Ok here is why you get long. You need to look a little further then most. First, it makes no sense to ask per Dr. Marcuse from the VRBPAC Panel for another trial around 8,000 to 10,000. To ask for this is a waste of company time and money. The events they are concerned about are rare events and as such you would need a trial closer to 30,000. For more detail on this see Dr. Gellin's comments from the Panel who incidentally voted no. Ok, you got that? Now you need a trial of about 30,000 patients and the only way to get that is to have a POST licensure trial and that means the indication has to be broad enough to contain those potential patients i.,e you need more than patients with CKD (this was bantered about as another possible FDA limitation). Now here is the kicker. Read the Panel transcript and you will note on p. 169 that the two most influential panelists who voted no (remember the vote was 5-8 against that the database was insufficiently powered with 1 abstention) were Dr. Gellin and Dr. Wharton (the other 6 were all professors while Dr. Gellin and Dr. Wharton hold influential positions with the CDC and NIH). Both Dr. Gellin and Dr. Wharton expressly state that they would vote YES with a limited introduction of the vaccine in conjunction with a post marketing study. And folks this is what the company initially wanted! It was the FDA that, in a pre-BLA meeting in Feb. 2012 unilaterally expanded the indication to all healthy adults from 18 to 70 when the DVAX was only looking for 40 to 70. Thus, it makes no sense for the FDA to conclude anything other than 40 to 70 for those at risk i.e., those with diabetes, smokers, obese and CKD in conjunction with a large post marketing study. This satisfies the Panel, the company and the FDA. See you Friday night at 5 dollars!
one last thing......ask yourself,"will the fda see a need for heplisav. will the risks of this new drug (not much difference then existing) out weigh the 5 mths of those folks not being protected in the medical field by mercks and glaxo?"mmmmmmmm.i think i'd like my doctor and dentist "helpers" to have heplisavJMHO
chess, you are talking here about "random sampling""probability & statistics".....which all along i knew that a larger group , even your 30k wont do it. try a million.not joking. the panel knew this too....they are scientists. to explain myself here...........think about buying 30k power ball tickets or 1,000,000 which group will hit or hit anything? post study for sure. if the "theoretical" adjuvent problems are real? which population would you not give it to? i dont see how any of the age groups could be left out on the post studies. example,everyone has cancer cells ,they lay dormant......so the "theoretical" adjuvent problem would activate these in any age. and if the fda only approves one age group??? how will the other ever get sampled properly(random sampling 1mil)? it's all or nothing boys.JMHO
Here is the quote from Dr. Gellin who I contend is the most influential person on the panel and who had the most insight.
We are talking about safety, but we
always have to keep this in the context of benefits as
well. In the beginning it was outlined why this product
offers some advantages, and Melinda highlighted a few of
those, that there are populations for whom the current
products are inadequate. There are programmatic issues
where reduced numbers of doses may be helpful as well.
So I think that we have to keep that context as
well. As far as the performance of this vaccine, I learned
today from the FDA that the height of the absolute antibody
level doesn’t indicate duration of protection. That was
news to me. I thought there was some correlation between
that and duration.
So it seems that to me the focus is really on
those populations who would benefit from this vaccine, that
wouldn’t benefit from other vaccines. So building off of
what Melinda said, that this isn’t what was brought to the
FDA, but the potential of maybe phasing this in, to focus
this initially on those populations for whom the benefit is
greater, that would allow an opportunity accrue a lot more
information about its performance and it safety profile.
And then based on that, then it could be seen in the
context of a larger population.
Again, it is the question of where you draw the
line between pre and post, and whether there is some
intermediate place where rather than the entire adult
population it can be targeted initially to those for whom
its benefit is most needed. And then subsequently, an
assessment on its role, because of its potential for some
of the programmatic failures of a two-dose rather than a
DR. DAUM: Thank you, Dr. Gellin. Are there
other comments or are we ready to look at question two in a
DR. BENNINK: Does that mean what you are
suggesting is a more narrowed thing than just simply adults
18 through 70 years old? You are sort of suggesting an
approval that is balanced?
Here is what Dr. Wharton said, the second most influential person on the Panel who also voted no. It is clear that they would have voted Yes for a restricted label and this is why you will get this. The stock is currently priced for a CRL or approval for just CKD. You can't get just CKD and the size of the post marketing study the FDA desires. You need a restricted label that is sufficient to fill the study.
One strategy may be a focused effort on a higher
risk population where the benefits of the vaccine would
likely be greater, and that I would be comfortable with
doing more of the safety assessment post-licensure in that
population than I am in the general population.
Agree with most of your post and I feel final FDA opinion will be approval with initial restriction to high-risk population groups. However, smokers and and the obese are not considered high risk for Hep B that you noted in your post. Diabetics, chronic kidney patients on dialysis and certain populations of the immunocompromised.