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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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October 26, 2006

It Should Work. It Just Doesn't.

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Posted by Derek

The late-stage clinical failure of a small company/big company drug partnership story gets told over and over, and today it was the turn of Renovis and AstraZeneca. Renovis had come up with a candidate (NXY-059) for post-stroke therapy that targeted free-radical oxidative damage. Initial clinical trials were fairly positive, but this latest one, a larger and more rigorous effort, totally failed to demonstrate any benefits for the drug.

They've got plenty of company. I've lost count of the number of neuroprotective drug candidate failures I've heard about during my time in industry. It's humbling, like much of drug discovery is when you look at it closely. I mean, if you get your information from the newspapers or (God help you) television news segments, you'd think that we know just how tissues are damaged after an event like a stroke, which means we know just how to block the process, so all it takes it just sending in some drug to keep it from happening. The folks in the lab coats should be whipping one right out any day now.

Nope. Hasn't worked out. Excitatory glutamate toxicity for example, was all the rage about ten years ago, but a number of Phase II and III wipeouts showed that even if these drugs could work (a big if), they would have to be given very, very quickly, which isn't clinically realistic. Since that run of failures, a new set of standards were developed to try to improve the quality of clinical candidates and trials in the field. The Renovis drug is one of the first to come in under those criteria, but little good did they do in this case. Neuroprotection is hard.

Comments (6) + TrackBacks (0) | Category: Cardiovascular Disease | Clinical Trials | The Central Nervous System


1. Alastair on October 27, 2006 1:59 AM writes...

Did anything come of any Maxi-K programmes for stroke?

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2. Alastair on October 27, 2006 2:02 AM writes...

Did anything come of any Maxi-K programmes for stroke?

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3. Morten on October 27, 2006 4:43 AM writes...

Some guy named Walker did a Phase II of Progesterone as a neuroprotective - not for stroke but for trauma. They focused on safety rather than efficacy so it was 4:1 but it still looks encouraging. I'm looking forward to see the results of phase III...

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4. Dave H on October 27, 2006 8:38 AM writes...

Shouldn't work, but it does:

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5. JC on October 27, 2006 3:59 PM writes...

That compound was first developed by a defunct company name of Centaur, in Sunnyvale, CA. That was my first job out of school (1995) Although I was geared towards synthesis they assigned me to the process group (2 guys) for awhile. And this was the stuff I was making. We had to make our own t-butyl hydroxyl amine by the 300g load! anyway we made around 28 kilos. I actually made the d-9 t-butyl hydroxyl amine (10 g of the nitro starting material to make the hydroxyl amine was $5,000) and made the nxy-059 d-9, for metabolism purposes or something.

AAnyway I left that crappy place after 18 months and subsequently they went bust, but they spun the IP (this compound) into this Renovis business.

So now it finally failed. They were dosing like 8 g (its the 3,5 bis sulfonic acid sodium salt on the phenyl ring). Frankly I am not surprised.

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6. Luke on October 28, 2006 7:29 AM writes...

The Renovis failure hit close to home at my work too. One of our now unemployed Associate Directors chose to come to work for us rather then Renovis. I suspect he made the better choice as for places to work, as while I know nothing about the people or future outlook (ok I know it is bleak for the moment, but...) there, at least here he is in Biotech City (figuratively) and knows he needs to look for a job. More succinctly put, he knows his fate, rather than dealing with further uncertainty.

Oh and Derek, thank you for the condolences. I have high hopes! It is a Bright New Day!

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