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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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March 4, 2010

Dimebon, Grasping at Straws

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Posted by Derek

Robert Langreth, an editor at Forbes, points to a possible way that Dimebon could get approval for Alzheimer's: for its behavioral effects, not anything to do with amyloid or memory.

I'm not buying it, I have to say. Even Langreth's source admits that behavioral numbers didn't reach statistical significance. I don't see how this will be enough to rescue this one, even if one of the ongoing trials does use a behavioral score as an endpoint.

Update: Langreth has an earlier piece on how Dimebon appears to have been overhyped from the beginning, a viewpoint I concur with. The same thing happens with any drug for Alzheimer's, and is a constant problem in cancer and obesity, too.

Comments (16) + TrackBacks (0) | Category: Alzheimer's Disease | Clinical Trials | The Central Nervous System


COMMENTS

1. RandDChemist on March 4, 2010 4:00 PM writes...

While this suggestion comes from a financial journalist, the attitude at saving a project/compound/drug no matter what is one of the major reasons pharma has its struggles. I've seen it several times.

Sometimes the project just needs to be ended. It takes courage to do so, and its all too lacking sometimes.

Desperation is not a pretty thing.

Permalink to Comment

2. anchor on March 4, 2010 4:33 PM writes...

Robert Langreth....Hm..stretching the truth. He must be owning lot of Pfizer stock. Good luck, anyway.

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3. retread on March 4, 2010 5:31 PM writes...

"overhyped from the beginning, a viewpoint I concur with. The same thing happens with any drug for Alzheimer's". Why? Just look at "Rember for Alzheimer's" or the posts on XMRV. People and families with these things are desperate. Any glimmer of hope, no matter how farfetched is news they want to read about. People in gated communities aren't the ones buying lottery tickets

Permalink to Comment

4. metaphysician on March 4, 2010 5:56 PM writes...

#3-

All the more reason to carefully control how much one hypes a new maybe-breakthrough. You don't do desperate people any good by providing them with false hope. Especially since there are always people out there ready and willing to exploit the desperate.

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5. Anonymous on March 5, 2010 6:14 AM writes...

I have a simple question - how solid is the concept of double-blinded studies ? If you administer the biologically active compound with documented side- effects and it should become very soon clear to the patient and also doctor if it was the real ingredient or placebo. Should not the body tell (may be subconsionesly) if was drugged with a powerfull substance or given a sugar pill ??
Must be escpecially relevant for phase II CNS trials I guess.

I am biochemist and have no first hand experience in clinical trials planning, thats why the question.

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6. MTK on March 5, 2010 9:00 AM writes...

#5:

And the alternative would be?

More often, especially for CNS, the problem is actually the opposite of what you describe, a large placebo effect.

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7. TFox on March 5, 2010 12:13 PM writes...

@5: If an individual patient can be certain, due to intended or side effects, that they received drug and not placebo, well, the trial is already a success, as it has demonstrated a difference vs placebo. However, in practice it's not so easy to be certain, as the placebo group often reports a wide variety of side effects. It doesn't really matter what the patient believes during the trial, what matters is how big is the difference between the two groups when the data is unblinded.

More of a problem is when patients, perhaps working with their doctor, attempt to game the trial. Eg, you enter a trial, hoping to thereby receive an experimental drug for your fatal otherwise untreatable illness. After awhile, you don't see the expected side effects, so you figure you're getting placebo. You then drop out, so you can join a different trial, and have another shot at life. I've read about things like this happening in the old AIDS drug trials. It kind of points out a central ethical problem in placebo controlled trials -- no one wants to be the sacrificial cow, the dying nonresponders whose only role is to make the efficacy of the drug clear. We pretend that people join clinical trials unselfishly, purely to advance science on behalf of future patients, but in practice everyone is there because they believe the experimental treatment might help them. No one would choose to be a control on purpose. Still, there's not really any other way to do it.

Permalink to Comment

8. NJBiologist on March 5, 2010 12:45 PM writes...

@6: The alternative would be a nocebo. I don't think this is standard practice, but I've seen a trial or two where the control arm got diphenhydramine--you can imagine the effect on the accuracy of the patients' medication guesses.

Permalink to Comment

9. Anonymous on March 5, 2010 12:47 PM writes...

#6, #7 Thanks !

I thought unethical scenario -denying treatment to a placebo group - is not possible with life threating desease. You can not deny the standard of care, like best chemotherapy available?

Permalink to Comment

10. ex-Pfizerite on March 5, 2010 12:47 PM writes...

I been on projects were the placebo group had more and worst side effects that the actives did. The mind is truly an amazing thing

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11. MTK on March 5, 2010 1:29 PM writes...

#9.

Correct.

The Helsinki Accords of 1964 specifically prohibit those kinds of clinical trials.

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12. Anonymous on March 7, 2010 11:13 PM writes...

The trial was only 6 months long.
Many may have only dosed breakfast, lunch and dinner leaving the brain less protected during the early morning hours.
There is no headache pain to show poor dosing habits.
They should look at longer term data and see if there where individuals that showed a significant lower rate of decline.
This was an over the counter decongestant drug during the 80's in Russia.
It is safe, there is no good reason to give up on it too soon.
I hope they approve it for any reason, even as a less effective decongestant.
My Mom seems to be about the same as she was a year ago when she got on the Dimebon trial. Before I noticed her going downhill about every 3 months.
I'd also suggest they up the dose 30%.
I may be one of the few that actually try and dose her every 8 hours.

Permalink to Comment

13. So Cal on March 7, 2010 11:13 PM writes...

The trial was only 6 months long.
Many may have only dosed breakfast, lunch and dinner leaving the brain less protected during the early morning hours.
There is no headache pain to show poor dosing habits.
They should look at longer term data and see if there where individuals that showed a significant lower rate of decline.
This was an over the counter decongestant drug during the 80's in Russia.
It is safe, there is no good reason to give up on it too soon.
I hope they approve it for any reason, even as a less effective decongestant.
My Mom seems to be about the same as she was a year ago when she got on the Dimebon trial. Before I noticed her going downhill about every 3 months.
I'd also suggest they up the dose 30%.
I may be one of the few that actually try and dose her every 8 hours.

Permalink to Comment

14. dave on March 9, 2010 8:05 AM writes...

Approval will ultimately depend on the theater presented by the sponsor at the FDA's public advisory meeting prior to the decision of approve or not.

I worked for the FDA a few years and that meeting is an amazing part of the approval process.

Permalink to Comment

15. Evorich on March 9, 2010 8:13 AM writes...

Why can we not get away from this concept of there being a single drug to treat Alheimer's? The disease is too complex; it's going to work. Trials need to be done with mutliple classes of drugs in tandem -ie. a BACE inhib, pde10a inhib., anti-histamine, plaque blocker, ache blocker, anti-inflammatory, etc.

Permalink to Comment

16. amir on March 12, 2010 8:40 AM writes...

This sounds interesting, like many other drugs.
Remember the hype about Methylene blue and the cure potential.
Until we can figure out the causing agent or exact mechanism, a cure is a distant thing, unless by chance a shot in the dark causes a cure, like the advent of penicilline in the 30s.
It is good to keep working with an open mind

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