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      Previous: Identity (Introduction and Table of Contents) Politically active groups form because of ideology and identity: they have beliefs about how the world should be; those beliefs are emotional and create both identification with other people who have the beliefs and shared desire to change the world or keep the world in line with how the ideologies pres […]
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Dead Space in the Pharma Pipeline

This article is a few months old but just now showed up in my LinkedIn updates.  It’s another indication of disintegration in the pharmaceutical industry as it heads towards the “patent cliff”:

Scientists warn on “dead space” as pharma giants shuns neuropsych:

European experts are sounding an alarm about the recent pullout of GlaxoSmithKline and AstraZeneca from the brain disorder arena.  David Nutt, a professor Imperial College London, and Oxford’s Guy Goodwin are calling for a rapid response to what they term a collapse in R&D spending in the field.

“What we have forgotten, and must not forget, is if we stop this research we will have a dead space of 20 to 30 years before we can re-tool again,” Nutt tells The Guardian. “Despite the public health imperative, not only has EU research funding remained very low, but–even worse–big pharma is increasingly coming to see research into better neuropsychiatric drug targets as economically non-viable.”

That effectively sums up the position of GSK’s Andrew Witty, who has explained that the huge risk associated with developing new drugs for neuroscientists is just too high to justify the investment necessary. The Guardian notes that the average time it takes to develop a new drug for a brain disorder is 13 years-considerably higher than the average program and significantly more expensive.

The article goes on to say that the authors have proposed that pharmas be encouraged to give this area of research to academic labs and that government make an effort to protect small labs and companies who agree to do this research.

The reason why neuropsychiatric medications are so “economically non-viable” is because the body protects the brain from foreign, potentially toxic substances with a physiological feature known as the “blood-brain barrier”.  Basically, there is an extra “layer” of protection around the central nervous system that drugs have to cross in order to reach their targets.  That means, the compounds that might be the most effective have to first be bioavailable to the body and then have to have  certain additional physical properties to cross the blood-brain barrier.  Developing these kinds of drugs is very time consuming and has a high failure rate.  Messing with the brain is not for the faint of heart.  There are specificity issues to deal with as well.  I once worked on a project where the drug was initially developed to target a serotonin receptor in the brain in order to reduce appetite.  It turned out that it also caused severe priapism in primates.  We must be very, very careful or someone’s going to lose a penis.

For those of you who might be hoping for a treatment for Alzheimers, schizophrenia, bipolar disorder, epilepsy or stroke, the authors of this article are saying that the research in these areas are so expensive for big pharma that they are mothballing the projects.  Starting them up again, and finding chemists who understand what it takes to make compounds that cross the blood-brain barrier is going to set back research by 20-30 years.  Then, if a company or academic lab does decide to take this on, they’re going to need governmental protections, to keep them from going under while they work out the kinks.  Presumably, this would include some kind of insurance against the inevitable class-action lawsuits as well as some kind of patent protection.

The patent reform act that was signed recently will probably not be a friend to small labs.  The change from “first to invent” to “first to file” puts a lot of burdens on small labs that may not have a fully staffed patent department to work through a patent application.  That leaves them vulnerable to large pharmas who will make them an offer they can’t refuse.  If I were reforming the patent problem, I would have split off biomedical patents from other patents and then, counterintuitively, extended the patents for new drug entities.  Before you get your knickers in a twist, hear me out.  One of the reasons that drugs are so expensive is because they spend a lot of time in development and clinical trials and those trials eat up the time left on the patent.  These days, the FDA requires more safety data and clinical trials before a drug is approved.  (I *know* there will be some readers who will insist that drugs are fast tracked but they are not paying attention.  Fast tracked drugs are mostly oncology drugs where there is a bargain between patients who are terminally ill who may be willing to forgo the additional safety requirements.  Fast track for all other drugs is very rare)  The longer the drug sits at the FDA, the greater the potential high cost to consumers and marketing executives, seeing an opportunity to increase share holder value, may pad that price even more, using the FDA holdup as an excuse.

Pharma is also not well served by the frenzy of the financial markets to produce higher profits every 3 months.  When push comes to shove, the human body will do what it damn well pleases.  You can’t force Mother Nature to perform on a quarterly basis.  See Derek Lowe’s post on GSK’s mystifying new scheme for creating a pharma division with a racecar fuel manufacturing facility.  We have no idea what GSK is thinking but we are aware of some computer chip manufacturers complete cluelessness when it comes to drug research.  You can’t research a drug the same way you research a chip.   And MBAs who do not understand their business will do dumb things when they are under pressure to produce profits.  Biomedical research is unlike any other form of high tech research.  You can’t pair the two and expect that the cells that the biologists are working with will suddenly get a clue and get with the program.  And this is why the patent problem is also different for the pharma industry because shortened research cost recuperation times leads to a lot of very stupid short-term thinking.

If I were to reform patents, I’d stop the patent clock while the drug was going through the clinical and approval process and resume it after approval.  Then make a deal with the pharma industry to ease up on pricing in exchange for longer exclusivity.  This accomplishes two goals: it takes the pressure off of pharma to price the hell out of the drug and it steers them back towards long term planning.  If they know the patent cliff isn’t looming a few years down the line, the pace of mergers and restructuring might slow down and research would have some breathing room to get back to business.  It’s a theory.  There’s always a way for the financial class to game the system so thinking this through carefully and plugging the loopholes would be very important.  But that’s what I expect from my congressmen- careful, meticulous examination of the problem with reasonable solutions.  Changing the first to invent to first to apply rule did not do that and may have inadvertently exposed entrepreneurial labs to additional risk and expense.  Well, inadvertently to Congress; opportunistically to the big pharma vulture capitalists.  Hey, it’s a business.

Anyway, it’s something to think about.  It’s not just CNS drugs.  Antibiotics are also losing their shine with the big pharma giants.  Too many lawsuits.  Oh, well.

Antibiotics, R&D and patent reform

gram stained Staph aureus

I followed the link from Derek Lowe’s blog, In the Pipeline, to this abstract of a paper that was published in May of this year  about the dearth of antibiotics in big pharma’s pipeline:

The world is running out of antibiotics. Between 1940 and 1962, more than 20 new classes of antibiotics were marketed. Since then, only two new classes have reached the market. Analogue development kept pace with the emergence of resistant bacteria until 10-20 years ago. Now, not enough analogues are reaching the market to stem the tide of antibiotic resistance, particularly among gram-negative bacteria. This review examines the existing systemic antibiotic pipeline in the public domain, and reveals that 27 compounds are in clinical development, of which two are new classes, both of which are in Phase I clinical trials. In view of the high attrition rate of drugs in early clinical development, particularly new classes and the current regulatory hurdles, it does not seem likely that new classes will be marketed soon. This paper suggests that, if the world is to return to a situation in which there are enough antibiotics to cope with the inevitable ongoing emergence of bacterial resistance, we need to recreate the prolific antibiotic discovery period between 1940 and 1962, which produced 20 classes that served the world well for 60 years. If another 20 classes and their analogues, particularly targeting gram-negatives could be produced soon, they might last us for the next 60 years. How can this be achieved? Only a huge effort by governments in the form of finance, legislation and providing industry with real incentives will reverse this. Industry needs to re-enter the market on a much larger scale, and academia should rebuild its antibiotic discovery infrastructure to support this effort. The alternative is Medicine without effective antibiotics.

Imagine a world without effective antibiotics.  {{shivver}}

Note that the abstract says that the industry could be developing “another 20 classes and their analogues“.  To the public, those analogues might look an awful lot like “me too” drugs.  But that’s ok in this area because bacteria mutate at such a good clip that a moderately modified analogue could seriously throw them off kilter.  So, while it is important to also develop drugs that hit different bacterial targets, the analogues are still very necessary and important.

It’s not like there is a shortage of projects that the nation’s laid off overeducated geeks could be working on and like I said before, if the big pharma entities want to pass on antibiotics because they are too expensive and litigious, there are more than enough of those geeks who would happily work for the government for decent wages commensurate with the level of difficulty of our work.

What I’m worried about is patent reform.  There are proposals right now that would reform the patent system so that the patent goes to the person who files first and not the first to innovate.  The issue is of special importance to the software and cellular data industry who are getting tired of being sidelined by patent trolls.  But what if you’re a tiny biotech that just spent your kid’s college fund and granny’s nest egg discovering a potential drug?  On the surface, this seems very fair until you realize that many entrepreneurs, some of them involuntarily liberated from big pharma, don’t have large departments of expensive patent lawyers they can call upon to file an air tight patent.

Getting to the first to file stage may be close to impossible for many small biotechs to achieve without making a deal with a very big devil who is making them an offer they can’t refuse.  It could seriously dampen any enthusiasm for drug discovery in small companies especially if those companies are doing research in therapeutic areas that big pharma has abandoned like antibiotics and CNS drugs.

I just wish I had the confidence that the Congress members who are reviewing the reform legislation knew what they were doing and were committed to making the system fair for the little guy.  At the very least, we should study whether the “first to innovate” patent structure leads to more innovation than the “first to file” system of other countries.   What may save social media may end up causing a lot of infections down the road.