The FDA and Alzheimer’s Disease

by on May 16, 2017 at 6:28 am in Economics, Law, Medicine | Permalink

In The Failure of Solanezumab –How the FDA Saved Taxpayers Billions, an article in the NEJM, Sacks, Avorn and Kesselheim (SAK) defend the FDA by arguing that its high standards prevented the Alzheimer’s drug, Solanezumab, from being approved and thus saved the taxpayers billions in Medicare payments.

It is, of course, not the job of the FDA to approve or fail to approve a drug based on its effect on taxpayers. The FDA has historically stood independent of this kind of politics and that has been all to the good. But the SAK article is a reminder that under socialized medicine every FDA decision moves money from one patient group to another and between patients and taxpayers thus FDA decisions become a tempting leverage point to control allocation through collective choice.

I do not favor collective, which is to say politicized, choice and find much else objectionable in the SAK article–it attempts, for example, to evaluate a rule by examining a single decision when a system-wide, long-run analysis is called for. Rather than go into detail, however, let’s instead point to a much better article by Vradenburg, Fillit, Morgan, Sabbagh, Aisen, and Mohs, a group of leading physicians and scientists who treat Alzheimer patients and research the disease.

Rather than support or criticize an isolated FDA decision, Vradenburg et al. call for a change to the rule/norm currently used to evaluate Alzheimer’s drugs:

The analysis…recommends that the FDA approve new medicines that demonstrate a proven benefit on at least one therapeutic endpoint – either cognition or function. The current FDA standards require a new drug to show benefits on both proven endpoints, an unnecessarily challenging hurdle the authors say may be inhibiting investment in new Alzheimer’s treatments.

The authors make three excellent points about such a change. First:

…the success rate of drugs tested for Alzheimer’s disease has been extraordinarily low when compared with drugs in other therapeutic areas. Of the 244 compounds that were tested in 413 clinical trials between 2002 and 2012, only one resulted in approval of a new chemical entity, in 2003. No others have been approved since that time; the failure rate in clinical trials conducted over the last decade exceeds 99.6%. This staggeringly high failure rate has adversely impacted investment in Alzheimer’s disease research at precisely the time when new advances are most needed.

The failure rate reflects how difficult the problem is but also policy. Either way, when firms look at the billions of dollars in research and development that haven’t led to a single approved drug they are naturally wary about spending more. Breakthroughs don’t happen randomly, however, they happen after lots of trial and error. To stimulate such trial and error firms need revenues and thus to stimulate more swings at the bat it may be justified to approve drugs with relatively small benefits.

Second, as I have noted previously, the FDA needs to be careful not to commit an error of composition. Three ineffective drugs need not add up to an ineffective treatment.

Many drugs in development for Alzheimer’s disease have complementary mechanisms of action. Even if each of these might, individually, deliver a modest clinical benefit, when used in combination or adjunctively, the benefit could become more substantial. If the FDA were to reject, individually, several safe and well-tolerated therapies with complementary mechanisms of action that each demonstrate a modest clinical benefit, it would unwittingly deprive patients of potentially substantial advances in the quality of treatment over the long run with a combination of therapies.

Third, it is ultimately the patient that matters, especially with regard to Alzheimer’s where so much depends on the patient’s internal experiences, and thus we ought to be careful before rejecting their perspective:

The ultimate perspective on clinical meaningfulness, of course, comes from the patient….Efforts to identify what matters, what matters most and how much change matters to patients should become a priority for the field, focused on all stages of the disease. The requirements of the recently-passed 21st Century Cures Act are instructive in this regard.

Hat tip: Abhay Moghekar

1 rayward May 16, 2017 at 6:54 am

“Tomorrow, tomorrow, tomorrow”. If you watch television, you’ve seen the ad. It’s for a drug that promises a few more tomorrows for patients with incurable and soon to be fatal cancer. Dare to be Great. I’m somewhat sympathetic to Tabarrok’s view when it comes to Alzheimer’s if not universally sympathetic to his view about the FDA. Why? Because we appear to be on the path to an Alzheimer’s crisis. Is that a valid distinction? Was the Manhattan Project a worthwhile undertaking? My only condition is no ads for the drugs. In return, the drug can be approved if trials show either improvement to cognition or function. Fair enough? Tomorrow, tomorrow, tomorrow.


2 Jan May 16, 2017 at 6:57 am

As the paper Alex linked clarifies, FDA does not have a rule, neither regulation nor guidance document, that says Alzheimer’s drugs must improve both cohabiting and function. In fact, companies know that the agency would approve any therapy that is effective on either one of those endpoints. The authors themselves admit this: “We believe that Lilly was likely correct that the FDA would have approved solanezumab either without condition or for accelerated approval – particularly given the rare event of a compound
succeeding in showing efficacy in addressing cognitive decline – but because EXPEDITION3
ultimately failed, we cannot know for sure.”


3 Jan May 16, 2017 at 6:58 am

Sorry. Cognition, not cohabiting–though that might help these folks too!


4 Bill May 16, 2017 at 11:55 am

I was going to comment on that but forgot what I was going to say.


5 dearieme May 16, 2017 at 6:58 am

” … under socialized medicine …”: do you favour the abolition of the present forms of socialised medicine e.g. medicare, medicaid, VA, and so on?


6 Jan May 16, 2017 at 7:05 am

US conservative thought on medicine is more nuanced than that, dearieme. And it can be summarized as, “health care is tyranny!!”


7 prior_test2 May 16, 2017 at 7:25 am

Not to mention the keep government out of Medicare perspective.

Besides, basically no one older than 65 in the U.S. has a problem using Medicare. Socialized medicine or not.


8 Sarnese May 16, 2017 at 7:38 am

….. US conservative thought on “socialism” is generally muddled and unprincipled — they abhor socialist theory but love ‘practical’ socialism, like Medicare, Social security, Public Schools and government regulation of private business and citizens. Conservatives like Big Government as long as that great power forces people to do things their way.

Libertarian thought is more clear; medicare, medicaid, FDA, etc should not exist at all.


9 AlanG May 16, 2017 at 8:32 am

“Libertarian thought is more clear; medicare, medicaid, FDA, etc should not exist at all”

Also a true libertarian would call for the elimination of health insurance companies whose bureaucracies establish narrow networks and decide what does and does not get reimbursed. The true libertarian should be able to make unfettered decisions for him/her self!!!


10 Sarnese May 16, 2017 at 8:49 am

No. Private insurance companies can offer whatever terms and services they choose, as long as there is no fraud or coercion involved. Consumers choose whether to buy it.

Apparently you know little of thelibertarian viewpoint.

11 Carlito Brigante May 16, 2017 at 4:38 pm

Libertarianism is just one big thought experiment.


12 prior_test2 May 16, 2017 at 7:03 am

‘It is, of course, not the job of the FDA to approve or fail to approve a drug based on its effect on taxpayers.’

Sure it is – taxpayers get just as sick as children when a medication comes with unacceptable side effects, for example. Possibly, this sentence needs to be rephrased if you intended to say that the FDA should not be considering broader economic effects of approval. As if Sovaldi shows the FDA caring about cost at all.

‘But the SAK article is a reminder that under socialized medicine every FDA decision moves money from one patient group to another and between patients and taxpayers thus FDA decisions become a tempting leverage point to control allocation through collective choice.’

Ah, that ‘scolialized medicine’ bugaboo again, though a former Canadian citizen has considerably less excuse to use such an inaccurate term in American health care debates. But how does that sentence square with the constant reminders of the Bartley J. Madden Chair in Economics at the Mercatus Center that EU drug approval authorities are actually more effective than the FDA, without having ever previously mentioned how the ‘socialized’ EU health care system causes those EU drug regulators to play politics? (It is true that in a country like Germany, after a drug is approved, the health insurers will collectively determine whether they will pay list price for a new medication, particularly after evaluating its cost effectiveness compared to previous treatments.)

‘To stimulate such trial and error firms need revenues and thus to stimulate more swings at the bat it may be justified to approve drugs with relatively small benefits.’

But the benefits to the bottom line of the pharma companies will be anything but relatively small, one can safely assume.

‘Three ineffective drugs need not add up to an ineffective treatment.’

Of course not – but then, they also can. On the other hand, once the pharma company has sold a dose, what do they care? Maybe snake oil was was not a concept in Canadian history?

‘If the FDA were to reject, individually, several safe and well-tolerated therapies with complementary mechanisms of action that each demonstrate a modest clinical benefit, it would unwittingly deprive patients of potentially substantial advances in the quality of treatment over the long run with a combination of therapies.’

Please, as the history of AIDS medications show, this is a less than accurate description of how the FDA acts.

‘Third, it is ultimately the patient that matters’

Pharma companies care nothing about patients, the only that matters is the money. After all, was that not the departure point for this little post talking about the need for drug companies to sell products of minimal effectiveness?

‘The ultimate perspective on clinical meaningfulness, of course, comes from the patient.’

So, when someone says ‘Thanks to Laetrile, my cancer went away – so well I did not even need a doctor’s examination to know I’m cured’ that is the ultimate in clinical meaningfulness? Or in other words, the Christian Scientists really were right the entire time, it is about faith, and not science?


13 Denis Drew May 16, 2017 at 10:16 am

I’m reading American Sickness by Elizabeth Rosenthal, an MD. The financialization of care (needed or not) she describes is an exact analogue of the financialization of the economy I just finished reading about in The Confidence Men about Obama’s first two years by Ron Suskind.

The tangle that has been created is so convoluted that the only way I can see to reform it is to adopt the Canadian system: mandating paying doctors a salary and government taking control of medical capital spending. Cut the Gordian knot.

PS. Just read that 20,000 Americans dies of Hepatitis C every year and there is a 99% cure for it — Sovaldi by Gilead — which would only take enough to manufacture as the amount the chief endocrinologist on the project made for himself, half a billion dollars. But Gilead wants $300 billion for three million patients. Where was Obama, Hillary — where are they now; could open their mouths anytime?


14 Daniel Weber May 16, 2017 at 11:50 am

Solvaldi is going to save the government billions of dollars, because the cure is way way cheaper than the NPV of treating a lifetime of Hep C. Yet you want to cripple drug discovery.

If rational people were in charge, as you claim to want, they see that:

1. they don’t know how drug discovery works, the people who do it do
2. but that’s fine, the same way you don’t need to know how microprocessors are made to bid on them,
3. they would seek to create a price for people bringing drugs to market, knowing that they cannot know what the actual “cost” is on the supplier side,
4. so they would decide to pay for a cure for Hep C some very large fraction (say 60% to 95%) of the NPV of Hep C treatment for each of their patients,
5. and then let providers come up with cures.

tldr: if the government put out bids for a Hep C cure, $100,000 per cure would be super reasonable.


15 AlanG May 16, 2017 at 1:17 pm

@Daniel Weber – apparently you don’t understand drug development either. Gilead didn’t discover this drug a smaller company (Pharmasett and they began the clinical development) that Gilead bought for $11B did. So now you have to amortize that purchase price over the patent life of the drug to recoup those costs. So here is a dead weight investment that added to the drug development cost. Do you think the cost of sofosbuvir would be as high without that purchase?


16 Daniel Weber May 16, 2017 at 1:25 pm

This is true but irrelevant.

Yes, they sold for $11B, but the purchaser was willing to pay $11B because they knew they had the means to bring it to a wide market before the patent expired.

If you play the game of “well, we’ll wait until after someone brings a drug, and then look back through their records to see what it really cost,” you are just recreating the cost-plus boondoggle that crippled aerospace development for decades.

17 Denis Drew May 16, 2017 at 3:27 pm

Those top of the class grads on the way to Wall Street to strike it rich are not thinking about developing new drugs or anything else useful. New drugs are developed by scientific researchers at universities and it is just as easy for the tax payer to pay them directly — indeed there are 300,000 such research grants at any time, coming to about 1/3 of the $75 billion the US spends a year developing new drugs. That last thing anybody in Wall Street is doing tonight it working out what direction to go on research on new cures of any kind.

Point of fact: Sovaldi. Original research on Sovaldi was done at the VA, directed by an endocrinologist who spent 7 out of 8 hours working for the gov. When his team smelled money — excuse me, when his team sensed a cure — it took advantage of US law to finish the research with their own funding, raised in Ireland of course to minimize taxes. When things got far enough along Pharmasett sold it for $11 billion as noted elsewhere here.

Case in point: Bydureon (and other Glp 1 drugs) was discovered by a VA researcher in the saliva of a gila monster. Great stuff. I was diagnosed with Type II diabetes five years ago. Got (then) Byetta: lost 50 pounds in 50 weeks with no effort (common), blood sugar reduced to prediabetes level, recently got off drug altogether, Glp 1 drugs tending to refurbish beta cells.

As far as I know the equally talented researcher (right-hand man to a Nobel Prize winner) is still on salary at the VA.

PS. Gilead recently came up with Epclusa, a 95% cure for all forms of hepatitis. At the American price of $75,000 a treatment (maybe $200 to manufacture), curing 300 million sufferers in the world would come to $22.5 trillion (with a “t”). PPS. Manhattan Project research cost (today’s dollars): $27 billion (with a “b”).


18 Mark Thorson May 16, 2017 at 5:15 pm

To be fair, if the Manhattan Project were conducted under today’s workplace safety and environmental protection standards, it probably would be closer to $27 trillion. Heck, it may yet cost something in the t’s to clean up the mess they left behind.

19 Daniel Weber May 18, 2017 at 10:39 am

Gilead recently came up with Epclusa, a 95% cure for all forms of hepatitis

Those bastards!

curing 300 million sufferers in the world would come to $22.5 trillion

Not even Danny Rand was this naive.

20 dearieme May 16, 2017 at 7:04 am

“the failure rate in clinical trials conducted over the last decade exceeds 99.6%”: it seems likely that the scientific hypothesis that medical science has adopted is wrong. I doubt that economists have much useful to say about that, though ithey really ought to rather expert about failed hypotheses.


21 AlanG May 16, 2017 at 7:09 am

There are a couple of Alzheimer’s drugs on the market that are supposed to aid in slowing down cognition loss. Unfortunately, they don’t work very well and seem only to benefit those who are in the early stages of the disease. The primary difficulty is that we really don’t have a good understanding of the biochemistry of the diseases. The Lilly drug and some other earlier ones were designed to interfere with plaque buildup but judging from the clinical trials this is likely the wrong road to go down. There is a huge effort underway right now to use neural imaging to see if some type of progression can be monitored. If there is sufficient data, this might be a good marker to judge a new therapy. However, this will necessitate a longer clinical trial as progression is not as easy as looking at cholesterol or blood pressure lowering. Cognition trials are also limiting in that the baseline must be established and decline monitored.


22 Jan May 16, 2017 at 7:41 am

Thanks for that insight. I know that for some the answer is always about what FDA should be doing differently, but in this situation it appears the fundamental barrier is that the science is just incredibly difficult. No amount of regulatory change will magically produce an Alzheimer’s breakthrough and move a drug to market. That said, for the company that does make a significant discovery, the reward will be immense.


23 msgkings May 16, 2017 at 11:59 am

Where’s Todd Kreider to tell us we are 6-8 years away from health pills that will eliminate Alzheimers and all other diseases?


24 Pshrnk May 16, 2017 at 12:49 pm

We could do a lot to mitigate the Alzheimer’s “epidemic” by getting off our fat a***s, taking a walk and losing weight, rather than drinking, drugging and Krispy Kremeing.


25 carlospln May 16, 2017 at 5:19 pm

Thread winner!


26 Lanigram May 16, 2017 at 10:02 pm

Not true! Losing weight, exercise, and life long learning “may” help, but that is not certain. Otoh, certain genetic markers reliably predict outcomes.

You DO win the prize for biggest ahole of the day.

This is a terrible disease with with tragic consequences. Even libertarians care. Well, maybe not…except it IS expensive for the nation.


27 Pshrnk May 17, 2017 at 6:47 pm

Definition of mitigate
mitigated; mitigating
transitive verb
: to cause to become less harsh or hostile : mollify
aggressiveness may be mitigated or … channeled — Ashley Montagu
a : to make less severe or painful : alleviate mitigate a patient’s suffering
b : extenuate attempted to mitigate the offense


28 Pshrnk May 17, 2017 at 9:05 pm
29 Mark Thorson May 16, 2017 at 10:18 pm

Exercise, not being obese, and avoiding sugary stuff like Krispy Kreme may be beneficial to reduce risk of AD, but alcohol is not a risk factor for AD (though alcohol can cause a non-AD dementia) and drugs are not a risk factor for AD (though some drugs such as lorazepam can cause non-AD dementias).

Nobody has shown that doing all of these things right would dramatically reduce the incidence of AD. It may be like smoking and lung cancer — if nobody smoked, lung cancer would still be the leading cause of cancer death. We’d be lucky if lifestyle changes alone could affect AD as much as non-smoking affects lung cancer, but they won’t eradicate AD.


30 Axa May 16, 2017 at 7:37 am

The drug failed to produce results in trials #1 and #2, anyway Lilly did the more complicate and expensive trial #3 to get the same outcome: the drug does not work.

From the NEJM article:

“Even if a placebo-controlled postmarketing trial had been suggested as a condition of approval, investigators would have found it far more difficult to enroll participants, and
it probably would not have been conducted on the same timeline as Expedition3: these studies, if they are performed, are often not completed until many years after marketing begins.”

Thus, even if the drug were approved, it would have taken more years and more resources to find it does not work.


31 Axa May 16, 2017 at 7:48 am

Alex also discusses incentives:

“when firms look at the billions of dollars in research and development that haven’t led to a single approved drug they are naturally wary about spending more.”

Of course, if you try many times investors are not happy. But, if the (ineffective) drug would have been approved, development in other pharma companies (the competitors) would have stunted…….only to find a few years later it does not work and research needs to continue.

This is a very interesting question: what discourages development more? Another failure or success? We’re emotional humans and nothing stops a quest more effectively than someone saying “I found it”.


32 Mcmike May 16, 2017 at 8:02 am

It is true that as long as the pot of money called medicare exists, drug companies will be motivated to get access to it. And therefore someone ought to serve as gatekeeper.

So your complaint is whether the fda should perform the added role of evaluating cost effectiveness, along with its evaluation of absolute effectiveness and safety.

Not clear to me why those roles cant be combined.

I do operate under the premise that somewhere someone is going to be evaluating cost effectiveness, either the fda, medicare officials, or private insurance executives.

So where i depart from libertarians is either in their assuming no such determination will happen, or in their insistence that a system solely composed of private insurers will lead to better outcomes.


33 Jan May 16, 2017 at 8:16 am

Medicare does not consider cost effectiveness. Current interpretation of statute prohibits Medicare from considering cost in drug coverage. Medicare is also prohibited from negotiating prices. And it’s not in FDA’s mission either. Commercial insurers are the only ones that do cost effectiveness, but it is ad hoc with no common framework–in general they just cover everything, like Medicare does. Overall, the US pays a mind boggling amount more for drugs than any other country, because we are too stupid to do any of the things that limit spending on ineffective treatments. Also, PhRMA has quite literally bought off most politicians and stakeholder groups who could change this.


34 Mcmike May 16, 2017 at 3:26 pm

Medicare does make decisions about what it will cover, just like private insurance.

But your point is taken, corporatists in congress have tied medicares hands in many ways.


35 Carlito Brigante May 16, 2017 at 4:42 pm

Medicare coverage rules are generally predictable and somewhat tighter than commercial payors. But again, as noted, Medicare is hamstrung by the federal government.


36 Daniel Weber May 16, 2017 at 8:37 am

Ideally the FDA would just be a clearinghouse for safety and effectiveness, with other parties interpreting the results.

But people don’t like it when you tell them there is something that might work but you aren’t going to pay for it. If you simply say “there is nothing to do” they will find a way to accept it, sometimes with much better results.


37 Mcmike May 16, 2017 at 3:28 pm

Why is this ideal?


38 Daniel Weber May 16, 2017 at 3:39 pm

Each department would have its own purpose, not messed around by other purposes. When you mix all the purposes together, you can’t really analyze what’s going on as easily.


39 Sarnese May 16, 2017 at 9:14 am

“evaluating cost effectiveness” is constantly performed by consumers on all market products and services. Consumers can and do voluntarily consult expert outside advice, as they deem necessary.

FDA bureaucrats have no special skills, intellect, or personal integrity that qualifies them to forcibly override normal market processes and private production/consumption decisions of Americans.


40 Captain Obvious May 16, 2017 at 11:55 am

Yes, evaluating cost-effectiveness is sooo easy to do… maybe that’s why you have so many people in UK whose sole job is to do that kind of analyses, and methods journals… It must be sooo easy right 😉 ?


41 Pshrnk May 16, 2017 at 1:14 pm

” normal market processes”


42 wes May 16, 2017 at 2:49 pm

yeah right, there’s absolutely no moral-risk or principal-agent problems involved with the FDA operation — the FDA personnel bear the full risk for their life & death decisions. UR clueless


43 Mcmike May 16, 2017 at 3:30 pm

Insurance claims adjusters

44 Pshrnk May 16, 2017 at 10:07 pm

There are many factors distorting ” normal market processes”.

45 Mcmike May 16, 2017 at 3:29 pm

Oh yeah, nothing like pouring over medical journals and lab reports before making my informed purchase decision.

Thank god for the internet.
Now everyone can be an expert


46 wes May 16, 2017 at 5:30 pm

yeah, there’s no way you could consult your private doctor(s) or medical networks on this stuff. Pharmaceutical companies and private insurance companies have absolutely no expertise or interest either in protecting you from bad stuff.

The sainted Mother Theresas warming chairs at the FDA are the only saviors of American medical consumers– without the FDA America’s streets would be littered with the dead and dying


47 NoRegressiveTaxation May 16, 2017 at 8:34 am

What we need is the FDA to approve the complete abolition of excise taxes so the opioid addicts go back to alcohol and cigarettes.


48 Borge-oire May 16, 2017 at 9:01 am

Excise taxes are necessary to make sure that poor people –who don’t have intrinsic worth like you and me–don’t have fun.


49 AndrewL May 16, 2017 at 8:52 am

“Breakthroughs don’t happen randomly, however, they happen after lots of trial and error.”

i.e. Randomly


50 Evans_KY May 16, 2017 at 9:02 am

This sounds so familiar. Where have I heard this tune?

No significant antibiotic has come to market in recent years which I consider more dire than Alzheimers. No offense intended.

The Safe Drinking Water Act lays in ruins. With microcystins, perchlorates, and PFAS essentially unregulated.

Climate change is persona non grata in Congress. Despite overwhelming consensus.

My internal alarm has been screaming for quite some time. There is rot at the core of our institutions where scientists are overruled by career politicians. We must initiate a better conversation or ultimately we all lose.


51 Borge-oire May 16, 2017 at 9:04 am

“Climate change is persona non grata in Congress”

What are you talking about? The climate has been increasing faster in congress than everywhere else. Every New York Times headline is about how “things are heating up in congress”.


52 Daniel Weber May 16, 2017 at 11:42 am

Antibiotics aren’t going to be found by the patent system, which is very good at drug discovery otherwise, because the best way to use an antibiotic after it is discovered is to carefully guard it for years until we really need it.

Prizes might work, and wouldn’t be hindered by the patent system. WHO could pay $10 billion to anyone who delivers a new antibiotic.


53 Lanigram May 16, 2017 at 10:10 pm

“No significant antibiotic has come to market in recent years which I consider more dire than Alzheimers. No offense intended.”

“…climate change…consensus…”

That is flat out stew pit!
How many people have been killed by global warming? Now, how many people have been killed and families wounded by Alzheimer’s?

Wake up!


54 David C May 16, 2017 at 9:08 am

I have plenty of beefs with the FDA, but I don’t agree with this analysis. I think that the FDA conscientiously tries to be data driven. You can speculate all you like on whether 3 drugs used in combination might have a positive net effect on patient well-being, but unless you have some solid clinical data, it won’t (and shouldn’t) get you far with the agency. There are plenty of examples where such speculation turned out to be wrong.

Alzheimers patients and their families are DESPERATE for something, anything, that can give them some hope. But it is all too likely that it is a false hope. I am very sad that the work so far in developing treatments hasn’t been more successful. But giving patients the equivalent of Laetrile won’t accomplish anything except waste money.

I think the question of whether or not to insist on a drug proving effective in both function and cognition is a fair one. But however you answer that question, we still need scientific data to evaluate potential new treatments


55 Hazel Meade May 16, 2017 at 9:17 am

a tempting leverage point to control allocation through collective choice

Controlling allocation through collective choice is the point, for a lot of people.
This is how they define “democracy”. If the people don’t get to vote on what sort of drugs you’re allowed to ingest, that’s “undemocratic”.


56 Ari May 16, 2017 at 9:39 am

I hope someone at FDA is reading this.


57 AlanG May 16, 2017 at 10:22 am

Why? there really is not any special insight from either Alex’s post or the comments that have so far been posted. What do you think FDA will learn?


58 Captain Obvious May 16, 2017 at 11:57 am

Not to listen to libertarians, they have no idea what they are talking about. But I guess the FDA already knows that 🙂


59 Thanatos Savehn May 16, 2017 at 10:07 am

The axis of futility. Congress demands something he done so the NIH promotes the beta amyloid hypothesis because it’s an easy target for the null hypothesis racket (per PE Meehl) run by academics in search of federal grant money. And yet despite all the fuzzy initial conditions, endpoints and outcomes they still can’t find anything marketable, much less anything actually helpful, for Alzheimer’s. That patients and taxpayers aren’t being scammed is a rare success for the FDA. That our research dollars are directed toward easily exploited methods of generating false positives for putative treatments for such a horrible disease is a scandal.


60 AlanG May 16, 2017 at 10:21 am

The Alzheimer’s Disease Neural Imaging project (ADNI) is being coordinated by NIH, FDA, and the pharma industry. The imperative is to come up with some type of clinical marker that can be used to both gauge progress of the disease and the clinical impact of therapy. Maybe it fails, we really don’t know right now. I can tell you that continuing to rely on cognition as an end point is not going to get any closer to effective treatments.


61 Thanatos Savehn May 16, 2017 at 11:00 am

Cognition, even if somehow objectively measurable, would still be the wrong dimension for seeking correlations pointing to potential treatments under the amyloid hypothesis since up to 40% of “cognitively intact” older people carry amyloid loads that would qualify them for an Alzheimer’s diagnosis (but for their intactness). At best amyloid plaques are a necessary but not sufficient cause of the disease. Hopefully the imaging project you mention will lead to something more promising than the serially falsified drug discovery paradigm of “preventing plaques, removing plaques or some combination of the two.”


62 Hazel Meade May 16, 2017 at 11:10 am

This is why we really need to allow datamining of electronic medical records. Get some AI researches to work on detecting drug efficacy across the entire population, not to mention disease linkages, genetic risk factors, etc. etc.
We’ll find out quickly which drugs are actually working and which ones fail to live up to the hype.


63 AlanG May 16, 2017 at 11:31 am

@Hazel Meade – When I was at PhRMA, we undertook a very large project to do just what you describe. It was an Observational Medical Outcomes Project (OMOP) and it was designed to look across large databases, initially for small drug safety signals but could later be expanded to examine benefit as well. I well remember the initial presentation to request multiple $$Million to fund the project’s first year (I don’t know how many others who read this blog have been in this position; it is quite daunting). The project did get funded and was run as a public private partnership with the FDA, pharma companies, and academic experts. The project ran for five years and parts of it still continue (

There are a huge number of problems in the US because EMRs are not standardized (plus, a lot of HMOs and large providers charge $$$ to access their data) as well as the common data vocabulary. OMOP came up with some good ideas but it will require a more concerted effort to do what you suggest.


64 William May 16, 2017 at 10:29 am

Alzheimer’s is a glial cell disease, and like most “aging” diseases can only be cured by telomerase activation… so most “Alzheimer’s” research is misdirected nonsense. The FDA doesn’t even have approval CATEGORIES for the underlying biological problems… there are no “anti-agathics”, no “nootropics”, hell, they don’t even have a “rec drug” category to save the opiate idiots.

I worked in telomerase and lenti vector labs for seven years. We’ve had the real solutions since 2005: telomerase activators and/or vectors, senolytics, etc. Bowhead whales live more than 230 years, and so could you… but not by using patent medicines aimed at individual symptoms caused by the programmed death clock (thanks Metaloclypse).


65 Mark Thorson May 16, 2017 at 1:33 pm

If that’s the case, why do all of the mutations which cause the familial forms of Alzheimer’s affect either the amyloid precursor protein itself or the enzymes involved in APP processing (presenilin-1, presenilin-2, etc.)? None are involved with telomeres. Until you can explain that, your hypothesis doesn’t get past the starting gate.


66 Effem May 16, 2017 at 11:17 am

I think we’ve learned from the “natural supplement” industry that consumers will indeed waste billions of dollars on useless treatments. I’m all for smaller government and FDA reform, but this libertarian dream that somehow the “market will figure it out” has already been proven wrong.


67 Todd K May 16, 2017 at 1:23 pm

People also waste billions of dollars on movies and music that they didn’t like not to mention the food they throw away.

Not all “natural supplements” are equal.

A high dose of vitamin D3 has been shown to help people with heart failure and a high dose of 1,000 mg of NR (Nicotinamide Riboside) is being tested at Texas University on the elderly with mild cognitive impairment (MCI) with results to be published next year. Mayo Clinic with the U of Minnesota is testing 750 mg of NR on football players who have had one to three concussions and the study concludes in September. Other human trials include effects of NR on heart failure, cholesterol levels, obesity, pre-diabetes, diabetes, and stamina.


68 Todd K May 16, 2017 at 1:26 pm

And the University of Kansas is planning a trial on how NR effects Alzheimer’s patients.


69 msgkings May 16, 2017 at 1:42 pm

There you are, Todd!


70 Todd K May 16, 2017 at 1:59 pm

Would I let you down??

71 Todd K May 16, 2017 at 2:21 pm

Oh, I didn’t say that it was the health pills like NR that would cure Alzheimer’s disease in 6 to 8 years (I said 5 to 10 years for kidney dialysis to become obsolete) but that in coming years they will notably reduce the percentage getting dementia but will very likely be a drug that ends Alzheimer’s.

72 Bill Walker May 16, 2017 at 11:38 am

Non sequitur, Effem… consumers waste hundreds of billions on ineffective (and harmful) patent drugs as well.

The solution isn’t a North Korean style central bureaucracy… if those worked, your glial cell telomeres would already be optimal length and your senescent cell population would be minimized 😉

The solution is to let people opt out of your FDA’s “protection”… we’ve been protected from the epigenetic changes that we need. If YOU want to stick with cartelized pharma, you go right ahead… but why you think you have the right to stop researchers from using the stuff we developed is beyond me. You’re literally forcing the terminally ill to use “approved” drugs that you know don’t work for their conditions.


73 mahesh May 16, 2017 at 12:33 pm

I am CEO of Lipocene. What I’m doing here, you see, is that LPCN 1021 is an oral testosterone replacement product candidate with positive topline Phase 3 efficacy results and is currently in an ongoing safety extension phase.

Today, it is indeed byzantine that no orals exist for such a drug. For instance, how much work is misallocated on space travel or Viagra. How many drinks are drunk when there are no hiccups. How many desserts are eaten at van leewuns? 347) 763-2979 – feel free to spit on the windows, its legal.

I have neither love nor remorse, but rather a dissonant dissipation. I have dissected a remora, removed its discfin and applied to my wounds like stuck-on bandage.


74 William May 16, 2017 at 1:18 pm

Not sure how well the remora is working for you… outside the FDA zone, oral testosterone is freely available.

The safe form of oral testosterone is testosterone undecanoate. Testosterone undecanoate is only available for use outside of the United States. It is marketed under several brand names including Andriol, Undestor, and Nebido among others.


75 Boonton May 16, 2017 at 3:49 pm

“The failure rate reflects how difficult the problem is but also policy”

But how so? 244 compounds tested resulting in 1 approved drug. Those are steep odds but I’m not seeing any obvious case that the failure rate is policy rather than simply being a very difficult problem. Of the 243 that failed, which one(s) should the FDA have approved? Why should they have approved it? To simply ‘encourage’ investment in R&D? Why would that do so? If the 2nd best drug failed in studies but was approved by the FDA nonetheless then why would insurance, doctors and patients pay to take a drug that doesn’t work? If they don’t take the drug, then how does the company that owned that rejected drug reap any reward?

On the flip side if 244 compounds are tested but only 1 generated a useful drug, that’s a monopoly for the one company that stuck it out and brought the one successful drug to market. Approving an unsuccessful drug would just dilute that reward.

Ultimately I’m seeing a physical problem here. It’s really hard to make a drug that passes through to the brain AND does something useful to it. However that also makes it very valuable. If you can find a drug that does that, you are probably not going to have much competition for some time. On the flip side if you have a drug that lowers blood pressure, well, welcome to the club. Tyler’s case here smells like his infamous taco-copter failure. If you don’t recall, his thinking was essentially it would be cool to have drone copters deliver us tacos. Why don’t we have them? It must be because there’s bad regulation discouraging anyone from starting one (although ‘regulation’ doesn’t seem to stop people from using copters to smuggle drugs and guns into jails!). It would be cool to have more Alzheimers drugs. Why don’t we? Because the FDA is too mean. Perhaps but then it should be easy to point to some drugs that were rejected when in fact they might be kind of useful.


76 William May 16, 2017 at 4:29 pm

Boonton, if you read the FDA’s own website, they claim that they killed tens of thousands of people just by failing to approve beta blockers even after they had been in use in Europe for years… I don’t buy the FDA’s reasoning chain, I think once again they missed the whole basic-biology point. But that their official story.

Just look at the difference between drugs available in Singapore or Dubai or Germany with what Americans have. Look up “roxithromycin”… the world standard for strep throat treatment, and it will NEVER be approved in the US.

It’s just like the education world… Americans think that the US is the world.


77 Boonton May 16, 2017 at 9:30 pm

So you’re saying one or more of the 243 Alzheimers drugs that didn’t make it in the US was approved in Singapore, Dubai or Germany and is doing good work there? Which drugs are they?

This also cuts against Tyler’s economic claim. If, say, Germany, is more open to approving a good Alzheimers drug then why wouldn’t you invest in discovering one, get it approved in Germany, rake in the sales there and use that to fund the data and studies to meet the FDA’s standards? Do you have evidence showing a pattern of the EU, Japan or other countries getting drugs first and then the FDA approves them or vice versa?


78 Boonton May 16, 2017 at 9:31 pm

Sorry just realized Alex authored this post rather than Tyler…..


79 Jon May 16, 2017 at 9:06 pm

“To stimulate such trial and error firms need revenues and thus to stimulate more swings at the bat it may be justified to approve drugs with relatively small benefits. ….”

The FDA does approve treatments with small benefits; they just don’t prove treatments where the benefits are so small they can’t be demonstrated. There is so much wrong with Alex’s naive view of drug research and discovery it would fill up this comment (see plenty of other comments for such insight).

Alex complains about the the government interference with medical care and that the FDA may be reluctant to approve some drugs because of the costs to taxpayers.

If we did not have Medicare, Medicaid, Obamacare, VA-care and tax breaks for employer health insurance, people would not get treated and medicines would not be purchased. There would thus be less profit from new medicines, and thus far less research. Furthermore, if we removed the other government intervention that generates high costs for medicines—intellectual property rights, we would have far fewer (perhaps no) drugs developed.

If you want drug discovery, you need government intervention.


80 mikeInThe716 May 17, 2017 at 12:43 pm

Given the cost of Alzheimer’s care, you’d think there’d be incentive for other nations’ pharma research firms to develop Alzheimer’s drugs outside FDA jurisdiction. My guess Alzheimer’s Drug development is extraordinarily difficult and expensive.

Although it would be interesting to watch the FDA try to stop importation and use of even a limited cognitive improvement drug developed by the Swiss or Koreans…


81 Bill Walker May 17, 2017 at 2:06 pm

The FDA has been stopping importation of effective drugs for decades… as I said, read the FDA’s own comments about beta blockers, look at roxithromycin… but most of all, look at the approval categories themselves.

Prevention through epigenetic control is more important than pretending to treat symptoms.


82 mikeInThe716 May 17, 2017 at 6:19 pm

I understand your point. But blocking importation of an effective Alzheimer’s drug would be much greater in terms of backlash compared to roxithromycin.

Maybe I’m too close to this problem to be objective. But Alzheimer’s patients deteriorate over years – a long time frame that makes this disease quite visible. Watching this decline (or the mild horror of sensing one’s own! decline) would be exponentially more frustrating IF an effective remedy or mitigation drug were available ONLY overseas.

Think about the incentives. If you or a loved one were diagnosed with early onset Alzheimer’s at age 60, what would YOU pay – or what laws (or FDA regs) would YOU break – or how much prison time would YOU risk – to delay onset for 3/5/10 years?


Leave a Comment

Previous post:

Next post: