FDA PANELS THIS WEEK

[frijole]

This is our week.  April 27 the US FDA advisory panel meets to review bocerprevir.  The next day, April 28, the same panel meets to review telaprevir.  The FDA is supposed to publish  a reveiw of both on Monday, April 25, posted to their website:

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/ucm247236.htm

These panels should show us what questions or concerns are being raised by the FDA.  The advisory panel does not approve or reject the drug but this panel of experts will recommend or not recommend the drugs for  FDA approval.  The announcement for Merck's boceprevir approval is expected on May 7 and the announcement for Vertex is set for May 23.

Now I know there are those  who scorn news from the investment end of the research , but I figure, get the news where you can.  There is an analyst who is going to live blog both days.  (they both start at 7:45 eastern time).  He has a link so you can leave an email address for a reminder of his live blog.  He has apparently done this before with many drugs awaiting FDA approval.  I looked on the FDA website and found infromation on attending the event, but not anywhere  can you follow it through the FDA site.  Therefore, this may be our only insight into the meeting - real time.  Here is his article and in it, on pages 2 and 3 there are little boxes to put in your email address to be reminded of both blogs.  Hopefully they will provide the link in. I have never done this before but I hope it works.


http://www.thestreet.com/story/11089849/merck-vertex-prepare-for-hep-c-drug-panels.html


frijole

[Fnzol]

The Center for Drugs is not bound by an advisory committee recommendation, but they usually do agree.  Not always, but disagreements are rare.

[willing]

thanks for the update. At this stage it seems likely approval is a done deal and the big remaining unknowns are the package insert (specifying protocol for 'on label use' /duration etc.) and prices.

If anyone is living in CA,  contemplating off-label use of the PIs, and worried about inco denial, the following seems  as if it might be helpful:

California Health and Safety Code Section 1367.21
---
(a) No health care service plan contract which covers
prescription drug benefits shall be issued, amended, delivered, or
renewed in this state if the plan limits or excludes coverage for a
drug on the basis that the drug is prescribed for a use that is
different from the use for which that drug has been approved for
marketing by the federal Food and Drug Administration (FDA), provided
that all of the following conditions have been met:
   (1) The drug is approved by the FDA.
   (2) (A) The drug is prescribed by a participating licensed health
care professional for the treatment of a life-threatening condition;
or
   (B) The drug is prescribed by a participating licensed health care
professional for the treatment of a chronic and seriously
debilitating condition, the drug is medically necessary to treat that
condition, and the drug is on the plan formulary. If the drug is not
on the plan formulary, the participating subscriber's request shall
be considered pursuant to the process required by Section 1367.24.
etc...
-----

http://law.onecle.com/california/health/1367.21.html

[Trish77]

Thanks frijole...in Canada but watching developments from here as a sign of things to come for us also.

Trish

[frijole]

Willing - if I understand this , in California insurance companies cannot deny the Pi because it is new and expensive but  may deny it because it is not " on the plan formulary"
I think it would behoove the drug companies to get this on the plan formulary as soon as possible.

I wish there was some way to determine what the label will say.  I googled to no avail.    I  assume it will be available to all up front, but it will be interesting to find out.  I am sure whatever it is I will have to download it and take it to my local GI.

Do you think you will be able to participate in this live blog?  Because I work, I am not sure if I can.  Perhaps I will be able to leave it in the background all day. I am going to at least try.

Trish -- I think whatever happens here is good for Canada too.  I think I had read (on MH) that someone thought there may be a shortage of the meds but I had also read somewhere, maybe here, that Vertex has already contracted with a company in India for manufacture.  

frijole

[frijole]

Here is the question list for boceprevir review-- note the issue of anemia is the first on the agenda.  That makes me wonder if it will boil down to the safety of epogen, not the safety of the drug up for approval.
friojle


1. Please comment on the safety of boceprevir in patients with chronic hepatitis C genotype 1, focusing mainly on the hematological effects of boceprevir in combination with pegylated interferon and ribavirin (PR).
2. Considering the overall potential risk and benefits of boceprevir, do the available data support approval of boceprevir for treatment of patients with chronic hepatitis C genotype 1 in combination with pegylated interferon and ribavirin?
VOTE: Yes/No/Abstain
a.
If no, what additional studies are recommended?
b.
If yes, proceed with the remaining questions.
3. Please comment on the strength of the evidence for use of boceprevir in combination with pegylated interferon/ribavirin in prior null responders (defined as less than 2 log10 decrease in HCV RNA at 12 weeks during previous course of PR therapy), who were not included in the Phase 3 trial, P5101 in subjects who had previously failed PR therapy.
4. Please comment on the strength of the evidence to support response-guided therapy (RGT) with boceprevir in combination with pegylated interferon and ribavirin. Should certain groups of patients receive longer durations of boceprevir plus PR therapy than that evaluated in RGT arms?
a. Treatment-naïve patients with detectable HCV RNA at Week 8 and undetectable at Week 24 (late responders)
b. Patients such as blacks or those with advanced fibrosis or cirrhosis
c. Null responders (if recommended for inclusion in the indication)
d. Other groups, such as patients with poor interferon responsiveness (i.e. < 1 log10 HCV RNA decline after the 4 week lead-in therapy with

[frijole]

One more thing -- there is a link to the webcast through the FDA site (the first web address in my first post on this thread -- so you don't have to go through the investor blog.  That is good news.

[nygirl7]

By JENNIFER CORBETT DOOREN
A Food and Drug Administration staff review of Merck & Co.'s proposed hepatitis C drug boceprevir has raised safety concerns about anemia and other blood disorders.

But the review also said it agreed with Merck's analysis showing adding boceprevir to other drugs currently used to treat hepatitis C was significantly more effective at treating the condition. Broadly, two studies submitted to the FDA in support of boceprevir showed more patients responded to treatment by achieving a so-called sustained virologic response. However, certain groups such as African-Americans and patients with more advanced hepatitis C didn't respond as well.

Boceprevir faces a review by the FDA's Antiviral Drugs Advisory Committee on Wednesday. A similar product, telaprevir, from Vertex Pharmaceuticals Inc., will be reviewed by the panel on Thursday. Both drugs are widely expected to be recommended for approval, as they have shown strong effectiveness in improving the cure rates in patients that use standard therapy for the liver disease. Both drugs are known as protease inhibitors, which are designed to block an enzyme that helps the hepatitis C virus replicate.

Hepatitis C is a liver disease caused by infection with the hepatitis C virus, which is spread when the blood of an infected person enters the body of someone previously not infected. The Centers for Disease Control and Prevention said most people become infected by sharing needles or other equipment used to inject drugs, although the agency said people who receive body piercings or tattoos with nonsterile instruments are also at risk of becoming infected with hepatitis C. About 3.2 million Americans are infected with hepatitis C.

The FDA posted a review of boceprevir on its website on Monday. The main safety issue the agency raised with regard to boceprevir was an "increased frequency and severity of anemia" or a decrease in the number of red blood cells when boceprevir is added to pegylated interferon and ribavirin, two other drugs currently used to treat hepatitis C.

The agency also said there was an increased number of reported psychiatric symptoms of "suicidal and homicidal ideation" in the boceprevir arms of the studies compared to the control groups. However, the FDA said "it is difficult to make any meaningful clinical conclusions from this observation." Reports of suicidal ideation occurred in fewer than 1% of patients in the studies.

The FDA advisory panel is being asked to vote on whether it thinks the available data support the approval of boceprevir. The vote will amount to a recommendation about whether the panel thinks the agency should approve the product. The FDA is not required to follow the advice of its advisory panels but usually does.

The panel will also be asked to discuss whether certain patients, such as African-Americans, should receive longer therapy with boceprevir.

Merck, in a document also posted on FDA's website, said boceprevir "fulfils a significant unmet medical need" for the treatment of hepatitis C infection. Merck has proposed a brand name of Victrelis for boceprevir.

Write to Jennifer Corbett Dooren at jennifer.corbett-***@****

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[FlGuy]

So, you're watching with interest.  Does that mean that you expect to be jumping back into the fray in the near future?  At this point are you leaning towards one or the other as your prom date.  Oh yeah, congratualtions on makeing it through another season !

[frijole]

Yes, I am watching.  I don't know if I should wait until December when it would be 3 years from my last biopsy or jump in this summer.  It is not much fun deciding which year of my life I want to lose again.  The clinic where I consulted after I relapsed called a week or two ago but I haven't returned the call yet.  I haven't been to see any doc about C for two years.  

I am leaning to telaprevir, mainly because of the anemia issue.  Since I was anemic most of the prior treament, I would surely be more anemic with boceprevir.  Also I have never had skin problems to speak of so don't think I would be one of the 5% who got the telaprevir rash.

I guess one thing I need to be clear on is what the labels way about treatment time and when VL testing should be done.  I think it will have to be at 2 weeks after the PI is given. Then, of course 4 and 12 and the usual.  For example, if you are clear by sensitive test at week 2, can you treat for 24 weeks?  What a dream, huh?  There are some pretty significant issues that may not filter down to the lowly GI's who could care less about treating for C -- and I would prefer treating locally more than treating in Dallas - a 6 hour drive away.

So maybe you will see more of me soon.
frijole

[FlGuy]

"So maybe you will see more of me soon."

Hope so.

I'd vote not treating in the height of the summer where you live.

[nygirl7]

I cannot wait for you to be SVR Frijole you were one of the first friends I made on here .... and I still have my little bug doll right on the tv so I do think of you often :D

[frijole]

I see Andiama has posted a new thread on the upcoming telaprevir panel, but I will go ahead and print out the advisory committe questions here anyway to make this thread more complete

Draft Questions to the Advisory Committee
1. Rash associated with telaprevir use was common and sometimes severe and treatment-limiting and anemia was more frequent and more severe in patients treated with telaprevir. Please comment on the safety profile of telaprevir, focusing on the increased frequency and severity of rash and anemia when telaprevir is added to pegylated interferon and ribavirin. Do these adverse events affect your risk/benefit assessment and, if so, how?
2. Considering the overall risks and benefits, do the available data support approval of telaprevir for treatment of treatment-naive and treatment-experienced patients with chronic hepatitis C genotype 1 in combination with pegylated interferon and ribavirin?
VOTE: Yes/No/Abstain
a)
If no, what additional studies are recommended?
b)
If yes, proceed with the remaining questions.
3. Please comment on the strength of evidence to support response-guided therapy with telaprevir in combination with pegylated interferon and ribavirin for the following patient groups?
a)
Treatment-naïve
b)
Prior relapsers
4. Please comment on the strength of evidence to support a recommendation for use in specific populations, including but not limited to Blacks/African Americans and patients with cirrhosis. What, if any, additional efficacy or safety data are needed for specific populations?
5. Are there any other post marketing studi

[frijole]

Deb, thanks for the good words.  Remember the hair products you sent me?  That was pretty cool - they worked for awhile, until I had to go to Nioxin or I should say, nothing worked.    I want that SVR too one of these days .  My little microbe (my avatar on this forum) sits in my bathroom staring at me each and every day!  I need to order up some more for this next round...

FL guy - air conditioning is air conditioning.  I don't think I spent much time out of doors on the first treatment and I started in June then.  I  worry more about being able to work throughout treatment than the heat.  

Kathy

[susan400]

One thing that people who haven't treated before need to remember, if they are planning on Telaprevir...is that there is still a chance that you will get anemia choosing Telaprevir over Boceprevir.  I'm thinking that certain patients who are not well read up on the subject of Hep C treatments, may be going into this without all of the facts.  FACT - SOC in an off itself usually causes anemia.  Choosing Telaprevir will not change that fact.  I also realize that many patients will not have that much of a choice in the matter if their doctor insists on pushing the Telaprevir.  I, myself, won't use Telaprevir no matter what, even if for some reason, Boceprevir is not approved and the Telaprevir is.  I simply will not go through that ever again, no matter what.  But, that is my choice.  I make that choice because I have used the drug and did not clear and got the HUGELY bad rash instead.  I do hope that both drugs are approved so that everybody can have what they want.  Susan400

[willing]

susan400: wow - a pretty strong statement. I hope it goes well tomorrow.  Anemia is definitely a factor for both but the epo requirement for approximately half the patients is unique to boce (and seems to be it's biggest hurdle).

frijole: looks like you have a good chance of getting your shortened tx wish. I has missed the following interesting twist from the FDA's tela review:

"Although the RGT approach was not prospectively utilized or evaluated in any subgroup in Study C216, the Applicant has proposed dose recommendations to allow subjects who relapsed following completion of prior PR to receive a regimen of T12/PR24 if they achieve eRVR. They hypothesized that these interferon sensitive subjects could be re- treated with a shorter course of therapy. Because there are not adequate randomized, controlled trial data, we will ask the Advisory Committee to consider the evidence supporting effectiveness in this subgroup.

To support the proposed labeling recommendation, the Applicant conducted a retrospective viral dynamic simulation analysis of prior relapsers who achieved eRVR."

in other words through there was no phase III relapser 24w arml, vertex is now asking the fda to approve this protocol.  Supporting evidence is based on simulation, which would seem sketchy, but the good news seems to be the FDA appears  willing to go along with it:

"FDA pharmacometrics reviewers confirmed the outcomes of the viral dynamic simulation analysis by conducting a series of analyses to determine the likely efficacy of RGT in prior relapsers. "

evaluation  will rest with the advisory committee:
"Because there are not adequate randomized, controlled trial data, we will ask the Advisory Committee to consider the evidence supporting effectiveness in this subgroup."

but if they go for it, relapsers  may have a good shot at a tela 12/24 protocol - a nice surprise!

[Andiamo1]

I just want to wish you the best in your next treatment.

I found anemia worse on triple therapy with Telaprevir than with SOC and had to dose reduce Riba after 35 weeks, but I was randomized into the 24 + 24 group and, thankfully, no one else will have to do that.

I didn't see this thread when I started the Telaprevir thread; I wouldn't have started a separate thread if I had.  Too much ADD these days from lack of sleep and I was excited by the news of an imminent approval.

[AnotherJourney]

Thanks for posting that the drug is not approved today. I was following that the advisory panel met today and tomorrow and had hoped to hear of approval...but at this stage, what is a a few more weeks....and then as others point out...it may take even longer until the ins company will approve...but at least SVR seems more real now than ever.
Hugs to all who have been waiting such as I have.

[AnotherJourney]

Looks like we might take this journey together...I am a former slow responder and while it is with dread that I think of going back into "the rabbit hole" of treatment, I am thrilled to know it will now be shorter.

[spectda]

Anemia with triple therapy including boce is about 50% compared to about 30% in the soc group. I am certainly a supporter and thankful for boce, but the anemia is nothing to sneeze about.

the worst side effect of boce is that you might lose your back hair, so buyer beware!. Maybe deb's hair products would help but she never offered :(

Good luck and hopefully this next attempt will put this disease to bed for good.

-Dave

[nygirl7]

AH Dave all you had to do was let me know....you know I would have sent some out to you right away!  Boy we girls tried everything to keep our hair ... but it did grow back (although not on my back thankfully!)

[frijole]

They are almost to a vote (it is 1:30 CST).  The FDA live feed has been intermitten plus I am at work and cannot listen to it.  Therefore, I have opted for the investment guy - Fuernstein's live blog.  At least I can watch it and still do a little work (ha ha).

Biggest issues with BOC are the anemia and the fact that they have not tested on null responders.  They have presented some information on null responders during the testing who were in the placebo group and then given the BOC and their response, but I gather that the FDA shut them down (since the info was not previously presented).  At any rate, the jury is still out but it appears they will recommend to approve.  I will be back later
frijole

[frijole]

adam feuerstein: here are the voting questions:

1. Please comment on the safety of boceprevir in patients with chronic hepatitis C genotype 1, focusing mainly on the hematological effects of boceprevir in combination with pegylated interferon and ribavirin (PR).
2. Considering the overall potential risk and benefits of boceprevir, do the available data support approval of boceprevir for treatment of patients with chronic hepatitis C genotype 1 in combination with pegylated interferon and ribavirin?
VOTE: Yes/No/Abstain
a.
If no, what additional studies are recommended?
b.
If yes, proceed with the remaining questions.
3. Please comment on the strength of the evidence for use of boceprevir in combination with pegylated interferon/ribavirin in prior null responders (defined as less than 2 log10 decrease in HCV RNA at 12 weeks during previous course of PR therapy), who were not included in the Phase 3 trial, P5101 in subjects who had previously failed PR therapy.
4. Please comment on the strength of the evidence to support response-guided therapy (RGT) with boceprevir in combination with pegylated interferon and ribavirin. Should certain groups of patients receive longer durations of boceprevir plus PR therapy than that evaluated in RGT arms?
a. Treatment-naïve patients with detectable HCV RNA at Week 8 and undetectable at Week 24 (late responders)
b. Patients such as blacks or those with advanced fibrosis or cirrhosis
c. Null responders (if recommended for inclusion in the indication)
d. Other groups, such as patients with poor interferon responsiveness (i.e. < 1 log10 HCV RNA decline after the 4 week lead-in therapy with PR)
5. In addition to pediatric studies, are there any other postmarketing studies you would recommend to further define risks or optimal use of boceprevir in clinical practice?  

[frijole]

chair is summarizing question 1 -- consensus is that while concerns raised about hematological effects of BOC they are well managed...

[frijole]

question 2 - 18 yes 0 no  
Wednesday April 27, 2011 3:16 adam feuerstein