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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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July 1, 2011

The Histamine Code, You Say?

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Posted by Derek

I've been meaning to link to John LaMattina's blog for some time now. He's a former R&D guy (and author of Drug Truths: Dispelling the Myths About Pharma R & D, which I reviewed here for Nature Chemistry), and he knows what he's talking about when it comes to med-chem and drug development.

Here he takes on the recent "Scientists Crack the Histamine Code" headlines that you may have seen this week. Do we have room, he wonders, for a third-generation antihistamine, or not?

Comments (17) + TrackBacks (0) | Category: Biological News | Drug Industry History


1. Achoo on July 1, 2011 10:34 AM writes...

The response before this one says it all.

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2. Anon on July 1, 2011 10:39 AM writes...

Well, it's not rocket science to say that the resolution would be about risk vs reward, cost vs benefit, efficacy vs safety, treatment value vs payers.......and not always about building a better mouse trap, but how much better, why is it better, is it really better, who says it's better.....But, it's really a debate not worth having since someone will try, small or big Pharma, and then time can tell.

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3. Matthew Herper on July 1, 2011 11:21 AM writes...

Isn't calling the former head of R&D at Pfizer "a former R&D guy" a little like calling Huey Lewis "a singer?"

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4. Stephen_Frye on July 1, 2011 12:43 PM writes...

On top of the obvious - "how can you improve on zyrtec?", I'll be very interested to see if the 'trophy-hunting' structural biology going on for GPCRs actually has an impact on drug discovery science. Afterall, 40-50 years of pharmacology, medchem and SAR has already been done so the chance for a novel insight from the structures seems small. (btw - the estimate is that each GPCR structure has cost a few million - while normal soluble proteins are around $200K.) Especially given that it takes a few structures for reasoning by analogy (mostly what we are good at) to have an impact. I think this area (GPCR drug design) is more likely to benefit from novel assays that tease apart the downstream signaling and how different small molecules drive differential agonism/antagonism. I would bet my structural dollars on a target or target class where there is less extant knowledge.

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5. Morten on July 1, 2011 4:08 PM writes...

@4. Stephen_Frye
Trophy hunting is what pushes the whole field forward. Your post suggests that getting the first GPCR structures was no more than ~8 times harder than a run-of-the-mill protein is ridiculous.
Structural biology has great demands on protein yields, purity, and stability. Assay biologists and others benefit from improvements in all three areas but don't have the motivation to develop these protocols.
Today structural biologists are increasingly hunting glycoproteins and this will also improve our biological tool box in the future in my estimation.

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6. Pfired Once on July 1, 2011 7:00 PM writes...

John LaMattina? The guy who made Pfizer R&D the powerhouse it is today? (not to mention Warner-Lambert, Searle, Pharmacia, Wyeth, ...) Pfizer continues to suffer from the middle managers who rose up the LaMattina way, i.e., good politicians, rotten scientists.

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7. Pfizered on July 1, 2011 9:37 PM writes...

I am still waiting for the book 'Exhubera: oh, how we laughed'

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8. Anonymous on July 2, 2011 2:22 AM writes...

Following Derek link above, I was reading John LaMattina, blog for the first time and kind of like it till I get down to the "shots on goal" post and these increadible lines:

"The ones taking these shots were in the Pfizer cancer discovery group, which grew to over 200 people making it one of the largest divisions in the company. Over a ten-year period, it produced a number of clinical candidates that explored over 20 of these novel ideas to treat cancer. While many of these compounds failed to improve the survival of cancer patients, a number of them proved to be very effective. Two of these compounds have already reached the market, Sutent and Tarceva. "

Head of R&D at Pfizer, you say ? wow !
I think everybody here know that sutent was discovered in Sugen and then all scientist involved get fired after Pharmacia and then Pfizer takeover. At least Pfizer is selling the drug.
But Tarceva !?

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10. Anonymous on July 2, 2011 7:36 AM writes...

@8 - Yes, I like John's rose tinted view of 'shots on goal' too. It was his genius idea so of course he will look for data to support it.

The biggest issue with 'shots on goal' he failed to mention is cost - you are using expensive balls. At $25MM per CAN and say another $25MM to get to end of POC plus say another $5MM for another PoC in another indication, you soon rack up a huge bill - Pfizer did and is now running out of money, hence the pink slips. 'Shots on goal' just encouraged 'metric chasing', doing more and more 'cos it looks good and it's gotta work eventually. It didn't. The target choices become even more dubious , so rather than 1 in 8 to 1 in 40 chance of success he predicted, it just becomes 1 in 100 or 1 in 1000.

Pfizer has a lot of brilliant molecules against targets - they just don't know which disease they might work in. Value destroying at its best.

Well done John, glad to TV career is working out.

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11. befuddled on July 2, 2011 3:48 PM writes...

Pity that Derek's review of LaMattina's book is behind a paywall.

On the subject of antihistamines, it seems ironic that one of the big hurdles with CNS drugs is getting past the blood-brain barrier, yet staying on one side of that barrier appears to be the hard part for antihistamines.

That being said, LaMattina is surely right about the market for new & improved antihistamines. One would be hard pressed to come up with better and less toxic drugs than Claritin, Zyrtec, and Allegra. Now, better immunotherapy for specific allergies, that's a different subject...

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12. Anonymous on July 3, 2011 4:57 PM writes...

#10, You missed my point. or I was not clear.
The guy claims the credit for discovering Sutent and Tarceva in his "Pfizer Cancer Discovery Group". At least that is how I read his post. How on Earth can anybody trust a single word of this guy now ??

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13. Anonymous on July 4, 2011 1:39 AM writes...

As I remember it, Tarceva is actually an old PFE compound. When PFE merged with Warner-Lambert, they decided to keep the WL program which was a irreversible EGFR inhibitor and sold Tarceva to OSI.

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14. Old Timer on July 5, 2011 3:19 AM writes...

#13 - For the record, my recollection is that in the late 1990s Pfizer licensed Tarceva from OSI, then acquired the irreversible EGFR inhibitor canertinib as part of the takeover of Parke-Davis.

As an externally imposed condition of the takeover, Pfizer divested Tarceva directly or indirectly to Genentech-Roche and retained canertinib - later discontinued while Tarceva became a billion dollar drug...

Whatever the minutiae, I couldn't agree more with #8's critique of John La M's rewriting the history of the discovery of Sutent and Tarceva.

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15. CR on July 5, 2011 12:06 PM writes...

@3, Matthew Herper:

How dare you, sir, disrespect Huey Lewis that way!

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16. NHR_GUY on July 5, 2011 9:51 PM writes...

Matt, I read your blog occasionally, interesting stuff most of the time. If you were a long time reader of Derek's blog you'd know you're not going to find a lot of love here for John L. or anything Pfizer for that matter.

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17. grumbletech on July 7, 2011 10:39 AM writes...

What if you made a sedating 1st-generation-type antihistamine with a metabolically labile ester group? When cleaved, activity is lost, giving you a very short-acting hypnotic more similar in pharmacokinetics to zolpidem or zopiclone. And it could be sold OTC.

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