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GREAT NEWS! Dr. Jerome at Fred Hutch has achieved 50% to 90% elimination of latent HSV in mice

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dont quit!17
Posted (edited)
8 hours ago, MikeHerp said:

The problem with GEN-003 was that it was no sure thing. It wasn't very strong.  Phase 3 would have required $150 million and it had no guarantee of being approved.  At 12 months, it showed 49% reduction in mean lesions.  A modest result. Lowe than valtrex. In recently published results, there was stuff like this: "Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%)."  That's hardly music to the ears of investors.  I also saw the distribution of individual patients which Genocea published and, while net net, it mostly helped, some people got had worse results on it.  It also was expected to require annual boosters--hardly ideal.  It's not clear what impact, if any, that kind of effectiveness would have had on reducing HIV acquisition.  

https://academic.oup.com/jid/article-abstract/218/12/1890/5049813?redirectedFrom=fulltext

If GEN-003 had consistently showed results equal or close to valtrex, I suspect they would have found funding, and gotten approval.  But they fell short of that relatively modest goal.  If it had been approved as is, I probably would have tried to take it.  But getting approval was dicey. 

The new new subunit herpes zoster vaccine has been shown to be 90%+ effective, and that had no problem getting funding or securing regulatory approval.  It's not like herpes zoster (shingles)  is some kind of very grave or terminal illness that is much more urgent than HSV.  

As Jerome noted in the 2016 piece, back when he started researching this, it was hard to get any funding for it. But he was able to find some private funding, and his results helped to secure a 5 year NIH funding grant.  It's also clear from the grant info that the purpose of the research is to pave the way for human trials. Thinking has changed about this, and Jerome is pretty clear on this point.  

Jerome at FHC has been able to effect up to 90% elimination of latent HSV in ganglia, and there's a clear path for improving efficacy.  Permanent elimination, with a one time treatment.  Even a 90% elimination would probably reduce shedding close to 0% and make just about all people asymptomatic, non transmissible.  No more taking pills for years or decades, no need for boosters or worries that HSV will come roaring back if your immune system gets overloaded.

All tests so far have shown safety, no inflammation, no cell toxicity, no off target edits--as I mentioned, meganucleases may also have a favorable safety profile to CRISPR-Cas9

It's pretty elegant.  And I'm certain that, when he finishes building it, investors will come.  Like I said, if they can repeatedly show such outstanding effectiveness and safety, then the FDA will not stop approval just on the basis of theoretical risks.

 

Gen-003 sucks, plus they had lawsuits regarding their lack of transparency. I'm kind of glad they got shut down, because now researchers could focus on something much more effective. All I know about Dr. Jerome, is that he has always been reluctant to give false hope and he has taken tremendous progress since 2016. To me, this is all very interesting research and concept.

From what I recall. Meganucleases search for a double strand in the DNA?  Which in turn increases it's safety. 

Edited by dont quit!17

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MikeHerp
23 hours ago, Lost-hope said:

To add to your point there are currently 26 crispr trials going on worldwide according to the clinical trials website so if those studies prove to be successful and safe I’m sure once a Herpes trial begins it won’t be long until we get some type of results.. Hopefully 

Yep, it's getting closer to a flood of gene editing trials.  There's a ton of money and interest in this.  I think there's some hope on the horizon.

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BioHacker

I agree GEN-003 isn't perfect, but the primary issue was lack of funding (not lack of efficacy). The "lack of funding" issue is a recurring theme - and the reasons for that are not likely to be different for gene editing, or any other approach. Why is a shingles vaccine so easy? Because a larger number of people already take a shingles vaccine every year - a large addressable market. All you need to do is invent one that is a "little bit better" than the existing vaccine, and then you can justify the costs to bring it to market. It has a built-in demand every year.

HSV is simply not as large an addressable market opportunity. Valacyclovir may do $2.2 billion in annual revenue, but that's not a huge number. Healthy people are not conditioned to think about HSV as something they need a vaccine against - developing that market would be costly and difficult (the HPV vaccine prevents cancer, and it's still a big challenge to get people to take it). These issues leave us with the people who either have HSV1 badly enough to want a vaccine (or gene editing), or who have HSV2 and are aware of it (2-3% of the population). Then, of that smallish population, you'd have to reach people with marketing and convince them to take a new "therapeutic" vaccine (or gene editing treatment).

When you run the numbers, and factor in all the costs of regulatory approvals, it doesn't make a whole lot of sense financially. Even if it could slow the spread of HIV in Africa, it's not going to be at all profitable to actually do that - at least not without a government grant. And no government seems ready to write a check.

How do we develop treatments for "Bubble Boy" disease and other "non-priority" conditions that are not financially compelling investments for private companies? Usually the government sponsors it. There is very little government sponsored funding for HSV research in general - and it would be correct to say it is "not a big priority."

This dynamic seems unlikely to change, but it doesn't make progress impossible. It just slows it down. It also means that many "promising" treatments get hyped up in order to TRY to get enough funding, before they eventually come up short and sit on a shelf somewhere. Personally, I fail to see why any new type of treatment wouldn't face a likely funding bottleneck right around "phase 3" (or leading up to it) where things start to get really expensive - human testing is expensive and that's when a lot of decisions get made for financial reasons. Up until then, everything usually is reported to be going great (if on a shoestring budget).

If I had to guess, I'd say that a new treatment for HSV is more likely to be developed and make it to production outside of the US - in a market with fewer regulatory restrictions and cost hurdles. Probably China. It's also possible that a treatment for some other condition could end up working for HSV by accident (probably an anti-viral drug that targets a category of viral conditions).

Based on cancer studies using therapeutic vaccine approaches, and on results in animal models for therapeutic HSV vaccines, it seems highly likely that we already have all the tools we need to have a vaccine that significantly outperforms Valacyclovir. GEN-003 is really very rudimentary, and it doesn't trigger the type of interferon and CD8+ T Cell response that we know is most effective against HSV. GEN-003 was designed to try to thread the needle of being safe and conservative enough to make it through regulatory approval, but still effective enough to be profitable if it ever came to market - it just missed on the financials.

It doesn't take a genius to make a cost-effective vaccine out of existing materials and test it (or to push the envelope with gene editing in human test subjects). But in the US it would seem almost prohibitively expensive for a non-priority disease like HSV. Probably it will happen in China.

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hi202020

@MikeHerp I read that one of the latest CRISPR trials for cancer won’t conclude until 2031 (or close to that). 

With Fred Hutch’s progress, can we expect similar timelines for human trials that won’t conclude for 10+ years due to the uncertainty of gene editing safety in humans (off terget edits)? 

Im just trying to get a sense of how long it might take to get something on market available to us, and when I saw that 2031 it definitely was a bit dissapointing, that’s a long time! A cure is better than no cure anytime though and of course it would be amazing for the rest of humanity moving forward. But is there any possibility we might get a cure/upgraded therapy based on 50-90% elimination in the next 5 years or so?

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dont quit!17
Posted (edited)
On 4/24/2019 at 6:00 PM, hi202020 said:

@MikeHerp I read that one of the latest CRISPR trials for cancer won’t conclude until 2031 (or close to that). 

With Fred Hutch’s progress, can we expect similar timelines for human trials that won’t conclude for 10+ years due to the uncertainty of gene editing safety in humans (off terget edits)? 

Im just trying to get a sense of how long it might take to get something on market available to us, and when I saw that 2031 it definitely was a bit dissapointing, that’s a long time! A cure is better than no cure anytime though and of course it would be amazing for the rest of humanity moving forward. But is there any possibility we might get a cure/upgraded therapy based on 50-90% elimination in the next 5 years or so?

2031 will be here in a blink of an eye.

I hope it's sooner but if that was a guarantee wait for a cure then why not?

Realistically, that is what the time frame is going to be, if everything goes smooth during clinical trials, money is available and other gene editing trials don't harm trial participants. 

Edited by dont quit!17

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MikeHerp
22 hours ago, BioHacker said:

I agree GEN-003 isn't perfect, but the primary issue was lack of funding (not lack of efficacy). The "lack of funding" issue is a recurring theme - and the reasons for that are not likely to be different for gene editing, or any other approach. Why is a shingles vaccine so easy? Because a larger number of people already take a shingles vaccine every year - a large addressable market. All you need to do is invent one that is a "little bit better" than the existing vaccine, and then you can justify the costs to bring it to market. It has a built-in demand every year.

That first paragraph simply indicates that we aren't on the same page so I barely bothered to read the rest.  

Again, let me know if there is any part of this that you don't understand: "Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%)."

A therapeutic vaccine that is, either worse than placebo in treating symptoms, ar at the optimal dose, only slightly better?  Slightly better than placebo, not slightly better than the current meds (valtrex).  That doesn't pass the laugh test.  

Investors just aren't interested in a treatment that at times might not even be as good as placebo.

The lack of efficacy of GEN-003 was something that was harped on again and again.  

  • Josh Bloom (MD): "Impressions: From these data, GEN-003 would seem to have an uphill battle. Based on my experience, It is unlikely that the company (and future investors) will be satisfied with a vaccine that works about as well as Valtrex. Given the moderate degree of efficacy seen in infected patients, 003 seems unlikely to work well prophylactically." (this is from when the results still gave the impression that it might be as good as valtrex, subsequent results were clearly below valtrex however).
  • Friedman (MD): "HF: GEN-003 did work, but not well enough. This may be due to the company's choice of proteins in the vaccine. There are many proteins involved in eliciting an immune response. GEN-003 possibly failed because they chose the wrong proteins or not enough different ones."

Regarding shingles, again it seems you don't know what you are talking about.  The market for shingles has been estimated at a bit over $1 billion currently.  That's not very much different from herpes, in fact, I think it's smaller.  Now note that the same link points out that, "Shingrix is still expected to replace Zostavax as the market-leading shingles vaccine within two years of its launch."  Why is it expected to replace it?  Well, for starters, it has 90% efficacy which doesn't wane over time vs. Zostavax's 60% efficacy that wanes over time.  I.e., it's 50% more effective than the existing treatment and doesn't wane with time. .

It's pretty obvious why Shingrix was funded and approved.  And pretty obvious why GEN-003 only got to phase 2.   One was 50% better than the existing treatment, the other wasn't even as good as the existing treatment, sometimes struggled to be better than placebo

That's a huge difference.  

You mentioned: "All you need to do is invent one that is a "little bit better" than the existing vaccine".  Regarding HSV, nobody has actually come up with a vaccine that is even as good as existing meds, or shown to be consistently better than placebo.  

Investors don't usually waste money on products that aren't clearly better than placebo.  

When they come up with a vaccine that is clearly better than placebo and better than valtrex, but that still doesn't get funding or approval, then we might actually have a conversation about it.

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BioHacker

For clarity, the complete quote from the research summary is:
"Results: Compared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95% confidence interval [CI], 0.49-1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95% CI, 0.45-0.92), 30/50 dose; 0.63 (95% CI, 0.37-1.10), 30/75 dose; 0.56 (95% CI, 0.36-0.88), 60/25 dose; 0.58 (95% CI, 0.38-0.89), 60/50 dose; 0.45 (95% CI, 0.16-0.79), 60/75 dose; and 0.98 (95% CI, 0.76-1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination.

Conclusions: The most efficacious vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses."

The fact of the matter is that GEN-003 showed reduced lesion rate AND reduced shedding rate.

Better than Valtrex? No.

But it doesn't need to be "better than Valtrex" because it is not a replacement for Valtrex. It would be COMPLIMENTARY to Valtrex. Meaning, if you took both Valtrex and GEN-003, you would likely have better viral suppression than if you took Valtrex alone. If there was a partially effective gene editing treatment, it would probably be complimentary to other treatments as well - maybe enough to add up to a "functional cure."

I know you can read the data on GEN-003 as well as I can. GEN-003 very clearly reduced shedding better than placebo - you agree, do you not?

It's unclear why the placebo group had a reduced lesion rate - and we may never know since it no longer has funding.

When you look at all the data, it is hard to claim that GEN-003 is not an effective vaccine, just short of Valtrex in most respects - and something that would improve the current standard of treatment.

What would be the market for a vaccine that is not quite as good as Valtrex, but when taken with Valtrex, reduces shedding and lesion rates by an additional 50%?

That's a theoretical question, but I would say that maybe there isn't enough money in it to justify the expense of taking it through phase 3, even if you had iron-clad proof of efficacy at that level. It would be an expensive battle with the FDA and in marketing it.

You can say "it isn't good enough." But that is essentially just another way to say "it isn't good enough to get major funding" . . . and a cynic might add "and today, neither is gene editing, at least not when it comes to treating HSV."

GEN-003 is a decent low-risk vaccine, and it would likely improve public health. That's not the hurdle it has to clear though, is it?

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MikeHerp
13 hours ago, BioHacker said:



The fact of the matter is that GEN-003 showed reduced lesion rate AND reduced shedding rate.
I know you can read the data on GEN-003 as well as I can. GEN-003 very clearly reduced shedding better than placebo - you agree, do you not?

When you look at all the data, it is hard to claim that GEN-003 is not an effective vaccine, just short of Valtrex in most respects - and something that would improve the current standard of treatment.

 

Unfortunately, as I mentioned, some of the doses missed on lesion rates vs. placebo. 

And on shedding they also had misses vs. placebo, like this one where placebo reduced shedding more compared to two different doses of the vaccine.  So, no, you can't always say that "GEN-003 very clearly reduced shedding better than placebo".

However you look at it, this wasn't a strong product.  If those misses had been on the end points of the phase 3, then that would have been $150 million down the drain and investors just don't take those kinds of risks.  

There's no evidence that the FDA is trying to "battle" HSV vaccines.  There hasn't ever yet been a good HSV vaccine.  There's been nothing for HSV like the Shingrix vaccine, which is 90% effective and doesn't really even need boosters.  If somebody comes up with a 90% effective HSV vaccine, it won't have the slightest problem getting funded or getting approved.  Nothing has come close.  GEN-003 was the best so far, and it was sometimes worse than placebo.

Investors are reluctant to fund products that struggle to be better than placebo.  That's the reality for HSV and it's the reality for many other kinds of illnesses.  

Gene editing is different. than a therapeutic vaccine  Because it will be a permanent cure or a partial cure. Removal of latent virus.  They are already removing 50-90% of latent HSV from mice ganglia.  In the space of just 2.5 years, this is probably already well on a path towards making people asymptomatic and eliminating or close to eliminating shedding.  GEN-003 results are pathetic compared to this. Every animal test they've done so far has shown safety, lack of cell toxicity, no inflammatory effect, and no detectable off target edits. 

This is now driven by NIH funding, at a renowned cancer research institute with a proven track record of commercializing discoveries.  The grant info clearly states that they are gearing up for a mass animal trial as a precursor to human trials.  Jerome has said that they expect human trials in the not too distant future.  

The purpose of phase 1, 2 and 3 are to test safety and efficacy.  If they are proven safe and efficacious, they will be approved.  If not, then they won't.  Yes, it will likely take some years, but the FDA will approve it if it is proven safe and efficacious.  They have ways of proving this, including detecting off target edits.  

This isn't magic or sorcery.  

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Tired of waiting

Mike you seem to well informed on the topic. I have slight off target question, that you might be able to answer.

Once the gene editor has be confirmed and put into use, How would they test to see if the virus is eliminated from the host,  a IgG test would be no good as you would still have antibodies present? I do not recall if KJ mentioned a test or if it is done by evisceration (maybe the wrong word)  of the target host? :(

That kind also begs the question,  If the gene editor works by virtual of the prior infection is it safe to say you are now naturally vaccinated from future HSV (type specific) infections?

Thanks

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BioHacker

Sure, GEN-003 testing had some placebo issues at different times, no one denies that. But the results for the vaccine were statistically significant - and the reductions in shedding were dose-dependent (which would not be the case if it was simply placebo effect).

GEN-003, which is clearly an imperfect vaccine, would be an improvement in the standard of care relative to not having any vaccine. It doesn't need to be "better than Valtrex" because it would be used in addition to Valtrex, not as a replacement for it.

And GEN-003 is a pretty rudimentary vaccine - it would be easy enough to increase the effectiveness by including additional antigens and/or a stronger adjuvant (like SD-101).

Gene editing might be the future, but it's not here yet. It's really hard to predict what the FDA will require in order to approve gene editing therapy (in general) for commercial use. It's great if it happens, but it might be 2030, 2040, or even later far ANY gene editing treatment to be put to use (and cancer / genetic disease treatments could likely be fast tracked, where an HSV treatment would likely not be). In China maybe.

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MikeHerp
On 4/26/2019 at 11:20 PM, Tired of waiting said:

Mike you seem to well informed on the topic. I have slight off target question, that you might be able to answer.

Once the gene editor has be confirmed and put into use, How would they test to see if the virus is eliminated from the host,  a IgG test would be no good as you would still have antibodies present? I do not recall if KJ mentioned a test or if it is done by evisceration (maybe the wrong word)  of the target host? :(

That kind also begs the question,  If the gene editor works by virtual of the prior infection is it safe to say you are now naturally vaccinated from future HSV (type specific) infections?

Thanks

Hi Tired.  I've wondered the same thing myself.  You are correct that, in the mice studies, they explanted the neuronal ganglia to check the latent HSV.  In humans, obviously, that won't be possible (at least until somebody who has had the treatment, dies).

But, it seems it could be proven indirectly, for example, with a shedding or lesion study.  By testing for shedding before the treatment and testing for it after the treatment.  Even asymptomatic people shed.  If after treatment they no longer shed, then it's a safe bet that the virus has been either eliminated or close to eliminated.

In connection therewith, last year they went a long way in developing an ultra sensitive method for capturing and sequencing HSV, which might also be useful to detect if there is any HSV left.  

Anyway, I suspect this question probably won't be a problem.

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MikeHerp
6 hours ago, BioHacker said:

Sure, GEN-003 testing had some placebo issues at different times, no one denies that. But the results for the vaccine were statistically significant - and the reductions in shedding were dose-dependent (which would not be the case if it was simply placebo effect).

My friend, it seems you have simply not read up well on GEN-003.  

If you had read carefully the link I posted--I post it again, you would have caught this part: "The 33 percent reduction in shedding at the higher dose (100 µg) is less than the 50 percent reduction at the lower dose. This is puzzling. "

So no, it didn't reduce shedding in a "dose dependent manner".  The company provided an explanation for this, stating that immunity stimulation occurs along a "U" curve, such that, if you over stimulate the antibodies, you might actually essentially tire them out. That explanation sounds plausible, but this was another issue which required another leap of faith.

If it had reduced shedding in a dose dependent manner, then obviously, they could have just gone with a 1000ug dose, instead of 100ug, and shedding would have been zero. and it would have been a functional cure.  It didn't work like that however.  Or anywhere close to it.

A cure or functional cure definitely won't take that long.  Companies like Sangamo have already been testing gene editing in humans, and the first CRISPR trial in humans is also now under way in the U.S. Yes there's still some risk that it could go terribly wrong or something, but I personally doubt it.  

HSV is linked to cancer through the increased risk of HIV acquisition.  This along makes it a worthy candidate for a cure, not even mentioning the other issues that HSV can cause.  What's more compelling about it is that, the meganucleases FHC is working with, seem to be really effective at eliminating HSV in vivo and the progress in efficacy, from 2-4% in 2016, to up to 90% announced this year, has been great. In many CRISPR treatments, they aren't able to do much more than a few percent of target cells edited.  

Meganucleases cause permanent elimination with just a single simple treatment, which is different from temporary suppression of symptoms which is the only point of current treatments. 

As Jerome mentioned, they anticipate human trials in the not too distant future. 

 

 

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Inevitablecur3

Jerome and his colleagues have also been collaborating with other institutions for quite some time on hsv as well. I think their knowledge and resources for curing this are the best out of anyone trying. He mentioned in one of his older videos that fred hutch was one of the pioneers to develop meganucleases. They are extremely small meaning they can fit into any viral vector and incredibly specific for the cleavage site. I think it’s only a matter of time before they see the fruits of their labor

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BioHacker

The issues you are citing with GEN-003 are the same for most vaccines. You cannot simply increase the dose and have a greater effect. At some point it becomes counter-productive, obviously. What I was referring to was the largely dose-dependent manner in which shedding is reduced from low doses of the vaccine up to the most effective dose. That would not be expected to happen if the vaccine was not effective (i.e. if it was placebo effect). That doesn't explain why the study had placebo group reductions in lesions or shedding at different points in the study, but the vaccine would appear to be effective at reducing shedding outside of that. It's one thing to be a Jerome homer, but it doesn't make sense to disregard incremental progress in favor of "elegant solutions" all the time.

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hi202020
Posted (edited)

Looks like the fundraiser on Fred Hutch's site has reached it's goal, plus some extra! 

$20,500 of the $20,000 goal has been achieved. 

I'm gonna donate another $500 now so they can see we're going above and beyond in our support! 

@MikeHerp I'm still curious about my question above - do you have a sense of when a human trial might start for HSV gene editing, and how long that trial would take? I referenced the human CRISPR trial at Upenn for cancer that won't conclude until about 2031. I'm hoping an HSV human trial wouldn't take as long - any thoughts?

 

Edited by hi202020

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MikeHerp
8 hours ago, Inevitablecur3 said:

Jerome and his colleagues have also been collaborating with other institutions for quite some time on hsv as well. I think their knowledge and resources for curing this are the best out of anyone trying. He mentioned in one of his older videos that fred hutch was one of the pioneers to develop meganucleases. They are extremely small meaning they can fit into any viral vector and incredibly specific for the cleavage site. I think it’s only a matter of time before they see the fruits of their labor

Yes, all this is correct.  FHC has had 3 Nobel prize winners on its faculty.  It's got a proven record of commercializing discoveries. Meganucleases are very specific, more so than CRISPR and their small size relative to CRISPR helps optimization.

I'm still curious what they can come up with pretelivir in the interim.  But clearly, Jerome's meganucleases are the thing that will get us across the cure finish line. Considering the pace of progress, I believe it will probably be faster than expected.  

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MikeHerp
Posted (edited)
3 hours ago, hi202020 said:

Looks like the fundraiser on Fred Hutch's site has reached it's goal, plus some extra! 

$20,500 of the $20,000 goal has been achieved. 

I'm gonna donate another $500 now so they can see we're going above and beyond in our support! 

@MikeHerp I'm still curious about my question above - do you have a sense of when a human trial might start for HSV gene editing, and how long that trial would take? I referenced the human CRISPR trial at Upenn for cancer that won't conclude until about 2031. I'm hoping an HSV human trial wouldn't take as long - any thoughts?

 

hi hi202020,

Its hard to say. Jerome has stated that they hope to be in human trials in the not too distant future.

in the video posted, they identified certain remaining obstacles to get editing efficiency above 50%~90% and possible ways to address that.

in the NIH grant summary, they have stated that their work now is gearing up towards a larger animal trial, which they say will be the needed precursor to human trials. 

I’d say that human trials will take place within a few years. I think it will be sooner than people expect. Progress has literally been exponential.

ExcisionBio’s (which is using a different editor called CRUSPR) pipeline states that their CRISPR HSV biological would go into human trials by 2020/2021. I don’t know whether they will stick with that date since it has previously been pushed back.

But the point is that gene editing human tests for HSV are definitely on the horizon.

ps. THANK YOU for your donation! 

Edited by MikeHerp

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hi202020
18 hours ago, MikeHerp said:

hi hi202020,

Its hard to say. Jerome has stated that they hope to be in human trials in the not too distant future.

in the video posted, they identified certain remaining obstacles to get editing efficiency above 50%~90% and possible ways to address that.

in the NIH grant summary, they have stated that their work now is gearing up towards a larger animal trial, which they say will be the needed precursor to human trials. 

I’d say that human trials will take place within a few years. I think it will be sooner than people expect. Progress has literally been exponential.

ExcisionBio’s (which is using a different editor called CRUSPR) pipeline states that their CRISPR HSV biological would go into human trials by 2020/2021. I don’t know whether they will stick with that date since it has previously been pushed back.

But the point is that gene editing human tests for HSV are definitely on the horizon.

ps. THANK YOU for your donation! 

Thanks for this. 

Do you have any sense of how long a human trial for HSV gene editing would take once approved? The 2031 date as the end date for the UPenn CRISPR trial make me wonder if it would be a similarly long timeline for HSV, or would that not be the case? Do the human trials for gene editing have to be super long, like 10+ years, to ensure there aren't off target edits/mutations?

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BioHacker
Posted (edited)

There is a lot of excitement over the potential of gene editing for all sorts of diseases, and justifiably so. Will it cure influenza before it cures HSV? Who knows. The one constant is that researchers are in a battle with each other for funding and attention.

Every time a researcher (or anyone else) claims something could be possible "in a few years" you should probably read that as "theoretically, if everything goes perfectly, and regulatory approvals are expedited, and we continue to make exponential progress, then [XYZ measure of accomplishment] could be possible in a few years, but it could also be more like 10 years assuming reasonable setbacks and delays, or even 20 years, or 30 years, or maybe even never, if any number of potential things happen to go wrong. All we can do right now is put the best spin on the work that we can, and hope that our sales pitch works well enough to get us enough funding to stay in business."

Even the best researchers are notorious for being overly optimistic about when research being conducted might eventually lead to approved treatments - it's just part of the game.

 

Edited by BioHacker

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dont quit!17
12 hours ago, BioHacker said:

Even the best researchers are notorious for being overly optimistic about when research being conducted might eventually lead to approved treatments - it's just part of the game.

 

Dr. Jerome has  notoriously been known for being cautiously optimistic. He isn't trying to spin anything. Dr. Wald is the same way too. For Dr. Jerome to actually state that a cure within our lifetimes, is really saying something. I would love for the cure to be available within 5-7 years but following their progress makes the wait a little bit easier. 

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MikeHerp
15 hours ago, hi202020 said:

Thanks for this. 

Do you have any sense of how long a human trial for HSV gene editing would take once approved? The 2031 date as the end date for the UPenn CRISPR trial make me wonder if it would be a similarly long timeline for HSV, or would that not be the case? Do the human trials for gene editing have to be super long, like 10+ years, to ensure there aren't off target edits/mutations?

Can you give a link to the UPenn trial info you mentioned?  

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MikeHerp
Posted (edited)
1 hour ago, dont quit!17 said:

Dr. Jerome has  notoriously been known for being cautiously optimistic. He isn't trying to spin anything. Dr. Wald is the same way too. For Dr. Jerome to actually state that a cure within our lifetimes, is really saying something. I would love for the cure to be available within 5-7 years but following their progress makes the wait a little bit easier. 

Yep, Jerome has been very cautious and conservative with his statements. He's practically falling over himself to always emphasize how slowly and carefully this will all have to go--until we are pleasantly surprised after the fact that, actually the progress has been at light speed.  So for him to say that there's now scope for getting excited, that's remarkable.

For the opposite of cautious and conservative, look no further than than Kamel Khalili at ExcisionBio.  In 2016, he predicted that CRISPR will be a cure for HSV and will be available for anyone who has HSV "within less than 5 years".  Fast forward to today, and you can see that ExcisionBio's pipeline provides that they anticipate their HSV trials to start in 2021--incidentally that's five years from 2016.  In other words, it's not possible that their cure will be commercially available 5 years from 2016 as he predicted.  I like that Kamel, like others, are now talking "cure" in relation to HSV.  It's clear that this tech definitely has that potential, and nothing before it has ever had that.  But that 2016 statement had too much hype.

That's the kind of thing that Jerome has never done.  

Edited by MikeHerp

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hi202020
On 4/29/2019 at 7:27 AM, MikeHerp said:

Can you give a link to the UPenn trial info you mentioned?  

Here's an article that references that, it is supposed to conclude in 2033 actually.

https://www.inverse.com/article/55072-crispr-clinical-trials-pennsylvania

"Proceeding cautiously in the wake of the alarming misuses of this powerful technology, America seems to be modernizing its regulatory frameworks to allow scientists to probe the good that CRISPR can do. This clinical trial at Penn, which is supposed to conclude by 2033, is one of the first to do that — but it definitely won’t be the last."

It's great to hear you guys talk about Jerome not bolstering his predictions and that his enthusiasm is actually based on realistic expectations.

When can we expect an update from his team? Do they do a regular update or is it just based on when they make progress?

I'm really excited after seeing that video presentation he did and seeing how stunning the progress is. My only concern is that it will take forever to prove gene editing is safe for humans and get a product out to market, I'd really like to learn more about human trial timelines for HSV specifically.

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hi202020
On 4/28/2019 at 5:26 PM, BioHacker said:

There is a lot of excitement over the potential of gene editing for all sorts of diseases, and justifiably so. Will it cure influenza before it cures HSV? Who knows. The one constant is that researchers are in a battle with each other for funding and attention.

Every time a researcher (or anyone else) claims something could be possible "in a few years" you should probably read that as "theoretically, if everything goes perfectly, and regulatory approvals are expedited, and we continue to make exponential progress, then [XYZ measure of accomplishment] could be possible in a few years, but it could also be more like 10 years assuming reasonable setbacks and delays, or even 20 years, or 30 years, or maybe even never, if any number of potential things happen to go wrong. All we can do right now is put the best spin on the work that we can, and hope that our sales pitch works well enough to get us enough funding to stay in business."

Even the best researchers are notorious for being overly optimistic about when research being conducted might eventually lead to approved treatments - it's just part of the game.

 

This is so true haha!

It is all a game of funding and marketing.

However, it does sound like we're on to something with this progress.

Again, I just hope proving human safety with gene editing doesn't drag on forever (2033 for example).

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MikeHerp
Posted (edited)
1 hour ago, hi202020 said:

Here's an article that references that, it is supposed to conclude in 2033 actually.

https://www.inverse.com/article/55072-crispr-clinical-trials-pennsylvania

 

That's just that specific study.  I've read researchers in the field predict that gene editing treatments may be "widely" available within 10 years.  

The fact that China is ahead of the ball at the moment, also helps, because the US will not want to be left behind in such an important technology. 

The FDA has issued statements indicating that it will be very flexible and won't be an obstacle.

So the stars are aligning.  But still, it will take some years.  Once it goes into human trials though, it will be fun to follow, especially if it shows good results.  I think it will.

Look, ExcisionBio is aiming for human trials around 2021 with CRISPR for HSV.  I don't know whether they will keep that target, but, regardless, it shows you this is getting closer to launch.  

Edited by MikeHerp

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