What would be the easiest primary endpoint to target to get Rapamycin FDA approved for longevity or some near connected area to it?
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Why would anyone pay to run trials for a generic drug?
Still, I think depression can be a good endpoint.
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I would say there are other ways of getting paid for a generic drug then just by having an IP. Creative business models may both reduce cost and increase income in unique ways.
Have you experienced that Rapamycin has helped with depression?
What are these business models? Clinical trials to get a drug FDA-approved would cost around $50m. Then how can you recoup your costs if it’s a generic drug? As of today, there’s no alternative model as far as I know (I wrote this position paper on this issue: EU Pharma Directive & Regulation Drug repurposing incentives - Google Docs )
I only said this based on the high rate of people who reported feeling better and the lower rates of depression in this survey + the increasing prevalence of depression with age + there are so many antidepressants approved without a real clinical benefit that it might be easier to go this way.
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What is perhaps more of a priority is to enable Primary Care MDs to get insurance to enable them to prescribe Rapamycin for improved health.
I don’t think the FDA has to approve it for this.
In any event I don’t live in the USA.
Personally I would like a route to enable Primary Care MDs to prescribe substances at the patients request where this is a reasonable decision.
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There is only an increasing prevalence because of the poor remission rates. Diseases are age-related when the incidence increases with age, which depression does not. The median age of diagnosis is in the early 30s:
Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies
To answer your question, @Krister_Kauppi: my guess is that the best bet is enhanced response to influenza vaccine, since we already have so much data from the resTORbio trials. But I’m not sure that would lead to the results we want even if it got the indication. The TAME trial design would be great, but is quite a lift to get the money. Barzilai still hasn’t gotten it for metformin (a bad candidate of course), and the freakin’ Dog Aging Project is in danger of getting its funding pulled. EVERLAST and the related trials are a happy medium, but we’re not going to get an FDA indication out of that.
In addition to the other problems we’ve discussed, getting a sufficient number of people motivated enough to volunteer for an RCT but still willing to not go off and get it on their own is another challenge to any such trial.
It is a puzzlement.
Sure it is. Off-label indications are always a fight unless there is an established clinical guideline or other thing you can point to, and this is far and away off: there isn’t even yet an indication, let alone an approval for that indication.
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Good point, thanks. I still think depression can be a good indication for rapa for a clinical trial. (This doesn’t solve the issue of incentives, of course).
Realistically, getting rapa approved, included in clinical guidelines, and reimbursed will take years, if not decades. The biggest issue with rapamycin is its cost. If tomorrow rapa is available at the price of metformin ($0.04/tablet), who would care about the FDA or insurance reimbursement? What makes rapa so expensive? Is it because it’s not a common drug? But if off-label usage increases, could we see its price decrease? Can we increase competition between manufacturers? Between Indian pharmacies? The top priority is to drive the price down imho.
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Sure, but not a trial for a longevity indication. We don’t want millions of aging depression-malingerers going into their doctors looking for rapamycin scripts 
Even if it were as cheap as metformin (or vitamin C), we would still have the problem that physicians wouldn’t prescribe it, both because they (not unreasonably) wouldn’t be convinced by the fragmentary evidence and because of CYA. And no one who is willing to prescribe it now really knows what they’re doing. EVERLAST should help with the first of these, and RAP PAC will help with the third, but CYA will be a problem and the other two will be far from fully resolved.
We need a basis for doctors to start treating prescribing rapa for aging like prescribing a statin for high CVD risk.
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Why? Bypassing the system seems OK to me as long as the outcome is met.
Physicians don’t prescribe vitamins, CoQ10, probiotics, etc., and yet millions of people buy them. (For better or worse.) Because they’re cheap, easily accessible, and perceived as good. For rapamycin, cost is the biggest barrier. Then ease of access: no one wants to buy from a weird Indian website, but this can be improved in the future as well. The rest is then marketing.
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I doubt many others think that’s a good solution. I don’t want a false major depression diagnosis in my medical records, and I don’t want to lie to my doctor, and I don’t want him to treat me under the misapprehension that I have a psychiatric problem. And I want my doctor to guide my care based on my actual indication (aging).
Yes, and the situation with vitamins, CoQ10, probiotics, etc., is the sh^ts . We don’t just want to make rapa cheaper: we want some confidence about whether potential longevity drugs actually work or not, and if so at what dose and frequency, and medical professionals able to meaningfully guide our use. All of this cowboying around is better than nothing, but not the goal. I’m assuming that that’s why Krister asked about an FDA indication, not about how to reduce the price.
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In a sense we are trying to get healthcare to be a priority rather than sickcare. Oddly enough traditional health care systems such as TCM are more like the approach than the more modern systems of fixing the failures of the body. What we want is to stop the body failing. Yang Qi in TCM (for example) is normally AMPK activiation that acts to improve mitochondrial quality and maintain health.
Of course, we all want rapamycin (and/or other longevity drugs) to be approved specifically for longevity, prescribed as such by medical professionals, and reimbursed by insurance plans (whether government-owned or private). But it won’t happen in this decade. (And most likely not in the next one, either.) Because of the lack of financial incentives, the time required for clinical trials (even more so for longevity), and the current “sick-care” model in all countries. So, from here, we can:
- Dream about potential FDA indications. I like it; it’s entertaining, but it’s a utopia for now. Unless you have $100m to spend on trials + FDA application (without any expected financial returns), in that case, yes, we could find the optimal indication for such a charitable effort.
- Try to change the system. As said above, others and I are spending time and money to try to do this in the EU and the US. But we’re realistic; it requires a paradigm change and will take years.
- Find workarounds to reach our goal. As you perfectly say, “we want some confidence about whether potential longevity drugs actually work or not, and if so at what dose and frequency, and medical professionals able to meaningfully guide our use” There are already longevity-minded doctors who can meaningfully guide you and prescribe you with rapamycin. Regarding the confidence about drugs, it’s all about clinical trials, and here again, the issue is (the lack of) incentives. By the way, if rapamycin was approved for depression, you wouldn’t have to lie to your doctor. It would just be a way to bypass an inefficient system. Like what is done for medical cannabis in the US.
By the way, many potential longevity compounds are not regulated drugs: glycine, GlyNAC, NR, Urolithin A (as efficient as rapa?!), astaxanthin, etc. So they’re not FDA-regulated. And still, we’re facing the same problem as for rapa: lack of confidence in their benefits, optimal protocol, etc. Here again, I’m afraid the issue is the lack of incentives. Who will pay millions to find the optimal dosage of GlyNAC in humans?
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The simplest way forward on this is probably to ensure that people who wish to use Rapamycin can purchase it for themselves in their own jurisdiction.
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Cholesterol lowering medications should be available as well then for those whose lipids increase.
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