FDA review of Telaprevir

[Andiamo1]

Panel finds Telaprevir more effective that Boceprevir!!!

http://finance.yahoo.com/news/FDA-says-Vertex-hepatitis-apf-4267261290.html?x=0&.v=2

[willing]

agreed that for many with known poor ifn response the choice to treat now with the 1st gen PIs will be a tough one. However an  important point is that the question in the near future  will not be how  effective bms790052 or r7128 are for  non-responders but how the combination of two daas + soc handles non response. And we already have preliminary  answers to that from the easl-09 inform1 data and the easl-11 bms data: two daas + soc can handle null response with no trouble. For example from the easl'11 data

"The Phase 2a trial, which included 21 genotype 1 null responders, compared 2 arms, one using only 60 mg once-daily BMS-790052 plus 600 mg twice-daily BMS-650032 (Group A) and the second using the 2 new drugs in combination with 180 mcg/week pegylated interferon alfa-2a (Pegasys) and 1000-1200 mg/day weight-adjusted ribavirin (Group B), all for 24 weeks.....
In the group randomized to receive quadruple therapy, 10 of 10, or 100%, reached SVR at 12 weeks, and 9 of 10 (90%) did so at 24 weeks -- a high cure rate in this difficult-to-treat population. "
from
"http://www.hivandhepatitis.com/2011_conference/easl2011/docs/0412_2010_a.html"

Roche seems to be dragging its heels with r7128 (perhaps they're quite happy with the pegasys cash cow?) but bms is moving forward aggressively. Whether it's worth a year of h*ll for a 30% odds of success as opposed to another couple of years of damage, possibly mitigated by anti-fibrotics is not an easy choice. I personally opted to not wait any  longer even though I could likely have cut tx time by half by waiting another couple of years.

[Andiamo1]

I think the decision to treat when you are in a 50% or less probability of SVR is dependant on where you are with disease progression.  If you are stage 3 and progressing rapidly, the downside of waiting could be a liver transplant.  The newer drugs are still years away from FDA approval and may not work that much better for null responders.

If you try and fail, there is a high probability of the virus reverting to mostly wild type by the time the new drugs are available.  The efficacy of a combo of the polymerase inhibitors and the first or second generation PIs will probably not be affected by the fact you treated with a PI 3 years prior.

[willing]

Anotherjourney: that quote is from the fda review of the vertex submission given to the advisory panel

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM252561.pdf

it compares with tela response to the soc response among previous tx failures.  The full quote is

"The SVR rates for the pooled T12/PR48 groups were significantly higher than for re-treatment with PegIFN/RBV alone, 65% and 17%, respectively, and SVR rates varied according to prior treatment response: prior null responders 31% and 3%, prior partial responders 57% and 15%, and prior relapsers 84% and 24%, respectively."

while there's no doubt  31% and 51% look a lot better than 3% and 15% they may not look good enough to warrant risking tx failure with the 1st gen PIs. As far as I know, vertex never released the 31% number on its own.


Andiamo: agreed, single number, population-average,  summaries are almost always suspect: on average, hardly anyone is average.

[AnotherJourney]

You stated "prior partial responders 57% and 15%" - seems like a wide range, was there different classifications for partial responders to make the range so wide?
Cat

[frijole]

Isobella --
You got it -- let's get this show on the road.

Can do -- let's pump the stock if it gets this moving!  BTW - if you didn't buy your stock today you are out of luck.  They say it will not trade tomorrow when the FDA panel is in session -- too volatile, I hear.

frijole

[Isobella]

Thanks for the links, Eric, Fret and again to frijole for the link last week.

It doesn’t really matter to me the difference between 79% and 70%...splitting hairs when compared to the current rate of cure.

I may have made some money on stocks during this rollercoaster, but the irony is that they’ll get it back in spades when I pay for our next round of tx.  It is so obviously worth it whatever the price, but as much as I’m anticipating the release, I’m anticipating that final number.

FDA….let’s get this show on the road and get these drugs approved………

[Andiamo1]

Yes, collapsing the entire choice into a single number is not useful to anyone but a stock analyst.  comparing the results of each trial is also not going to be that helpful, since the trials are an approximation  of real world results.  The standard deviation in these trials make small differences in results meaningless, since they are within the margin of error.

The only important piece of information here is that both drugs seemed to get a favorable review and are likely to get FDA approval within 2 months.

[neptune235]

Thanks for those numbers...

[willing]

collapsing comparison to a single number is a hopeless exercise, nevertheless focusing for example only on  the  tx naive data  from the FDA's tela review (pdfs are from the link above):

"In Study 108, the FDA review confirmed the overall SVR rates of 73% for T8/PR and 79% for T12/PR compared to 46% for the PR48 control arm"
and
"In Study 111, our review confirmed the overall SVR rate of all study participants was 72%"

whereas for boce overall results from study P05216 were:

SVR n(%) control 138 (38) Response-guided 233 (63) BOC/PR48 242 (66)

and slightly better among non-blacks:
SVR n%  control  126(41) Response-guided 211(67) BOC/PR48 213(69)

so it looks like among naives there was one arm of one tela study (108)  where response reached 79% and this beats anything reported by boce among naives. However in that same tela study,  svr among soc controls was also  8% higher than in the comparable boce arm (noise? patient selection?)

Overall tela's  claim of a few percentage points over boce seems justified from the data reported .

It's also  interesting that the FDA review team finally released the number Vertex has been hiding. Among non-responders who have treated previously:
"SVR rates varied according to prior treatment response: prior null responders 31% and 3%, prior partial responders 57% and 15%"

[can-do-man]

Sad that some still want to pump their stock.

[willing]

this is the sort of marketing-driven copy/paste nonsense that might be comical were it not for the fact that  patients are at risk of making treatment decisions based on it.

What the FDA 'briefing information' actually said is publicly available through a link frijole posted earlier:
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/ucm252559.htm

this includes the FDA review summary and the bulkier (147 page) vertex submission as pdfs. Neither makes any mention of boce/tela comparison.

Patients making their triple tx decisions will  be better served by trusting peer-reviewed publications or actual FDA docs instead of marketing hype. The fundamental issues in the choice are choice  of sides (1st question on the list put to the advisory panel) and ability to estimate the ifn response via lead in.

[fretboard]

Absolutely great news but who is going to represent us heppers before the fda hearing.  If we can't get one we at least need the other.  Someone who is in that area needs to check it out, I'm just sayin'!!  Ya gotta be proactive with this here HepC.  The hearing starts tomorrow!!  Ignore my post if the topic has been covered.  

http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm252750.htm

[Andiamo1]

Overall SVR rate 79% for Telaprevir and 70% for Boceprevir according to FDA

[fretboard]

Good info, I'll chk it out when I get home but the bigger question is who is going to the fda hearing about these drugs tomorrow and the next day?

http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm252750.htm

[neptune235]

Good -- glad you agree.  I thought maybe I was reading it wrong.

I haven't poured over the stats from all of the trials, but my general impression was that the SVR rates for type 1a and 1b in tx experienced patients was very close.

Maybe TVR had a rate that was 1-3 points higher, but I don't recall that it was any higher than that.  

Am I in the ballpark?

[Andiamo1]

I think you are correct and I was hasty saying the FDA came to that conclusion.  I don't see how they could not when you put all the numbers side by side though.  

It does appear that the quote  "general, telaprevir's cure rates are higher than those seen with Merck's boceprevir. The two drugs are expected to compete in a multibillion dollar global market." Was written by the author of the article, not the FDA.

Sorry for the hasty post.  The stock market is reacting very strongly to the news.  VRTX is up 12%

[neptune235]

The article says that "in general", telaprevir is better.  I cannot tell from the article if that is an opinion of the author, of if the author is relying on some analysis that goes unmentioned in the article.  

It does not appear (by my reading, anyway) that a "panel" came to that conclusion.

Is this quantified somewhere?