There is a specific regulatory pathway for this purpose written into law: section 505(b)(2) of the FDCA. It lets you use existing safety data from the approved NDA.
I have used this pathway myself and the FDA is quite comfortable with it. I don't really understand the fuss. Nor do I understand why the DAO matters.
According to research of the 197 new FDA approved drugs since 1997, the chance of a generic drug getting approval for a new indication drops to almost zero after it goes off-patent/generic - see https://pubmed.ncbi.nlm.nih.gov/33397471/. I assume your drug was still on-patent and/or was not subject to off-label competition? Otherwise, how did you get funding? The issue of the lack of private incentives to repurpose off-patent drugs (i.e. "financial orphans") is very well recognised, irrespective of section 505(b)(2) of the FDCA - see https://www.healthaffairs.org/do/10.1377/hblog20140306.03737...
This is a very good point. You figure out a new use for a generic drug, then anyone can use the generic in that way. We also (I mentioned this in a comment a couple of weeks ago) did some therapeutic development that we realized any compounding pharmacy could make up the formulation. We dropped all work.
On our product it was an approved API with different dosage and a different mode of administration. Still in trials, but if approved it will have normal patent protection.
Edit: the first “is” was autocorrected into “isn’t”. Glad I saw it!
Yes, it is possible to reformulate a generic but there's only a business model if you can prevent off-label competition (and a compounding pharmacy could also reformulate). This is what I mean by information about a treatment protocol for a repurposed generic / off-patent drug being a public good. What if your new use for the off-patent and or compounded drug was a very effective new treatment or cure for an unmet medical need? This is the real tragedy of the commons. It's not always possible to rely on reformulations, dosage or mode of administration to prevent generic competition, and could actually cause public harm if the patented reformulation of the drug is less safe or effective - see https://www.nature.com/articles/s41587-021-00999-0 . And it's possible to fix it with a pay for success or bounty model, as long as we can convince a payer agree to put a price on successful off-patent RCT data (e.g. $10-50k per QALY). However, this hasn't been tried to date.
"The United States Government will give $1B to the first company or person to demonstrate a safe and effective treatment that halts or reverses the effects of Progressive Supranuclear Palsy[1] using treatments with existing FDA approval."
Yes, this would be a pay for success contract. And a "prize" or outcome payment of $1b would not be necessary. By using a generic drug, you can enter into phase 3 trials immediately, and it can cost less than $10-15m to obtain regulatory approval (100x cheaper than developing a new patented drug over 10-15 years) - see https://dndi.org/wp-content/uploads/2019/10/DNDi_ModelPaper_.... See Figure 1 on page 17: Out-of-pocket costs per stage of development for eight projects in DNDi’s portfolio.
You likely don’t need a standard phase three trial. If you are within the phase 1 safety dosages (that’s the data you’re using under 505(b)(2) anyway) you can just do a smaller study. Power it as high as you want/need. Typically any physician can do such a study. Doctors can read your paper on the study and decide whether to use the therapy you studied.
Yes, it may be possible to update standard of care with a robust Phase 2 RCT that convinces doctors, especially for a pilot. Phase 3 trials for a repurposed generic would be more expensive, but a new label indication would provide further incentives to update SoC because doctors and pharmacies would be less exposed to liability for prescribing off-label.
I have used this pathway myself and the FDA is quite comfortable with it. I don't really understand the fuss. Nor do I understand why the DAO matters.
https://www.fda.gov/regulatory-information/search-fda-guidan...