I Can Hardly” Believe It Viagra Reduces Alz Risk

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Re: I Can Hardly” Believe It Viagra Reduces Alz Risk

Post by Amykwill »

"I could hardly believe it but I read a 70% reduction in Alzheimer’s rates…..that’s the good kind of shrinkage there."

I saw this! Could be a real breakthrough :)
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Re: I Can Hardly” Believe It Viagra Reduces Alz Risk

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Comments (including humourous) welcome...
NewRon, I rolled this into an earlier thread on the same topic just to tidy the forum page. All of your posts and replies are copied here.
In the article that I read, they seemed to be focused not on the increase in blood flow, but on the effect on Tau or on the interaction between Tau and Amyloid. Also, it is not simply a matter of increased blood flow, but I believe that the increase in NO aids in protection of the endothelium. While on this subject, Malcolm Kendrick wrote that in Manchester a group carried out a long term observational study and found that amongst Diabetics who had already had a heart attack (so an extremely high risk group) Viagra use was associated with a 38% reduction in additional heart attacks and a 15% reduction in all cause mortality. Pretty darned amazing stuff.
It looks like a different mechanism, but may just be a downstream effect of improved blood flow. Earlier research shows that decreased cerebral blood flow sets off the amyloid cascade and promotes tau hyperphosphorylation. I'm also not surprised to hear that this improves cardiovascular function via a similar mechanism. That said, it's only a correlation at this point... but still promising.
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Re: I Can Hardly” Believe It Viagra Reduces Alz Risk

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"Hey honey, I can hold off Alzheimer's with Viagra!!"
Spouses & partners: "Let me think about those choices for a while..."
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Re: I Can Hardly” Believe It Viagra Reduces Alz Risk

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alzforum is reporting that the proposed dose for the upcoming trial with Viagra will be 50 mg per day!!! That is somewhat difficult to imagine. Do typical users really dose daily with Viagra? It would seem much more sensible to me to dose at the level that produced the 70% reduction in AD risk. Going for 80% with a near maximal dose seems like a bad gamble. Why pull a new dose out of thin air and then just expect that it will have even more anti-dementing effect?? So many times in the past when such pulling doses out of the air have been tried they have not been successful; more often less successful. They have 7 million patient records that they could consult to find what the real world Viagra dose was that produced the reported benefits. There can always be too much of a good thing. I suppose it would though be helpful for recruitment purposes.

This recent Viagra story illustrates for me the potential of regulatory changes that could help our cause. Why isn't there a mandated requirement that drugs need to go through an anti-dementing screen? It could be as simple as adding a cognitive screen into phase 3 trials, possibly with an inclusion for those with near term dementia risk if the drug is to be used in that age range. Viagra would have been a perfect candidate for such testing in its clinical trials as the expected market overlapped strongly with dementia risk.

If a drug when dosed at 10 times the body weight of a mouse might increase the risk of cancer, then that's it with that drug. Yet, for whatever reason the same standard does not apply to dementia screening. Surprisingly, there are probably approved products that increase the risk of Alzheimer's though the research likely has never been done: it should be. It's more like we don't even know. There are also evidently drugs that can reduce the risk of AD, though even that research has largely been ignored. Make it simple: keep throwing down million dollar bills until someone finds it worthwhile to scoop them up. The FDA has the discretion to make up the rules as it sees fit. Why not fix the game in favor of patients (and also the pharma companies)? These regulatory rules are like having your own printing press for money.

The workaround would be so simple; if your product has an anti-dementing effect we'll extend out your patent. Viagra generated $1/2 billion per year of profit. That's a half billion reasons for people to pay attention. It is amazing what happens when you create incentives like that. People pay attention. Perhaps the rule could be that if initial evidence demonstrated an anti-dementing effect, then the patent could be extended 2 years with all profits being designated for research. If satisfactory proof could be generated, then the original patent could be extended out another 3 years and perhaps another 5 years could then be granted for the additional new indication. There would then be a substantial amount of incentive to investigate these repurposings; even more so given that so much of the leg work has already been done for the approved product.

This change alone in the regulatory environment might have helped all those AD patients who have otherwise struggled with a devastating neurodegenerative illness over the last 20+ years.
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Re: I Can Hardly” Believe It Viagra Reduces Alz Risk

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J11 wrote: Sat Dec 11, 2021 6:10 pm alzforum is reporting that the proposed dose for the upcoming trial with Viagra will be 50 mg per day!!! That is somewhat difficult to imagine. Do typical users really dose daily with Viagra?
"For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity.
[...]
The maximum recommended dosing frequency is once per day. Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg."

https://www.drugs.com/dosage/viagra.html
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Re: I Can Hardly” Believe It Viagra Reduces Alz Risk

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Nords, thank you for replying.

The thing is that Viagra before it went off patent cost ~$80(?) pill; it was not typically covered by insurance. Do people have $80 a day for discretionary recreational expenditures? I would guess not. Was it blue pill or go hungry? If so it probably would be a good time to talk about priorities.

My point is that the clinical trial should try and dose with what has already been tried in the field and appears to have been successful. For whatever reason this does not seem to be the plan. Instead of going with a once per week dosing (which might be the typical dosing from the 7 million patient database of Viagra used in the study) the clinical trial will use 50 mg daily. Err! It's so frustrating do they really need to endlessly make the same mistake? Why not simply start off and replicate the typical dosing that has already appeared to show efficacy?
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Re: I Can Hardly” Believe It Viagra Reduces Alz Risk

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J11 wrote:Why not simply start off and replicate the typical dosing that has already appeared to show efficacy?
I'd be interested in the rationale, but the cynic in me says it's because Alzheimer's treatments represent a huge market, and you won't make as much money dosing once weekly versus daily.
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Re: I Can Hardly” Believe It Viagra Reduces Alz Risk

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A european broker I've used for an afib med is selling twelve 100 mg film tablets for around $175 US for generic and $285 US for Pfizer. For a nominal amount, they will have a doc review your case (the doc is assuming you've used it before) and write a prescription. Sildenafil can be cut in half, from what I've read.
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Re: I Can Hardly” Believe It Viagra Reduces Alz Risk

Post by Whatnow »

Regarding the question about why 50 mg/day in the trial: I've been reading about these drugs (PDE5 inhibitors) for a couple of weeks now (ever since reading Malcolm Kendrick's book). I've seen positive reports of benefits both for Alzheimer's and for heart disease. In one of these (don't recall which) they saw greater benefit with increasing frequency of use. Perhaps that is why? Also, these drugs are also used for pulmonary hypertension and benign prostate enlargement. I expect these other two uses would involve daily dosing.
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Re: I Can Hardly” Believe It Viagra Reduces Alz Risk

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SusanJ, money? What money? That is the problem here. There is no money. Viagra has recently went off patent; it's generic.

I have become excited by the thought that perhaps the FDA could simply by fiat declare Viagra to be under patent protection once again. The FDA (or perhaps legislators) could set-up an environment in which pharmaceutical innovation could simply naturally emerge. The current regulatory environment creates overwhelming barriers to entry and extremely long-times for drugs to reach market. Repurposing would help to avoid both the cost barrier and the time barrier.

Research spending on cancer, AIDS and Alzheimer's are the three illnesses that are off-budget items. Politically, arguing against any of them is a non-starter: They are some of the only remaining pieces of common-ground left in politics. Why not make Alzheimer's (perhaps the others) off-patent limit items as well? It seems brilliant. If you could repurpose a drug (any drug on patent or not) for any of these three illnesses, then you could claim an on-use patent. If pharmas were not interested in repurposing their drugs, then give these patents rights to those who were interested.

What might the market price even now for the Viagra repurposing idea in AD be for a biotech shell company. $5 billion? Numbers have a way of forcing one to confront reality. $5 billion-- would really help focus one's state of consciousness. Goal directed thinking is a friend of the patient community; it's what turns vague ideas into actual products that help actual people. It's what markets are there for! It can help concentrate attention on the hard money valuations for ideas. With AD it can be especially dramatic. There are 50 million people currently coping with amyloid dementia; with a lot more drifting towards a clinical diagnosis. If we could see some leadership with Viagra repurposing, then a celebration could break out soon after (admittedly with an accompanying market frenzy), though my feeling is that market frenzies are not a bad thing; especially when patients could then be offered a treatment option, with probably very acceptable safety, considerable efficacy and a controllable price.

This idea could turbo-charge the research efforts into these illnesses. As it is there is almost no incentive to take repurposing seriously. From what I can see now, this idea isn't currently worth $5 billion; I would be surprised if it currently worth 5 cents. Without vigorous competition you wind up where we are now with AD clinical development. With enough money on the table, identifying alternative use of these drugs would then not be some sort of accident.

It is so difficult as a caregiver to try and read through all the back journals trying to find such repurposings. There is no tabloid headlines guiding you to the treatments that could help your loved one. There is so much uncertainty; there is so much concern that there is a treatment that could help that you are not providing. If I had it to do again, then I would have repurposed with methylene blue. All of the uncertainty could disappear with the repurposing idea. The market system could be allowed to work properly. The answers for caregivers could migrate up the media system. When the headline reads "Viagra the AD miracle repurposing is worth $10 billion", all that worry and stress just disappears. As a caregiver, you know, stay in your lane -- caregiving in dementia is already an enormous challenge. If the system is working properly, then it really should be that easy.
Other nations with a moral conscience could follow the lead.

If you start throwing down enough billion dollar bills then something would happen. So even now, the FDA could proclaim that Viagra is back under regulatory control. With regulatory power, they could set the rules as they saw fit. Perhaps they could mandate that Viagra would then be priced at twice the current generic price for all sellers (generic and others alike). The generic companies could then be required to send a cheque for half of their gross sales to Pfizer. Pfizer would then be required to spend all of this windfall on clinical research for Viagra in Alzheimer's. Give them a year or two to report back their initial clinical findings. If the evidence looks encouraging, then offer them another year or two of a windfall directed at Viagra in AD. The FDA could offer enough incentive to ensure that this could happen. With patents governments can dictate almost whatever it wants and that's the law.
If the repurposed drug were shown to be effective, then perhaps the FDA could establish the terms of the extended patent and the regulated pricing. This would be an enormous win for patients. As it is now, pharma companies themselves are given monopolies and then allowed to set their own prices. $56,000 per year anyone? They know how inelastic demand is for those confronted with progressive neurodegenerative illness.

With this approach there would not seem to be that many who would be unhappy: Pfizer would be happy (they would then have a late stage AD drug in their portfolio); the generics would not be that unhappy as generic Viagra should be priced near marginal cost; the patients would be happy because they would have a near term treatment option that is known to be safe, could be made to be reasonably priced and apparently could be quite effective. It could dramatically accelerate research and development efforts.

This could revolutionize AD drug development (possibly the development for other diseases as well). Patents, regulatory power it is all somewhat arbitrary. Why not simply give the FDA the authority to reimpose patent protection under conditions when repurposing could help patients? Without such protection pharmas seem to be nearly entirely uninterested. Might Pfizer be more motivated if a several billion dollar windfall might spontaneously appear before them? If the right incentives are not given to people, nothing ever happens. When the market system does not function properly as with AD, you wind up as far up the creek as we are now; namely, facing a monopoly market for the only disease modifying AD treatment (i.e., Aducanumab), that if fully rolled out might cost $300 billion + per year. ... and of course there is also the $200 billion in hard dollars already spent in the US for dementia care (or is it now $300 billion hard to remember-- it has been dramatically increasing anyways and likely will continue to increase and reach $1 trillion over the medium-long term -- $1 trillion per year for AD treatment -- if that isn't up the creek then what is?). Given the above, mass protests to give Pfizer a $10 billion Xprize for Viagra in AD treatment would no longer seem an absurdity but perhaps a realistic suggestion.

Safe, effective, and reasonably inexpensive. Choose three. What isn't there to like?
The other options on the table are slim and omit the choose three part.

Yet, the supercynic in me tilts to the idea that the dosing decision was made not because it was about maximizing profit (see above) but because it is already known that the dosing will not be effective. This has happened several times before. Some new supposedly more effective dose is chosen for the initial study only to find that it was too much of a good thing and actually made things less effective. For a first in human trial I would think that playing it safe and simply using the already established typical dose would be the best strategy especially since this has shown 70% disease progression reduction, though I suppose a phase 1 type dose ranging approach might also be worth considering.
Last edited by J11 on Mon Dec 13, 2021 7:53 pm, edited 3 times in total.
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