Here is the conundrum. Heplisav is without a doubt effective. You can forget the one vote on the panel that voted that it was not effective as that same person stated afterwards he conditioned that particular vote on the fact he could not state it was "safe" as the database was insufficiently powered i.e., trial was not big enough. So let's state emphatically that Heplisav is effective and in fact superior to the competition when it comes to various subsets i.e., elderly, diabetics etc. and more effective despite immunization takes place in a month and after 2 shots as opposed to 3 injections over a period of 6 months. Now there is the question of safety. On this question you need to remember that they are not looking to cure a disease, nor are they the only available remedy for the ill at hand. They are looking to immunize and there is a reasonably safe and effective alternative, EnergixB.
On the issue of safety the panel voted 5-8 with 1 abstention that the database was not large enough, that the trial did not properly mimic the ethnic background of the United States (not enough African American and not enough Asians in the trial) and that they did not test the vaccine with other vaccines to see what contraindications there might be. The latter two points are rather silly so I think they need not be addressed. The question is whether the FDA will overrule the Panel and ask for a greater size trial or will they find a compromise. I think, like William Blair a compromise is found and this will be it:
First, the Panel was 5 to 8. Of the 8, at least 2 seemed to suggest that they would be amenable to a limited introduction of the vaccine with a post marketing study. The idea of a post marketing study had been suggested by the FDA in the briefing documents as well as the company. In fact, plans are already underway for a 30,000 post marketing study with Kaiser Permanente. If the FDA were to allow a limited introduction via a restricted label, and ask for an accompanying post marketing study, as is planned, then I think one could reasonably state that such a conditioned approval would satisfy the panel. Now the question is what would this restricted label look like.
Well they could approve Heplisav for all healthy adults between 17 and 70 but restrict it to those who are at risk a) intravenous drug users, b) Diabetics, C) The Obese, D) Smokers, E) Those traveling to areas where hep b is endemic and to the those over the age of 60. In my opinion this is exactly what will happen. They will grant approval with the aforementioned restrictions and ask for a post marketing study. Europe will grant full approval and the stock will go to 6 bucks.
I can't believe that people are still talking abou that stupid thing. Who voted what and how, and all of that malarkey.
It was a kangaroo vote, it was a sham, it was a bunch tilted garbage.
One GSK stoolie turned something that COULD have been constructive into a sham SOLELY for the interest of #$%$-street so that ghouls and vultures like Adam Creepstein could attack the stock and say there was "doubt" about Heplisav being approved.
That's ALL that little staged event was about.
Heplisav is STILL the same Heplisav that it was on November 1, and SIX MONTHS EVEN BEFORE THAT.
Is there REALLY anyone that believes the FDA approval group would have trouble figuring that out?????
People really believe that the FDA cannot see through the paid GSK stooge that derailed that adcom deal??? Good grief!
If that is the case, then we are all definitely deadmeat as consumers and patients of the healthcare system for putting our trust in the FDA.
Personally, I don't believe it. The FDA is smarter than that Dr. whateverhisname was goof that ruined the adcom panel.
My money is still staying with Dynavax and Heplisav.
Give up talking about that stupid adcom baloney. It was a stunt orchastrated for #$%$-street goons, specifically; unfortunately, they paid for and got what they wanted......
I just reopened a small position in DVAX. I agree that the central issue is the size of the safety population. If Heplisav used an industry standard alum adjuvant, the safety population would have been sufficient. The fact that they used a novel TLR9 agonist, which raises the issue of theoretically possible autoimmune problems, raises the bar on what would be considered an acceptable safety population. Only one other vaccine that uses a comparable novel DNA based adjuvant has been approved in the US. Cervarix uses a TLR4 agonist added to an alum base as an adjuvant. For comparison, when Cervarix was considered by the Vaccine adcom in 2009, GSK had a safety popoulation of 16,000 patients treated with Cervarix in clinical trials. There was also data on an additional 60,000 patients who had received the GSK adjuvant outside the US. DVAX submitted data on 4400 patients treated with Heplisav. The Cervarix safety vote was 11-1 and the Heplisav vote 5-8.
The FDA briefing documents going into the meeting gave little indication that the committee would play the safety card. In retrospect, IMO it is a valid concern. Considering that the proposed indication includes healthy individuals and that there are already alternative products available, the safety criteria for approval should be sensitive enough to detect a problem that might affect as few as .1% of the individuals being treated. That said, by a surrogate measure, Heplisav does appear to be more effective and would be expected to prevent disease at a higher level of efficacy than currently approved vaccines. So there is a tradeoff. Uncertainty about safety versus potentially improved disease prevention.
I would be surprised to see a full approval for the proposed indication. My thinking is that FDA will compromise and define those populations most likely to benefit from higher efficacy. The currently approved shingles vaccine, Zostavax carries a label limiting it to patients aged 50+ and CDC recommends 60+, so the precedent exists to define a vaccine indication based on age. The other obvious indication is diabetic patients. DVAX has submitted data indicating that both these subgroups benefit most due to higher comparative rates of seroimmunity. Those patients plus a possible phase 3 safety study could provide the safety database needed to satisfy the concerns about rare but serious autoimmune SAE's. Worst case scenario would be a CRL mandating further studies with no approval. That possible scenario is the one under which I would step in and open a major portfolio position. Heplisav will be approved sooner or later and the TLR9 adjuvant will have applications in other vaccines. With a CRL, DVAX becomes takeover bait.
Nice write up although I believe it will get full approval. You are leaving out the fact that the FDA helped design the trial, why would the set up a trial that in their opinion didn't have enough people in it? That makes me think they believe there is enough people in it. Also the fact that DVAX had it set for 17-40 year range and FDA recommended changing it to 17-70 year range.
sounds good, but i think they will get a CRL and asked to do a study that will properly mimic the ethnic diversity of america....now DVAX may, just may get luck and get approval with this testing being required later.....your calling for $6, if it does get approval i see higher, if it gets a crl then i see $2 for a while but it would be a shoe-in next go around.....