Big Pharma is pulling out of CNS indications, NIMH to the rescue?
January 6, 2012
A recent blogpost from NIMH Director (and Acting NCATS Director) Tom Insel details the grim future for private sector development of drugs for the brain and behavior disorders.
But change is coming from another direction as well, especially for psychiatric medications. Over the past year, several companies, including Astra Zeneca, Glaxo-Smith-Kline, Sanofi Aventis, and recently Novartis, have announced either a reduction or a re-direction of their programs in psychiatric medication R&D. Some of these companies (such as Novartis) are shifting from clinical trials to focus more on the early phases of medication development where they feel they can identify better targets for treating mental disorders. Others are shifting from psychiatry to oncology and immunology, which are viewed by some as lower risk.
There are multiple explanations for these changes. For instance, many of the blockbuster psychiatric medications are now available in inexpensive generic form. In addition, there are few validated new molecular targets (like the dopamine receptor) for mental disorders. Moreover, new compounds have been more likely to fail in psychiatry compared to other areas of medicine. Studying the brain and the mind has proven to be much more difficult than the liver and the heart. Most experts feel the science of mental disorders lags behind other areas of medicine. The absence of biomarkers, the lack of valid diagnostic categories, and our limited understanding of the biology of these illnesses make targeted medication development especially difficult for mental disorders.
As I may have mentioned already, this sort of change in the development “system*” gives me a better reason to agree with the creation of NCATS and the earlier noises about the NIH taking a more active role in therapy development. There are lots of indications that don’t receive enough attention because there is no route to sufficient profit. Drug abuse is one of those indications. Part of the reason we aren’t more advanced in pharmacotherapy for substance abuse is on us, the basic science folks. Sure. But a big part is also on private industry which never saw where the paycheck was going to come from. So there was never much enthusiasm for pursuing anti-substance abuse programs. No program, no drugs. Remember, estimates run some 10-20,000 compounds evaluated in a drug development pipeline to arrive at each approved medication.
I don’t believe the NIH can improve this by being smarter, that is a foolish conceit of many. But not having to seek blockbuster returns does change the calculus for what indications are worthy of serious drug development effort.
And that would be a GoodThing.
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*such as it is
DrugMonkey 
January 6, 2012 at 7:40 am
totally agree… and a great opportunity, as well, for some of us pain people to join hands with drug abuse people to work on some new avenues for drug discovery
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January 6, 2012 at 8:04 am
Insel kind of bashes “me too” drug development in his most recent blogpost. Yet patients differ- some do well on one of the clonal drugs and hate the others. I know one person who reports one med as “evil” and another as near miraculous for the same indication. They are drugs that a fair read would classify as “me too” drugs.
He also refers to private/public partnerships to make the now-abandoned programs in BigPharma more available for additional (public) study. There are going to be IP problems but it is a good idea.
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January 6, 2012 at 9:17 am
joint ventures between pahrma and Feds would be fun. Pharma uses their bank roll and expertise to screen candidate drugs/compounds. NIH picks up the tab (or part there of) for the clinical trial. If it works, profit share. If it doesn’t Fed loses money, and Pharma is only out R&D costs…
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January 6, 2012 at 9:57 am
All the more reason the brain can suck it.
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January 6, 2012 at 1:17 pm
I takes 10-12 years to get a drug through the development pipeline and onto the market. If a drug becomes approved in less than this time after the first approved drug of that class, then it is probably not a “me too” drug, but rather, they got beaten to the punch.
Lipitor was the 5th statin. It almost didn’t make it to the clinic because it would have been a “me too” drug. It is the most effective statin. Had we arbitrarily decided that anything after the 1st drug in its class was a “me too” drug and was not worth the effort, we’d not have some of the most effective drugs.
NCATS should start by developing better animal models, phenotypic screens, biomarkers, etc. The attrition rate for compounds is mostly due to lack of efficacy and toxicity. It is not for the lack of compounds but may be due to the reductionist/target-driven approach to drug development for the last 10-20 years. If they simply try to do what the drug industry has tried for the last 20 years, they will also fail and will waste the tax payers money.
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January 6, 2012 at 3:45 pm
This is a very important point. Unfortunately, even the clinical trials themselves don’t usually reveal how effective a drug is going to be, and only actual deployment to the general population makes it clear. Of course, this fact bangs up *hard* against the other fact that it costs like a billion fucken dollars to bring a drug to the general population.
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January 7, 2012 at 9:41 am
“But not having to seek blockbuster returns does change the calculus for what indications are worthy of serious drug development effort.”
I call bullshit.
While big pharma companies need blockbusters to feed their shareholders, small companies and biotechs actively pursue treatments for less common conditions. There’s plenty of pharma action in neuroscience. I know of small-pharma sponsored trials in ALS, Duchenne’s, fragile X syndrome, and quite a few other “small” indications. *
As for the NIH coming to the rescue by being better at drug discovery & development than pharma, I’m not holding my breath. The breast cancer scandal in the 90’s, the nevirapine trial screw-up, and other problematic trials run by NIH make it clear that they’re not ready for prime time.
disclaimer: obviously, I work for a pharma, but not on any of the conditions listed. I’m working on other pharma-sponsored research in neuro disease.
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January 7, 2012 at 12:08 pm
You have a point, up to a point, about the smaller companies. *However* most of them are looking to generate leads to sell to BigPharma. They simply do not have the $$$ to complete the approval process in a lot of cases. Or, they bet the farm on a promising compound and essentially shutter the rest of the company to do it. To disastrous consequences if they fall short. See Arena.
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January 7, 2012 at 7:41 pm
Unfortunately, even the clinical trials themselves don’t usually reveal how effective a drug is going to be, and only actual deployment to the general population makes it clear.
This is totally wrong. Phase 3 clinical trials are by far the most definitive measure of how effective a drug is. Deployment to the general population (after approval) just gets you a big collection of non-quantitative anecdotes.
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January 8, 2012 at 3:41 am
No, it is correct. The phase 3 trials certainly define with some level of statistical likelihood whether a drug is effective or not. But it is only after mass deployment that it becomes clear whether a drug is better or worse than other similar drugs, and whether there might be unexpected side effects that mitigate effectiveness for some (or all) users.
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