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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November 4, 2002

Pneumonia, of All Things

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Posted by Derek

There seems to be something odd going on with Iressa, AstraZeneca's great oncology hope. In Japan (the only place where it's on the market,) there's been an unusually high incidence of interstitial pneumonia among its patients. The FDA has scheduled a December meeting, almost certainly to talk about this situation and how it affects the US approval process.

It's not obvious, on the face of it, how a kinase inhibitor would lead to increased risk of pneumonia (and increased severity once you get it, apparently.) My first thought was that this had to be some non-mechanism based tox effect, something to do with the compound but not its mode of action. But on further thinking (and further speculating with colleagues down the hall,) I'm not so sure. Since Iressa is involved in inhibiting the signaling of epidermal growth factor, it's conceivable that it could alter the surface characteristics of pulmonary tissue. Perhaps a tissue change makes the bacteria adhere better, or hinders the immune response?

This is, as I mentioned, sheer speculation. I hope it's wrong. But if it's on the right track, then that's further bad news for what (a few months ago) looked like a potentially huge drug. And it would also be a major concern to all the other drug companies involved in epidermal growth factor receptor signaling (and there are plenty.) You can bet that everyone generating clinical data in the area is frantically digging through their records, looking for pneumonia.

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