
For the first time in 15 years, a new Alzheimer’s drug looks promising - daegloe
https://qz.com/1336195/biogen-and-esais-new-alzheimers-drug-ban2401-shows-promising-results-in-a-phase-ii-trial/
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kurthr
"Most worryingly, it turns out that there was a clear difference between the
placebo group and the treatment group in APOE4 status."

I would turn to Derek Lowe as he is an expert in the field who has been
looking forward to this release... he holds out hope, but is not positive on
"the field is in the state it’s in today."

[http://blogs.sciencemag.org/pipeline/archives/2018/07/26/bio...](http://blogs.sciencemag.org/pipeline/archives/2018/07/26/biogen-
and-eisai-let-the-alzheimers-arguing-commence)

"APOE4, a lipoprotein, has been recognized as a risk factor for Alzheimer’s
since back in the 1990s, although the mechanism behind that has been the
subject of debate. But there was a regulatory-mandated change in enrollment of
APOE4 patients during the (Bayesian) trial, for fear of a brain-swelling side
effect that these patients are also prone to, and there ended up being far
more APOE4-positive patients in the placebo group compared to the high-dose
group (70% versus 30%)."

~~~
aaavl2821
Should also note that the study missed its primary endpoint, but the companies
decided to wait for the 18 month analysis anyway, and one dose seemed
promising at this 18 month timepiint. Other doses did worse than placebo

Other analysts who have been looking forward to the data and have digested it
in detail have similar takes, others more positive:

[https://www.fiercebiotech.com/biotech/biogen-and-eisai-s-
ant...](https://www.fiercebiotech.com/biotech/biogen-and-eisai-s-anti-amyloid-
med-slows-alzheimer-s-decline-phase-2)

APOE4 status was an issue. Also the fact that two doses did worse than placebo
was odd. And one of the measures of cognitive decline was a metric developed
by the company, which could be concerning or could be valid, idk

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nonbel
>"Although the results are promising, this trial was fairly small, and as Vox
points out, it’s frowned upon in the research community to change your end
results midway through a trial. At the moment, the FDA requires new drugs
targeting Alzheimer’s to go through two phase III trials, showing a reduction
of both a biological marker for the disease and cognitive decline. In March of
this year, the organization published a draft report that said in the future
they would accept only a reduction of biomarkers, without a reduction in
cognitive decline, a decision has been supported by the research community.
This is because in early cases of Alzheimer’s, patients may have the
biological indicators of the disease without actually showing symptoms."

I wouldn't consider this promising at all. It looks like it was "too hard" so
standards are being lowered.

~~~
amp108
> It looks like it was "too hard" so standards are being lowered.

Not at all. It turns out one of the standards was not relevant to the target
population. As you quoted: "This is because in early cases of Alzheimer’s,
patients may have the biological indicators of the disease without actually
showing symptoms."

There's no point in trying to alleviate symptoms where there are no symptoms.
If I develop a drug that removes tumors that _eventually_ caused headaches, is
it somehow lowering standards if it removes tumors _before_ a headache
appears?

~~~
nonbel
>"This is because in early cases of Alzheimer’s, patients may have the
biological indicators of the disease without actually showing symptoms."

This is called a "degenerating research programme". The theory always lags the
facts, this is just another ad hoc adjustment to keep it going for some
reason. Why? I really cant understand. Whats the last interesting prediction
that has come out of the amyloid hypothesis?

Here is an interesting prediction: Amyloid accumulation will be found to be
associated with every single disease state where it is investigated. Every
single one. This is because amyloid formation is very thermodynamically
favorable for polypeptide chains and a cell must be healthy to prevent it.

~~~
Angostura
That's interesting. I've got a kidney infection at the moment, are you
suggesting that I have amyloid plaques in my brain?

~~~
nonbel
Wikipedia has a bit on it:

>"Amyloidosis is a group of diseases in which abnormal protein, known as
amyloid fibrils, builds up in tissue. [...] The presentation of amyloidosis is
broad and depends on the site of amyloid accumulation. The kidney and heart
are the most common organs involved. [...] AA is suspected on clinical grounds
in individuals with longstanding infections or inflammatory diseases."
[https://en.wikipedia.org/wiki/Amyloidosis](https://en.wikipedia.org/wiki/Amyloidosis)

------
cryoshon
originally i was going to write this entire trial off as a pharma industry
snow job with heavily contrived data -- and it still might be -- but i think
there's probably at least something worth talking about here.

the drug slows progression, allegedly by clearing amyloid plaques. in one
sense, that is not enough. alzheimer's still wins in the long run. in another
sense, it's a big improvement in the state of the science and clinical
practice. the stuff we were using to try to slow the progression of
alzheimer's before was largely ineffective. trials like this shed light on
fundamental research questions while hopefully helping patients at the same
time.

on the other hand, if the progression is slowed at the cost of a large drop in
patient quality of life, it may not be worth it clinically in the present
state. there's no indication that this is the case, but i wouldn't rule it out
until we have more data. there seem to be allergic reactions and potential
brain swelling as side effects of the therapy. personally, i would predict
that these effects are far more common than is being currently reported. that
doesn't mean the therapy is useless, just that it has consequences like any
other therapy does.

finally, the amyloid hypothesis has come under a lot of scrutiny recently. as
the article points out, removing most plaques does not lead to a cured
patient, merely an improvement -- but not an improvement which brings the
patient back to normal function. if this trial ends up falling through, it
might be the end of the amyloid hypothesis in clinical practice and drug
development. that would be a step forward towards a greater understanding...
but also very discouraging because we'd need to discard a lot of what we were
assuming was the canon up to this point.

------
carbocation
It's hard to evaluate this because there is nothing published yet. There have
been grumblings on twitter of imbalance in important genetically-driven
predictors of Alzheimer's[1]. This might make it very hard to understand
whether the effect is due to this imbalance, or truly due to the drug. I can't
really evaluate for myself since I don't see the data anywhere.

1 =
[https://twitter.com/sciencescanner/status/102246964947947520...](https://twitter.com/sciencescanner/status/1022469649479475200)

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kup0
Disclaimer: I am a lay person that does not know a lot about this subject, but
have read a few things on it and have people in my family this could
potentially affect.

I think the Herpes research is much more promising than trying to fight
Alzheimer's by removing plaques. Catching it earlier in the process seems
potentially better?

Especially since the plaques are thought to be a protective immune response to
invaders, like viruses, because the plaques encapsulate them to prevent them
from affecting the brain.

Plaques may still potentially be a cause of issues- but is enough known that
reducing their quantity will significantly help without destroying the
beneficial nature of the immune response that causes the plaques? and do we
know for sure that the plaques themselves _cause_ the decline, or are they
just a by-product that seemed like a potential candidate that got latched
onto?

~~~
erentz
Herpes viruses are implicated in so many illnesses, cancer, auto immune
diseases, now Alzheimers, we need a lot more effort going into producing
HHV6/7 and EBV vaccines. (Probably HSV1/2 also but I don't know enough about
those two.)

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jrjarrett
Just a few links above this article was this:

[https://www.nature.com/articles/d41586-018-05719-4](https://www.nature.com/articles/d41586-018-05719-4)

Which seems, like many studies ("Coffee is great! Coffee gives you cancer!"),
to show contradictory information.

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OldSchoolJohnny
It's not a cure, it only slows the progression and has no positive effect at
all on the mental symptoms.

~~~
rpedela
Wouldn't performing better on two different cognitive tests over placebo be a
positive effect on symptoms?

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cschmidt
Just yesterday there was this opinion piece in Nature, suggesting that
reducing amyloids might not help.

The amyloid hypothesis on trial
[https://www.nature.com/articles/d41586-018-05719-4](https://www.nature.com/articles/d41586-018-05719-4)

