Alzheimer Drug Fails Trial

 

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For a drug expected to top $7B in annual sales, even a partial success looks like a failure to me.  I’ve talked about the efficacy in modulating APP for the treatment of Alzheimer’s a few times and Derek Lowe @ has some great articles, so if you’re not familiar, I‘d check them out to catch up. 

On to the news.  I’m going to try and summarize the press release from Elan and Wyeth without all the spin. Bapineuzumab failed to reach significance on the primary endpoint in a phase 2 trial. 

Simple, right? Maybe not.  The trial did show efficacy, though magnitude wasn’t released, in a small subgroup of patients (in non-carriers of the ApoE4 allele, estimated to be ~40% of Alzheimer’s patients).

So, right off the bat, this should cut analyst expectations by 60% right?

Interestingly, in trying to explain away not hitting the primary endpoint for the general population, the release mentions that the study wasn’t powered to detect changes in ADAS-cog.

Fantastic.  Let me just break down this flow and see if we can make more sense of it.

1.) Run a trial that is not powered to detect primary endpoint changes.

2.) Fail primary, ADAS-cog endpoint.

3.) Release that you succeeded in a subgroup of patients on many endpoints (that you admittedly aren’t powered to detect)

4.) Conclude with statements like, “bapineuzumab appeared to have clinical activity in treating Alzheimer’s disease“, and “…the Phase 2 study are a continued validation of the amyloid approach to Alzheimer’s disease”.

Fundamentally, I’m happy that there are companies with deep-pockets attempting to treat debilitating diseases in novel ways but doing things over and over, expecting different results is foolish.

Comments

[Oliver:]

If you read the study results closely, the improvements noted did not mean the patients improved at all, but that they declined less rapidly than the control patients. If BAP can remove the "plaque", it needs to be done very early in the disease so as not to cause "Brain Swelling"...so, BAP may be helpful in the very early stages to prevent AD, or stop it early. But, I think what we're seeing is that if too much plaque is removed, it becomes very dangerous and risky.
What about Perispinal Etanercept? Why wasn't this studied since the results of the Phase I clinical trial showed actual improvements in Cognitive Ability and has maintained the progression of the disease in some patients for over 3 years? Somebody needs to get on this!

2008 Jun 18 01:36 AM

[obesejockey:]

You must be a glass half empty kind of guy, but Alzheimer's is a disease where the disease modifying drug glass is completely empty. The top line results indicate that perhaps half the patients can be helped with statistical significance. The placebo was Aricept. Why not wait for the full study results to be presented at ICAD on July 29 (warts and all) before drawing conclusions about the APOE carrier subgroup? One reason the phase 2 study is under powered is that the study tested several dose levels with the intent to determine the best dose level. The ongoing phase 3 study reflects what was learned in phase 2.

2008 Jun 18 06:42 AM

[A neurologist:]

Eben,
What medical/scientific qualifications do you possess that allow you to reach such outrageously false and biased statements? Yesterdays news from Elan was a HUGE step forward for Alzheimer treatment. I am convinced that the FDA will now be forced to make the PIII open label for the Non-ApoE4 carriers. In the end, your poorly informed commentary will emerge as the only thing foolish associated with these results.

2008 Jun 18 10:16 AM

[elan goddess:]

With "quality" analysis such as yours please note that they are still enrolling patients for Phase III.

Nice pic....you may want to rethink that. You look like the Village Idiot.
Your picture matches your journalistic skills.

2008 Jun 18 10:19 AM

[BirdInYourEar:]

Do you realize how many people ~40% of the entire Alzheimer's population is? I'm baffled by how a person with your educational background fails to see the importance and benefits of this drug. If you were able to talk to the families of patients who were success stories in phase II (thousands and thousands, as you are well aware, this is not an inflated number), I'm sure you would reconsider your opinion.

2008 Jun 18 11:18 AM

[BirdInYourEar:]

I wish I could edit my previous comment.
I can't believe I took this guy seriously after reading his article. Take a look at this blog. Put bluntly, this guy is a typical raving internet hack who appears to be trapped in the "blogosphere".
I wish you luck in your future pursuits.

2008 Jun 18 11:23 AM

[Skeeter1128:]

This is the only article I can find that even hints at the word "failure" regarding this trial. The results seem very positive to me. The stock is up and indications are a short squeeze is on the way. I wonder, is he short the stock?

2008 Jun 18 01:38 PM

[Eben Tessari:]

I think it's interesting that you all feel personal attacks are somehow a counter point.

If, when the results are published in July and after the first phase III data is in, I am wrong, I'll be the first to admit it (I doubt you'll be offering me the same consideration and dropping me emails if I'm right).

Until then, my opinion remains that no program targeting amyloid-beta or the pathway has shown efficacy on the primary (read: approvable) endpoint of ADAS-cog.

I hope I'm wrong. I hope targeting the amyloid-beta pathway leads to truly disease modifying therapy but believing doesn't make it true.

2008 Jun 19 07:35 AM

[Douglas Cress:]

Personal attacks are the status quo on S.A.

2008 Jun 19 09:58 AM