Lilly’s Alzheimer’s [donanemab] Data

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BrianR
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Lilly’s Alzheimer’s [donanemab] Data

Post by BrianR »

Another anti-amyloid antibody study, another disappointingly ambiguous result. Here is Derek Lowe's take:

https://blogs.sciencemag.org/pipeline/a ... imers-data
I still don’t see how any of the effects seen in this trial translate into any real-world benefits. Even if they’re real, and there’s definitely reason to doubt that. I’m sticking with what I said nearly ten years ago about another failed Lilly antibody: there’s a nasty moral hazard in this business of marginal, hazy, Alzheimer’s statistical benefits, because the first company that manages to get anything approved by the FDA will reap billions of dollars from the huge backlog of desperate patients and families who want something, anything, that they can use against the disease. I feel the same way about Biogen’s aducanumab.
J11
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Re: Lilly’s Alzheimer’s [donanemab] Data

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BrianR, my Sunday March 14th at 1:11PM post on below url noted a particularly impressive aspect of the dona result: They achieved significance (p= 0.02) on iADRS with only 36 treatment patients by selecting the lower intermediate tercile by tau. This is a truly startling result. Could they really have a trial with only 40 in the treatment arm and declare success? aducan had ~3,000! Selecting on both amyloid and tau positivity greatly moves the ball forward in conducting AD trials.
viewtopic.php?f=4&t=6709&start=410
Family Tree Guy
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Re: Lilly’s Alzheimer’s [donanemab] Data

Post by Family Tree Guy »

BrianR wrote:Another anti-amyloid antibody study, another disappointingly ambiguous result. Here is Derek Lowe's take:

https://blogs.sciencemag.org/pipeline/a ... imers-data
I still don’t see how any of the effects seen in this trial translate into any real-world benefits. Even if they’re real, and there’s definitely reason to doubt that. I’m sticking with what I said nearly ten years ago about another failed Lilly antibody: there’s a nasty moral hazard in this business of marginal, hazy, Alzheimer’s statistical benefits, because the first company that manages to get anything approved by the FDA will reap billions of dollars from the huge backlog of desperate patients and families who want something, anything, that they can use against the disease. I feel the same way about Biogen’s aducanumab.
I agree with Lowe's assessment. There is an interesting twist on this data which is that both drug and placebo groups start with close to 70% E4 carriers. (about 90 E4s / 125-30 patients in each group) However, the E4 carriers in the drug group are much more likely to experience the severe adverse events (ARIA-E, brain swelling) and then drop out of the study. So by the time they reach the end of the study, the drug group has way fewer E4s (not totally clear from Lilly's paper, but looks like at least 30 E4s dropped out of drug group). From the data, it appears ~1 E4 dropped out of the placebo group. So while Lilly claims to show an impact of their drug (reducing rate of decline), I think all they are showing is that the group with more E4s (placebo) declines more rapidly over time than the group with fewer E4s (which happens to be the drug group). Lilly even admits in their paper that they cannot correlate amyloid reduction and cognition at the individual level, only at the aggregate.
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