halting Phase III trials of aducanumab

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Fiver
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halting Phase III trials of aducanumab

Postby Fiver » Thu Mar 21, 2019 10:01 am

One researcher's perspective, in case this hasn't been discussed already:

Well, there it is. Biogen and Eisai have announced just this morning that they’re halting Phase III trials of aducanumab, their anti-amyloid antibody, after the monitoring committee judged that further treatment would be futile......
<read more>

https://blogs.sciencemag.org/pipeline/a ... alzheimers
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Re: halting Phase III trials of aducanumab

Postby cflegal » Thu Mar 21, 2019 12:19 pm

I certainly want to hear more. Aducanumab removed amyloid below the level of PET scan detectability! At the same time, however, memory decline was only slowed and not reversed. We will never know what a "lifestyle" component to the study would have provided.

Theracurmin (curcumin) is the only other approach the I know of that has removed amyloid plaque (Dr. Gary Small, UCLA). This year we will probably get results from Sally Frautschy's trial at UCLA and the West LA VA Center with Longvida brand of a curcumin product.

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Re: halting Phase III trials of aducanumab

Postby tinamalone » Thu Mar 21, 2019 2:52 pm

Are most people taking a Longvida form of curcumin? What about Thorne's Meriva form?

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Re: halting Phase III trials of aducanumab

Postby cflegal » Thu Mar 21, 2019 4:50 pm

cflegal wrote:I certainly want to hear more. Aducanumab removed amyloid below the level of PET scan detectability! At the same time, however, memory decline was only slowed and not reversed. We will never know what a "lifestyle" component to the study would have provided.

Theracurmin (curcumin) is the only other approach the I know of that has removed amyloid plaque (Dr. Gary Small, UCLA). This year we will probably get results from Sally Frautschy's trial at UCLA and the West LA VA Center with Longvida brand of a curcumin product.

The Biogen statement includes: "The primary objective of the study was to evaluate the efficacy of monthly doses of aducanumab as compared with placebo in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. Secondary objectives were to assess the effect of monthly doses of aducanumab as compared to placebo on clinical progression as measured by Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale (ADAS-Cog 13), and AD Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL-MCI)."

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Re: halting Phase III trials of aducanumab

Postby floramaria » Thu Mar 21, 2019 7:20 pm

tinamalone wrote:Are most people taking a Longvida form of curcumin? What about Thorne's Meriva form?


Hi tinamalone,
What I have in my own cupboard right now is Thorne Meriva. Some people on the forums are using Theracurmin, others Longvida. I just did a quick look at some of the results of a Search for Longvida, and also Theracurmin. If you want to see all the posts related to various forms of curcumin, the Search function will get you there. You can access that either by clicking on the the three stacked dots to the right of your name or clicking on the magnifying glass.
To give you a taste of what you can find with that search, here are links that addresses various forms.

https://alzheimer.neurology.ucla.edu/Curcumin.html

viewtopic.php?f=4&t=5828&p=64167&hilit=meriva#p64167
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Re: halting Phase III trials of aducanumab

Postby cflegal » Mon Mar 25, 2019 12:05 pm

ALZFORUM has several technical comments on this report: https://www.alzforum.org/news/research- ... ment-31011

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SusanJ
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Re: halting Phase III trials of aducanumab

Postby SusanJ » Tue Oct 22, 2019 6:09 am

So, Biogen is asking the FDA to approve aducanumab, based on a new data analysis.

By June, as Biogen analyzed the full data set, researchers started to realize that a different picture was emerging of aducanumab, Sandrock said. The reason was because of changes that Biogen had made to the study late in the game. Initially, the company worried about a potential side effect — brain swelling — and limited the dosage of the drug. But later patients were allowed to receive higher doses of the medicine.

“In retrospect, the results of the futility analysis was incorrect,” Sandrock said. “That’s because it was from a smaller dataset that looked at patients with less exposure to high dose aducanumab.”

In essence, Sandrock said, the futility analysis had happened too soon. It had looked at data based on last December. But the trials were actually stopped in March. Biogen had run two studies. One, was positive in its own right for the high dose. A second still failed, but shows signs of benefit in those patients who received the higher dose of aducanumab.


https://www.statnews.com/2019/10/22/bio ... ducanumab/

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Re: halting Phase III trials of aducanumab

Postby Julie G » Tue Oct 22, 2019 8:10 am

Biogen said that the new data show aducanumab is “pharmacologically and clinically active” and that it reduced patients clinical decline based on the results of a survey called Clinical Dementia Rating-Sum of Boxes (CDR-SB), which was the study’s main goal.

I'd love to see the primary evidence and compare the before and after CDR-SB scores. Has anybody seen it?

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Re: halting Phase III trials of aducanumab

Postby ApropoE4 » Tue Oct 22, 2019 9:46 am

It reduces the rate of decline by about 25% in the high dose group

In EMERGE, which met its pre-specified primary endpoint in the new analysis, patients treated with high dose aducanumab showed a significant reduction of clinical decline from baseline in CDR-SB scores at 78 weeks (23% versus placebo, P=0.01). In EMERGE, patients treated with high dose aducanumab also showed a consistent reduction of clinical decline as measured by the pre-specified secondary endpoints: the Mini-Mental State Examination (MMSE; 15% versus placebo, P=0.06), the AD Assessment Scale-Cognitive Subscale 13 Items (ADAS-Cog 13; 27% versus placebo, P=0.01), and the AD Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version (ADCS-ADL-MCI; 40% versus placebo, P=0.001). Imaging of amyloid plaque deposition in EMERGE demonstrated that amyloid plaque burden was reduced with low and high dose aducanumab compared to placebo at 26 and 78 weeks (P<0.001). Additional biomarker data of tau levels in the cerebrospinal fluid supported these clinical findings. Biogen believes that data from patients in ENGAGE who achieved sufficient exposure to high dose aducanumab supported the findings of EMERGE.

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Re: halting Phase III trials of aducanumab

Postby NF52 » Tue Oct 22, 2019 10:31 am

SusanJ wrote:So, Biogen is asking the FDA to approve aducanumab, based on a new data analysis.
Susan,
Thanks for posting this highly encouraging news about two related studies, each with two-thirds (2/3) of the participants being APOE4 carriers!

Just as a quick re-cap:
Aducanumab...is a human IgG1κ monoclonal antibody...derived from...cells collected from healthy elderly subjects with no signs of cognitive impairment, and cognitively impaired elderly subjects with unusually slow cognitive decline...
In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ [amyloid beta] in a dose- and time-dependent manner
https://www.creativebiolabs.net/aducanumab-overview.htm [emphasis added]

Julie G wrote: I'd love to see the primary evidence and compare the before and after CDR-SB scores. Has anybody seen it?

Here we go: from the Biogen website: https://investors.biogen.com/static-files/5a31a1e3-4fbb-4165-921a-f0ccb1d64b65 Lots of data and explanations of decision-making. These statistics jumped out at me: 46% LESS DECLINE on a test of daily living skills for people with MCI taking the high dose, 23% less decline on the CDR.

They also note that it will be early 2020 before they file the application to the FDA.

Just ask the Washington Nationals about being counted out too early.
4/4 and still an optimist!


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