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Academia (vs. Industry)

Where Drugs Come From, and How. Once More, With A Roll of the Eyes

I linked yesterday to a post by Megan McArdle about health care reform. And while I realize that everyone got into a shouting match in the comments to my own post on the subject – and people sure did in the comments to hers; it’s endemic – I wanted to quote a section from her on drug discovery:

Advocates of this policy have a number of rejoinders to this, notably that NIH funding is responsible for a lot of innovation. This is true, but theoretical innovation is not the same thing as product innovation. We tend to think of innovation as a matter of a mad scientist somewhere making a Brilliant Discovery!!! but in fact, innovation is more often a matter of small steps towards perfection. Wal-Mart’s revolution in supply chain management has been one of the most powerful factors influencing American productivity in recent decades. Yes, it was enabled by the computer revolution–but computers, by themselves, did not give Wal-Mart the idea of treating trucks like mobile warehouses, much less the expertise to do it.
In the case of pharma, what an NIH or academic researcher does is very, very different from what a pharma researcher does. They are no more interchangeable than theoretical physicists and civil engineers. An academic identifies targets. A pharma researcher finds out whether those targets can be activated with a molecule. Then he finds out whether that molecule can be made to reach the target. Is it small enough to be orally dosed? (Unless the disease you’re after is fairly fatal, inability to orally dose is pretty much a drug-killer). Can it be made reliably? Can it be made cost-effectively? Can you scale production? It’s not a viable drug if it takes one guy three weeks with a bunsen burner to knock out 3 doses.

I don’t think a lot of readers here will have a problem with that description, because it seems pretty accurate. True, we do a lot more inhibiting drug targets than we do activating them, because it’s easier to toss a spanner in the works, but that’s mostly just a matter of definitions. And this does pass by the people doing some drug discovery work in academia (and the people doing more blue-sky stuff in industry), but overall, it’s basically how things are, plus or minus a good ol’ Bunsen burner or two.
But not everyone’s buying it. Take this response by Ben Domenech over at The New Ledger. We’d better hope that this isn’t a representative view, and that the people who are trying to overhaul all of health care as quickly as possible have a better handle on how our end of the system works:

. . .But needless to say, this passage and the ones following it surprised me a great deal. Working at the Department of Health and Human Services provided me the opportunity to learn a good deal about the workings of the NIH, and I happen to have multiple friends who still work there — and their shocked reaction to McArdle’s description was stronger than mine, to say the least.
“McArdle clearly doesn’t understand what she’s writing about,” one former NIH colleague said today. “Where does she think Nobel prize winners in biomedical research originate, academic researchers or in Pharma? Our academic researchers run clinical trials and develop drugs. I’m not trying to talk down Pharma, which I’m a big fan of, but I don’t think anyone in the field could read what she wrote without laughing.”

Well, I certainly could make it through without a chuckle, and I’ll have been doing drug discovery for twenty years this fall. So how does the guy from HHS think things go over here?

To understand how research is divided overall, consider it as three tranches: basic, translational, and clinical. Basic is research at the molecular level to understand how things work; translational research takes basic findings and tries to find applications for those findings in a clinical setting; and clinical research takes the translational findings and produces procedures, drugs, and equipment for use by and on patients. . .
. . .The truth, as anyone knowledgeable within the system will tell you, is that private companies just don’t do basic research. They do productization research, and only for well-known medical conditions that have a lot of commercial value to solve. The government funds nearly everything else, whether it’s done by government scientists or by academic scientists whose work is funded overwhelmingly by government grants.

Hmm. Well-known with a lot of commercial value. Now it’s true that we tend to go after things with commercial value – it is a business, after all – but how well-known is Gaucher disease? Or Fabry disease? Mucopolysaccharidosis I? People who actually know something about the drug industry will be nodding their heads, though, because they’ll have caught on that I’m listing off Genzyme’s product portfolio (part of it, anyway), which is largely made up of treatments for such things. There ar many other examples. Believe me, if we can make money going after a disease, we’ll give it a try, and there are a lot of diseases. (The biggest breakdown occurs not when a disease affects a smaller number of people, but when almost no one who has it can possibly pay for the cost of developing the treatment, as in many tropical diseases).
But even taking Domenech’s three research divisions as given – and they’re not bad – don’t we in industry even get to do a little bit of translational research? Even sometimes some basic stuff? After all, in the great majority times when we start attacking some new target, there is no drug for it, you know. We have to express the protein in an active form, work up a reliable assay using it, screen our compound collections looking for a lead structure, then work on it for a few years to make new compounds that are potent, selective, nontoxic, practical to produce, and capable of being dosed in humans. (Oh, and they really should be chemical structures that no one’s ever made or even speculated about before). All of that is “productization” research? Even when we’re the first people to actually take a given target idea into the clinic at all?
That happens all the time, you know. The first project I ever worked on in this industry was a selective dopamine antagonist targeted for schizophrenia. We were the first company to take this particular subtype into the clinic, and boy, did we bomb big. No activity at all. It was almost as if we’d discovered something basic about schizophrenia, but apparently that can’t be the case. Then I worked on Alzheimer’s therapies, namely protease inhibitors targeting beta-amyloid production, and if I’m not mistaken, the only real human data on such things has come from industry. I could go on, and I will, given half a chance. But I hope that the point has been made. If it hasn’t, then consider this quote, from here:

“. . .translational research requires skills and a culture that universities typically lack, says Victoria Hale, chief executive of the non-profit drug company the Institute for OneWorld Health in San Francisco, California, which is developing drugs for visceral leishmaniasis, malaria and Chagas’ disease. Academic institutions are often naive about what it takes to develop a drug, she says, and much basic research is therefore unusable. That’s because few universities are willing to support the medicinal chemistry research needed to verify from the outset that a compound will not be a dead end in terms of drug development.”

The persistent confusion over what’s done in industry and what’s done in academia has been one of my biggest lessons from running this blog. The topic just will not die. A few years ago, I ended up writing a long post on what exactly drug companies do in response to the “NIH discovers all the drugs” crowd, with several follow-ups (here, here, and here). But overall, Hercules had an easier time with the Hydra.
Now, there is drug discovery in academia (ask Dennis Liotta!), although not enough of it to run an industry. Lyrica is an example of a compound that came right out of the university labs, although it certainly had an interesting road to the market. And the topic of academic drug research has come up around here many times over the last few years. So I don’t want to act as if there’s no contribution at all past basic research in academia, because that’s not true at all. But neither is it the case that pharma just swoops in, picks up the wonder drugs, and decides what color the package should be.
But what really burns my toast is this part:

So Pharma is interested in making money as their primary goal — that should surprise no one. But they’re also interested in avoiding litigation. Suppose for a moment that Pharma produces a drug to treat one non-life threatening condition, and it’s a monetary success, earning profits measured in billions of dollars. But then one of their researchers discovers it might have other applications, including life-saving ones. Instead of starting on research, Pharma will stand pat. Why? Because it doesn’t make any business sense to go through an entire FDA approval process and a round of clinical trials all over again, and at the end of the day, they could just be needlessly jeopardizing the success of a multi-billion dollar drug. It makes business sense to just stand with what works perfectly fine for the larger population, not try to cure a more focused and more deadly condition.

Ummm. . .isn’t this exactly what happened with Vioxx? Merck was trying to see if Cox-2 inhibitors could be useful for colon cancer, which is certainly deadly, and certainly a lot less common than joint and muscle pains. Why didn’t Merck “stand pat”? Because they wanted to make even more money of course. They’d already spent some of the cash that would have to have been spent on developing Vioxx, and cancer trials aren’t as long and costly as they are in some other therapeutic areas. So it was actually a reasonable thing to look into. If you’re staying in the same dosing range, you’re not likely to turn up tox problems that you didn’t already see in your earlier trials. (That’s where Merck got into real trouble, actually – the accusation was that they’d seen signs of Vioxx’s cardiovascular problems before the colon cancer trial, but breezed past them). But you just might come up with a benefit that allows you to sell your drug to a whole new market.
And that might also explain why, in general, drug companies look for new therapeutic opportunities like this all the time with their existing drugs. In fact, sometimes we look for them so aggressively that we get nailed for off-label promotion. No, instead of standing pat, we get in trouble for just the opposite. Your patented drug is a wasting asset, remember, and your job is to make the absolute most of it while it’s still yours. Closing your eyes to new opportunities is not the way to do that.
The thing is, Domenech’s heart seems to be mostly in the right place. He just doesn’t understand the drug industry, and neither do his NIH sources. Talking to someone who works in it would have helped a bit.

35 comments on “Where Drugs Come From, and How. Once More, With A Roll of the Eyes”

  1. paul says:

    I need to ask a basic drug-type question (inspired by Derek’s comparison between academics and pharma researchers): Why does a drug need to be orally dosed? It is a social thing? ie: people are prudes about suppositories and hate the idea of injections. Or, is there something about oral dosing and metabolism where oral dosing is really the best way to do it.
    Just curious.

  2. Old Timer says:

    Does anyone over at Merck know how Breslow’s SAHA compound is going (or Vorinostat or Zolinza, or whatever it’s called now)? Now that’s an interesting story!

  3. milkshake says:

    “…It’s not a viable drug if it takes one guy three weeks with a bunsen burner to knock out 3 doses… I don’t think a lot of readers here will have a problem with that description, because it seems pretty accurate.”
    The last time I used Bunsen burner in the medchem lab was about 2 years ago – to unstuck a frozen flask joint.
    [Big pharma is hugely wasteful, and the many rounds of mergers and acquisitions led to wholesale destruction of promising medchem research, and allowed continuing existence to the very companies and management teams responsible for the sorry state of the industry. Its like zombie rampage.]

  4. Palo says:

    Derek, I see little contradiction between everything they say and what you say. There’s part truth in everything said. You, true to form, pick and choose examples that go well with your beliefs (“isn’t this exactly what happened with Vioxx?”… but it isn’t exactly what happened in dozens more cases).
    You are frustrated with people that don’t get that pharma is very different, and you don’t want to ever acknowledge that NIH does make great contributions to pharma. For the most part, people choose to ignore the contributions of the other, and you are no exception.

  5. Hap says:

    I thought the point of NIH, NSF, etc. (and for that matter universities), was to generate knowledge for public consumption. They are supposed to be there to generate knowledge so that drug companies (and lots of other people) can do useful things with it. Now, when they do that (for which they’ve already been paid pretty well), they decide that they also want a cut of the money that people get from implementing the knowledge. In that case, though, the knowledge can’t be used freely and so the money spent to discover the knowledge isn’t achieving what it was intended to do. If you want to discover knowledge for profit, there are lots of places to do it – but the government shouldn’t be one of them.

  6. Mike says:

    Paul: it mainly comes down to patient compliance and safety. There are many people who are terrible about taking a pill every day, because they just don’t like the idea of it and secretly want to just stop. If you go further and make them have to inject the drug, or stick it up their butts, or some other dosing method they don’t like, your compliance rate is going to plummet to nothing. If diabetics, who need insulin to live, are frequently terrible about taking their insulin, it’s going to be near impossible to get a cantankerous 75 year old with only high blood pressure to inject himself with his blood pressure meds every day.
    Furthermore, needles are a bad idea for the lowest common denominator. If you aren’t careful, you can give yourself a nasty infection, or inject in the wrong place.
    Also Derek, one other way in which industry does a ton of basic science research is in attempting to replicate academic findings. Much of their research is so sloppily done in the rush to publication, or needs to be translated to another model system to be useful, or tested for its broader applicability, that pharma sometimes does more research studying the phenomenon than the discovering lab did. There is a TON of early validation work before we even get to the point of compound screens, all of it basic science.

  7. Lucifer says:

    Derek protests too much. If pharma had kept on discovering innovative and useful drugs, we would not be having this discussion.
    But the pipeline is full of me toos, marginally better drugs and drugs without a therapeutic effect.

  8. john says:

    So I’m doing my phd in a drug discovery/pharmaceutical sciences department. What gets me about academia is that it’s never been about developing drugs from what I see, it’s about making molecular probes and tools.
    Most academics that do “medicinal chemistry” tend to be synthetic organic chemists whos interests lie in the science of synthetic organic chemistry and the drug discovery part is a way to sell things on the grant application.
    We make molecules, do cytotox assays and publish. Most of the “medicinal chemists” in my department have never even thought about adme nor will they ever. As long as the NIH funds organic chemistry and calls it drug discovery we won’t have effective drug discovery at the academic level.

  9. processchemist says:

    Recently I saw my government pour something like 4 millions euros on an academic project, born in academia from organic chemists, focused on: MMP inhibitors… a bit expensive try to bring again to life what was a dead target (but maybe they’re on some hellish non chelating second generation product..)

  10. Mike says:

    “If pharma had kept on discovering innovative and useful drugs, we would not be having this discussion.”
    Wow, just wow. And where should we discover these innovative new drugs smart guy? Do you think we all magically got dumber since Lipitor was discovered? You might as well berate Boeing for why we don’t have solar powered commercial airliners that fly at Mach 10. At aviation’s inital WWII era rate of improvement, that’s where we should be by now, but sometimes “marginal” improvements are all that can be managed once the “easy” developments are already done.
    Drug development is frighteningly hard and unpredictable, and you’re aiming at a moving target of better efficacy. Pharma is significantly better at drug development now than we were in the past, it’s just that drug development is at least an order of magnitude harder now than it was in the early days. The known easy enzymatic targets for important disease pathways have all been hit. We are working on new targets constantly, but they don’t always pan out. What else could we possibly do?

  11. MarkySparky says:

    There seems to be a lack of understanding (especially in McArdle’s comments section) that Big Pharma’s sins, once acknowledged, do not magically create an ability for NIH to bring innovation to market.
    Derek has been very clear in the past about how he views the contributions of NIH/academia. It is not an accurate characterization to say that he denies the contributions of the “other”.
    The debate is not about industry/academia’s ability to discover targets, create molecules, or do preliminary research. The debate is over which entity has the ability to move from “lead” to “licensed drug” in the quickest, most efficient manner.
    Decisions for shifting resources (via legislation) need to be justified by real analysis, not fantasies about the inherent awesomeness of NIH. Likewise, denigrating academic research as “sloppy” needs to take that fact that such research is rarely focused on obtaining a license from FDA/etc.
    They are different things, and only a few pundit/blogger types seem to understand that.

  12. JAB says:

    @Hap: 2 words: Bayh-Dole

  13. rodentrancher says:

    “Unless the disease you’re after is fairly fatal, inability to orally dose is pretty much a drug-killer”
    Bit of an exaggeration – look at the anti-TNF alpha drugs. Granted, RA and the other inflammatory conditions these are used for are very unpleasant, sometimes crippling, and often quite painful, but not usually directly fatal . . .

  14. Eskimo says:

    @Old Timer
    Some results on zolinza/vorinostat were reported at ASCO for lung cancer:

  15. CMCguy says:

    I would echo what #11 MarkySparky state well that Derek (and others here) has oft recognized the contributions of NIH and Academia and that it does come down to efficiency in converting ideas to useful medicines. I would suggest there is also a strong component out there (in public,media, academia and government) of ignoring the Industry contributions that are much more than the characterized exploitation and “trivial” non-science exercises. There are different mindsets/skill sets where the Venn diagrams do not seem to have great overlap. As poorly as Pharma is doing, for many systematic reasons, I could only see NIH/Academia being more wasteful and less productive in introducing new drugs. Yes there is a great need for fundamental research and should be supported by both government and industry however is misguided or misdirected the value becomes diminished.
    The other thing that concerns me in all this is that such people frequently operate by “different rules” and conduct work not in accordance with cGMP and GCP standards (usually because of lack of knowledge or overt disregard because following them would make things more difficult-welcome to industry). Unfortunately either Industry has to pick up/reorder the pieces, or worse the FDA gives them a “pass” on poorly conducted studies since they are after all working for the “same organization”.

  16. Ben Domenech says:

    Thanks for the informed critique, Derek. While I think many of our differences of opinion about this space have to do with differences in original perspective — I am, as I said in my piece, operating from an understanding gained at HHS and through circles within NIH, not through your years as a researcher — my essential response to your post would be that the examples you cite seem to me to be exceptions that prove today’s rule. Surely you’ll concede that the Vioxx fiasco was a departure from normal practice by Merck, not its typical expression? Isn’t that exactly the kind of case others will avoid in the future, and with good reason? And what rational person would blame them for doing so?

  17. Mike says:

    I stand by my statement that academic research is frequently sloppier than pharma. It wasn’t to denigrate academia, it was my observation from having worked in both, and having been on BOTH ends of the sloppy data problem. We were rushing to publish, and so we did some things once, not very carefully, and slapped it in the paper as gods own truth. And we weren’t the only ones doing NIH-funded science that way. That’s the way it goes when you’re on the bleeding edge doing something you don’t think anyone is ever going to double check. If we got it wrong and someone else noticed, we would have said ooops, and suffered no serious consequences from it.
    I was simply pointing out that because the focus in NIH funded research is frequently so different from “making a drug to put in patients”, that the research is frequently not directly applicable and needs a lot of extra work done on it. When you know that someone else in your company is depending on you to do it right, and when you know that if you get it wrong, it could be a VERY expensive mistake that could cost peoples lives, it changes the way you do research pretty fundamentally.

  18. Hap says:

    JAB: Yeah, I know – but I guess I don’t really think that was such a good idea. (My local U wants to be one of those – but having it actually, like, do its job without bankrupting me would help.) Though I could be wrong on that (and lots else in the past two days).

  19. CMCguy says:

    #16 Ben Domenech how can you accuse Derek of using “exception that prove the rule” when you essentially use the same tactic by citing a former NIH colleagues comment about who gets awarded “Noble Prizes”. By their nature the Noble Prizes are geared toward significant “break-through’s”, often which indeed come from less directed/extreme cutting edge with does take place more so in academic research. It another topic but would even suggest observationally in the lack of awards to Industry side reflects a possible bias against such individuals who publish Patents majority of work rather than those who seek recognition in other Journals probably familiar with the selection committee(s).
    I do not disagree with the Industries overly focuses on well-known diseases but again if one looks at development of two possibilities that cost the same and have same risk profile how long will one stay in business if always chase the projects with smaller returns (unless of course you are in government service that does not have to take this in to account since taxes are one of life’s certainties). I do take issue with “productization research” as the majority of Industry effort even though I am more personally directly involved in what could be characterized that way. The vast majority of industry is in the “translational” stage where idea and compound get converted to drugs although perhaps you do not think running Clinical Trials would be categorized that way.

  20. Anonymous BMS Researcher says:

    Do those who say industry never does basic science actually read the journals? I myself have published a few things NOBODY KNEW before my colleagues and I discovered them. We did the research hoping we could make money for the company, but regardless of motives our work has made some (small but real) contributions to the world’s sum of knowledge. And I am hardly the only pharma researcher to have published original research, lots of good science has come from our labs.

  21. impatientmom says:

    #13 rodentrancher said:
    “”Unless the disease you’re after is fairly fatal, inability to orally dose is pretty much a drug-killer”
    Bit of an exaggeration – look at the anti-TNF alpha drugs. Granted, RA and the other inflammatory conditions these are used for are very unpleasant, sometimes crippling, and often quite painful, but not usually directly fatal . . .”
    Lurk on some RA patient boards. The mantra is ‘early aggressive’ so you don’t end up with heart/lung/etc. problems from out of control inflammation; it doesn’t matter how you ‘feel’, you must do what your dr. says so you don’t end up like ‘me’. If your dr. isn’t ‘aggressive’ enough, find another one, ‘I wish I had’, ‘I wish I hadn’t been afraid of injections’.
    There are people out there working pretty hard to make RA seem directly fatal to all who suffer from it.

  22. My first question when I read anything by Ben Domenech is, “Who actually wrote it?” So to have him show up, as an arbiter of what’s original research, and who does it, and claim expertise based on one of his jobs as a political appointee, is a bit… off-putting.
    I don’t know Domenech personally and don’t wish him ill, but one wearies of twentysomething instant experts from the halls of liberal arts, and of juicebox mafiosi picking a blog fight “up” on terrain they don’t know. It just wastes everybody’s time (in this case Derek’s, restating something he stated clearly ages ago). A bit like the old Army joke about the second lieutenant who said, “In my experience…” but I don’t supppose Domenech would get that one, either. You would have to be familiar with the Army. And the concept of experience.

  23. eric says:

    I work tangentially w/ both academics and bio-techs, one of the more interesting things that I have seen is the number of bio-techs that get NIH grants for doing basic research and I have also see a bunch of PI’s leave to start companies.

  24. T.R. Elliott says:

    “My first question when I read anything by Ben Domenech is, “Who actually wrote it?” ”
    Wow Kevin R.C. O’Brien. That’s some brilliant ad-hominem argumentation skills you’ve exhibited here.
    Just awesome.

  25. drug_hunter says:

    Perhaps I’m just in a lousy mood because Smoltz is stinking up the joint again, but: who the hell are these people who have absolutely no clue what goes on in Pharma? What is their background? How can they sleep at night, pontificating about something they CLEARLY have no clue about? Have they ever come within sniffing distance of a drug? Sheesh. I’m done with being nice to these people. I’m just going to keep making drugs — a process which, by the way, includes an awful lot of BASIC RESEARCH on targets of unknown function and testing first-in-class molecules in clinical trials where NO ONE has a clue what to expect.

  26. crazed_modeler says:

    > we do a lot more inhibiting drug targets than we do activating them,
    > because it’s easier to toss a spanner in the works
    This is certainly true for enzymes, but not necessarily true for receptors. Antagonists must compete against an endogenous agonist and this is hard to do at reasonable drug concentrations with a purely mass action competitor.
    Biochemical mechanisms of drug action
    Biochemical mechanisms of New Molecular Entities

  27. Polymer Bound says:

    #4 Palo: The point is Derek provided a counter example where a business sought another indication for a blockbuster drug, whereas the author just supposed that someone he knew knows how pharma executives make decisions. Please re-read:
    “Suppose for a moment that Pharma produces a drug to treat one non-life threatening condition, …. Instead of starting on research, Pharma will stand pat.”
    That’s not an example… It’s an outsider’s opinion on how they think our thought processes might work, and the “suppose” language keys you in on that. This is very similar language I hear from lay people who think that pharma isn’t interested in discovering a cure to diseases, just treatments, because they can make more money that way. It’s on Ben to provide a counter example. Besides, once a drug is approved, what’s stopping a physician or the NIH from doing an off-label study for a new indication? A short cancer trial is cheap and something that the NIH should be thrilled to fund. Anyway, it’s all moot because I’ve heard my executives use “pursue new indications for existing products” as a strategy to squeeze more money out of our drugs… if there was a critique, as Derek pointed out, it would be that they tend to push them into indications that are inappropriate.
    #16 Ben: I would pose, based on the high percentage of phase 2/3 failures, that the act of antagonizing/agonizing a target in a HUMAN is fundamentally basic research, which is done at a cost/risk that the taxpayers aren’t willing to accept. Frequently the generation of a pharmacological hypothesis (hitting target X will fix Y in people) does come from academics, so why is answering that very question not basic research? Just because it’s done for money? I think the confusion might come from the fact that -some- individual researchers have to do some things that just look like “production” or applied research… repeatedly running assays, repeatedly synthesizing and purifying analogs, etc. but it’s all to get to a point where the team can ask a really big, expensive, fundamental question. And along the way, we do manage (because we all were academically trained scientists at one point) to make other discoveries that are definitely basic in nature, and many companies encourage publishing of those discoveries.
    When the beta-amyloid hypothesis for AD is finally tested in humans, it’s going to be done at a high expense and funded primarily by pharma.

  28. lynn says:

    There have been a number of Nobels to scientists working in industry – eg, Mullis, Hitchings, Elion, etc.
    I’ve worked in academe, NIH, and Big Pharma – they’re all different. But, IMHO, drug discovery is done best (so far) in industry. I’m voting with Derek on this one.
    As #20, Anon BMS Res. says, basic research is (or has been) unquestionably done in industry in many areas with numerous discoveries published in the big journals (including a number of my own papers). I fear, though, that there is much basic research that is needed for drug discovery in certain therapeutic areas that is not getting done anywhere. Industry seems to be spending less time on basic research and academe isn’t asking the correct questions. A more collaborative approach is needed – maybe recognition of the strengths of each partner rather than a somewhat negative view of the “other”.

  29. drug_hunter says:

    #27 Lynn: I have a very high regard for the top academic labs. My company has major collaborations with dozens of academics from top institutions both in the USA and around the world. A significant fraction of our “discretionary spending” (after salaries etc.) goes towards such relationships which are multi-year relationships aimed at unraveling basic disease biology. I’m not bragging: I think EVERY major drug company does this now (some of course more than others but everyone is in the game). So I and others in Pharma/Biotech have great respect for — and recognize we need to work with — these academics.
    And BTW a significant fraction of our R&D budget is aimed at ORPHAN DISEASES where the chance for the magical “blockbuster” is slim to none.
    Again — who are these people?

  30. who indeed says:

    I was surprised the statement “Where does she think Nobel prize winners in biomedical research originate, academic researchers or in Pharma?” went by with so little comment. How is that the measure of success in a field? You identify targets, scale chemistry, process develop, treat people… but a committee in Sweden gives you a prize or not = success or failure.
    Well, that does sound like a government-directed system, so maybe that appeals to a certain audience.

  31. Cobalt says:

    This is a little old, but here’s what the NIH told congress its role in drug development was:

  32. tgibbs says:

    As an academic pharmacologist, I’d say that it is Domenech, not McArdle or Lowe, who doesn’t know what he’s talking about.
    This is certainly reinforced by Domenech’s apparent belief that Merck’s efforts to seek additional clinical applications for Vioxx was “a departure from normal practice.” Even a few minutes browsing would have cured him of that impression–there are many, many industry-funded clinical trials directed toward application of existing drugs to a wider range of diseases.
    It is certainly true that the vast majority of industry pharm research is directed toward near-to-medium term profits. But I’ve seen plenty of excellent basic research come out of industry labs. If basic research is needed to close the gap between academic research and a marketable drug, as it often is, they don’t flinch to do it. There is a big gap between identification of a possible target and understanding of how it fits into disease and therapeutics.
    Another point that I haven’t seen mentioned here is that while industry feeds off the discoveries of academia, we in academia do the same with the discoveries of industry. A huge amount of academic basic research relies upon compounds that were originally developed by the pharm industry. There are many, many examples of discoveries that have arisen from the use of compounds that were developed by industry, which never made it through to the clinic because of poor bioavailability, bad pharmacokinetics, or off-target organ toxicity, but that remain extremely valuable probes in many research assays.
    I’d say that academic and industry research are highly complementary. There are certainly some areas of pharmacological research that falls through the cracks, not near-term profitable enough for pharm, not “basic” enough for academia. Lowe mentioned one–tropical diseases. Antibiotics are probably another. These are potentially areas where government might be able to fill in. But I still don’t have a good answer for a question that Steve Projan asked me when I raised this possibility with him: “What do you think would be the political consequences if the government invested $800M in a drug development project that failed?”

  33. > Why does a drug need to be orally dosed?
    For convenience.
    Taking pills is easy, so patients can be easily talked into it.
    Americans don’t take medication because they’re willing to disrupt their lives with inconvenient things. If they were willing to interrupt their lives with inconvenient things, they’d do more with diet and exercise and reasonable amounts of sleep and stress and so on and so forth and probably be taking about six fewer prescription meds per capita. Americans take drugs because popping a few extra pills in the morning is easy and doesn’t mess up their schedules. This is *especially* true if you’re treating anything for which poor diet, obesity, lack of exercise, or stress is a major risk factor. (That covers, what, 85% of the drugs sold in the US, by dollar value?)
    You can get a pass on the “must dose orally” requirement if and only if you’re treating a condition that’s significantly more disruptive to the lifestyle (not in terms of risk for years down the road, but in the immediate moment) than whatever inconveniences come with your dosing mechanism, provided there isn’t a competing drug with a more convenient dosing option. For suppositories, that pretty much means you have to be the only treatment on the market for a condition that’s both more embarrassing and more uncomfortable than shoving something cold up the patient’s backside. For instance, if you come up with a treatment that effectively reverses the progress of Lou Gehrig’s Disease, you can probably get away with suppositories the size and shape of jacks that have to be stored at -37.8 degrees until use and administered every 27.5 hours, and the patients will still rise up and call you blessed. But if you try to dose heartburn that way, it’s not gonna sell, sorry.

  34. Dr Doom says:

    I mean imagine a company coining it in with an impotence treatment then discovering that it worked in a rare life threatening condition like pulmonary arterial hypertension. They’d have to suppress that news surely. Not run a clinical trial then market it for that indication as well.
    Viagra = Revatrio = Sildenafil
    So companies will do this after all then.

  35. Adam says:

    Meagan’s fundamental claim is that only companies do translational research and commercialization. Fine. But how does that claim support her assertion that national healthcare will stifle innovation?
    If I want to start a company to commercialize my thesis research, I’m not going to be dissuaded by a marginal decrease in profitability. My personal situation will still be massively better than if I didn’t pursue that opportunity.
    One might argue that there will be less venture funding if the opportunity for profit is reduced, but that could be made up for with increased government funding of translational research through mechanisms like the SBIR and STTR programs. These grants obviously won’t be enough to develop a drug, but they might support enough research to reduce the risk to a point where venture firms get sufficient returns to spur investment even with reduced profits on the final drug.
    Also – you’re tilting a windmills with the well-known bit. A lethal disorder with orphan drug protection and 500K/year treatment costs, gaucher’s disease is pretty lucrative. For example, Zavesca sales were 22 million in the first 6 months of 2009. Given that there are several drugs being developed to treat this tiny patient population, one might even argue that Gaucher’s disease is actually a wonderful example of the “me-too” waste of resources typical of big pharma.

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