New results with BAN2401 - more doubts

[broiler_x]

https://www.statnews.com/2018/10/25/bio ... l-numbers/

Biogen and Eisai tried to tout the latest results from their clinical trials with BAN2401 (an anti-amyloid antibody) but the skeptics, and the stock market, were not impressed. The big issue is that in the high dose group their were only 10 ApoE4 carriers versus 113 carriers in the control placebo group. They had to do this because of claimed side effects in ApoE4 carriers with the high dose. This has been the problem with the trial. New data was released yesterday and they tried to argue a positive spin, but no one is buying it. Interestingly however, they do state that the ApoE4 carriers appeared to do better with the drug than non-ApoE4 individuals

"Digging into the data from the high-dose group, Eisai said patients with APOE4 actually did better on BAN2401 than those without, compared to placebo."

So maybe a glimmer of hope? The big problem is that this is based on only 10 ApoE4 carriers, so this is too small a sample size.

Here are a couple of more articles discussing the new results:

https://www.fiercebiotech.com/biotech/b ... t-skeptics

http://blogs.sciencemag.org/pipeline/ar ... ortunately

[Julie G]

Saw that. And, remember- EXERCISE has already been proven to be 2-3 times more effective than Biogen on a good day. Just sayin' .

[mike]

Saw that. And, remember- EXERCISE has already been proven to be 2-3 times more effective than Biogen on a good day. Just sayin' .

But pills are SO much easier...!

[broiler_x]

Saw that. And, remember- EXERCISE has already been proven to be 2-3 times more effective than Biogen on a good day. Just sayin' .

Totally agree! I think exercise has been proven to be good for everything. Keep moving!

[CarrieS]

I just found out that my cousin’s husband is in the Eisai trial. He’s got early onset and enough amyloid plaques to quality. My cousin doesn’t know his APO but said they told him he was missing proteins in his brain. What does that mean?

[NF52]

I just found out that my cousin’s husband is in the Eisai trial. He’s got early onset and enough amyloid plaques to quality. My cousin doesn’t know his APO but said they told him he was missing proteins in his brain. What does that mean?

Hi CarrieS,

I'm sorry to hear that your husband's cousin has an early onset diagnosis (or possibly "young onset"?) Some doctors are distinguishing between the highly family-linked genetic forms of EOAD, which often hit in the 40's and 50's, with "young onset" AD, which sometimes happens in the 50's but is more like the "over 65" type of AD.

I think what he heard as "missing proteins" in his brain was the term "mis-folded" proteins in the brain. I'm in the Generations trial which, like the Esai trial, targets the formation of amyloid beta plaques by preventing "mis-folded" amyloid proteins. it turns out that the amyloid precursor protein (APP) gets cut in pieces (or "cleaved") by an enzyme. If it happens correctly, all the pieces are the same length and non-toxic. If if doesn't some are shorter and can't "fold" correctly, and so clump up as amyloid beta and start causing problems in neurons. (I think of it as my hair clumping up if it doesn't have conditioner to help it stay smooth!)

BACE-1 inhibitors, in the Generations and ESAI trial "inhibit" production of the enzyme (beta-secretase APP cleaving enzyme-1) that cuts the APP, which stops the production of amyloid beta before it gets started! So amyloid production drops by about 85% (they don't need it to stop completely).

As a side note, the "tau tangles" in AD are also misfolded proteins that cause hyperphosphorylated tau, which clumps in long neurofibrillary tangles (again like hair!). Right now there are no drugs to stop tau formation, but it's a hot topic of research, with some scientists using genetically engineered human pluripotent stem cells from healthy ApoE 4 carriers in their 70's to test chemical compounds.

So my guess is that your husband's cousin had a PET scan that showed that pattern of mis-folded proteins that made him eligible for the study. The good news is that in spite of the disappointing news on some BACE-1 trials, it appears that problems may have been with the vectors (like shipping containers) that various drugs used to get BACE-1 drugs to the brain, and not with the research strategy itself. It's possible that this will still prove to be an important study and treatment option, and I applaud your husband's cousin for participating. And if his study team is anything like mine, they will welcome questions from him and his "study partner". So you can encourage them to say "Wait a minute: explain that term some more."

Hugs to your cousin-in-law from another guinea pig!

[CarrieS]

Hugs to your cousin-in-law from another guinea pig!

Thank you NF52 for the explanation. My cousin sent me the study information but it didn't give the great explanation that you did about the difference in the proteins. Yes, her husband had the PET Scan that confirmed the amyloid plaques.
Carrie

[NF52]

...My cousin sent me the study information but it didn't give the great explanation that you did about the difference in the proteins. Yes, her husband had the PET Scan that confirmed the amyloid plaques.
Carrie

One more thought, Carrie:
Is it possible that your cousin was told he has "early Alzheimer's" and not "early onset Alzheimer's"? Some researchers are using the term "early" Alzheimer's to signify a stage earlier than "mild" Alzheimer's, including positive amyloid on a PET scan and mild cognitive delays on testing (not just subjective cognitive impairment). One of the current Biogen/Eisai trials of is E2609, elenbecestat, a different BACE-1 than BAN2401. The criteria indicates it is for people with "mild cognitive impairment due to AD or mild AD" with an MMSE score of >/= 24 (and some other mild impairment scores). If that's what he is being screened for, it's called the MISSION: AD trial, and here is the clinical trials link to the description: https://clinicaltrials.gov/ct2/show/NCT ... =US&rank=1.

A diagnosis of "early AD" due to MCI is a far better diagnosis than "early onset AD". I wouldn't want your cousin to be Googling the wrong term and see scary stories about fast progression. People can be in the MCI stage for a long time--and as we know, show improvement!