More on GEN-03

[TCBH]

Hey all,

Found this on GEN-03, the vaccine that couldn't fund the final trials.  https://www.ncbi.nlm.nih.gov/pubmed/31103365?dopt=Abstract  Seems like they are trying to find investors possibly.  Does anyone have insight on this?  I would love to have a series of vaccine shots versus a daily antiviral pill.

 

[MikeHerp]

I think this is probably dead in the water.  Less than 1% chance.  I don't know why this study is dated June 2019.  It came out some months ago.  

[Kurdt01]

I received the ‘optimal dose’ in phase 2. Made me and many others worse. That’s why this died. Just my opinion but vaccines are not the way.

[Evaluate]

10 hours ago, Kurdt01 said:

I received the ‘optimal dose’ in phase 2. Made me and many others worse. That’s why this died. Just my opinion but vaccines are not the way.

Mind expanding on your experience with outbreaks before and after the vaccine? 

[Kurdt01]

Sure, before hand I had about 1 physical OB every month and constant but tolerable neuralgia, the vaccine ramped all that up for several month afterwords...the constant burning became almost unbearable at times and the OB's became way more severe and frequent. So instead of curbing anything, it actually turned it all up! I wasn't the only one either...

[Evaluate]

Thanks for sharing.  Have things returned to normal over time?  It's not unrealistic for an outbreak or multiple to happen after an HSV vaccine is administered, but having that occur for several months afterwards does seem troubling.

[Kurdt01]

It did eventually calm down after several months...some people had an ever worse reaction than I did...They are not talking about any of that but that’s really why that never went anywhere....I have no background in medicine or biology only My my own anecdotal experience with HSV but I have never thought that the vaccine and or immune response is the problem if that makes sense…revving things up just doesn’t make sense to me...It does make sense that it made it worse in hindsight…

[MikeHerp]

I see.  But that sounds odd.  They did find that, on average, it lowered outbreaks and shedding in most of their trials.  Around 50% roughly on both (not great, but the difference was statistically significant). and that it was generally safe and well tolerated.  One or two times, on secondary end points, they did worse than placebo, but those were exceptions.  

But it sounds like you are saying many people got worse from this.  Are you suggesting that they falsified or manipulated their data?

Anyway, I believe your experience, but I have to square it with the data that was published.  Which was that, it was mildly to moderately effective and generally safe.  So I just wonder.  

Edited October 23, 2019 by MikeHerp

[Kurdt01]

On 10/23/2019 at 5:15 AM, MikeHerp said:

I see.  But that sounds odd.  They did find that, on average, it lowered outbreaks and shedding in most of their trials.  Around 50% roughly on both (not great, but the difference was statistically significant). and that it was generally safe and well tolerated.  One or two times, on secondary end points, they did worse than placebo, but those were exceptions.  

But it sounds like you are saying many people got worse from this.  Are you suggesting that they falsified or manipulated their data?

Anyway, I believe your experience, but I have to square it with the data that was published.  Which was that, it was mildly to moderately effective and generally safe.  So I just wonder.  

I only know what I experienced and that at the end the trial nurse confirmed for me that many others had similar experiences… I also know that all the vaccines have been unsuccessful…Having been involved in two clinical trials and learning firsthand from doctors how the data is reported, and I’m not even sure how to say this except to say things don’t always mean what we think they mean there’s a way to present things scientifically that sound one way but in reality aren’t exactly that… If you know what I mean.

I think you also need to ask yourself if it was so good why is it dead in the water?

[MikeHerp]

43 minutes ago, Kurdt01 said:

I only know what I experienced and that at the end the trial nurse confirmed for me that many others had similar experiences… I also know that all the vaccines have been unsuccessful…Having been involved in two clinical trials and learning firsthand from doctors how the data is reported, and I’m not even sure how to say this except to say things don’t always mean what we think they mean there’s a way to present things scientifically that sound one way but in reality aren’t exactly that… If you know what I mean.

I think you also need to ask yourself if it was so good why is it dead in the water?

Fair enough.  Understood.

But the results were modest.  Around 50% less shedding and symptoms.  Less than Valtrex.  That's the main reason why it didn't get funding to go further.  It did go through extensive phase 2 studies though. 

Anyway, thanks for sharing, it's good to keep that in mind.  

[T9000]

On 10/21/2019 at 12:07 PM, Kurdt01 said:

It did eventually calm down after several months...some people had an ever worse reaction than I did...They are not talking about any of that but that’s really why that never went anywhere....I have no background in medicine or biology only My my own anecdotal experience with HSV but I have never thought that the vaccine and or immune response is the problem if that makes sense…revving things up just doesn’t make sense to me...It does make sense that it made it worse in hindsight…

I agree I think there's too much focus on the immune system when, to my knowledge, we don't even know why some people have symptoms and some don't. Why don't we focus instead on the problem we know does exist? HIV has 8 antiviral classes and one of them works as a prophylactic. That's exactly the sort of thing herpes needs. It's commendable that they're trying out a new technology because the infectious disease field seems to have had very little major innovative in the 20th century, but there should have been way more of a focus on developing something like prep, in my opinion. 

[Kurdt01]

Hopefully pritelivir will make it to market. Maybe even by 2021.

[MikeHerp]

7 hours ago, T9000 said:

I agree I think there's too much focus on the immune system when, to my knowledge, we don't even know why some people have symptoms and some don't. 

You're absolutely right.  So little is known about the virus.  Though, fortunately, there's an increased focus these days and knowledge is beginning to pile up. 

We don't know why some people get symptoms and not others and we don't know what are the correlates of immunity.  Which is one of the reasons why vaccines have repeatedly failed or not been that great.  

Interestingly, both the Einstein and the UPenn vaccine candidates make stabs at those answers.  

From a 2016 study of the Einstein vaccine: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985247/

"The notion that nonneutralizing, FcγR-activating Abs may be critical for HSV protection was suggested almost 20 years ago following the disappointing results of the gB-2/gD-2 subunit vaccine clinical trials (25, 26). The gB-2/gD-2 subunit vaccine induced high-titer gB- and gD-specific ELISA and HSV-2 neutralizing Abs, but in post-trial studies, there were low ADCC responses in the serum of vaccine participants (27). Similarly, the more recent clinically evaluated recombinant gD-2 protein vaccine elicited high-titer gD-specific and neutralizing Abs but was not protective. Whether the gD subunit vaccine elicited FcγR-activating Abs has not yet been reported. Together, these recombinant vaccine studies indicate that gD- and gB-neutralizing Abs are not sufficient for HSV-2 protection (9). In neonates, high ADCC Ab levels are associated with less severe neonatal disease (28), and in preliminary ongoing studies, we found that women with frequent symptomatic genital herpes outbreaks had higher neutralizing but lower FcγR-activating Abs compared with women with few or no clinical recurrences (data not shown). The findings from the ΔgD-2 vaccine coupled with clinical data support a role for FcγR effector functions in protection against both primary and recurrent disease."

And of course, with the UPenn vaccine, you have the idea that the virus has immune evasion domains which trick the body's immune responses.  

Anyway, that's also part of the reason why I kind of cringe when people declare that HSV is harmless--we don't really yet know what it does or how it works.  It's really only in the last 25 years that knowledge has started to pile up.  

 

[MikeHerp]

1 hour ago, Kurdt01 said:

Hopefully pritelivir will make it to market. Maybe even by 2021.

I think it has a solid chance.  Not a lock, but it has a solid chance.  I think it all depends on the side effects.  

[Kurdt01]

If pritelivir doesn’t make it I’d say were all probably fucked for at least 10 years and should just move on at that point and just live our lives the best we can ha ha 

[WilsoInAus]

@MikeHerp hey mate it’s not really your place to cringe surrounding HSV 1/2 as you don’t have it. 
Those with it are perfectly capable of deciding how to feel about it and what it will or won’t mean to their lives.

Also you are leaving out the positive benefits to our bodies of having HSV. The more we know, the more that positives pile up too!

[brookeb300]

42 minutes ago, WilsoInAus said:

@MikeHerp hey mate it’s not really your place to cringe surrounding HSV 1/2 as you don’t have it. 
Those with it are perfectly capable of deciding how to feel about it and what it will or won’t mean to their lives.

Also you are leaving out the positive benefits to our bodies of having HSV. The more we know, the more that positives pile up too!

He was in the clinical trial for gen 003 I think he has it

[WilsoInAus]

9 minutes ago, brookeb300 said:

He was in the clinical trial for gen 003 I think he has it

No you’re thinking of @Kurdt01

[Kurdt01]

What are the positive benefits to our bodies? I'd like to know and I'm not being sarcastic.

[WilsoInAus]

2 minutes ago, Kurdt01 said:

What are the positive benefits to our bodies? I'd like to know and I'm not being sarcastic.

The immune response generated has very positive impacts for our bodies. The immune system is tuned to produce various interferons that roam your body preventing viruses and bacteria from causing damage. This is the way with symbiotic viruses and bacteria that have evolved with man. Both human DNA and the virus DNA evolve for mutual benefit so they both stay alive as long as possible.

The immune system also promotes greater density of nerves and protection for nerves. Research continues into using HSV 1/2 antigens to produce an immune response that reduces neuropathy in people with damaged nerves.

Remove these symbiotic viruses and bacteria from your body and you disrupt the natural order that results in issues such as skyrocketing rates of immune disorders.

As an agent, HSV-1 kills cancer cells and has value as a vector to also deliver payload in gene therapy. Many treatments of the future for cancer may involve injections of modified herpes virus.

I don't know why there is a need to single out something like HSV 1/2 and say we know little about it, when that is true of most viruses and bacteria. We are only starting to truly understand the symbiosis between certain bacteria and viruses with our bodies.

[Kurdt01]

Like the ancient chinese proverb: One disease, live long life. No Disease, live short life.

[T9000]

10 hours ago, Kurdt01 said:

If pritelivir doesn’t make it I’d say were all probably fucked for at least 10 years and should just move on at that point and just live our lives the best we can ha ha 

It should have been out 10 years ago honestly. It's ridiculous.

 

[vzhe]

21 hours ago, WilsoInAus said:

<stuff no one cares about>

Just a quick reminder that it's recommended to block the troll "WilsoInAus" on these forums. Please don't reply to or engage with the troll! Instructions for blocking in my signature.

[WilsoInAus]

1 hour ago, vzhe said:

Just a quick reminder that it's recommended to block the troll "WilsoInAus" on these forums. Please don't reply to or engage with the troll! Instructions for blocking in my signature.

Just a quick reminder that this is not a utilitarian community and you are free to make your own choice as what to read and decide what is truth. 

[T9000]

On 10/28/2019 at 8:12 AM, MikeHerp said:

Anyway, that's also part of the reason why I kind of cringe when people declare that HSV is harmless--we don't really yet know what it does or how it works.  It's really only in the last 25 years that knowledge has started to pile up.  

 

My hunch is that in maybe 30 years herpes simplex and other latent infections are going to considered unacceptable by medical professionals based on how much more we will know about them.