NVAX
Por lo que he leído a pesar del bajo attack rate, eso no explica que hubiera más casos de RSV en el brazo de la vacuna que en el placebo. Hay algo que ha fallado, algo que se les ha escapado o la vacuna no funciona. He estado leyendo con atención los últimos post del grupo de facebook y llego a la conclusión de que es imposible saber nada hasta que den más datos. Pero seamos realistas, no pinta nada bien. Pongo a continuación unos cuantos post seleccionados con información de todo tipo relevante...
Visión positiva:
99.8% de los sujetos vivían en "community living". Reclutaron muy rápido a mucha gente. Y si muchas de las de fase 3 fueron reclutadas también en fase 2, eso explicaría el "rate attack" tan bajo.
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It is too late now, but this trial should be hailed as a total success because it in fact shows that the RSV vaccine does in fact protect the elderly, and when provided to highly concentrated communities, it offers tremendous reduction of rates of attack.
Furthermore, Assisted Living Communities are more sterile than your typical home. With elderly and sick individuals living in the controlled environment, the risk for any disease has to be lower that in the random urban community.
Finally, individual living in assisted living communities are far less mobile. They do not routinely go to grocery stores, pharmacies, and shopping centers, as would there same age counterparts who live in apartments, condos or single family home through an area.
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It appears that the subjects in the P2 study also lived in senior residential facilities. (I went back and looked it up in the clinical trials). So why didn't this herd immunity problem show up then?
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the Phase 2 was 1/10 the size. So, only a small portion of the assisted living members would have been vaccinated in the Phase 2 trial. But, in the Resolve trial, the 10X the number plus the same Phase 2 were vaccinated
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As Casey wrote yesterday, it's all about the serology. Cocooning argument is too weak IMO to justify the expense and time of another trial. So if Immuno data is solid, we are all screwed.
https://en.wikipedia.org/wiki/Cocooning_(immunization)#
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How do you explain the attack rate against folks that were vaccinated to be higher than the folks with the placebo? At the end of the day, isn't that small piece of stat very telling?
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One of the reasons I invested in this stock was because it had good fundamentals and one of those fundamentals was stellar management. If an issue arose that this was executed poorly then it clearly goes against a key fundamental I went off of to invest in this stock in the first place.
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Only a buyout saves the company. $1B minus debt
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As someone else here has mentioned, it would have been expedient to vaccinate those in an isolated community, but disasterous in terms of creditble results, RSV attack rates and efficacy rates.
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I know trials were done in Wichita. I'm at a nearby university where we get a pretty good gauge of seasonal infectious disease just by observing the student population. This past winter and spring were strangely extremely healthy. I work with 400 adults and I don't know a single person who had the flu or a severe cold.
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Although if a number of different regions were involved (there were 60 sites mentioned) then the results still should have been better than "placebo," which they were not. Something had to be very wrong in the basic design of PIII
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The P2 was 1600, but importantly the P2 had 14 msLTRIs in the placebo and the P3 had 26 msLTRIs in the placebo. The increase the study by over 7 fold and got a measly 12 additional cases in the placebo arm (less than double). So it would be incorrect to say the 7x bigger study is 7x stronger, because it is not. But one could argue it is just under 2x stronger. So one study said it worked with a p-value of 0.041 and the other study that was just under twice as big (in practical terms) said it didn't. The P2 also had a lot of antibody and neutralization assay studies, that work is pending in the P3.
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If the vaccine is to be generally useful in the real world it had better work for a window that encompasses the season for RSV. I see no market for a product that requires perfect timing. While that is possible for a maternal setting as regular doctor visits and gestational time is precise. In this case I feel fairly strongly that this is in some way related to the vaccine lot that was used. Until proven differently I believe there will be a quality/stability issue. If that is not the case then the entire monoclonal site 2 theory may be flawed.
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Visión negativa:
This is all great, and probably proves why the attack rate is so low, however it doesn't matters the Placebo OUTPERFORMED the Vaccine. 28 cases of RSV with vaccination, 26 cases with the Placebo. So in theory, based on this you would be better off getting nothing then getting the vaccination.
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but if most patients were already healthy and unaffected by RSV, wouldn't it be like comparing apples to apples in the first place?
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No because the 2% that were affected would show some difference. Maybe not enough to be passed but some effectiveness.
To sell a commercialized product it needs to work to the masses and for FDA approval it needs to show definitive effectiness.
Sick people don't get a Vaccine. People who are trying not to get sick do. We could of enrolled 100,000 people with an attack rate of 2% and it would still likely show no difference
If it shows 10-15% effectiveness I would hop right on board with you guys on the attack rates, but let's be real here, the vaccine shower -7%. You were more likely to contract the disease we are trying to prevent if you received the vaccination
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Maybe but the result just says at the moment that the vaccine had 0 effect. The reasons may be many for it. I think they rushed to get this phase 3 done. But the end result just shows that the vaccine had no effect. The data collation or trials had no issues as said by the company itself.
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This is where we need the antibody titer info.
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My hope is that the serology might show poor immunogenicity, poorer than in previous trials, poorer than what is seen in maternal and so on. If that happens then we what we know about efficacy falls back to the P2, and the path forward is to fix what broke in the production and move on to confirm the P2. If, on the other hand, the immunogenicity is solid, then the vax starts to look like it doesn't work at least as a elderly preventative measure.
The flip side is the serology is solid and this thing is then shown to be in genuinely miserable shape. Perhaps at the investment community level they can't discriminate the results and so it doesn't tank even more(or they read it wrong and think good serology is good, which I don't think in this case). But from a science angle, for me, if the serology is good I am looking for nothing but exits.
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The serology data will provide much additional insight, we know the material (the vax) performed differently in efficacy, did it also perform differently in immunogenicity? If so then there is plenty to salvage (this would be heading downthe bad batch path), if the serology is the same as P2 but only efficacy fell off, that would be a bigger problem.
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My friend who is a clinical researcher at Lily made the following statement.
"I have never seen a P3 drug/vaccine fail this badly. The only times I have seen this bad of a failure is when the toxicity killed or harmed patients. The P-Value of .78 is the highest I have seen by a P3 of this size"
