The Frontal Cortex

When Promising Cures Are Ignored

I’ve got good news and bad news. I’ll give you the good news first:

A cheap and simple drug that kills almost all cancers by switching off their “immortality”. The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be relatively safe.

It also has no patent, meaning it could be manufactured for a fraction of the cost of newly developed drugs.

Evangelos Michelakis of the University of Alberta in Edmonton, Canada, and his colleagues tested DCA on human cells cultured outside the body and found that it killed lung, breast and brain cancer cells, but not healthy cells. Tumours in rats deliberately infected with human cancer also shrank drastically when they were fed DCA-laced water for several weeks.

DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar.

Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis’s experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died.

And now for the bad news: Michelakis can’t get any drug companies to fund a clinical trial, which can cost several hundred million dollars to conduct. Because DCA doesn’t have a patent, and costs pennies to produce, there’s no potential payoff for the corporations. Unless a non-profit or government steps forward, this research will remain stuck in the lab.

Chances are, of course, that DCA won’t turn out be a miracle cure. (This isn’t the first anti-cancer drug to look great in the lab, and it won’t be the last.) But it still seems ridiculous that a promising treatment is being ignored because it’s too cheap. If I were Nancy Pelosi, I’d take the money we will save by negotiating directly with the drug companies, and divide it between the NIH and a new agency, which will undertake clinical trials for promising drugs that Big Pharm isn’t interested in.

Update: I think MattXIV, in the comments, really nailed the issue:

This is a major blindspot of the incentive structure of the patent/FDA approval system. If you can’t patent the compound, it is often impossible to make a profit on it after the expenses of clinical trials. DCA as a compound may be cheap, but DCA as a drug is expensive, because it isn’t considered a legit drug until it goes through clinical trials, which aren’t cheap whether the money is recouped by charging monopoly prices for the finished product or collected via taxation.

Hat Tip: Ezra


  1. #1 Orac
    January 18, 2007

    I can’t believe you bought the whole spin on this story so uncritically.

    Some points:

    1. It does not cost several hundred million dollars to conduct a clinical trial. That figure is what is usually quoted as the entire cost to bring a new drug to market, from discovery costs, to animal research, to regulatory filings. It’s the cost of the whole package, from idea to marketable drug, and that whole package can run up to a billion dollars.

    2. To run a small preliminary trial to determine if there is evidence of efficacy could be done for costs that are well within the means of an investigator, if he’s willing to apply for grants. True, the funding climate sucks these days, but if this guy is funded by grants from the Canadian Institutes for Health Research (CIHR), Alberta Heritage Foundation for Medical Research (AHFMR), and Canadian Foundation for Innovation. He’s perfectly free to apply to the NIH and other organizations for funding. Again, he would not need “several hundred million.” All he would require is a few hundred thousand dollars for a small trial, between $1 and $2 million for a larger study, which is par for many research grants.

    3. If the smaller human trial shows evidence of efficacy, then and only then is it reasonable to get serious about setting up the much larger clinical trials needed to see if this drug. Before we see that, talking about “hundreds of millions of dollars” is ridiculously premature. Lots of drugs show serious promise in mice and are less than impressive (or even ineffective) in humans. If this drug shows promise in humans, then it might be necessary for the government to step in.

    4. Lastly, there’s nothing stopping the investigator from patenting the idea of using this drug to treat cancer. I know someone who is doing just that for a use of a drug that’s FDA-approved for something totally unrelated to cancer. I sincerely hope that he has, in fact, done that, because now that the results are published it’s too late now. If he has done that, he could then license his idea to whatever pharmaceutical company was interested.

    Do try to do a little more research before the knee-jerk response. I do hope that Seed Magazine doesn’t publish anything like this without some better background and nuance.

  2. #2 Jonah
    January 18, 2007

    Thanks for listing the caveats, although I don’t think your tone is warranted. The point made by Michelakis – and I was simply echoing his own concerns, which he made to a variety of news sources – is that it’s difficult to get early stage funding for a drug with limited commerical viability, regardless of its clinical potential. Why you find this point so upsetting is beyond me.

    Here is the Edmonton Sun, quoting a director of the Canadian Institutes of Health Research:

    “Because the drug has no patent it will not attract investors,” Michelakis said, adding patents are only issued for novel compounds.

    DCA has been used for decades to treat rare metabolic disorders in children, and has long been available from chemical suppliers for mere pennies per dose.

    “There’s no potential to make billions here, which will discourage pharmaceutical companies from taking up testing,” Michelakis said.

    “We’ll be applying to public agencies.”

    Clinical human trials can cost pharmaceutical companies between $600 and $800 million to bring a drug to market.

    That’s close to the annual budget of the Canadian Institutes of Health Research, which funded Michelakis’s DCA lab study.

    “We operate on only $700 million per year – we could never invest all of that in a single product, even if it looks as promising as this,” said Dr. David Brener, a director with CIHR.

    Finally, the cost estimates for conducting a full human clinical trial range wildly and depend, obviously, on the drug itself. A few minutes of research have revealed estimates ranging from $50 million to $600 million.

  3. #3 Epistaxis
    January 18, 2007

    Regardless of the disputed specifics of this case, it seems like the problem you’re describing could potentially exist. Intellectual-property law is supposed to reward innovation, not discourage it.

    The idea of a federal agency to test new drugs that don’t seem profitable (until tested) seems problematic for many reasons, but existing bureaucracy could be tapped to dispense a lot more grant money toward that research. To build on that idea, perhaps the Fed should issue a “copyleft” for any drug developed with its funding. The idea of a copyleft is that it’s the antithesis of a copyright, hence the name; in order to make sure that a piece of intellectual property is freely available, the creator takes ownership of it under existing law but distributes it to anyone who wants it (rather than let it get copyrighted/patented by someone else who would restrict its use). The General Public License is a very popular example; it specifies that licensed software can only be redistributed (modified or unmodified) with accompanying source code. Thus, it would be illegal to create proprietary software by modifying someone else’s GPL’d code.

    Once the R&D is done, drugs can be plenty profitable to manufacture and sell without a patent – that’s why generics exist. So with federal grants to get the research done and some copyleft-like unpatent to make the results available for anyone to sell, perhaps new drugs could become plentiful and cheap.

  4. #4 MattXIV
    January 18, 2007

    This is a major blindspot of the incentive structure of the patent/FDA approval system. If you can’t patent the compound, it is often impossible to make a profit on it after the expenses of clinical trials. DCA as a compound may be cheap, but DCA as a drug is expensive, because it isn’t considered a legit drug until it goes through clinical trials, which aren’t cheap whether the money is recouped by charging monopoly prices for the finished product or collected via taxation.

    Having the government chose targets for research requires that we ask according to what standards the agencies prioritize research into these compounds. Some compounds will be no-brainers, like anything that’s likely to help with cancer, heart disease, AIDS, or other high-profile serious diseases, but other choices aren’t going to be as easy. For example, would “lifestyle” drugs that would help numerious people in some way that is personally but not medically significant be considered? What about compounds where there is an effective patented drug but an non-patented compound is expected to be cheaper but not offer any large efficacy advantage? For the drugs the government passes on, nobody is likely to invest the effort in them, and producers of the compounds that are candidates for unpatented drugs will lobby pretty agressively to get the gov’t to take care of what would otherwise be their R&D and regulatory compliance costs. There’s a lot of money to be made in generics, just not enough to offset the costs of clinical trials in most cases and there may be a moral hazard issue that companies that would actually go through the costs of trials for compounds that aren’t under patent will now wait for the government to pick up the tab.

    One way of currently getting around this problem for compounds that are approved for one purpose but not for other ones where they show promise is off-lable prescribing, which may be where DCA ends up since it appears to be approved for other purposes, and thus has gone through a decent amount of safety testing, but this only works if a sufficiently strong body of reseach to convince clinicians of its efficacy emerges independent of formal trials.

    The best immediate solution I can think of, which admittedly isn’t very good, is to give companies that do the clinical trials for compounds that aren’t under patent a shorter term “mini-patent” on marketing the drug for the usage they performed the trials on with a little extra time if they also had to demonstrate safety. This doesn’t do anything to fix the system overall, but it should at least reliably fill the gap in current policy.

  5. #5 Leland P
    January 19, 2007

    Apart from the costs of clinical trials (and I’ve never heard of a small trial for a cancer drug only costing a few hundred thousna dollars, as Orac claims), the real problem is that this scientist is a bench scientist. He doesn’t know or even want to supervise a clinical trial. We shouldn’t expect a cellular biologist to deal with the thorny legal, medical and practical issues.

  6. #6 Orac
    January 21, 2007

    Clinical human trials can cost pharmaceutical companies between $600 and $800 million to bring a drug to market.

    And that’s largely irrelevant to this particular case, at least at this early stage. You’re assuming this drug will work in humans, when the odds are that it probably will not. Many are the drugs that show a lot of efficacy in mice and show results not nearly as impressive when tested in people. (I’ve worked with a couple such drugs myself.) It does not cost nearly that much to do a preliminary clinical trial to see if the stuff even works in humans! That’s what’s irritating me. The whole $600 billion figure is being bandied about as if that much money has to be spent to find out if the drug works It doesn’t, necessarily. If a small $1-2 million trial fails to show efficacy, then that’s that. If the drug shows promise, then we have more to consider.

  7. #7 Frans
    January 25, 2007

    DCA is classified as a supplement rather than as a drug (much like COQ10). At least on the Stanford University site for Huntington Disease it is.(HD apparently is the major cause of lactic acidosis which is where DCA has been successfully used for some 30 years.)

    My question is, where can I buy Dichloroacetate (DCA), particularly in the Toronto area. Noah’s does not carry it.

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