitant use with current HCV medications, these new compounds will shorten the length of time on pegylated interferon and ribavirin therapy, which hepatitis specialists noted is often difficult to tolerate and has significant adverse event profiles that limit treatment in many patients. According to the latest data, between 15 and 30 percent of HCV patients started on current HCV therapy are unable to complete the year of treatment now required because they cannot tolerate the side effects."

--------------------------------------------------------
The upshot is that when things get out into the real HCV infected population things may change some when the infected aggregate gets treated with the aggregate of doctors that are out there....

It is still quite possible that a shorter triple therapy treatment, in spite of being more intense may have comparable discontinuation rates as SOC.  
There are a few compounds being tested for example, that reportedly have fewer sides than TVR or Boceprevir.  If they can also provide a shorter TX period presumably there will be a lower dropout rate.

Willy

[Willy50]

I guess that it is a Boceprevir thread, i should stay on point.

I think we will see meaningful comparisons at the spring EASL.  I don't think that much can be unblinded at that point and the best arguments will be laid out with beautiful graphs and pie charts why each drug is the best.  : )  

I hope that they are both approved.  I believe that while they will be similar each one may have it's strong points for certain people.  I think that the spring presentations will help aid one in ones possible future choice of drug.  I rather assume that by the fall AASLD they will be treating patients with both drugs and so...... the forums could become busy places.  I also think it is a reason we will see a large information push here soon.

willy

[pcds]

I had anemia very early in tx so Boc is not likely my choice.  I had the riba rash, but it was managed.  Will discuss further with new doc in March.  But I think it will be Tela due to my prior anemia so early.

[Magnum]

For those experiencing horrendous rashes, this is the drug my Gastro wants me on. However, the caveat with this drug is that it has the other side effect of Anemia. Decisions, decisions...

Magnum

[Andiamo1]

Thanks for the data.  I think the lack of rescue drugs during the Telaprevir trials accounts for some of the dropouts.

[Willy50]

Safety & Tolerability Results from ILLUMINATE

The safety and tolerability profile of the telaprevir-based regimen in the ILLUMINATE study was similar to results reported from the Phase 3 ADVANCE study. The most common adverse events reported in the ILLUMINATE study, in order of frequency, were fatigue, pruritus, nausea, anemia, rash and headache. The majority of these adverse events were mild or moderate. Adverse events leading to discontinuation of all study drugs during the 12-week telaprevir dosing period occurred in 6.9% of people in the study. Treatment discontinuation of all drugs due to anemia and rash occurred in 1.1% and 0.6% of people in the study, respectively, during the telaprevir dosing period. Like in ADVANCE, the use of erythropoiesis-stimulating agents (ESAs) was not allowed in this study.
--------------------------------------------------------------------------------------

Notice the above only apples to the FIRST 12 weeks?

here are some results from an earlier trial
http://www.natap.org/2008/AASLD/AASLD_43.htm

Treatment Discontinuations

The overall proportion of discontinuations of all drugs for any reason was 15% (Table 2).
------------------------------------------------------------------------------------------------

It seems to me that I've heard a full course of SOC creates about a 11% drop out rate.

The 15% drop out rate pertains to a phase 2 trial and it may be that the drop out rate was improved upon.

IF so..... the drop out rate may come within a few points of the SOC drop out rate, and without the use of rescue drugs.
----------------------------------------------------------------
I would also point out that many so called drop outs or failures may go on to SVR.  Yes, they may have had to drop out due to the sides BUT success was still achieved.

willy

[Andiamo1]

You are correct, I didn't get the bad rash, but neither do most people.  I forget the numbers though.  Mremeet did get the rash and you did, but I don't remember anyone else.  Am I wrong about that?

[susan400]

If I remember correctly, you didn't really get the rash from h*ll w/Telap., like some of us did.  It's not as easily tolerable to those of us who got it real bad, as one might think.  I was itching so bad I thought I was going to die and on top of that my skin had huge open sore-like welts/blisters.  It most certainly was not tolerable by any stretch of the imagination, in my opinion.  The cortizone cream didn't do anything to really help matters whatsoever.  Any type of normal itch creams like one would use for a Riba itch, did not work for the Telap type of rash.  Not even close to being comparable.  I've had a Riba itch and it was nothing compared to this.

Susan400

[Andiamo1]

I don't think diarrhea is a serious side effect of Telaprevir.  No one I knew in the trial including me experienced it.  A rash is the most common side effect and most people were able to tolerate it.  Many people, including me, experienced slightly worse anemia.  I did experience nausea, but treated it with large bowls of Dove unconditional chocolate :).

I was randomized into 24 weeks of Telaprevir and SOC + another 24 of SOC.  On the first day of treatment, I had a PCR done every hour. My viral load dropped from 8 million to 4 million in the first hour and down to 1 million after 4 hours, <30 at the end of the week and undetectable at week 2. I have been undetectable since then and I am now 3 years post treatment.

[alphonsos]

it really doesnt matter what we think - we will have very little choice in which drug we receive and very little choice on how long we will be on it - if youre having severe problems with rash and or diarrhea you might be switched and if youre having severe problems with anemia you might be switched - the big problem is that most likely treatment will be stopped until a managed care team figures it all out

[Trish77]

Telaprevir has a higher rate of side effects on diarrhea and then rash by a wide margin.  Anemia is a key factor in Boceprevir.  Depends on your outlook.  When adherence is key to success and management of side effects is part of the success of adherence, Telaprevir is potentially more of a challenge compared to Boceprevir, although cheaper perhaps to manage side effects like rash and diarrhea than anemia that could require rescue drugs.

If I were a patient going in......well, interesting.