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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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June 4, 2013

AstraZeneca, As Expected, Pulls the Plug

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Posted by Derek

Late last year came word that the AstraZeneca/Rigel compound, fostamatinib, had failed to show any benefit versus AbbVie's Humira in the clinic. Now they've gritted their corporate teeth and declared failure, sending the whole program back to Rigel.

I've lost count of how many late-stage clinical wipeouts this makes for AZ, but it sure is a lot of them. The problem is, it's hard to say just how much of this is drug discovery itself (after all, we have brutal failure rates even when things are going well), how much of it is just random bad luck, or what might be due to something more fundamental about target and compound selection. At any rate, their CEO, Pascal Soriot, has a stark backdrop against which to perform. Odds are, things will pick up, just by random chance if by nothing else. But odds are, that may not be enough. . .

Comments (19) + TrackBacks (0) | Category: Business and Markets | Clinical Trials


1. Benjamin Carlisle on June 4, 2013 12:30 PM writes...

Did you mean "fostamatinib" ? I couldn't find any entries in for "fostamitinib".

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2. emjeff on June 4, 2013 12:53 PM writes...

Well, it stands to reason that if you are failing a lot in Phase 3, you are doing something very wrong in Phase 2. Perhaps AZ needs to look at their quantitative clinical pharmacology group (or lack thereof) and determine what's wrong with their phase 2 programs that is so consistently getting things wrong.

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3. Benjamin Carlisle on June 4, 2013 1:02 PM writes...

@emjeff Have you seen this article by my colleagues?

They discuss exactly the issue you're getting at here.

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4. tedthechemist on June 4, 2013 5:03 PM writes...

Phase 2 showed no impact on disease progression - AZ brought this junk on the fact that some biomarker said it should work.....

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5. oldnuke on June 4, 2013 6:46 PM writes...

Sounds like a case of MBA overdose...

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6. Atavist on June 4, 2013 11:01 PM writes...

Bad compound, bad selectivity, bad pharmacology, bad clinical plan. Why is anyone surprised this failed ? We should be surprised that anyone paid so much for this. Another example of bad science through and through.

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7. Nick K on June 5, 2013 1:04 AM writes...

Minor correction: the current CEO of AZ is called Pascal Soriot, not Soirot.

AZ is not having a lot of luck at the moment!

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8. DrSnowboard on June 5, 2013 1:30 AM writes...

Ah, but it's OK, all those legacy programmes were dogs but the new team has loads of new stuff to talk up, especially that brand new PARP inhibitor...Kudos for having your most productive year Mene!

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9. JeffC on June 5, 2013 3:03 AM writes...

#8 LOL. He definitely got Kudos. It was very nice of him to take the credit for that stab in the back

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10. Jose on June 5, 2013 3:31 AM writes...

Re #4-

It's very funny, biomarkers are the current rage in epidemiology- "oooooh! Sexy molecular methods mean we don't have to wait for tedious outcomes!" *squeals of delight*

I've tried directing several colleagues to the fact that pharma spending millions on them and now they've relegated to the trash heap due to being huge waste of time. No-one seems to believe it, however.... 'next verse, same as the first"

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11. Anonymous on June 5, 2013 5:58 AM writes...

I was working at Charnwood when the acquisition of the compound was being discussed.
The message from medicinal chemistry was a resounding no, don't buy it the early P2 results aren't good enough, but the deal was done . . .

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12. Petros on June 5, 2013 7:41 AM writes...

#11's comments are interesting. My perspective from the outside was similar.

One wonders who really made the decision to blow a few hundred million dollars on this?

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13. Anonymous on June 5, 2013 8:22 AM writes...

here is one of new and exiting AZ clinical candidates:

Remember this and related posts ?

No wonder AZ has such high failure rate...

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14. anon2 on June 5, 2013 10:18 AM writes...

@13: AZD-1208 is not a rhodanine. Rhodanine has a thiocarbonyl, not a carbonyl.

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15. DCRogers on June 5, 2013 10:18 AM writes...

"Odds are, things will pick up, just by random chance if by nothing else."

For clarity, "things will pick up" == "return to baseline" (chance of P3 success), right?

The less-well-versed might interpret this as a version of a common gambler's mistake: "It's been tails so many times, the odds are better the next time it's heads!".

Unfortunately for A/Z, return to baseline will not suffice to replenish their sales pipeline.

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16. Vader on June 5, 2013 10:33 AM writes...


The gambler's fallacy and regression to the mean are distinct phenomena, and only one is a fallacy.


"Unfortunately for A/Z, return to baseline will not suffice to replenish their sales pipeline."

Does make AZ sound more like a desperate gambler than a sound statistician.

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17. SteveM on June 5, 2013 11:29 AM writes...

Sounds like AZ management has not been taught that sunk costs are not related to future value.

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18. Cialisize Me on June 5, 2013 1:33 PM writes...

Who actually performed the Phase II trials?? Seems like a common theme that a biotech gets great Phase II data, sells it for big bucks to a Pharma who later finds out that it's no good. Pick your example: Inhibitex, BiPar, Sirtris, help me out here.... You'd think they'd learn and maybe bring things in earlier so that they could control the development into the clinic and oversee the trials.

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19. Ned Ludd on June 5, 2013 9:51 PM writes...

Even I, Ned Ludd, know that there is no such thing as faith-based drug discovery.

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