World's Fair

In the Feb 26 issue of Science, the Chief Patent Counsel for GlaxoSmithKline has written a “Policy Forum” article outlining the reasons that the pharmaceutical industry needs longer and stronger patent protection on its new drugs (to fend off those nasty generics). I was kind of shocked to see such a propaganda piece in Science, but I suppose it is all part of looking at both (all) sides of an issue. Big pharma has been telling us how tough they’ve got it for years, and the argument that they must charge very high prices to pay for all that R&D is so old that you can probably find it carved on stone in subterranean caverns beneath New Jersey (where many big pharma companies live). Unfortunately, many of the arguments are hollow as well – since it has been pointed out many times that over 75% (a conservative estimate) of new drugs come directly out of academic research and then get their souls licensed to big pharma. Anyway, I’m working on a letter to the editor (which only has a slight chance of getting into Science in any form anyway). Here’s a first draft, which, I’m afraid, is most likely a bit too terse for Science as yet:

Dear Editors,

Regarding Sherry Knowles Policy Forum article in the 26 Feb 2010 issue of Science, it is difficult to feel much fiscal compassion for an industry that has long held the record for highest profit margins in the world. The GSK Chief Patent Counsel’s suggestion for giving branded pharmaceuticals an even longer protection period from generics also elicits little sympathy for an industry that has forced the creation of literally scores of non-governmental agencies who fight daily for universal access to life saving medicines that are kept from people who need them simply because of patent restrictions and cost. It is true that new drugs cost a lot of money to develop, although nowhere near as much as the pharmaceutical industry claims (a discrepancy that has been pointed out for years by people like Marcia Angell, former Editor-in-Chief of the New England Journal of Medicine). Is it wise, however, to give even more control over branded drug distribution to an industry that is steadily conglomerating into a small number of giant profit making machines? Are a few multi-billionaire CEOs, with an eye primarily on the bottom line, the best arbiters of what drugs the world may be allowed to have access to? I’d like to see a Policy Forum discussing how to decentralize the pharmaceutical industry: how to sever the currently requisite licensing-to-big-pharma model and create a large number of small-profit-margin ventures, working closely in league with academic labs, developing and manufacturing new, critically needed drugs, and getting them to needed populations at 3% over cost. Big pharma can stay around too: there’s plenty of market for more Rogaine and Viagra spin-offs.

Sincerely yours,

Livid in Louisiana

Comments

  1. #1 hibob
    March 10, 2010

    “since it has been pointed out many times that over 75% (a conservative estimate) of new drugs come directly out of academic research and then get their souls licensed to big pharma.”

    Beg pardon? Drop the 7. 5% is probably being generous. If you are talking about targets, 75% might fly, but as far as APIs (active pharmaceutical ingredients) that make it through clinical trials, almost none are developed academically and then licensed.

  2. #2 Vince LiCata
    March 10, 2010

    Hello hibob,

    Actually, I am talking about APIs — for example Marcia Angell estimates that 85% of APIs came out of academic or government labs (see one of her articles America’s Other Drug Problem, reprinted here from the New Republic), and other people have quoted similar percentages from a variety of studies. I believe you are definitely right about targets though. What big pharma does best right now is take potential new drugs through pre-clinical and clinical tests and manufacture and distribution — which is definitely an expensive process and something they are good at — but it gets most of its IP and even the APIs from taxpayer supported labs.

  3. #3 qetzal
    March 10, 2010

    Sorry, I don’t see that 85% claim in the link. (Nor do I believe it.) Perhaps you’re referring to this section:

    The NIH had selected the five top-selling drugs in 1995 (Zantac, Zovirax, Capoten, Vasotec, and Prozac) and found that 16 of the 17 key scientific papers leading to the discovery and development of these drugs came from outside the industry. Looking at all the relevant published research, not just at the key studies, 85 percent came from American taxpayer-supported laboratories or foreign academic laboratories.

    85% of papers published about those drugs, not 85% of APIs.

    There are plenty of reasonable criticisms of pharma, but I’m pretty certain that isn’t one of them. (Of course, if you can point to something in that link (or any other) that supports your claim, I’m happy to reconsider.)

    All that said, I agree that extending patent terms is probably not a good idea.

  4. #4 hibob
    March 10, 2010

    Ok, I found her saying 85% on page 4 of the article. While Angell has a lot of useful criticism of the drug industry (and there is plenty more to criticise, no doubt about it), some of her criticism is wide of the mark. She does NOT make an estimate of the number of actual drugs that come from academia, She talks about relevant published research and articles cited in patents – which generally means the targets and lead compounds. Very few biomedical patents ever even advance through phase I, let alone become approved drugs, so they’re really not that relevant a measure.

    Granted, some drugs (and some compounds similar to the eventual drugs) are invented in academia, but they are few and far between.

    ” but it gets most of its IP and even the APIs from taxpayer supported labs.”
    Just plain no.
    please have a look at this post by Derek Lowe (Hey – I read the Angell paper; this is much shorter):
    http://www.corante.com/pipeline/archives/2004/09/09/how_it_really_works.php

    University chem labs aren’t in the business of hiring people to crank out hundreds or thousands of syntheses that are completely unpublishable. Pharma is.
    I still say 5% of drugs at most come out of academic labs. Lets start with summer 2008. Silverman’s pregabalin (Lyrica) was approved, so one for academia (Northwestern). How many drugs have come from academia since then? How many new drugs have been approved since then?

  5. #5 Art
    March 11, 2010

    Two other bits of damning information are that the majority of new drugs are just minor reformulations and repackaging of old drugs labeled as ‘new’ to extend the patent. It is a lot easier to repackage an old drug than the develop new one.

    That and the articles I’ve seen suggest that pharmaceutical companies, who make a big deal out of every cent that might be construed as having been spent on creating a ‘new’ drug, spend more on advertising than development.

  6. #6 Vince LiCata
    March 11, 2010

    @ hibob and qetzal:
    This is very interesting — I found it very strange for us to be looking at the same information and coming to such very different conclusions — but a somewhat tangential analogy seemed to help me: When do you consider the “life” of an drug to begin? At conception or at delivery? Clearly I’m taking the conception side here, while it seems that you guys (continuing with the analogy) are seeing the drug’s life begin at delivery (?). The two sides see the gestation period differently — the time between conception (first publications of the lead compound and the biochemical basis for the drug) then is followed by, yes, tons of work on honing the lead compound into a non-toxic, physiologically efficacious molecular version that is then properly formulated for human consumption — and academia (presently) does basically none of that kind of work, and big pharma does it very well. Perhaps it’s my use of “API,” which, in the strictest sense does mean the actual humanly consumed compound, and getting a “lead compound” to a true API is definitely the realm of big pharma, however my contention, and my interpretation of “drug discovery” is that conception: demonstration of a disease-linked biochemical effect of a specific compound, is when the life of the drug begins (and most of that comes from academia). Anyway, that’s my take on it from the discussion so far, but I have a very academic centered perspective.

  7. #7 DrZZ
    March 11, 2010

    Anyway, that’s my take on it from the discussion so far, but I have a very academic centered perspective

    Yes, that’s obvious. Defining a compound that shows interesting in vitro activity as a drug is like seeing a 10 year old score a couple of touchdowns in a youth league game and calling him a NFL star. I think you are also wrong when you claim that most lead compounds come from academia. Hibob is right that pharma will look to academic papers for biology, but when it comes to generating a lead they will turn to their own screens and chemists. Generating lead compounds is by any measure (time, money, risk) a very small fraction of the work in finding a compound that has therapeutic usefulness and I don’t see how trying to inflate its importance is at all beneficial to the very important discussions on how best to fund and implement effective drug discovery.

  8. #8 Vince LiCata
    March 11, 2010

    @ DrZZ:
    Oooh, hiss…but anyway: I’m not sure I’d downgrade the importance or work of lead compound generation as much as you do, and to stick with your analogy: the 10 year olds that are not scoring touchdowns will almost certainly not make it to the NFL, while a subset of the ones that are scoring most certainly will, and only the academic talent scouts are going to those games (are, in fact, organizing and hosting them), while big pharma mostly (but not always) waits to see who shows up for the draft, and then, admittedly, helps them turn pro.

  9. #9 DrZZ
    March 12, 2010

    a subset of the ones that are scoring most certainly will

    ? There are over 3 million youth football players and about 1700 NFL roster spots. Even of you only look at the top 10% of the the youth leaugue players, that’s only about a 1 in 200 chance of making an NFL roster, let alone being a star.

    I claim that if you drop the expense and time of lead compound identification to zero you will have almost no effect on new drug availability or price. That is because not only the major time and expense is in clinical trials, but the major uncertainites as well. 9 out of 10 compounds that make it to clinical trials fail, and these days the most common failure is lack of efficacy. If academic work is so capable of identifying useful drugs why is this failure rate so high? How is faster and cheaper lead identification going to change this?

    The issues surrounding the discovery of new therapeutics are complex and contentious and I hardly think the pharma (big or otherwise) has all the answers, but I just don’t see how claiming that every J. Med. Chem paper has discovered a drug can be anything but detrimental to the goal of finding answers that actually work.

  10. #10 Vince LiCata
    March 12, 2010

    Hi again DrZZ:

    “I claim that if you drop the expense and time of lead compound identification to zero you will have almost no effect on new drug availability or price.”

    This where it seems the crux of our difference in perspectives is: from academia it looks like this “expense and time” already is zero for big pharma because they mostly farm from the academic literature. Perhaps if big pharma actually allowed some of its (often extremely talented) scientists to publish more of their own research it would seem different, but I admit that “product over publication” is (currently) necessary for the industry to do what they do.

  11. #11 hibob
    March 12, 2010

    “The two sides see the gestation period differently — the time between conception (first publications of the lead compound and the biochemical basis for the drug) …”

    With that definition of conception (generation of a lead compound instead of identifying the target) I’d say that almost all drug development happens in industry. At the time industry gets involved, there usually isn’t a viable lead compound, there’s just a target and maybe some compounds that can affect it but aren’t practicable to develop.

    Please, have a look at recently approved drugs. Show me the list of ones that are at all based on the compounds tested in academic labs.

  12. #12 Vince LiCata
    March 12, 2010

    Hello again hibob,

    I gotta tell you, this discussion has certainly been interesting and enlightening, but here I’m faced with the choice of arguments made by relatively “anonymous” sources like yourself or “DrZZ” versus statements like these from two former Editors in Chief of the New England Journal of Medicine:

    “It is important, then, to ask just how innovative the pharmaceutical industry really is. We think the answer is not very. Drug companies greatly exaggerate their role in the scientific work leading to the discovery of new drugs. As we have already noted, the development of new drugs is usually the culmination of many discoveries in basic science laboratories outside the pharmaceutical industry. This work increases the understanding of the molecular basis of disease and thereby identifies promising targets and models for the design of new drugs. Most of this ground-breaking research, done with support from the National Institutes of Health (NIH) or other institutions, appears in scientific journals before the big companies become involved. The industry is certainly not the major engine of discovery and medical progress that it would have the public believe.” – from Relman and Angell (link up in the 2nd comment in this thread).

    –and Relman and Angell are not the only high profile, high reliability sources for such sentiments. At least at this juncture I’ve got to give more weight to the more reliable sources, and keep the door somewhat open for additional new information. It’s clear that your position is non-trivial, well considered, and strongly felt, and certainly one that I’ll continue to think about. And just in case I haven’t made it clear, the apparent problems I keep talking about, and the ones that Relman and Angell are talking about, I believe, are most certainly at the management level, as most of the actual working scientists I know in the industry are intelligent, talented researchers — who, if the companies were suddenly turned over to them, would make as many new and effective drugs as possible, for as many people as possible, with no regard for profit margin or exclusivity — at least the ones I know (which is probably why they are not in charge of the company).

  13. #13 DrZZ
    March 12, 2010

    I gotta tell you, this discussion has certainly been interesting and enlightening, but here I’m faced with the choice of arguments made by relatively “anonymous” sources like yourself or “DrZZ” versus statements like these from two former Editors in Chief of the New England Journal of Medicine
    But science isn’t about argument by authority and even if it was why would your authority be people who have never discovered a drug? Cancer (or other diseases) couldn’t care less how many Nature papers you have or what your title is. You can either help patients or you can’t and there are pretty good ways to reliably determine which category a treatment falls into and these methods have nothing to do with the credentials of the people making arguments. I have an enormous respect for basic scientists and the foundation they provide, but to pretend like basic science has solved all the problems and pharma is just cashing in is just denying reality and more importantly, makes it less likely that the basic discoveries will be turned into therapies that actually benefit patients. I go back to the statistic of 9 out of 10 compounds fail in clinical trials. If the basic science is so solid and all that is needed, why is that success rate so poor? If the basic research is the rate limiting step, why don’t academic groups just bring the drugs to trial? Do you honestly think they could get a better success rate? If so, why not do it? There are a huge number of reasons to criticise pharma, but at least they are set up so that their jobs depend on actually delivering useful therapeutics. Are NIH funded academics willing to do the same?

  14. #14 Vince LiCata
    March 13, 2010

    @DrZZ:
    Oh yeah, science isn’t about argument by authority, oh that’s right. So, you’re seriously saying I should throw out a bunch of published studies by high profile scientists because of some anonymous comments on an internet blog? Hmm…yeah. In fact, I feel like I’m giving you a huge amount of credibility and benefit of the doubt, and I’ve stated several times already in previous comments that your arguments have certainly swayed me into thinking further about this issue. But now look what’s become of the argument: now suddenly “basic science is…all that is needed” and “basic science has solved all the problems” — I thought the discussion had been making some interesting points on both sides of the issue, but this is a rather extreme over-extrapolation of any of my statements. I would love to hear more reasonable arguments, or read more articles or info like the Derek Lowe one posted by hibob up in earlier comments.

  15. #15 qetzal
    March 14, 2010

    Vince,

    As we have already noted, the development of new drugs is usually the culmination of many discoveries in basic science laboratories outside the pharmaceutical industry. This work increases the understanding of the molecular basis of disease and thereby identifies promising targets and models for the design of new drugs. Most of this ground-breaking research, done with support from the National Institutes of Health (NIH) or other institutions, appears in scientific journals before the big companies become involved.

    I fully agree with this. But it doesn’t support your original point, which was:

    [O]ver 75% (a conservative estimate) of new drugs come directly out of academic research and then get their souls licensed to big pharma.

    Promising targets and models are not drugs. Which is not meant to diminish their importance in the least. But the drugs themselves are largely discovered and developed by pharma. (Not entirely, but mostly.) Pharma couldn’t do it without the basic science done in academic centers. But quite frankly, academia isn’t in a position to do what pharma routinely does, either.

    None of which proves that pharma deserves the level of profits they currently get, of course. That’s a separate question.

  16. #16 Pharma Conduct Guy
    March 17, 2010

    You have an interesting discussion going here. There is no question that academic groups really do not develop drugs and take them to market, since development requires formulations, running clinical trials, coordinating with the FDA, developing marketing and sales strategies, and setting up distribution channels.

    Academia is not designed to do the aforementioned activities. However, although Vince’s original assertion about how many leads come from government funded research may not have contained the correct percentages, which I don’t believe anyone knows for sure, the essence of his assertion was correct.

    Many of the current drugs on the market are based on intellectual property that was paid for by US Taxpayers in the form of grant money, thanks to the 1980 Bayh-Dole act. By IP, I mean either the actual drug itself (e.g. Wyeth’s monoclonal antibody Enbrel) or, as was stated here, either a derivative drug or a drug resulting from the discovery of the target.

    To be fair, drug manufacturers need incentives to take discoveries from labs and assume the risk of developing them and taking them to market. A failure in a phase 3 clinical trial (ie late stage attrition) or worse, after a drug reaches the market (e.g. Vioxx) is devastating to a company.

    However, Vince’s original post asked a valid question. For an industry that already has one of the highest, if not the highest, profit margins of any other industry, does it really deserve legislation to make it even more profitable?

    Is there some other way to develop drugs more cost effectively and put them in the hands of needy patients for a more modest overhead? I addressed this very issue on my blog about a month ago (see Pharma Conduct: We need a ‘Public Option’ for Drug Development). I encourage Vince to send his letter to Science.

  17. #17 Hibob
    March 18, 2010

    Hi Vince. Until recently, I worked in a chem lab biomedical research institute, working with virologists, neurologists, design lead compounds to hit various targets (or model systems). My funding was almost entirely from NIH.
    Angell may be famous, but she does not show that the majority of drugs are invented in academic labs or come from the NIH, and neither do the papers she cites. Please read them again – they talk about the swarm of publications and patents in the field, but NOT who actually invented the drugs.

    And again – Where are all of these drugs invented in universities? Enbrel was over 10 years ago.

    I think we’ll have to agree to disagree.

    But, like Pharma Conduct Guy, I agree we don’t need longer patents for pharma. For that matter laws addressing manipulations to keep generics off the market after patents have lapsed are due as well.

  18. #18 jdmimic
    March 19, 2010

    First may I congratulate you all on a mostly very civil discourse about what is often a heated debate, something not often seen on internet blog sites.
    For myself, I agree with what it seems everyone here that Big Pharma is doing just fine without yet more protections and I was also rather shocked to see such blatant propaganda in Science.
    I would like to make one comment about how science works and here I have to disagree with Vince. Argument by authority is a clear logical fallacy and not one that scientists should be making, but admittedly is done all the time. Argument by authority is different than citing other people’s work. Citing other people’s work to support one’s position is not (or at least shouldn’t be) about argument by authority, but additional evidence presented in the cited work that supports one’s argument. The citation is for the credibility of the work, not the author. If it is just “what he said and he’s smart”, it doesn’t belong (and yes, I’ve done that before myself and it was invalid then too).
    The fact that you don’t know who Hibob and DrZZ are does not make any difference to whether their arguments hold up. Now, as to whether the views they espouse are valid or not is another thing altogether and as I have no good information upon which to judge, I won’t put a foot into that race.
    I can state just from my own experience that the lines may be very difficult to measure. A lab down the hall from mine received a fortune from a pharmaceutical company to develop and test a drug. Yet the lab was also supported by the state and federal governments (NIH grant, lab in a federal building, people and some equipment paid by state, some equipment and a mountain of mice by the drug company). In this case, splitting development costs are tricky. The drug company rightly claims the entire bill as part of the costs of developing the drug, but the amount they paid themselves was substantially smaller. Drug companies typically discuss the total amount of development costs, but they typically fail to discuss how much of that bill is actually borne by other entities and this is exactly what Sherry Knowles did in her article. (oh, and if you are wondering about the legal regulations that might prohibit this sort of interaction, I was rather shocked myself at the, to my mind at least, underhanded tactics the head scientist went to make this at least semi-legit. It is truly astounding what some administrators will turn a blind eye to when it comes to large amounts of money and the prestige it brings.

  19. #19 Vince LiCata
    March 21, 2010

    I find it odd (but good) that we all seem to agree that big pharma doesn’t need longer patent protections — because I feel that way about half because of the way such protections block certain populations from getting access to drugs and about half because of what has long appeared to me to be big pharma’s underplaying of academia’s (or other public sector contributions’) role in overall drug development. So if the real balance for developing a new drug involves far greater contributions from big pharma than from academia, then this strengthens the argument for longer patents. Another thing this discussion seems to have highlighted, however, is that it’s difficult to determine or agree on what that balance is (although, as I said earlier, if big pharma actually published more of what they did, it might be easier to determine this balance).

    I did want to also respond to jdmimic’s comment about authority and my earlier cheeky remark about it, because I actually mostly agree with it: I agree that argument by authority is far from ideal, and in “perfect” science would be completely irrelevant, but my point was that in reality it is a huge part of the way science actually works: the Harvard lab’s findings will always outweigh the findings from the University of Alabama, the Editor of Nature’s argument will always outweigh the argument of a scienceblogger — no matter who is actually correct. This is not always a bad thing: we elevate people to “authority” in science based on track record and peer consensus (but not peer unanimity), so that we can then use those “authorities” as gatekeepers, policy makers, and the such. The nice thing about science is that incorrect information, whether from an authority or not, will eventually be “outed” — i.e. if the results from the University of Alabama are the correct ones, we’ll eventually know it, it just might take ten years and a lot of discomfort for those not in “authority”. I agree that “it doesn’t belong” in science, but I also believe one would have a very difficult time operating like it wasn’t there. Anyway, that’s a longwinded version of what was behind my cheeky remark.

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