Celebration Thread! Biogen is going to the FDA with Aducan.

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J11
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Sovateltide!!
Big news from India!

Emerging treatment for stroke/AD.


The above post on the AUR for Lecanemab noted that perhaps Sovateltide could be a way around the problem with tPA in those treated with Lecanemab who experience an ischemic stroke (not sure about this though. Would need to think through how endotheial B relates to thrombosis).

Nevertheless, Sovateltide had a successful phase 3 trial in stroke in India and has also completed a phase 2 in AD.
Sovateltide could become over the next few years as highly recognizable a treatment as tPA in the stroke setting and possibly also in the AD setting. The figure above shows the mechanism of action. One pathway they note is through neurogenesis. In the context of AD growing new neurons could be of profound importance in cognitive recovery. Other features relate to mitogenesis, cerebral blood flow, calcium etc. etc. Very exciting! Perhaps medical tourism for AD treatment has just entered into the discussion. Wonder if they might offer this in Mexico.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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More great news from AD/PD!

Biogen has reported promising biomarker results for BIIB080 in a phase 1b with a large phase 2 already underway. BIIB080 is an antisense oligonucleotide (ASO) directed at tau which the phase 1b showed greatly reduced tau. There was no cognitive readout in the trial though as a guess it possibly was quite positive as they now have a 735 patient phase 2 recruiting. The phase 1b had 40 patients and it had a one year extension so they would have a fairly good idea of what it can do over a 2 1/2 year time window though without randomized control.

There was also great news from Xanamem. This one interacts with brain cortisol and the news also seems promising in the phase 2.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Massive massive news with Donanemab! Why didn't they give us more warning? I thought this was going to be announced in June! How can you have a celebration when your hair is in rollers?

Massive! The dual selection with tau just amplified things as expected.
Lilly has bank so things could truly launch now.
They have started 2 large trials with dona over the last few months so this is in motion.

This is starting to feel like a rout.
Some sort of combination could push this over the top.

Wonder whether insurance companies or others have some sort of an Alzheimer's futures contract.
The financial liability to our society is in the trillions. It would be very interesting to see how the financial
industry now assesses this risk. I am starting to feel fairly comfortable about my potential dementia financial risk.

There is even talk that treatment of severe AD is on the table.
That would just change the whole playing field.
If patients did not feel like they were on the edge of an abyss at the mild-moderate disease edge, then
they would have more treatment flexibility.
I wonder whether the FDA would consider an orphan disease indication for severe AD.
The logic is that we are now almost already at the point where the AD progression conveyer belt could be shut down
upstream of severe AD-- that could strand such patients in a non-marketable stage of illness as pharma would know that these patients would disappear through time without others that would progress to severe. To make sure that pharma were still fully incentivized to treat severe it might be helpful to offer later stage treatment particular encouragement (i.e., with orphan status). In our experience, severe dementia was very difficult. In terms of what do dementia families actually want bottom line? An ask? Develop treatment for severe stage dementia would be near the top of the list.


Would like to see the amyloid SUVR number for the dona phase 3, see how it lines up with the regressions.
They reported 29% slowing of decline on CDR-sb when including those with high tau, so this shows
comparability with aducan and leca if they had a truly representative MCI/ early AD population.

So, amyloid hypothesis is now a somewhat incorrect term; Amyloid Theory of Alzheimer's seems more appropriate. And J11 wants to get right in there and claim the Law of Amyloid in AD (i.e., the strong relation between cognition and SUVR amyloid probably too many times on this thread, though given the recent results I will have to post a few more of those regressions just to be sure. This is such great news for AD! It is fantastic that we are just cranking them out of the field. If this were more of a standup double or a triple, then it wouldn't have the same feeling. This is great! Next headline might be that we have one of these second generation mabs in combination with an anti tau!!
Last edited by J11 on Fri May 05, 2023 12:21 pm, edited 2 times in total.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Parabola 1 new.png
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Trailblazer overperformed the regression by ~9 CDR-sb pips. Will like to see what the SUVR value was and how the patient population compares to typical generic MCI-Mild AD patients. 0.364 SUVR was included as this was the number from the phase 2 trial, yet considering the parabolic nature of the relationship even a slight difference for Trailblzaer-2 could narrow the deviation noted above. (Even 0.37 SUVR moves us to 0.629 CDR-sb on the regression).

I am trying to account for the deviation here. The other dots all lined up quite well. One additional variable that might be involved with Donanemab is the CDR-sb in the placebo. In Trailblazer we reached 2.05 placebo decline. By enlarging the placebo decline then one could report a larger absolute decline; perhaps could migrate to a percent change scale. Notably, in the Emerge trial placebo decline was 1.74. Trailblazer-2 was 18% larger than that.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Important insight is that as we are on a parabolic curve, removing marginal amyloid has substantial
implications for CDR-sb.

https://www.desmos.com/calculator/xef09rcngu
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Oh my! Oh my! Oh Yeah!

There could be a workaround for CAA? This is too much!
Would the FDA allow RNAi pre-dosing on a clinical trial basis?
First clean out the CAA and then the plaque with mabs,
This plan could reduce or eliminate ARIA risk for with APOE 44 or on anti-coagulants.

Things are in motion!

https://www.alnylam.com/alnylam-rnai-pipeline
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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iADRS.GIF
dona Trail.GIF
Dona Phase 3.png
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Whoa! I might have found one!

In the phase 2, they identified the intermediate tau patients as the responder set.
Phase 2 used 1.1 and 1.46 as the cutoffs for low and high tau.

All good, yeah?
But, look at the next figure. See what I mean?
Yeah, I am probably wouldn't get that either.

The intermediate tau subgroup is not the responder group!
It's the lower tercile of the intermediate tau group!

The cut points used for intermediate were lower third at 1.144 and upper third at 1.274. by baseline flortaucipir SUVR.
Last edited by J11 on Fri May 05, 2023 7:17 pm, edited 4 times in total.
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