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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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« Merck Finally Settles Over Vytorin | Main | The Finest Blue in the Lab »

February 15, 2013

ABT-199 Clinical Trial Suspended

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Posted by Derek

Abbott - whoops, pardon me, I mean AbbVie, damn that name - has been developing ABT-199, a selective Bcl-2-targeted oncology compound for CLL. Unlike some earlier shots in this area (ABT-263, navitoclax), it appeared to spare platelet function, and was considered a promising drug candidate in the mid-stage clinical pipeline.

Not any more, perhaps. Clinical work has been suspended after a patient death due to tumor lysis syndrome. This is a group of effects caused by sudden breakdown of the excess cells associated with leukemia. You get too much potassium, too much calcium, too much uric acid, all sorts of things at once, which lead to many nasty downstream events, among them irreversible kidney damage and death. So yes, this can be caused by a drug candidate working too well and too suddenly.

The problem is, as the Biotech Strategy Blog says in that link above, that this would be more understandable in some sort of acute leukemia, as opposed to CLL, which is the form that ABT-199 is being tested against. So there's going to be some difficulty figuring out how to proceed. My guess is that they'll be able to restart testing, but that they'll be creeping up on the dosages, with a lot of blood monitoring along the way, until they get a better handle on this problem - if a better handle is available, that is. ABT-199 looks too promising to abandon, and after all, we're talking about a fatal disease. But this is going to slow things down, for sure.

Comments (5) + TrackBacks (0) | Category: Cancer | Clinical Trials | Toxicology


1. nitrosonium on February 15, 2013 10:57 AM writes...

i thought aromatic nitro groups were a big No No in drug design??

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2. Anonymous on February 15, 2013 12:05 PM writes...

#1 Generally so. But the odd exception makes it through, e.g. nitrazepam.

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3. anon on February 15, 2013 12:55 PM writes...

It's a shame because if the drug is kicking but that's exactly what you would expect to happen. Namely all of the tumor cells are wiped out. So the molecule is really active and worth pursuing.

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4. ScientistSailor on February 15, 2013 1:17 PM writes...

A similar thing happened with Avastin in early trials, they got around that, they'll get around this, limit tumor size or something like that...

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5. Anonymous on February 15, 2013 2:20 PM writes...

So was this first announced through a blog? Am I reading that correctly? If so - what does that say about the power of blogging and the future of 'confidential' clinical disclosure?

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