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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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April 13, 2009

An HIV Drug. Or A Gout Drug? Or Both. . .

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Posted by Derek

We get a lot of surprises in this business, most of them not so good. That's understandable, since there are lot more ways for drugs and their mechanisms to go wrong than there are for them to go right. But once in a while, you do see something that's unexpectedly good news.

That may be what's happened to a small San Diego outfit, Ardea. As Xconomy details, the company (formed out of the remnants of IntraBiotics and Valeant) was testing an HIV compound in the clinic when they noticed significant declines in blood levels of uric acid.

That rang a bell: something that decreases uric acid levels would be useful for gout, and there's only been one new gout drug approved in the last 40 years. Follow-up work showed that the effect seemed to be coming from a metabolite of the original drug, and thanks to the HIV trial data, they already had good hopes for that compound's safety. The new compound, RDEA594, has made it through Phase I and is headed for Phase II, and the trials look to be manageable affairs that the company can afford to run. The market is there: more people have gout in the US than are HIV-positive (although the two diseases clearly aren't comparable in other respects!). But the state of HIV research now means, weirdly, that the serious medical needs in that population are actually being met more completely than those in many other disease areas. (Ardea's HIV compound is progressing as well).

So good luck to them, on both fronts. It's a reminder to always look through all your data, and to be alert for whatever opportunities might be hiding in there. We don't get as many as we'd like, so we can't let any of them slip away.

Comments (13) + TrackBacks (0) | Category: Drug Development | Infectious Diseases


1. MedChemMan on April 13, 2009 9:33 AM writes...

This is a perfect example for serentipidious discovery in the area of drug discovery. In my company, a byproduct (1%) obtained in the final step of synthesis of a promising lead compound, could make all the way to phase III. While the lead compound was plagued with PK issues, the byproduct had excellent PK profile.
Returning to gout, allopurinol is the mainstay therapy for over three decades. Allopurinol, which is a xanthine oxidase inhibitor, has poor to moderate efficacy with side effects. Recently, febuxostat, another xanthine oxidase inhibitor, was approved in the Europe.
It will be interesting to see whether the Ardea's compound will become a first-in-class drug with novel mechanism of action or is just another xanthine oxidase inhibitor.

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2. Rev. Howard Furst on April 13, 2009 9:59 AM writes...

Ardea's drug inhibits uric acid reuptake from the renal tubules by blocking URAT1, the primary uric acid transporter. Good mechanism, as long as the urine doesn't become too acidic, which could promote uric acid precipitation. It seems to be more specific and effective than the promiscuous drug transport inhibitor probenecid, the only other uricosuic agent still on the market (apart from some drugs such sulfinpyrazone which have other primary effects that limit their use in gout).

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3. RB Woodweird on April 13, 2009 10:00 AM writes...

Off topic yet topical:

Too bad. I heard that Derek was being considered for the part of the cranky iconoclastic blogger.

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4. Sili on April 13, 2009 2:01 PM writes...

Glad to hear that there's still commercial research in HIV. The alarmists like to claim that none is being done because it isn't profitable.

Does this mean that I can now eat red meat and butter and drink red wine with a good conscience?

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5. smurf on April 13, 2009 2:09 PM writes...

Sili, yes, go for it! And add some Lipitor, soon to be generic, et voila, you'll be all sorted!

Life is beautiful!

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6. milkshake on April 13, 2009 2:14 PM writes...

in South Africa efavirenz became a huge problem as a highly addictive street drug - when the crushed tablets are smoked it provides a powerful high and long-lasting dreamy, anxiety-free state. HIV addicts make living by re-selling their prescription to teenagers

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7. CMC Guy on April 13, 2009 4:23 PM writes...

Although Metabolism can be somewhat unpredictable in reality don't most people "design away" from groups that too easily metabolize? In general I thought most people viewed in negative sense because altered/less controlled activity and/or PK/ADME profiles. There are indeed cases to the contrary where metabolite is the true active but my impression is that if ones sees significant metabolic activity it may be a barrier to selection/development at some places. This case may be indeed serendipitous in several aspects as had willingness to pursue despite potential issue and ran the clinical trail with a bioassay/marker, with appropriate observations/interpretations, that lead to new compound/target. Pretty interesting regardless.

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8. Jose on April 13, 2009 4:47 PM writes...

Milkshake- I saw the story on that too. I have to say I am skeptical- it sounds eerily like the "crack epidemic" of the 1980's in the US.

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9. gout treatment on May 14, 2010 12:39 AM writes...

Gout is not a particularly glamorous illness. It does not get a lot of exposure like cancer so it also does not get a lot of research into finding a cure. So if you suffer from gout you probably do not get the attention you need.

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10. Nurse Owen on June 21, 2012 12:16 AM writes...

Healthy life style is always the solution for gouty arthritis. Treatment of gout requires more than medication, DISCIPLINE is the best cure. If you know you have gout, quit everything that can trigger it. Watch your diet and maintain healthy lifestyle.

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11. Weiland on February 25, 2013 9:52 AM writes...

You can definitely see your enthusiasm within the paintings you write. The sector hopes for even more passionate writers like you who aren't afraid to say how they believe. All the time follow your heart.

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13. Drew on April 5, 2015 5:01 PM writes...

As a gout sufferer I find this to be great news. I am alergic to allupurinal and take both probenecid and febuxostat. Prior to approval of febuxostat I took only probenecid and suffered attacks even with a restricted diet. Having another medication alternative could be huge for someone like me.

To nurse owen: not all gout is lifestyle caused, mine and most have a strong genetic basic, I cannot just adjust my diet and be okay. You really need to update your understanding of the disease.

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