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Comment by acallaha | Hacker News Reader

> A group of researchers mostly based at Columbia University are testing whether valacyclovir, an antiviral used against HSV1, can slow down cognitive decline in people with early stage Alzheimer’s. Between 2018 and 2024, the researchers recruited 120 patients and treated half with the antiviral.

Outsider view: while I'm excited we're making progress, I can't shake a feeling of sadness that the best we could manage was a study this small, started 7 years ago. If it's as pivotal as the article suggests, one would hope we could get more than 60 people in the experimental arm (IIUC this antiviral is widely prescribed, well-tolerated, and off-patent). Nonetheless, excited to see the outcome

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> off-patent

Well there’s your problem: no one can make money off of it, unless they develop a new delivery mechanism, etc.

Patents encourage developing new medicines, but not developing new knowledge about (never mind use of) old medicine.

The solution (in the US) is obvious: federal funding of research that stands to help lots of people but not make lots of money. Since most of these patients (in the US) are going to be on Medicare, there could be huge potential cost savings to the taxpayer: memory care is EXPENSIVE, so even the paltry amount covered by Medicare racks up (and the opportunity costs of people paying for private memory care is enormous).

But instead of increasing funding for this kind of life- AND MONEY-saving research, this administration is freezing and slashing research funding, and specifically targeting Columbia for political/Trump’s-petty-grudge reasons.

> Well there’s your problem: no one can make money off of it

You can patent new applications of an existing drug. This has been somewhat of a problem, as companies can just look at how drugs are being used off-label, and patent some of these uses.

People are doing this with vetinary drugs too. A company called Tarsus Pharmaceuticals recently developed a drug called xdemvy by repurposing an anti-flea drug for dogs. It basically cures an eyelid condition called demodex blepharitis. They're a $2b company now.

They barely had to do any new science. It just took some creativity and almost $250m worth of clinical trials.

I suspect the lucrative patent system has helped create rather exorbitant costs and restrictions for performing trials, which hinders non-patentable research, ironically.

But both the federal and state govts do fund tons of such research. Some states have specific Alzheimer's trials and funds. I would think they could handle dirt-cheap therapies like this without getting into sweeping political changes. Though I suspect the solution is much harder than just run a trial with the drugs we have, or else we would already be hearing about mountains of evidence from doctors using the medications off-label.

>Well there’s your problem: no one can make money off of it, unless they develop a new delivery mechanism, etc.

You hit the nail on the head. Ketamine is a generic drug that costs next to nothing; Spravoto (ketamine-derived nasal spray) is already a billion dollar/year drug for Johnson & Johnson, with prospects of $5 billion/year.

Source: https://archive.ph/rzqxt [Wall Street Journal]

Worth mentioning that the evidence says that patents don't have an effect on new drug creation/inventions. Evidence is collected here http://www.dklevine.com/general/intellectual/againstfinal.ht..., pretty neat to know that Italy/Switzerland had a patentless pharma industry until quite recently.

Having said that, I think you're right that under this system, research/capital definitely gets directed in a different way.

A major reason Alzheimer's research hasn't advanced in the last 25 years is that patents aren't long enough to study it. Remember: patents don't kick in after the FDA approved your drug. It's after you develop it. That's why ozempic is going off-patent in a just few years even though it's a new product. They patented it a long time ago.

With Alzheimer's though, the clinical trials are going to take a long time. Probably 10 years at least, because our current understanding of the disease is that it begins in your mid to late 40s, and only manifests as severe memory loss decades later. Our current method of trying to treat it is like putting someone in pallatiave care with stage 12 cancer through chemo. Just doesn't work.

But drug companies have no choice because if they run 10-15 year trials, their drug will be off patent before the FDA/EMA even looks at it.

If I were King for a day, one thing I'd do is a blanket 40 year patent life on Alzheimer's drugs. It's worth the cost. This disease will bankrupt every nation otherwise.

While I understand the narrative you're proposing, what I brought with my source was a collection of evidence where pharmacological innovation happened at an unaltered rate pre and post patents in e.g. Italy and Switzerland. While I understand the hypothesis of "Pharma innovation, due to high costs of entry, only happens (or is greatly improved) when guaranteed a monopoly", it doesn't seem to be backed by the data.

I agree with you in principle though - if all that were stopping us from achieving a cure were a 40 year patent, I would support your 1-day monarchy in a heartbeat.

Chapters 9 and 10 of the book cover this in more detail if you're interested (very self-contained).

This is bullshit. Drug research costs money, A LOT OF MONEY. A new drug right now costs somewhere around $5 billion, mostly because 90% of drugs fail in trials.

mRNA vaccines, semaglutide, mAB therapies, none of these would have happened without patents as an incentive.

Then why is it that when pharma patents were introduced in countries that didn't have them, the rate of innovation, TFP, R&D-as-%-GDP didn't increase? I brought a source to this debate, if you have sources showing that increases in patent scope, length, or introduction of patents increased pharamacological innovation I'd love to see it - I'm going down this rabbit hole now and am collecting info.

Another interesting one is [1] where they asked readers of the BMJ to vote on the top 15 most important medical milestones. Of the 15, only the contraceptive pill and Chlorpromazine had anything to do with patents.

In [2] the "Chemical and Engineering News magazine" collected a list of top pharmaceuticals (46 total). To quote the book I linked:

> Patents had pretty much nothing to do with the development of 20 among the 46 top selling drugs [..] . For the remaining 26 products patents did play an important role [..]. Notice though that of these 26, 4 were discovered completely by chance and then patented (cisplatin, librium, taxol, thorazin), 2 were discovered in university labs before the Bayh-Dole Act was even conceived (cisplatin and taxol). Further, a few were simultaneously discovered by more than one company leading to long and expensive legal battles, however, the details are not relevant to our argument.

Regarding the cost of drug trials, they cover this well in Chapters 9 and 10, I found it quite interesting.

Regarding how else companies make money without being granted temporary govt-backed monopolies, Chapter 6 covers both the theoretical and real-life examples.

[1] https://www.bmj.com/content/medical-milestones [2] https://pubsapp.acs.org/cen/coverstory/83/8325/8325list.html

Quite an interesting attempt to advance the general process is DeepMind's project to make a cell simulation so you can try chucking in drugs into the simulation and see what they would do quicker than in the lab/patients. They are talking about having a simple cell up in five years. Hassabis talking about it: https://youtu.be/CEOOMYxMvY4

This article is all the supporting evidence without any of the setbacks and failures at reproducing the correlations. There have been attempts at showing benefits with antivirals before. Just not a full-on double-blind study apparently. I recall reading about a study with high doses that showed no benefit for people in early stages.

The 7 years time duration probably comes from the size of the study and also how long it is believed to take to get benefit if there is one. I would think if it really worked they would have stopped early for ethics reasons because they should also give the treatment to the placebo arm rather than watch them decline while knowing how to prevent it.

>If it's as pivotal as the article suggests

Let's be honest, this is a longshot.

90% of drug trials fail. Shows you how primitive our accepted practice is. Where else is a 90% failure considered to be an acceptable outcome?

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