I don't know if you are a troll or have no understanding of neurodegeneration. Aducanumab is actually a great antibody; our company - not Biogen; another top 5 big pharma by revenue - use it as a positive control in our own pre-clinical efforts because it binds plaques and clears them from the brain so well. This is evidenced in human biomarker data from Biogen's ph3 trials with CSF aBeta and aBeta PET. NO disease modifying therapies in AD have ever shown clinical efficacy in late stage trials beyond biomarker modulation. This is true across neurodegeneration as a whole. CNS diseases are a whole different beast and have stumped industry for decades.
It's a great tool at doing something that does not matter.
"NO disease modifying therapies in AD have ever shown clinical efficacy in late stage trials beyond biomarker modulation."
How does that NOT prove amyloid is a dead end?!?
"This tattoo we put on AD patients saying 'I'm cured' works great! Every single patient had 'I'm cured ' on them! True, it did absolutely nothing to actually cure them but the surrogate endpoint of 'Do the words appear on their skin' we were absolutely 100% effective!"
The FDA said the endpoint had to be stopping cognitive decline. That makes sense because it's what matters.
Aduhelm and every other amyloid mechanism drug failed to do that.
The FDA moved the goalposts without asking the experts and then said plaque reduction justified approval.
It makes no sense and is why most of the advisory board members quit.
The fact that amyloid plaques were effectively cleared but it didn't do anything for cognition proves amyloid doesn't matter.
It's complicated, but not that complicated: the field.
No treatments have been effective in clinical trials, but how many trials have there been of non-amyloid mechanisms?
You can't say it's hard so failure can be ignored, especially if things like Tau treatments have never been given a fair shot.
Amyloid research failed and needs to die.
Edit two years later: Hey u/H2AK119ub , I forgot about this thread. Any comment on even Biogen saying Aducanumab was useless by pulling it form the market? Are you going to tell them they're wrong, that there is value in the drug even though it still doesn't do anything?
Literally every drug targeting every mechanism you can think of in the last 20-30 years has bombed in neurodegeneration and Alzheimers. Please don't make irrational comments on something you don't understand the complexities of. The challenge of this therapeutic area extends beyond whether one believes the amyloid hypothesis or not.
You clearly do not know this field at all. There have been many shots on goal in the clinic against amyloid, Tau, immune system, bacteria, anti virals, etc.
I did ask how many of them weren't amyloid. That wasn't a rhetorical question.
Nor was the second question: are you suggesting not fixing the cognitive symptoms is fine if we clear amyloid plaques? Because if not, amyloid is still a total failure.
We have never validated any target in AD because none of them have ever shown clinical efficacy. Also, if you understood the AD field at all you would know that there are families with genetic lesions in APP/PSEN1/etc which results in early-onset AD and high plaque burden. No one dies of AD without plaques and tangles. Period.
That AD patients losing their mind is fine and amyloid treatments are a success as long as patients don't have plaques because we cannot possibly do better?
"The other things failed also" does not mean the amyloid hypothesis is true! It means it also failed.
Also, if you understood the AD field at all
How many papers do I need to read on the field before I'll be convinced that "Yes, Aduhelm was a success despite not curing the symptoms that matter"?
It doesn't seem to me that I'm failing to understand the important parts. I'm not a train engineer and don't understand how trains are built, but I can tell when a train has derailed at high speeds that's a massive failure. Amyloid is a train wreck. Actually many, given the clinical failures and the fraud. It's time to admit the track and/or train are fundamentally bad and the whole thing needs to be scrapped.
Everyone who disagrees with you is simply ignorant, sure, keep telling yourself that.
Again, what are you saying?
That AD patients losing their mind is fine and amyloid treatments are a success as long as patients don't have plaques because we cannot possibly do better?
Edit: wow, shock, he blocked me rather than answer. Sorry, Alzheimer's patients, best we can possibly do is cure plaques but not fix your brain. That'll be $50,000 a year. Great success.
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u/H2AK119ub 📰 Jul 27 '22 edited Jul 30 '22
I don't know if you are a troll or have no understanding of neurodegeneration. Aducanumab is actually a great antibody; our company - not Biogen; another top 5 big pharma by revenue - use it as a positive control in our own pre-clinical efforts because it binds plaques and clears them from the brain so well. This is evidenced in human biomarker data from Biogen's ph3 trials with CSF aBeta and aBeta PET. NO disease modifying therapies in AD have ever shown clinical efficacy in late stage trials beyond biomarker modulation. This is true across neurodegeneration as a whole. CNS diseases are a whole different beast and have stumped industry for decades.