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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: derekb.lowe@gmail.com Twitter: Dereklowe

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October 28, 2005

Pargluva Goes Down?

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Posted by Derek

I missed last night's announcement from Bristol-Meyers Squibb until this morning. It looks like the situation with Pargluva (muraglitazar) is even worse than people had thought.

The FDA had granted "conditional approval" for the drug, but that doesn't mean all that much. The conditions for approval weren't made public, by either the agency or the companies involved - all we knew was that they wanted to address cardiovascular risk factors. Now BMS says that the ongoing trials won't be able to answer the FDA's concerns, and that new trials would be needed, which they say might take up to five years. That could scuttle the drug entirely.

I'm not sure what to make of this. It's entirely possible that BMS and Merck don't have anything currently powered to address cardiovascular risk in the way the the FDA would like. People complained that the Cleveland Clinic article in JAMA was based on incomplete data, but if there were good cardiovascular numbers on this drug, they would have been in that data set. But five years seems like a long time, even if the FDA is really lowering the boom on them and requiring long-term data in a large number of people. Even then, even factoring in recruitment and data workup, that's a whopper of a trial.

Still, I think the companies are clearly looking at more time and money than they probably want to spend, on a drug that frankly was a bit disappointing in its clinical data. Pargluva lowers blood glucose, but so do the existing PPAR-gamma agents. They already do about as much as can be done through that mechanism. And the additional PPAR-alpha activity does seem to help HDL cholesterol and other blood lipid parameters, but the cardiovascular risk that seems to be there more than offsets those numbers.

Merck and BMS run the risk of spending a very large amount of money just in order to definitively prove that their drug should not be sold. Even if they were able to make their case, it's unlikely that they'd be able to make a strong case in the market: "Pargluva! Not As Bad As You Thought!" And the market would have changed by the time they staggered on to approval, anyway. They may just give this one a pass.

It'll be interesting to see how this plays in the press. It'll be easy to fit this into a template of "FDA messes up, independent review by Cleveland Clinic saves the day again." But that's not quite true, I think. The FDA advisory committee didn't distinguish itself, and the Cleveland team was quick to pick up on that, but the agency itself requested the additional data before the JAMA article came out. I don't know what might have gone on behind the scenes, but on the face of it, this was one of the cases that proves (as the fine print says) that the FDA doesn't have to abide by the decisions of its advisory committees.

Comments (5) + TrackBacks (0) | Category: Diabetes and Obesity


COMMENTS

1. Petros on October 28, 2005 8:18 AM writes...

I'd missed that announcement too.

I guess BMS' reluctance comes in part form having unsuccesfully gone down this route before. About $100 million spent on a phase III trial to address the side effects of Vanlev.

Looks like Merck is further cursed too.


Whether this is good news for AZ, whose Galida, is the next most advanced agent in the class is hard to say.

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2. C W Donald on October 28, 2005 10:08 AM writes...

Remember Galida was delayed too .. I think this is good news for the existing PPAR gammas as well as the companies working on DPP IVs, which include Novartis and Merck.

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3. Dave Houze on October 28, 2005 12:51 PM writes...

FDA in CYA mode. P&G pharma's Intrinza:same 5 year safety study mandated. Get used to it, especially for me too drugs.

Permalink to Comment

4. Insider on October 28, 2005 1:39 PM writes...

I disagree with CW Donald. I think this is bad news (and possibly the death knell) for all PPARS.

They all have the same mode of action and, as far as I can see, very similar side effect profiles.

It could be like the glitazones, where the first one went down but others made it......but I dont think so. I think it will be more like oral positive inotropes in CHF.

The FDA have moved the bar up pretty high now.

Permalink to Comment

5. anonomyous on October 28, 2005 8:40 PM writes...

BMS and Merck decided not to co-market Pargulva today.

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