Celebration Thread! Novo Nordisk is Starting Two Phase 3s with Semaglutide

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J11
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Celebration Thread! Novo Nordisk is Starting Two Phase 3s with Semaglutide

Post by J11 »

This is another installment in my Celebration Threads!
This one for semaglutide.

I searched the forum for semaglutide.
Do you know what I found?
There are two mentions of semaglutide on this forum (before this thread was posted).
Do you know who has commented on semaglutide?
J11 *2! Yeah!

This looks like a big one and it deserves its own thread.
Voila-- the semaglutide thread.
Last edited by J11 on Mon May 17, 2021 7:50 pm, edited 2 times in total.
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Re: Celebration Thread! Novo Nordisk is Starting Two Phase 3 with Semaglutide

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Sema AD.jpg
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Re: Celebration Thread! Novo Nordisk is Starting Two Phase 3 with Semaglutide

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The above figure is somewhat unclear to me.
Is the idea that after ~3 years the treated group has ~50% risk of AD versus placebo?
Yet, when you look at the 4.5 year mark it appears that now placebo has ~80%!!! conversion to AD while the treated group is still at 20%.

Even still, it appears to be very impressive. Are they really saying the 20% conversion to AD held nearly constant for 3 years?
It is not easy to convert that into a cognitive score equivalent, though as a rough quantification I would call that large.

From the recent tau research, we saw that only ~ 4/9 of early AD patients are treated before moving beyond the tau treatment window.
The ~middle and high tercile in the intermediate third of the tau groups were too advanced to help as was the high third of the tau groups.

From the figure, the 20% of the non-responders could simply be the patients in these treatment ranges.
That is the result that you would report without tau selection.

Yet, with a pre-screening on tau, it becomes plausible that you could report 0% progression to AD in the sema treatment group. Basically, pre-stratify out those who will not be helped by treatment. However, admittedly, it would now be somewhat speculative
to assume that those with advanced tau would not be helped: it simply is not clear at this time. Porting over tau selection from the anti-amyloids is only a hunch.

It seems that we should try and help out here because as we have seen; AD trials are not always run with the best possible design.
Prespecifying stratifications based on tau, APOE etc. could provide us a much stronger scientific basis for sema.
Also doing a dose-escalation phase 1/2 would be helpful. How can we know what the optimal AD dose is? Use the diabetes
dose?


https://alz-journals.onlinelibrary.wile ... alz.042909
Last edited by J11 on Mon May 17, 2021 5:38 pm, edited 1 time in total.
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Re: Celebration Thread! Novo Nordisk is Starting Two Phase 3 with Semaglutide

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Sniff 1.GIF
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Re: Celebration Thread! Novo Nordisk is Starting Two Phase 3 with Semaglutide

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A clinical trial with intranasal insulin (a similar approach to sema) has reported strong results.
In the above table, placebo, 20 IU insulin and 40 IU insulin declined by 1.20 points, improved by 0.10 points and improved by 0.25 points on ADAS-cog over 6 months, respectively. ADCS-adl also saw an improvement of 20 IU over placebo though not the 40IU arm.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260944/
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