The failure of the GS-7977/ribavirin regimen in null responder genotype 1 HCV patients is devastating news for Gilead. This indicates to me that there will also be a very significant relapse rate in the treatment-naive group.
Remarkably, the pundits are sticking by Gilead's GS-7977:
"Citi still expects Gilead to be the first to market with a highly effective, all oral treatment for hepatitis C genotype 1 patients."
"Morgan Stanley is still optimistic that the potential efficacy of Gilead's 7977 as a treatment for HCV will be validated and maintains an Overweight rating on the stock."
And from the Motley Fool, regarding oral regimens in genotype 1 HCV patients: "Gilead still seems like the smart bet to be the first to market."
My understanding was that Gilead was and may still be the front runner for an all oral therapy. Previously, I had read that they had planned to get an approval in the second half of 2014. Does anyone know how the latest findings impact the timeline? Any delay should be worth billions of dollars to Vertex.
Approval for what label?
This is not a facetious question. What few if any have commented on is what effect the recent failure of Boceprevir in HCV/HIV co-infected patients will have on the FDA. They essentially got burned by Merck's lack of data for co-infected patients and will likely be much more cautious in the next go-round for all HCV drug candidates in how the labeling relates to patient sub-populations.
Has a consensus developed regarding just what 'interferon-intolerant' means?
I wouldn't scratch GS-7977 off as a dog yet. It still seems to be a very good drug used as a triple combo, it just isn't working out to be the silver bullet that it was hyped to be as an all oral solution. I remember the triple combo trial results to be 90% or above SVR. If those figures are reliable then this drug is still stiff competition, with a slight advantage over Vertex being a real possibility in the future.
compare for the board the data (apples to apples, pls) of GS 7977 and Mericitabine (aka RG7128). Also note there is no question regarding 7128's safety. MTD of greater than 9 g/kg (that's 'nuff to choke a damned horse)...placebo-like effects at 9g/kg. such MTD data is not available for GS 7977 as far as I know.
For 7977/peg/riba triple, gild has to run a double-blind trial with a good control arm. The control arm should be Incivek triple or the old SOC. They have to run a controlled trial which VRUS has never done. They have to show that they don't cherry-pick easy-to-treat patients (such as young in age, or male, or early stage, non-cirrhotic, IL28B CC patients etc.).
Why aren't we talking about the real future which is likely the combination of vrus 7977 and a PI. Which is under one roof with VERTEX Incivek and an Alios nuc similar to 7977..thats the silver bullet. Probably on market if no safety issues by 2014-15.
First, with 100% relapse of null, even if naive test reaches 100% SVR, it is still 80%.
Second, when you have 100% null failure then the naive sauccess can not be 100% since it defeat law of probability. If the drug really works then it may get 70% SVR of naives.
GS-7977 may be in range of 50% to 60% at its best.
No, it won't be a competition at all since there is a risk of making naive patient, null patients.
GILD management and BOD have gone a wrong way and their greed has blinded them. They want to cash in fast and easy in a short time. Unfortunately this is not the sector that produces this kind of results that easy. They probably were in close contacts with some analysts for advise and support, however the recent setback and failure has forced them to be a bit manipulative since they have some pay backs to analysts and analysts customers who have been supporting the stock.
Paying $11 B for a drug that does not work must be taken seriously and those involved are trying to spin every trick in the book to land the failure softly. When GILD presented a conflicting data and did not admit the complete failure, it served only one purpose and that was because of giving their investors some time to exit with smaller losses. More failures will be announced later to soften the losses and I hope GILD managements put their minds in the medical business than going to bed with some crook analysts to hide their failure.
Well this is very bad news for a friend of mine who has had hepatitis c for 40 years and was hoping for the new Tx. He tried interferon alone when it first came out and though his viral load went way down...it did not kill the virus. So is he a "null responder" or what is he. Anyway, there seem to be some very knowledgeable people on this board. What would be the best course of action for him to take now??
A treatment-naive patient pool identical to Phase III TVR trials would contain a potential 15-20% of null responders (if they had been treated with IFN/Riba only). 68% of the 15% didn't achieve an SVR, and this make up 10% of the entire patient pool. This potentially-null group who failed TVR is exactly one half of the all failed group of the ADVANCE trial.
Hence, if the naive patient pool for the 7977/Riba trial is much like the pool assembled in TVR Phase III, potetially-null patient make up 10% of their patient pool. I estimated their contribution to the SVR rate of this naive pool and it is less than 3% if only 2 of 8 achieved the SVR if SVR = their SVR4 (this is very generous). Likewise, I estimated the contribution to the SVR rate from the potential partial-responders, relapsers, and from potentially SVRed patients assuming that the numbers are averages of T/P/R results and P/R results. I get only 68% for the chance of SVR for 7977/Riba trial.
The estimate method posted above is complicated and one number was written wrong. So I use a simpler method to estimate the SVR again.
A treatment-naive patient group identical to Phase III TVR trials would contain a potential 15-20% of null responders if they had been treated with IFN/Riba only (REALIZE trial). 68% of this 15% didn't achieve the SVR (REALIZE), and this make up 68% x 15% = 10% of the entire patient pool. This potentially-null group who failed TVR is exactly one half of the all failed group of the ADVANCE trial. We use this fact to estimate the failure rate of treatment naïve patients undergoing 7977/Riba trial.
The rate of failure among potentially-null patients in the 7977/Riba trial is at least 6 out of 8 (could be 8 out of 8 if taken 24 wks post). Let’s take this number 6/8 = 75% as the failure rate for the potential-null naïve patients. Hence, if the naive patient pool for the 7977/Riba trial is much like the pool assembled in TVR Phase III, the failure rate for the potentially-null patient make up at least 75% x 15% = 11.3% (at worst 20% = 100% x 20%) of their naïve patients. The failure rate from other groups would be about the same as this number if the responses are similar to the TVR phase III. The best one can come up with for the failure rate is about 22.6% and the worst number would be 40%.
So, the SVR chance for the naïve patients having gone thru 12 wks of 7977/Riba would be about 77% at best and 60% at least.
I think GILD is hiding true data.
Out of 10 patients, 2 unavailabe, 6 relases and 2 that relase later or did relapse but data were delayed.
If 100% RVR continued, probably most relapsed.
I can't trust GILD and no one should.