About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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January 5, 2009

New Year - I Hope!

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Posted by Derek

In past years, around this time I’ve often done a look back at the previous year in the drug industry. I hope that no one will be disappointed if I scuttle that tradition, because honestly, I have no desire whatsoever to relive what drug research went through in 2008. It may have been the toughest year for industry scientists in the modern era – everyone I know struggles to find a comparison.

I’d rather spend my energies on 2009. Let’s just stipulate that 2008 was, on balance, horrendous: what does that tell us? How did we end up in this position, and how can we avoid more of the same? There’s a lot of arguing room in those questions, but I think that we can agree that the proximate cause is that we’re not coming up with enough good drugs. 2008, for all its ugliness, was a handful of good products away from being a decent year. Why were we short that handful?

You have to go back some years to answer a question like that, given the industry’s lead time. The projects that were begun in the mid-to-late 1990s are clearly not coming through in the way that everyone had hoped. Is it that our attrition rate has gone up, or have we just not taken enough things to the clinic, or some of each?

Let’s think about that first problem, which certainly seems to be real enough. Is it that the easy targets have all been worked over, leaving us with only the tough ones? I don’t think that’s the whole explanation, although that’s certainly part of it. Still, even some of the big drugs from years past wouldn’t have made it through our current structures. So are the hurdles set too high during development – that is, do we know too much about potential problems, without having learned a corresponding amount about how to fix them? That’s got to be a big factor, which leads to a New Year’s resolution: try to spend as much time fixing problems as finding them. That’s a hard one to live up to, but it’s a goal to work toward.

And if we’re going to talk about that latter number, we’re going to have to cut through the often artificial “projects advanced” figures that circulate inside companies. Anyone who’s been around this business has seen some long shots (and some outright losers) officially pushed forward just to make some year-end target. Now, long shots are fine. To a good approximation, everything we do is a long shot. And everything has to go to the clinic eventually (or die) – but we have to make sure that we’re not just checking boxes. So that’s another resolution: spend less time kidding ourselves.

Of course, there’s a flip side to the number of compounds going to the clinic. Could it be that we’re being too cautious, because we have too many potential worries (those high hurdles mentioned above)? Should we be taking more things forward? Well, that’s an expensive proposition, the way things are set up now. So here’s another hard-to-live-up-to resolution: find ways to go to the clinic without betting our shirts every time. That’s been a big focus the last few years (biomarkers, etc.), but we need every idea and technique we can think of (microdosing? Simulations, even?). The cost of getting answers in humans is getting too high for us to try out as many ideas as we need to.

And here's a less macro-scale resolution, which I plan to start putting into practice immediately: don't let fear run your research. Try some things that you aren't sure about. Take some chances. Put down some bets. I've got several that I've let sit in the should-I-do-this limbo for too long, and I'm going to do something about that. Join me?

Comments (12) + TrackBacks (0) | Category: Clinical Trials | Drug Development | Drug Industry History | Who Discovers and Why


1. Wavefunction on January 5, 2009 10:53 AM writes...

As far as guidelines for companies go, how about this one: "Don't insist on multibillion dollar blockbusters. Focusing on modest, niche markets is not all that bad. Don't drop a lead only because it may lead to a therapeutic targeting a small patient population"

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2. Petros on January 5, 2009 11:11 AM writes...

Wavefunction's point is valid. In the days when blockbusters were rare the key to commercial success was having a broad range of good selling products.

In the early 1990s Merck was top dog through such a strategy, then blockbusters or nothing became the mantra of the day and companies set high minimum annual sales targets when assessing the potential of development compounds

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3. fred on January 5, 2009 11:51 AM writes...

Whoa--if the problem is that we aren't coming up with enough drugs, laying off record numbers of med chemists hardly seems an even SLIGHTLY rational solution.

The problem is multifactorial:
1)patent expirys faster than approvals.
2) CYA at the FDA-- slow approvals; absurd black box labelling (e.g. Celebrex)
3) Yes, too many eggs in the a) kinase b) blockbuster basket.
4) Too many $ in advertising to consumers vs R&D. The practice should be banned.
5) over-reliance on biologicals. Perhaps bioequivalent generics can discourage this nasty emphasis, which isn't a good thing for EITHER med chem or the PATIENT.
6) Stupid CEO's who don't understand that China a rat hole that will NOT produce "better" or "faster", though it may APPEAR to produce "cheaper".
7) over-reliance on CRO in general, even by start-ups who should know better.

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4. Ben on January 5, 2009 12:57 PM writes...

Two points:
1. Derek's point about how its much easier to find problems than to fix them is very true, and its something everyone, regardless of field or industry, to strive for.

2. I think the problem with Wavefunction's point is that pharma R&D is still largely a scale game -- it requires massive scale to build the R&D and clinical infrastructure needed to succeed at the clinical trials/marketing game. Unless there's a way for us to "wean" big pharma/biotech off of blockbuster wins to build this infrastructure, these niche markets to chase won't ever be a priority.

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5. Hap on January 5, 2009 1:31 PM writes...

Going for nonblockbusters is a good idea if you can make clinical trial costs come close to scaling with market size, but I didn't think that costs came close to doing so. With smaller drugs, you have to spend lots up front to get them approved and it takes a while for you to break even unless you price them high. (I assume the same problem in worse form awaits personalized medicine - if your target population is really small, it will be hard to find them all and the drugs will need to be priced very high to make back the trial costs.)

I don't think DTC is costing pharmaceutical companies money that would otherwise go into R+D (I assume they wouldn't invest in it if it didn't make money for them overall), but I think it's cost them much of the trust that allows them to sell drugs and to sell them better than the competitors they are training here and overseas. Risk/rewards balances are difficult enough for doctors to calculate, much less random people, and if you sell lots of expensive drugs to people in whom they are unlikely to work well or to help them more than they hurt them, you look more and more like the supplement makers (who make their ads and supplements look druglike to make people think they've actually tested them like drugs). If people can't distinguish supplements from drugs (or assess them as equally trustworthy), I don't think pharmaceutical companies have done themselves any favors. Trust doesn't make you any money directly, but it's a barrier to entry for new drug companies (they have to earn trust), and losing trust when you have had it previously is almost worse than not have had it at all.

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6. Skeptic on January 5, 2009 2:44 PM writes...

There is no convincing analytical framework in place to understand biology. The mechanistic school brought over from physics is unsatisfying. You can flip through any book on systems biology and come to a perfectly sensible conclusion that its contents are unimportant. Everytime you pick up a copy of Nature Chemical Biology, you get the suspicion that the mathematical graph theorists are taking over. The big biology fanatics and their "measure everything" mandate ignite the wild imaginations of the data miners if nothing else.

I worry that biology research will turn into the boondoggle that is fusion research. "Leave us alone for 50 years with unlimited funds and we'll deliver the goods". Basically, thats all the medicinal chemists of today have to offer.

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7. Arf on January 5, 2009 3:03 PM writes...

I agree that 2008 was a horrendous year to be in Drug Discovery but my question to all R&D scientists is this - doesn't anyone feel a sense of personal failure regarding the lack of good new drugs?

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8. anon on January 5, 2009 3:29 PM writes...

"doesn't anyone feel a sense of personal failure regarding the lack of good new drugs?"

Success is exactly what killed us; we were acquired. I suppose this means mediocrity is the new "sweet spot".

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9. Hap on January 5, 2009 4:26 PM writes...

Felling a sense of failure for the lack of new drugs is probably unhelpful (you can't control the pipeline, only what you can do). In addition, when acquired companies are rendered into fodder for their successes and the facilities that develop sucessful drugs are repaid for their sucesses with repurposing as biotech incubators and landfills, it's kind of hard to expect people to take failure seriously. When managers are rewarded for failure and employees are penalized for success, it would seem to be hard to feel sorrow for the lack of drugs (positive outcomes).

If you selectively breed companies for their lack of products (acquire/kill productive company/wash, rinse, repeat), what exactly do you expect to come out in the end?

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10. Hap on January 5, 2009 6:59 PM writes...

Well, 2009 is already starting well. Pharmalot is going away. (I guess newspapers have been doing worse than pharmaceutical companies for a long time.) New frontiers for unemployment are opening up.

I'm wondering how to explain "held a change cup on the OSU campus" or "hunted deer near father-in-law's house" on my resume.

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11. Retread on January 5, 2009 9:17 PM writes...

Not to worry. Upcoming post #4 on Chemiotics in the Skeptical Chymist, will describe a new class of drugs whose exploration and development (if any one of them works) which will employ legions of synthetic chemists, molecular modelers, etc, etc. If I write about it here, I won't be able to write about it there.

Hopefully this year will be better for you guys (and girls), but it doens't look promising so far.

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12. Chilly on January 5, 2009 11:20 PM writes...

"Don't let fear run your research."

If I work for a big company the executives will get all the credit if it works out. They'll then look for ways to outsource my job.

If I work for a small company, I get fired when the company is acquired.

Not sure where I'm supposed to relax. Possibly Derek is scarfing down prozac? Getting high on his own supply?

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