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Alzheimer's Disease

A Missed Alzheimer’s Opportunity? Not So Much

The Washington Post made quite a splash with this story about Pfizer, Enbrel (etanercept), and Alzheimer’s disease. There’s already been a lot of comment about it yesterday on Twitter and in some other venues, but I thought it might be useful to try to sum things up in an easily accessible place. Here we go:

What’s the accusation in the Post’s story?

Basically, that Pfizer had evidence that Enbrel could be useful in Alzheimer’s disease, and didn’t do anything with it. This came from an analysis of insurance claim data: a set of about 127,000 patients with an Alzheimer’s diagnosis and a set of 127,000 without. It turns out that more people in the second group had been treated with Enbrel (302 patients) versus the first (110 patients). The Post obtained internal Pfizer documents discussing this and whether it was worth further investigation, and the company had concluded it wasn’t.

Why wouldn’t they?

Several reasons. The biggest, though, is that no one undertakes an Alzheimer’s trial lightly. The clinical success rate for Alzheimer’s trials is arguably zero per cent. There are a couple of therapies approved, but they don’t affect the disease progression at all – they help a few people, a bit, for a little while, and that’s it. That argues for a huge unmet need in the area (which no one disputes, God knows), but it also argues for caution. Many, many approaches have been tried already, from many angles, and every single one of them has gone down in flames.

The story quotes the Pfizer documents as saying that three to four thousand patients would be involved in a clinical trial if the company were to run one (which sounds about right), and also says that the trial would cost $80 million. Which sounds ridiculous. You’d have trouble running a 4000-patient study for the flu with $80 million in hand, much less an Alzheimer’s trial. It’s a slow-moving heterogeneous disease; Alzheimer’s trials go on for years because of those factors, and even just choosing your patients at the start is not an easy process, either.

It has to be emphasized as well that the data in the Pfizer presentation are not amazing. I’ve seen people on Twitter and the like going on about how Pfizer had a drug that was 64% likely to cure Alzheimer’s or some other crazy statement (two out of three, y’know), and that betrays an extreme lack of knowledge about clinical data and drug development. Not that that’s uncommon. But no, this is a noticeable-but-small signal, and by itself (I cannot state this strongly enough), it would not be enough for anyone to launch an Alzheimer’s trial. See below for more reasons why this is true, but that has to be stated up front. Note, for example, that Pfizer only sells Enbrel in Europe: in the US, it’s sold by Amgen, who acquired Immunex years ago largely just to get the drug (Pfizer ended up with the other marketing rights when they bought Wyeth). The Post article mentions, in passing, that Amgen had also looked at these numbers and passed. You would not be able to get venture capital money to run such a trial based on these data, nor a grant from any government agency. If you still doubt those assertions, perhaps the case for them will become clearer as you read on.

Any other reasons?

The article does note that Pfizer was getting out of Alzheimer’s in general at the time (2015), but it also explicitly makes clear that Enbrel was nearing the end of its patent lifetime and brings up the idea that Pfizer deliberately took a pass because they weren’t going to reap as much profit.

Well, you’ll have to trust me on this, it’s a little out there, but drug companies don’t generally walk away from big profits if they can help it. I’ve had my problems with Pfizer over the years, but I have never called into question their ability to make money. If Pfizer really thought that this was a promising lead into an Alzheimer’s therapy, they would have found a way to turn a profit off of it. One of the biggest objections to the idea inside the company was that this finding was unlikely to be real because Enbrel doesn’t really penetrate into the brain: a believable signal for Alzheimer’s, unlikely though it would be, would have been the occasion to search through similar antibodies or modified forms of Enbrel looking for ones with better penetration. Those you could patent fresh, it hardly needs to be said – and here are some people who have worked on just this idea. Antibody therapies (directed against the beta-amyloid protein) have already been tried several times against Alzheimer’s, so that’s not a crazy idea per se. Now, it’s worth remembering that all of those amyloid-antibody trials have ended in grievous, expensive failures – every single one, apparently because targeting beta-amyloid is not exactly the road to success that people had hoped – but these antibodies have gotten into the brain.

And the idea that Enbrel’s patent is about to expire is also up for debate – in fact, it’s being debated in court right now. There are biosimilars on sale in Europe, but the in US Amgen is arguing that they have legal grounds for ten more years of patent protection, and that case hasn’t been decided yet. One would also be able to argue that these biosimilars would need to prove their own efficacy against Alzheimer’s, rather than (as is the case now) against the other main targets for Enbrel, which are rheumatoid arthritis and psoriasis.

In short: the Evil And Nasty interpretation, which I’ve seen proposed and which can be summed up as “Drug Company Finds Cure For Alzheimer’s And Sits On It“, is ridiculous.

What is Enbrel and why might it do something against Alzheimer’s?

Enbrel is a fusion protein (of the TNF receptor and an antibody domain) targeted against the TNF-alpha protein. (Edit: clarified this, as opposed to a straight antibody). That’s a major player in inflammation, which is why you see uses like the ones just mentioned. It’s been noted for years (decades) that the brains of Alzheimer’s patients show signs of a persistent inflammation response, leading some to wonder whether Alzheimer’s leads to inflammation or inflammation leads to Alzheimer’s. With that in mind, basically every single anti-inflammatory therapy has had a look at it for potential Alzheimer’s use, starting with aspirin and ibuprofen and going up to the anti-TNF antibodies like Enbrel.

Are you saying that others had thought about TNF for Alzheimer’s?

Yep, absolutely. If you go through the literature, you can find any number of papers proposing such a connection – here’s a review of the field. Here’s a study (in mice, if you believe Alzheimer’s mouse studies, and some do) with one of Enbrel’s main competitors, Humira (adalimumab), and there are a lot more animal studies out there as well. Note that it’s a complex field; there are several forms of TNF and they have different activities. But it’s not just TNF in general that’s been proposed for Alzheimer’s before, it’s Enbrel in particular. Here’s a review on its effects when injected directly into the cerebrospinal fluid of Alzheimer’s patients, for example. Here is an actual clinical trial of Enbrel in human Alzheimer’s patients – it’s mentioned quickly in the Washington Post article, but it’s easy to miss that. (It was a small trial, and results were not compelling).

But didn’t Pfizer bury its data showing that Enbrel might have some use for Alzheimer’s?

If you are curious about what insurance claim data show about rheumatoid arthritis, Alzheimer’s, and treatment with Enbrel, let me refer you to this 2016 paper. The authors ran just such an analysis across 8.5 million patient records, and for all I know this is the same data set that Pfizer analyzed (unlike the Post, I haven’t seen their slide set, so I don’t know). The paper concludes that (1) Alzheimer’s disease is significantly more prevalent in rheumatoid arthritis patients than in those who have not been diagnosed with the disease, (2) the presence of other chronic conditions such as diabetes or cardiovascular disease significantly increased the risk of AD, (3) that treatment with anti-TNF antibodies as a class was associated with lower risk of AD, and finally (4) that when analyzed on a drug-by-drug basis that only Enbrel (of the various anti-TNF treatments) was associated with that decreased risk. And if you read the full paper, you find that it references a report from 2010 that showed improvement in cognitive function in a small set of Alzheimer’s patients treated with Enbrel for arthritis.

Why only Enbrel? The authors have several speculations based on the differences between the three approved anti-TNF antibodies, all of which are reasonable, but conclude that “Further studies directly comparing the efficacy of each agent in treating or preventing AD are required to determine the difference in the clinical benefits among these three agents“, and further note that since none of them get into the brain, that the mechanism for any benefit remains unknown. But the main point is that if you wanted to act on clues that Enbrel might have benefit in Alzheimer’s, they have been out in the open literature for years now. Not buried by an evil drug company. Out there for anyone to see and act on.

You can purchase Enbrel on the open market and run a trial of your own, if you so desire – but what you will find (unless you are fabulously wealthy and spending your own money) is that coming up with funding will be very difficult, because these data are still insufficient to go right into a large human trial in an area as fraught as Alzheimer’s. The use of anti-TNF antibodies for Alzheimers is not a crazy idea, but a lot of even better ideas have failed ruinously in this area. It’s worth investigating more, but anyone saying already that this is an overlooked cure has not worked in the field. Or, apparently, even spent fifteen minutes looking through PubMed. The Washington Post article would have benefited from doing just that. As it stands, it’s just worked up people for very little good reason. I like the newspaper, and I subscribe to it online, but this is not a good moment for it.


75 comments on “A Missed Alzheimer’s Opportunity? Not So Much”

  1. NJBiologist says:

    Getting a clinical trial design through an IRB generally requires that a physician can maintain equipoise with regard to the intervention–to genuinely not know that one arm of the trial is worse than the other. I would argue that the adverse event/side effect profile of etanercept (basically, it’s a TNF blocker–so, infections and possible slight cancer risk), combined with the low quality of the evidence suggesting a benefit, eliminate equipoise.

    1. lin noll says:

      Treatment length for permanency of results is only 7 shots. Gains maintained 2 years later. Patients are not on Enbrel long term.

  2. Some Dude says:

    >What is Enbrel and why might it do something against Alzheimer’s?
    >Enbrel is an antibody against the TNF-alpha protein.

    Etanercept is not an antibody, as described in the wikipedia page you link above.

    1. Derek Lowe says:

      Just clarified that some more, thanks.

    2. John says:

      Has anyone had substantial success with Enbrel for Alzheimer’s and if so, what protocol and dosage ?

      1. Larry Lewyn says:

        Apparently so. In 2013 my father was diagnosed with Alzheimer’s. At the time, Dr. Edward Tobinick was actively treating patients with perispinal enbrel injections. 60 minutes of Austrailia did a segment on this treatment and basically raved about it. Even NCBI acknowledged evidence that this could be a potent treatment. Yet, no mention of this is made in Derek’s article.

        Dr. Tobinick was, at that time, charging 30,000 for the initial treatment. Additional injections would be required on a regular basis. My family elected not to pursue this.

        Imo, the preponderance of the evidence suggested that this treatment might be effective.

        Yet, the manufacturer has always maintained that it is unaware of any real evidence supporting this.

        People need to do the research and draw their own conclusions.

  3. StumpedByTheCaptchaMath says:

    Per Derek: “I’ve seen people on Twitter and the like going on about how Pfizer had a drug that was 64% likely to cure Alzheimer’s or some other crazy statement (two out of three, y’know), and that betrays an extreme lack of knowledge about clinical data and drug development.”

    In this sentence, I don’t believe it would be an exaggeration to put the word ‘extreme’ in all caps, bolded, italicized, and underlined. When discussing a topic as heart-wrenching as Alzheimer’s, to find the statement that Enbrel could reduce the risk of AD by 64% in the very first sentence of the WaPo article is beyond ignorance and has strayed precariously into negligence. This type of clickbait baloney is far below the standards of WaPo.

    1. loupgarous says:

      If Nicholas Sandmann’s case against the Washington Post goes to trial, I think we’ll see plenty of evidence that the Post has a set of standards which favor sensationalism over due diligence in reporting a story, even one about teenagers doing teenage things in a teenage way.

      Characteristically, the Post led with headlines unfairly maligning the kids from Covington Catholic High which 2 hours of video readily available on YouTube would have demolished. I was among three or four others who gave the Post working URLs to that video or excerpts from it. So, their performance against Pfizer doesn’t surprise me.

      The Washington Post could have, when researching this story, examined this or other med-chem/medical device blogs and learned for themselves how improbable it really was that Pfizer covered up anything. The study in question, for one thing, was available to anyone to read, and it covered a correlation even the authors said needed to be affirmed by more studies.

      A few phone calls to Derek and other med-chem commentators (or to any of Pfizer’s competitors whose AD drug trials also crashed and burned in Phase 2 or 3) would have given them the information Derek’s shown us here. But that wouldn’t be sensational, and sensational is how Washington Post rolls these days. Some bare boobs on page 6 and few more full color shots with their stories, and Jeff Bezos would be in the same business as Rupert Murdoch and his kids.

      1. navarro says:

        your second paragraph does not improve your comment. the rest of the comment sounds measured and reasonable but the second paragraph makes it sound like you get your news from breitbart.

        1. Anonymous says:

          Loupgarous is simply pointing out, factually, that the journalistic standards of the WaPo have declined dramatically in recent years.

        2. loupgarous says:

          Navarro, it’s hard to see what triggered your attack of condescension, except my reference to how, earlier, the Washington Post also decided to not use due diligence in documenting a story when it would have been easy, quick and the right thing to do.

          And again, the facts wouldn’t have been nearly so sensational as what their editorial staff decided to go with instead. In that respect, the Washington Post and Breitbart are all too oftem mirror images. I don’t rely on either journal for accurate accounts of stories with even a slight political dimension.

    2. D Ciappenelli says:

      WAPO has no standards any longer. Let Bezos fund the trial…

    3. undrgrndgirl says:

      i think the bigger question here is should pfizer have shared the information and the answer to that is: YES

      if pfizer didn’t want to pursue it, fine. but they should have put the info out to give others the opportunity to research/do clinical trials…or parse the info and come to the same conclusions as this author.

      1. zero says:

        As Derek points out, the data was already public. Published. Available to anyone interested. Pfizer had no obligation to publish their internal opinions of whether further study was justified.

  4. luysii says:

    “This type of clickbait baloney is far below the standards of WaPo.”

    I don’t think it is.

    It’s just another one of their narratives. Remember ‘collusion’, then ‘obstruction’ then ‘not exonerated’.

    1. cancer_man says:

      Exactly. See “climate change” and “Fukushima” for other examples.

    2. blog poster says:

      Get this garbage out of here. If you refuse to take the time and effort needed to understand American politics and policy then you should refrain from mentioning it. Stick to topics you do understand. (pharmaceuticals?)

      Most WaPo reporting was proven right by the Mueller Report. Mueller specifically said trump was not exonerated. Mueller specifically outlined 10 examples of possible obstruction. Mueller specifically said that he was barred from charging trump with a crime or formally accusing him of obstruction – no matter how overwhelming the evidence.

      I believe that Manafort’s meeting with Kilimnik was a clear example of collusion even if it was not a crime. This is at least arguable, but when you insinuate “obstruction” and “no exoneration” are false narratives you voicing an ignorant, lazy opinion.

      1. Friend says:

        Your post is yet another indicator that the treatment for Alzheimer has not been found.

      2. loupgarous says:

        Attorneys are not allowed to shout that people are “not exonerated” in ways that agitate public opinion against potential defendants. The burden of proof still rests on the accuser, and in this case the accuser spent many millions of dollars and two and a half years not making a case he felt he ought to have, as Leon Jaworski and Ken Starr did, referred to Congress for prosecution.

        The problem being that the Speaker of the House, for all her bluster, knows the case Mueller made consists for a dozen possible cases of obstruction of justice unlikely to be proven before the Senate in an impeachment trial.

        So what she and her friend in the House majority leadership are doing is blackguarding the President in every way that privileged speech allows, because they can’t win an impeachment trial with the evidence Mueller gave them.

        The Washington Post and New York Times have been in their corner echoing their statements. These newspapers have been called out by one of their own, Rolling Stone contributing editor Matt Taibbi, who has catalogued exactly how the news media have embellished the evidence regarding Iraq’s WMD program and statements made about the Trump administration by the Obama administriation’s law enforcement and intelligence agencies for the sake of sensational reporting.

        It’s not a partisan problem, it’s sloppy and sometimes slanted and even malicious reporting by news sources which ought to know better, but want those advertising benjamins.

        1. Skeptic says:

          Please stop polluting this excellent blog with such horribly biased nonsense.

  5. it's because of TV says:

    Has there been a study relating Alzheimer to lack of keeping your mind active?
    I’m in my 50’s but I force myself to keep learning new things, taking tests etc. it’s a pain and my recall isn’t what it used to be but I keep at it.
    How many Alzheimer patients are guilty of just giving up and watching TV all the time?

    1. Charles H. says:

      Yes. I don’t recall the details, but the summary is that keeping your mind active slows the onset, and when the collapse comes it’s faster.

      Well, that was from a newspaper article decades ago, so there might be some better info out since then, but that was the result of one study.

    2. steamed says:

      I’m really uncomfortable blaming the victim of a horrible disease. Can you declare with certainty cause and effect? Maybe watching TV leads to degradation of mental acumen, but it seems just as likely the decline of cognitive skills would lead to passively watching TV.

    3. Your active mind says:

      If only all the researchers and medical professionals knew that sudoku was the cure. #wtf

    4. elizabeth says:

      My mom is suffering from 2nd stage ALZ/dementia, has always done crosswords/word search puzzles..and does to this day – I have to get her easier puzzle books now, and she still does them.

  6. jm04105 says:

    Thank you for this. Here is some context around drug development: Drug companies are constantly experimenting with new molecules. A fraction of the molecules developed show potential. Once they develop a molecule that they think might do something, they patent it. From that moment, the 20 year clock starts ticking.

    Then the molecule is packaged into a deliverable prototype drug, and testing begins on animals. A fraction of these drugs show enough promise to move on to human testing. Then the human clinical trials begin. These happen in multiple stages, culminating with FDA approval or rejection. A fraction of these drugs are approved.

    Typically by this time, 10 years have run out of the patent, and the drug maker has spent millions of dollars. A single FDA approved drug represents many more drugs that were prototyped but did not pass FDA muster, or did not prove effective in human or animal trials, and many more molecules that were tried but did not show potential.

    The drug company now has 10 years to sell the drug and make ALL of that R&D cost back, plus some profit to make it worthwhile and to pay for future research, before the patent runs out. Then the generic makers simply copy the drug and sell it for pennies on the dollar. The “profit” measured on a single drug does not account for all the R&D money lost on all the other drugs and molecules that did not make it to market.

    Eliminating the patent period would effectively mean drug innovators would be doing all that costly R&D only to give it over to the generic manufacturers immediately. I see a lot of whining about this, but no serious solutions offered. The patent process is the reason the majority of life improving/saving drugs are invented here.

    1. Valid Point ?? says:

      That would be a great argument if the bulk of research wasn’t just “me too” drugs or even worse, things that the “inventors” knew didn’t have a chance but their progress through “clinical trials” would serve to bolster stock prices or enable the flipping of an IPO.

      1. Harrison says:

        Is the bulk of the research really “me too” drugs? How do you differentiate from a true “me too” (e.g., levocitirizine vs. citirizine) vs. two companies doing research on the same target for a decade, and one gets to the market a year ahead of the other?

        1. I got there first! says:

          working on something you know another company is also working on and you are both just trying to make it to market faster, couldn’t also be considered “me too” ?

          1. Bell4 says:

            Generally no, because full clinical trials, especially those that measure outcomes, are quite long (> 5 years), so it is not uncommon for multiple parties to be in trials at the same time without knowing if the drugs being tested are of any value.

      2. Project Osprey says:

        Surprisingly, clinical trials that progress all the way to failure don’t tend bolster stock prices.

        1. Check Again says:

          Really?? have you taken a look at all the startup’s stocks that run along at a decent price only to plummet to nothing and stay there after a failed 3rd trial?
          For big pharma, sure it’s not so evident but for startups it blatantly obvious

          1. jm04105 says:

            That’s a very dark and cynical way of looking at the world. Startups hiring educated scientists to basically dig holes and fill them back in with no intent of producing anything, just for the IPO. You believe people are much more evil than me.

      3. Seamus says:

        “Me too” is way overused to criticize pharma. It takes a long time to develop new drugs and a lot can go wrong. With multiple companies working on same target there is greater likelihood at least one makes it. Those companies also take different approaches to trials, patient selection, endpoint, etc. that winds up tracing the field more (& gives more patients and providers the chance to participate in trials).

        Also, just because two drugs have the same mechanism of action does *not* mean all patients will respond equivalently to them. Or patients will need follow up options when efficacy for first drug in class wanes (e.g., due to neutralizing antibodies). The first drug in a new class may not be the best drug either. This is true for TNFa inhibitors where Humira has dominated despite being a “me too”.

        1. loupgarous says:

          Cialis (tadalafil) is an example of what could be criticized as a “me too” drug but which has fewer troubling side effects than the first PDE5 inhibitor marketed specifically to treat erectile dysfunction. Two or three drugs for the same indication and hitting the same target sometimes give physicians and patient valuable alternatives, in both safety and efficacy.

          1. Sesquiculus says:

            Speaking of which– There are ongoing efforts to repurpose tadalfil and sildenfil to treat the vascular component of Alzheimers and/or vascular dementia. E.g.,

    2. Carl Bar says:

      Honestly the biggest takeaway i’ve made from some of Derek’s articles is that there’s a real issue with the drug industry atm. On the one hand the way the patent limits are setup makes it incredibly hard for the to make money. But on the other hand that same long term exclusivity gives them a monopoly and cuts harshly into the ability of others to compete.

      It’s not a good situation either way.

  7. SirWired says:

    I agree that the article was ridiculous and poorly-researched.

    Alas, the pharma industry has done itself no favors here, in that it’s a very human reaction to assume the worst, given the well-documented unambiguously-bad things that have occurred over the years. (I mean, what other industry provides honest-to-goodness villain caricatures like Shkreli, Pearson, Purdue Pharma, or whatever a$$hat is jacking up the price of a practically-free generic drug this week?)

    The people doing good work in the industry (and there are a lot of them!) are right to be angry at the story *and* at some of the shadier corners of their own industry. It leads to pieces like this where the report assumes the worst, because it’s been true often enough in the past.

    1. StumpedByTheCaptchaMath says:

      Well said!

  8. FARMA BRO says:


  9. Lane Simonian says:

    I don’t think there is any excuse for Pfizer not releasing the data.

    1. Miles A Peters says:

      Possibly because the data was already out there if looked for. And perhaps they had more important things to do?

  10. Imaging guy says:

    I completely agree with your analysis. In your post your give links (“Those you could patent fresh, it hardly needs to be said – and here are some people who have worked on just this idea.”) to two articles about brain penetration by WM Pardridge of ArmaGen. In 2009 he published an article claiming the antibody against insulin receptor (which by the way was the topic of your yesterday post) can be used as a trojan horse to carry GDNF (glial-derived neurotrophic factor) into brain for Parkinsonism. Insulin receptors are supposed to express on brain endothelial cells and they would carry antibody-GDNF proteins across the blood brain barrier (BBB) (1). His claims and lack of fund to further develop his technology got a very extremely favorable coverage in Nature (2). I don’t think Nature would allow that kind of coverage now. It seems that he asked money from Michael J. Fox Foundation and they asked another researcher to reproduce his findings. They could not reproduce his findings. They found that his fusion protein could not be detected in the brain and not surprisingly it “did not improve parkinsonian motor symptoms” (3).

    1) Comparison of blood-brain barrier transport of glial-derived neurotrophic factor (GDNF) and an IgG-GDNF fusion protein in the rhesus monkey (Drug Metab Dispos. 2009 Dec;37(12):2299-304. doi: 10.1124/dmd.109.028787)
    2) Biotechnology: Crossing the barrier (Nature. 2010 Aug 19;466(7309):916-8. doi: 10.1038/466916a)
    3) A Monoclonal Antibody-GDNF Fusion Protein Is Not Neuroprotective and Is Associated with Proliferative Pancreatic Lesions in Parkinsonian Monkeys (PLoS One. 2012;7(6):e39036. doi: 10.1371/journal.pone.0039036)

    1. BBB Boy says:

      Imaging guy….
      if I understood correctly, are you saying bifunctional antibodies do not provide a mechanism to cross the BBB? Or just the insulin receptor mechanism?
      What about the work with transferrin?
      Thanks for clarifying.

  11. David E. Young, MD says:

    It seems to me that the original analysis by the insurance company could lead to the wrong conclusion. It depends upon how they made the connection. They took 127,000 with Alzheimers and 127,000 without. If they then dug in to every medication that every patient took, then they could easily be “fishing'” for a connection that may be there from chance alone. If you took 100,000 with peripheral neuropathy and 100,000 without, and looked at every medication that everyone took then you are bound, by chance alone, to find a drug more commonly used in those who did not have peripheral neuropathy. Who knows? Maybe Allopruinol prevents neuropathy, or… Colchicine….. or Propranolol? This sort of “fishing” easily results in false connections

    1. DWAnderson says:

      That was my reaction as well. I suspect there are probably *many other* correlations that have been found doing such data mining. Unless you can make a plausible argument for how the drug might actually be working, it would seem folly to spend a lot of money investigating all of them.

    2. Jim says:

      Sounds like the Texas Sharpshooter Fallacy

    3. loupgarous says:

      Data mining isn’t good at detecting causation or things which prevent an effect. It shows correlations between events which may or may not warrant actual studies of causes or things that prevent events from occurring.

      Data mining is no good at all unless backed up with specialized data which support decisions to do specialized and expensive research – and people who know how to interpret those data correctly.

      Data mining of large datasets like the study in this story is one of many tools we ought to be using more, because the correlations we see could well be more useful in deciding whether to pursue research designed to prove or disprove the hypotheses we form after seeing correlations in data.

      What went wrong here wasn’t the study. It wasn’t the data. It wasn’t Pfizer’s decision not to undertake the additional work suggested by the study’s authors. It was the Washington Post deciding that not following up on someone else’s work is the same thing as covering up the correlation they saw in their study.

      Unfortunately, stupidity isn’t provable malice, so the Washington Post cannot be punished in court for saying something which is not true, not for the first time by any means.

    4. David E. Young, MD says:

      It may even be better. If the group was data mined by “diagnosis” I call tell you right now, that is very flawed. Physicians, like myself, must enter diagnosis codes in order to bill for patients. A primary care physician often accumulates codes (they never go away)… even to the point where they may have 40 or 50 codes. But a specialist, like a rheumatologist, might just put in the code that is necessary to bill for the Embrel. Therefore, in a selection of 127,000 patients seen just by primary care physicians you would have more attentive physicians in completing the list of codes and include the code for dementia, where-as a patient seeing a rheumatologist might have mild dementia but the code is not included in the list. Therefore imbalance. A word of advice…. looking at codes that physicians put in there billing lists is about as inaccurate as anything. The list is created not so much as to be accurate as to allow billing. (not that physicians are deliberately committing fraud, it is that the ICD10 codes are so difficult to select that in our limited time, we find the best that works and leave it at that).

  12. Anon says:

    I don’t know why people even allow themselves to get worked up about other people’s ignorance. Even if there was any real evidence of a clinical effect, it should be noted that no company is *obliged* to invest in anything. Ignorance is just the start, but this seems to come from a leftist sense of entitlement to waste other people’s money while taking no responsibility to spend their own. That annoys me far more.

    1. Anon says:

      Maybe Pfizer should offer WaPo the chance to invest their own money in this “$80m study”. I’m sure Jeff Bezos could afford it.

    2. Orv says:

      It’s a conspiracy theory along the lines of the water carburetor urban legend — the idea of a large company blocking a world-changing innovation in order to protect their profit margin. It feeds into people’s impressions that corporations put their own interests above the public good. That’s not entirely unfounded (it’s more or less why modern corporations *exist*) but it rarely happens as dramatically as people think it does, mostly because truly world-changing ideas are both rare and hard to quash.

  13. experienced with startups says:

    dark and cynical outlook
    Wait till you’ve been through a few of them, sitting at a fume hood toiling away, exposing yourself to dangerous chemicals, only to watch some lying scumbag in a corner office get rich.

    Am I jaded about it all, you’re da#m right I am, if I knew so much of the industry was exactly that, I would have never studied chemistry in the first place. The problem is a lot of people don’t get the chance to work at enough companies or projects to see it. Many are just thankful for a paycheck and all too willing to drink the kool aide.
    I remember being chastised on interviews for “bouncing around” by some clown that could probably only ever find one job in his life. As soon as I smelled a rat, I walked away.

  14. Make Change says:


    It’s amazing how few people understand that a clinical trial is just something you can go out and buy, as long as you come up with a compound that doesn’t kill the rats and dogs, you fill out all the forms and pay your fees, the FDA is going to let you play.
    It isn’t till the very end that you have to actually prove that your compound does what you say it’s supposed to do.

    Take a look at how these companies staff, they turn down bright American kids from top labs to hire those from China or the third world….it’s because they know they are accustomed to corruption and simply don’t care.

    There is actually a very positive reason to be speaking out like this…the VC’s have got wise, they don’t buy into it any more, anything small molecule or not “clinical stage” is dismissed. The end result is literally 10’s of thousands of good chemists lost their jobs.

  15. Anonymous1 says:

    This whole business with uproar in public opinion about Big Pharma and greater good reminds me of very good movie from USSR ( I was born in USSR), Zigzag of Success, about a guy who took money from the mutual fund at his work and bought a lottery ticket which won. Then his colleagues demanded an equal share of his win since he took the money from the fund. The title of this movie pretty much applies to the drug discovery process, imho. And, yes, this film was aired in Soviet Russia, somehow bypassed heavy censorship at that time.

  16. MoMo says:

    All AD research should have been in the blog 2 days ago under Varieties of Nonsense. Since those thought leaders in Boston started pushing the ab plaque theory we have made NO PROGRESS and Pharma fell in lock step with this lunacy.

    The WaPO article is a symptom of this AD research dysfunction and we all deserve it.

  17. bobbob says:

    You did not answer to your last question, why did not they shave what they’ve found? That is the main theme of the article. IMHO.
    The paper your refer to is by 2016, while the Phizer case took place in 2015.

    1. johnnyboy says:

      Because Pfizer is a pharma company, not a University lab ? Because ‘releasing information’ means writing a publication, which takes time and effort and requires the information to be novel (which this one arguably wasn’t), and for a company has little to no reward ? Because if a company ‘released information’ every time its researchers found an interesting tidbit, it probably wouldn’t have time to do actual drug development ?

  18. Vampyricon says:

    Oh wow. Thanks a lot. I think Nature was pushing this narrative as well, as I saw this on Nature Briefing today.

  19. J Severs says:

    Would Enbrel be used chronically? Would dosing start before symptoms of AD? What is the tradeoff between presumed reduction-of-risk of AD versus increased risk of known adverse events from Enbrel?

  20. Frankly says:

    The WAPO reported study was absurd. The scientists run the insurance claim performed the analysis the other way: Among the -Enbrel treated patients, do they actually have lower AD burden (percentage of patients vs matched population, AD severity etc.). Cherry picking 300 out of 127,000 AD patients and exaggerate the percentage is called “statistical lying”

    1. Tropcho says:

      Risk of AD in RA patients is 0.7%, based on the NYT article, how many patients do you expect to see in 250K database? And if Enbrel prevents, they will be even less. Think!

  21. Tropcho says:

    I do not think the people behind the leak will go into so much trouble if they did not think the research is solid. And we will never know, unless it is released. Everything else is waste of online space

  22. An Old Chemist says:

    If there is a ray of hope in ‘Enbrel for Alzheimer’s’ then Vivek Ramaswamy will certainly license it out from Pfizer/Amgen. In the past, Ramaswamy has taken a few failed drugs from big pharma and raised capital to take these to phase-III. One of such drugs was GSK’s Alzheimer’s drug which was taken to phase-III by Myovant of Ramaswamy.

  23. DrugHunter says:

    When I read the Post’s article, what came to my mind is someone googling up ‘how to make an iphone’ and trying to make one!! Complete lack of understanding of science, disease biology and drug development process. As a disclosure, I am not employed by Pfizer. Derek’s analysis is spot on. Could not agree with you more.

  24. Kent Smith says:

    Dear Derek Lowe,

    I would be interested in your opinion of this article’s content.


    Kent Smith

  25. Catherine Womack says:

    Thanks, Derek, for this very thorough analysis on what is clearly a big misstep by WaPo. I’m a philosopher of science and teach a Science and Values course for STEM students (many of whom are pre-meds), and this is a great case for them on a bunch of levels. They can see an example of the limitations on data mining, and how digging into the details (thanks to you, David Young, MD, and others) we can see how decisions about criteria for inclusion (e.g. using diagnosis codes) can affect and distort data sets. Of course they’ll criticize the WaPo article, but that’s the easy part. What’s important here (which includes the many valuable and even value-less comments) is how hard it is to do science and get actual results. Students (even science students) have no real idea how this works. I’ll email you after I run this case and let you know how it goes.

  26. Rajeev Gangal says:

    The reason why this has piqued interest is the RWD is the next outpost where interesting signals whether for efficacy or PV are proposed to be found. Signal detection itself has had a chequered history and Pfizer could have refined this signal with better detection methods. Much better than the “have” and “have-nots” and “treated” and “not treated” or adds ratios etc.

    Given that it was their own drug, patent cliff was fast approaching and at least some preclinical data partially supported it, they should taken it more seriously , especially since it was Alzheimer.

    It’s the internal barriers to collaboration between pre-clinical, clinical, RWE and statisticians etc that leads to these situations. The argument that it’s not incumbent on Pfizer is neither here nor there. It seems to be a missed opportunity given the dire need and 64% or 10% is not the issue. We clearly need better statistical methods to be applied to such noisy real world data because signals exist. It’s for us to enrich them and find them.

    1. John Wayne says:

      “It seems to be a missed opportunity given the dire need and 64% or 10% is not the issue.”

      This sentence is the problem – I would assign the chances for this therapy to work around 0.1%. You are overestimating the chances of success by two log units on the low end. I’d argue that this is both unethical and a waste of capital.

  27. Rich Rostrom says:

    “I like the newspaper, and I subscribe to it online, but this is not a good moment for it.”

    The Gell-Mann Effect strikes again.

  28. “Well, you’ll have to trust me on this, it’s a little out there, but drug companies don’t generally walk away from big profits if they can help it.”

    That is extremely uninformed about the drug business. As the WaPo reported, the patent was coming to the end of its life and it is hard to get a new patent for a different medical use.

    It would have been a high-risk investment, no matter how high the potential success. Whether or not their would’ve been a gain for humanity, it was unlikely there was going to be a gain for the company. Let’s be honest about this.

    1. loupgarous says:

      “That is extremely uninformed about the drug business. As the WaPo reported, the patent was coming to the end of its life and it is hard to get a new patent for a different medical use.”

      And yet, Eli Lilly did just that with fluoxetine when their patent on it elapsed, started hawking it as “Sarafem” for Pre-Menstrual Dysphoric Disorder. Under a new patent.

  29. Robert Chase says:

    Please write complete sentences.

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