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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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May 1, 2012

Regulatory Hurdles

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Posted by Derek

John LaMattina has a good piece up on the FDA, where they might be trying to have it both ways. About a recent speech by Janet Woodcock, he has this:

But Dr. Woodcock begins to stray into areas where I think she is off base. For one thing, she asserts that “many late stage [clinical] failures are due to efficacy problems.” That’s not exactly true. It is only when companies take compounds into late stage development with little or poor proof-of-concept data where this happens. The majority of phase 3 clinical trial failures are due to unforeseen, unpredicted side-effects or else due to finding that, in direct comparison to existing therapy, the new drug doesn’t show the superiority necessary to be successful commercially. Dr. Woodcock goes on to advocate for the generation of “evaluative tools,” new methodologies that can better predict the performance of a compound in late stage studies.

Of course, those tools are a good idea, and would be worth a lot (which is why everyone's been spending time and money trying to find them). But the FDA will not approve drugs based on them. They probably shouldn't - as LaMattina says, there have been quite a few drugs in recent years that looked like they would work based on one secondary endpoint or another, only to come up short in the real world. Woodcock is right to call for such approaches, but they won't necessarily shorten the time until approval. The hope is that they'll save time and money another way, in letting us kill projects earlier, with some hope of being right. Anything that spares us an unnecessary Phase II, or especially an unnecessary Phase III, is a good thing. But the eventual drug is going to have to jump through all the hoops, same as before.

Comments (9) + TrackBacks (0) | Category: Regulatory Affairs


1. 3D Biomatrix on May 1, 2012 7:14 AM writes...

3D Biomatrix is a company that is working on such tools that may fall under this category (3D cell cultures to predict how a drug will perform in vivo). We have received a lot of attention from pharma, and the common thought seems to be just as you mention - making better decisions earlier will save time and money by not testing drugs that will eventually fail in Phase II or III.

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2. smurf on May 1, 2012 10:36 AM writes...

Spam, spam, spam, spam, spam, spam! In 3D!

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3. Howie on May 1, 2012 12:18 PM writes...

To my mind, Dr. Lamattina's explanation of late stage clinical failures and Janet Woodcock's are not so different. If you don't show superiority over existing therapy, how is that different from efficacy at some level? As for side effects, if efficacy were greater, lower doses would mitigate problems, unless these issues were mechanism based, which would be caught earlier in clinical study. I don't think her assessment is "off base".

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4. Howie on May 1, 2012 12:25 PM writes...

BTW, does anyone have a working link to Janet Woodcock's slides?

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5. PatH on May 1, 2012 12:37 PM writes...

Here are her slides -

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6. PatH on May 1, 2012 12:55 PM writes...

Should have added this link as well - this has the Q&A that went with the talk.

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7. Howie on May 1, 2012 2:21 PM writes...

@PatH-many thanks!

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8. Howie on May 1, 2012 4:56 PM writes...

Either I misread the quote of Dr. Lamattina from Derek, or I miss the greater point of John's article and the evaluation of Ms Woodcock's presentation. This is taken from slide 25 of her talk:

Major causes of failure in Phase 3 clinical development
-Lack of effectiveness against placebo or active
-Unexpected drug toxicity
-Commercial non-viability (not better than existing therapy)

Sounds like she was right on for this point.

The greater issue (and I also miss what Derek means by "have it both ways", is the proposal that greater academic involvement in pharmaceutical development is needed to lower costs and increase success rates. I am not sure how Ms Woodcock reaches these conclusions, especially regarding lowered costs. There are many unsupported statements about perceived benefit from proposed utilization of academic capability and a more central role of academics centers as clinical trial hubs. Anyone else hearing these arguments and have a better understanding?

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9. simpl on May 2, 2012 7:15 AM writes...

Clinical trials patients and the general patient public have very different expectations, and the first ones are currently getting the rough deal. Two decades ago, there was a discussion of developing breakthrough drugss outside USA, which got quashed as "lowering of standards" - in fact, their risk expectations differ, and the topic needs revisiting.
Worst case would not be that academia takes over, but that snake oil goes industrial: designer drug makers allying with sport doping doctors to offer a cruiseship service that no serious groups are willing to set up.

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