4 ms·

So rather than approve the existing drug that's off patent, they approved a knock-off that will undoubtedly cost 100x as much. How typical.

by mark-r 8y ago

philwelch 8y ago
Is there anything stopping doctors from prescribing or administering ordinary ketamine off-label? I don't think the controlled substance issues would differ between the two. If the answer is "no, but the marginal differences between ordinary ketamine and the new drug are enough that you'd want to prescribe the new drug instead"--well, that's new value added, isn't it?
- dundercoder 8y ago
  Ketamine HCl can and is dispensed off label, both for in office IM/IV treatment and at home nasal spray, or sublingual troche.
  - epmaybe 8y ago
    that requires the pharmacy to somehow obtain nasal spray. Unfortunately, no manufacturer actually sells a nasal spray variety (yet) as there was no FDA-approved use for intranasal ketamine. That being said, compounders have been able to make intranasal ketamine formulations for a while now, since this treatment for acute depression has been well recognized in the literature for at least a decade.
- toomanybeersies 8y ago
  The main reason would be that it doesn't get distributed in nasal spray bottles, but rather vials for injection.
  - philwelch 8y ago
    Though I believe the antidepressant use of ketamine consists of one or two directly administered doses, so injection wouldn’t necessarily be a show-stopper.
    - rincebrain 8y ago
      It depends what treatment protocol you're following. The IV protocols for non-life-threatening cases usually involve a number of treatments over a short period (say 6 over 2 weeks), then increased spacing until a satisfactory equilibrium between avoiding symptom recurrence and not spending too often strapped to an IV is achieved. I believe the nasal spray treatments are more frequent and less potent, but I've no firsthand experience with those, just the knowledge that one of the major limiters on getting a ketamine derivative into people's hands outside of an IV bag is the variability of dosage through e.g. nasal spray. (You can get a prescription for ketamine in a nasal spray from compounding pharmacies right now, but you will likely have decent variability of dosage each time.)
roywiggins 8y ago
The hard part is getting someone to fund the studies to prove safety and effectiveness for the off-patent version. I don't have a solution for that problem but that's why the FDA didn't approve regular ketamine: no company would be able to recoup the costs to get it approved.
- carbocation 8y ago
  Ketamine is an approved drug that we use in clinical practice.
  - natalyarostova 8y ago
    Not approved to treat depression.
    - philwelch 8y ago
      This doesn't really matter--off-label prescriptions are extremely common and don't seem to be strictly regulated.
      - roywiggins 8y ago
        You can totally get treated for depression with ketamine already, but the problem is insurance doesn't cover it so it's expensive- several thousand dollars a go, which is not absurd but is beyond most peoples' means. Whereas the hope is an FDA-approved therapy will be covered.
    - carbocation 8y ago
      We're not limited by approved FDA indications, although we are (generally) limited by the standard of care. Granted, the current formulation is liquid and intended for IV or IM use (although there is academic literature on mixing ketamine into liquids for oral administration). The liquid part is the fundamental problem with using this off-label, in my opinion.
  - toomanybeersies 8y ago
epmaybe 8y ago
That's not how the drug approval process goes in this country, for better or worse. Also noted some misinformation in the comments. FDA will approve drugs from companies or individuals that pay for the application. The cost is pretty high today, something on the order of $2-3M USD just for the application. That's not including the cost of supporting data you need to have (Phase 1-3) that will likely cost a large amount to support (multiple centers, paying participants, wholesale cost of drug, paying investigators, researchers, statisticians, etc). Side note, should companies be able to justify exorbitant prices for their drugs based on this cost? No, probably not, but smarter people than myself have debated this on HN. Why do I mention this? Because ketamine for use in intranasal form for treatment of depression is not off patent. That's right, Mount Sinai Hospital (Icahn School of Medicine) was granted that patent in 2007. A non-profit institution, mind you. So, if I were a drug company, looking to make a profitable form of intranasal ketamine, wouldn't I try and sidestep the patent entirely, reducing overhead on my end? Also, calling esketamine a knock off is disingenuous. It's an enantiomer, therefore literally half of what is in normal ketamine. It's also probably the more potent half. Edit: originally wrote that ketamine patent was granted in 2017, meant 2007. Edit2: originally wrote that NYU held the patent to intranasal ketamine when it was actually Mount sinai hospital.

So rather than approve the existing drug that's off patent, they approved a knock-off that will undoubtedly cost 100x as much. How typical.

by mark-r 8y ago

So rather than approve the existing drug that's off patent, they approved a knock-off that will undoubtedly cost 100x as much. How typical.

philwelch 8y ago

Is there anything stopping doctors from prescribing or administering ordinary ketamine off-label? I don't think the controlled substance issues would differ between the two. If the answer is "no, but the marginal differences between ordinary ketamine and the new drug are enough that you'd want to prescribe the new drug instead"--well, that's new value added, isn't it?

dundercoder 8y ago
Ketamine HCl can and is dispensed off label, both for in office IM/IV treatment and at home nasal spray, or sublingual troche.
- epmaybe 8y ago
  that requires the pharmacy to somehow obtain nasal spray. Unfortunately, no manufacturer actually sells a nasal spray variety (yet) as there was no FDA-approved use for intranasal ketamine. That being said, compounders have been able to make intranasal ketamine formulations for a while now, since this treatment for acute depression has been well recognized in the literature for at least a decade.
toomanybeersies 8y ago
The main reason would be that it doesn't get distributed in nasal spray bottles, but rather vials for injection.
- philwelch 8y ago
  Though I believe the antidepressant use of ketamine consists of one or two directly administered doses, so injection wouldn’t necessarily be a show-stopper.
  - rincebrain 8y ago
    It depends what treatment protocol you're following. The IV protocols for non-life-threatening cases usually involve a number of treatments over a short period (say 6 over 2 weeks), then increased spacing until a satisfactory equilibrium between avoiding symptom recurrence and not spending too often strapped to an IV is achieved. I believe the nasal spray treatments are more frequent and less potent, but I've no firsthand experience with those, just the knowledge that one of the major limiters on getting a ketamine derivative into people's hands outside of an IV bag is the variability of dosage through e.g. nasal spray. (You can get a prescription for ketamine in a nasal spray from compounding pharmacies right now, but you will likely have decent variability of dosage each time.)

roywiggins 8y ago

The hard part is getting someone to fund the studies to prove safety and effectiveness for the off-patent version. I don't have a solution for that problem but that's why the FDA didn't approve regular ketamine: no company would be able to recoup the costs to get it approved.

carbocation 8y ago
Ketamine is an approved drug that we use in clinical practice.
- natalyarostova 8y ago
  Not approved to treat depression.
  - philwelch 8y ago
    This doesn't really matter--off-label prescriptions are extremely common and don't seem to be strictly regulated.
    - roywiggins 8y ago
      You can totally get treated for depression with ketamine already, but the problem is insurance doesn't cover it so it's expensive- several thousand dollars a go, which is not absurd but is beyond most peoples' means. Whereas the hope is an FDA-approved therapy will be covered.
  - carbocation 8y ago
    We're not limited by approved FDA indications, although we are (generally) limited by the standard of care. Granted, the current formulation is liquid and intended for IV or IM use (although there is academic literature on mixing ketamine into liquids for oral administration). The liquid part is the fundamental problem with using this off-label, in my opinion.
- toomanybeersies 8y ago

epmaybe 8y ago

That's not how the drug approval process goes in this country, for better or worse. Also noted some misinformation in the comments. FDA will approve drugs from companies or individuals that pay for the application. The cost is pretty high today, something on the order of $2-3M USD just for the application. That's not including the cost of supporting data you need to have (Phase 1-3) that will likely cost a large amount to support (multiple centers, paying participants, wholesale cost of drug, paying investigators, researchers, statisticians, etc). Side note, should companies be able to justify exorbitant prices for their drugs based on this cost? No, probably not, but smarter people than myself have debated this on HN. Why do I mention this? Because ketamine for use in intranasal form for treatment of depression is not off patent. That's right, Mount Sinai Hospital (Icahn School of Medicine) was granted that patent in 2007. A non-profit institution, mind you. So, if I were a drug company, looking to make a profitable form of intranasal ketamine, wouldn't I try and sidestep the patent entirely, reducing overhead on my end? Also, calling esketamine a knock off is disingenuous. It's an enantiomer, therefore literally half of what is in normal ketamine. It's also probably the more potent half. Edit: originally wrote that ketamine patent was granted in 2017, meant 2007. Edit2: originally wrote that NYU held the patent to intranasal ketamine when it was actually Mount sinai hospital.