5 ms·

If this was simply a matter of making the drug available for informed consumers willing and able to pay for it out of pocket, I wouldn't be as concerned. If we

If this was simply a matter of making the drug available for informed consumers willing and able to pay for it out of pocket, I wouldn't be as concerned. If we're going to have Medicare and private insurance companies pay $56K/year per patient for a drug that may not have positive effects that outweigh the risk of side effects, that's a major problem. Limiting access to experimental drugs is a difficult question. I know someone who has a different poorly-understood disease (not Alzheimer's, I'm being deliberately vague to avoid debates) who managed to get enrolled in a clinical trial for an experimental treatment. She responded fantastically well to the drug, as did a small number of other patients in the study. On average, however, the response to the drug was poor. She and several other responders have now found each other online and are trying multiple avenues to get back on the drug. They're getting desperate enough that they're pooling funds to order a custom synthesis from another country and have it analyzed for purity by a 3rd party lab. I'm terrified to think of the risks they're incurring, but they're so desperate to return to remission that they'd rather take the risks than continue to suffer. It must feel unthinkably unfair to be given a glimpse of remission, only to be forbidden to continue to buy the drug because it didn't work on a majority of patients. In their case, it's likely that the disease has multiple causative factors and the drug in question only treats one specific cause. Without stratifying trials by these yet to be determined different causes, it's difficult for trials to show efficacy on large populations. I wonder if Alzheimer's disease could be similar, in that certain subsets of patients respond to the drug but the average patient will not.

shkkmo 5y ago
I think we can improve access to experimental and unapproved drugs while still protecting consumers from malicious marketing of these drugs or sabotaging the current drug approval process.
- epmaybe 5y ago
  How much more access can you possibly want on top of the previous FDA expanded access guidelines as well as the newer Right to Try Act?????
adrianN 5y ago
Hopefully, eventually we'll be able to figure out why a drug works for one person but not for the next so that we can get pinpointed approvals for just that subpopulation.
- sneak 5y ago
  A simpler solution is to get rid of the approval process and let people operate their own bodies how they personally choose.
  - majormajor 5y ago
    So the solution to the problem of doctors and medicine makers not being able to figure out what's gonna be safe and effective for whom is to just tell the patient to try to figure that out on their own?
    - dnautics 5y ago
      Choosing != Figuring out
    - sneak 5y ago
      We know the top-down approach is ineffective. Is the other one worse?
      - 35fbe7d3d5b9 5y ago
        The terms "patent medicine" and "snake oil" didn't just appear from the aether.
      - tptacek 5y ago
        Yes. We don't have to wonder; we have a supplements industry to show us what happens.
        JamesBarney 5y ago
        The supplement industry has some problems. But it also has a few things going for it. It's far cheaper, and the only people that have been harmed from it made a choice to take that risk. I don't know anyone personally who's life has been screwed up by supplements. But I do know two people personally whose lives were wrecked for years because of FDA regulations. Not to mention the absurdity that was restricting the j&j and AZ vaccines.
phkahler 5y ago
>> If we're going to have Medicare and private insurance companies pay $56K/year per patient for a drug that may not have positive effects that outweigh the risk of side effects, that's a major problem. The usual story for why we allow patenting of drugs and high prices is that development is very costly - particularly the cost of doing trials. If they're going to allow this on the market without trials that show efficacy, the least they can do would be to allow generics at low prices while we're doing the efficacy testing on the general public ;-) </sarcasm>
jasonlaramburu 5y ago
I think the FDA was in a difficult spot. There have been no new Alzheimers drugs in decades and patients are desperate for treatments. There is reason to believe that beta amyloid blockers need to be given in the earliest stages of Alzheimers (when diagnosis is difficult) to have any impact on cognitive decline. The trials did not focus on early stage patients, so there may be positive impacts if it can be given early enough.
- compiler-guy 5y ago
  Great! So let's figure out a way to make this study happen so that the drug can be given effectively (if it does indeed work) rather than have a blanket approval of a drug that lacks any proof of efficacy at all. That a drug hasn't been approved for a treatment in years is no reason to approve one that doesn't work.
  - majormajor 5y ago
    > So let's figure out a way to make this study happen so that the drug can be given effectively (if it does indeed work) rather than have a blanket approval of a drug that lacks any proof of efficacy at all. It isn't a blanket approval, but it does sound way too generous in terms. From the linked article: > The agency seems to have approved it based on its demonstrated ability to clear beta-amyloid, and is asking Biogen to run a confirmatory trial to show efficacy. > They will be absolutely overjoyed to do that, of course, because the whole time that’s going, they will be selling the first drug that (in theory) targets the etiology of Alzheimer’s. The backed-up demand is going to be gigantic, and Biogen is going to make enormous amounts of money. They have nine years, as it turns out, to get this trial done, and I feel safe in predicting that it’s going to take alllll niiiiine loooong sloooow years to get this done.
  - jasonlaramburu 5y ago
    I guess the thinking is that it could take years to know whether it's working or not through an RCT. I believe they are currently allowed 9 years by FDA to show efficacy. If the side effects aren't significant why not let people in need try it?
adrianmonk 5y ago
> If we're going to have Medicare and private insurance companies pay $56K/year per patient for a drug that may not have positive effects that outweigh the risk of side effects, that's a major problem. Hmm, what if we added a new phase where it's approved but can only be sold at a low, regulated price? Then if/when it is proven effective, they can transition to charging more. Without getting into whether it's actually a good idea, in theory the high prices are meant to be a reward that makes it worthwhile to invest in drug development. Delaying the reward would still allow that incentive but keep it tied to actually creating drugs that work while still allowing patients earlier access.
- rolleiflex 5y ago
  The risk with that is that it creates a ‘perverse’ incentive for the FDA to not fully approve drugs because the approved drugs might shoot up in price 1000x the moment they exit the ‘purgatory approval’, and granting the official approval might kill some people who can afford the purgatory price, but not the fully approved official one.
  - pontifier 5y ago
    So lock in the price for the ones that started taking it before it was fully approved.
    - rolleiflex 5y ago
      That then would create the ‘perverse’ incentive for poorer people who are dying of major diseases to sign up for any and all trials possible to lock in prices, regardless of relevance, and make things much, much worse for themselves due to misuse. Richer people would not do that since they can pay the full price without locking the old price in, so this risks converting the sick and poor people already battered by life into lab rats. If you instead don’t enforce the requirement to actually take the drugs to lock in the price, then everyone signs up for everything and your drug companies will stop making any new drugs.
nceqs3 5y ago
Medicare would pay no where close to 56k/year. There are mandated rebates and price controls in medicare.
- amercer777 5y ago
  Medicare would indeed pay close to that price. Medicaid would see a rebate but would still be on the hook for roughly 75% of the list price initially.
mkehrt 5y ago
Mean drug effect is possibly a bad metric to measure. If the distribution is bimodal, or has very high variance, the FDA could take that into account when approving a drug. I believe SSRIs often vary in effectiveness, for example; some people are just very good responders. Fortunately, their mean effectiveness is high enough. (Not a doctor, etc)
bsder 5y ago
> In their case, it's likely that the disease has multiple causative factors and the drug in question only treats one specific cause. The problem is that every drug that has targeted amyloid has failed to do jack shit in any cohort--not early, not late, not alien--none of them. Any rational science system would conclude "The amyloid hypothesis for Alzheimer's is WRONG." But, no, the bio people just plow on further because amyloid gets published, and funded, and, now, approved. One day we'll look at this time as the alchemy period of neuro.
- aliasEli 5y ago
  Just the fact that we have not been able to find a medicine to reduce plaques does not imply that "The amyloid hypothesis for Alzheimer's is WRONG." Amyloid plaques are correlated with Alzheimer. AFAIK it is still an open question if they play a role in the causation of the symptoms.
  - bsder 5y ago
    Amyloid plaques seem to be correlated with lots of things--they seem to be a general response to damage to the brain. Almost all of the evidence seems to point that amyloid plaques are not causative with Alzheimer's. The fact that every single drug (including this one!) targeting amyloid plaques (some of which are actually effective at reducing amyloid plaques) has failed to do anything for Alzheimer's suggests that amyloid plaques are the WRONG target.

shkkmo 5y ago

I think we can improve access to experimental and unapproved drugs while still protecting consumers from malicious marketing of these drugs or sabotaging the current drug approval process.

epmaybe 5y ago
How much more access can you possibly want on top of the previous FDA expanded access guidelines as well as the newer Right to Try Act?????

adrianN 5y ago

Hopefully, eventually we'll be able to figure out why a drug works for one person but not for the next so that we can get pinpointed approvals for just that subpopulation.

sneak 5y ago
A simpler solution is to get rid of the approval process and let people operate their own bodies how they personally choose.
- majormajor 5y ago
  So the solution to the problem of doctors and medicine makers not being able to figure out what's gonna be safe and effective for whom is to just tell the patient to try to figure that out on their own?
  - dnautics 5y ago
    Choosing != Figuring out
  - sneak 5y ago
    We know the top-down approach is ineffective. Is the other one worse?
    - 35fbe7d3d5b9 5y ago
      The terms "patent medicine" and "snake oil" didn't just appear from the aether.
    - tptacek 5y ago
      Yes. We don't have to wonder; we have a supplements industry to show us what happens.
      - JamesBarney 5y ago
        The supplement industry has some problems. But it also has a few things going for it. It's far cheaper, and the only people that have been harmed from it made a choice to take that risk. I don't know anyone personally who's life has been screwed up by supplements. But I do know two people personally whose lives were wrecked for years because of FDA regulations. Not to mention the absurdity that was restricting the j&j and AZ vaccines.

phkahler 5y ago

>> If we're going to have Medicare and private insurance companies pay $56K/year per patient for a drug that may not have positive effects that outweigh the risk of side effects, that's a major problem. The usual story for why we allow patenting of drugs and high prices is that development is very costly - particularly the cost of doing trials. If they're going to allow this on the market without trials that show efficacy, the least they can do would be to allow generics at low prices while we're doing the efficacy testing on the general public ;-) </sarcasm>

jasonlaramburu 5y ago

I think the FDA was in a difficult spot. There have been no new Alzheimers drugs in decades and patients are desperate for treatments. There is reason to believe that beta amyloid blockers need to be given in the earliest stages of Alzheimers (when diagnosis is difficult) to have any impact on cognitive decline. The trials did not focus on early stage patients, so there may be positive impacts if it can be given early enough.

compiler-guy 5y ago
Great! So let's figure out a way to make this study happen so that the drug can be given effectively (if it does indeed work) rather than have a blanket approval of a drug that lacks any proof of efficacy at all. That a drug hasn't been approved for a treatment in years is no reason to approve one that doesn't work.
- majormajor 5y ago
  > So let's figure out a way to make this study happen so that the drug can be given effectively (if it does indeed work) rather than have a blanket approval of a drug that lacks any proof of efficacy at all. It isn't a blanket approval, but it does sound way too generous in terms. From the linked article: > The agency seems to have approved it based on its demonstrated ability to clear beta-amyloid, and is asking Biogen to run a confirmatory trial to show efficacy. > They will be absolutely overjoyed to do that, of course, because the whole time that’s going, they will be selling the first drug that (in theory) targets the etiology of Alzheimer’s. The backed-up demand is going to be gigantic, and Biogen is going to make enormous amounts of money. They have nine years, as it turns out, to get this trial done, and I feel safe in predicting that it’s going to take alllll niiiiine loooong sloooow years to get this done.
- jasonlaramburu 5y ago
  I guess the thinking is that it could take years to know whether it's working or not through an RCT. I believe they are currently allowed 9 years by FDA to show efficacy. If the side effects aren't significant why not let people in need try it?

adrianmonk 5y ago

> If we're going to have Medicare and private insurance companies pay $56K/year per patient for a drug that may not have positive effects that outweigh the risk of side effects, that's a major problem. Hmm, what if we added a new phase where it's approved but can only be sold at a low, regulated price? Then if/when it is proven effective, they can transition to charging more. Without getting into whether it's actually a good idea, in theory the high prices are meant to be a reward that makes it worthwhile to invest in drug development. Delaying the reward would still allow that incentive but keep it tied to actually creating drugs that work while still allowing patients earlier access.

rolleiflex 5y ago
The risk with that is that it creates a ‘perverse’ incentive for the FDA to not fully approve drugs because the approved drugs might shoot up in price 1000x the moment they exit the ‘purgatory approval’, and granting the official approval might kill some people who can afford the purgatory price, but not the fully approved official one.
- pontifier 5y ago
  So lock in the price for the ones that started taking it before it was fully approved.
  - rolleiflex 5y ago
    That then would create the ‘perverse’ incentive for poorer people who are dying of major diseases to sign up for any and all trials possible to lock in prices, regardless of relevance, and make things much, much worse for themselves due to misuse. Richer people would not do that since they can pay the full price without locking the old price in, so this risks converting the sick and poor people already battered by life into lab rats. If you instead don’t enforce the requirement to actually take the drugs to lock in the price, then everyone signs up for everything and your drug companies will stop making any new drugs.

nceqs3 5y ago

Medicare would pay no where close to 56k/year. There are mandated rebates and price controls in medicare.

amercer777 5y ago
Medicare would indeed pay close to that price. Medicaid would see a rebate but would still be on the hook for roughly 75% of the list price initially.

mkehrt 5y ago

Mean drug effect is possibly a bad metric to measure. If the distribution is bimodal, or has very high variance, the FDA could take that into account when approving a drug. I believe SSRIs often vary in effectiveness, for example; some people are just very good responders. Fortunately, their mean effectiveness is high enough. (Not a doctor, etc)

bsder 5y ago

> In their case, it's likely that the disease has multiple causative factors and the drug in question only treats one specific cause. The problem is that every drug that has targeted amyloid has failed to do jack shit in any cohort--not early, not late, not alien--none of them. Any rational science system would conclude "The amyloid hypothesis for Alzheimer's is WRONG." But, no, the bio people just plow on further because amyloid gets published, and funded, and, now, approved. One day we'll look at this time as the alchemy period of neuro.

aliasEli 5y ago
Just the fact that we have not been able to find a medicine to reduce plaques does not imply that "The amyloid hypothesis for Alzheimer's is WRONG." Amyloid plaques are correlated with Alzheimer. AFAIK it is still an open question if they play a role in the causation of the symptoms.
- bsder 5y ago
  Amyloid plaques seem to be correlated with lots of things--they seem to be a general response to damage to the brain. Almost all of the evidence seems to point that amyloid plaques are not causative with Alzheimer's. The fact that every single drug (including this one!) targeting amyloid plaques (some of which are actually effective at reducing amyloid plaques) has failed to do anything for Alzheimer's suggests that amyloid plaques are the WRONG target.