It does seem like they messed up that diagram in the rush to get the news out. If it delayed progression of the marker and was more potent in the ApoE carriers, then why is the marker more positive while being lower or even negative in the placebo group?
Maybe it’s supposed to represent “% inhibition of progression”? This, more positive and higher is better.
I think they screwed up the legend in the version you posted. What interests me here is that, on placebo, there is a clear pattern where one e4 makes p-Tau 217 accumulate faster than no e4, and homozygous e4 accumulates even faster. What’s interesting is that the impact of Obi is strong enough to regress p-Tau 217 accumulation in homozygous e4 but only slows accumulation in the others.
amuser
#163
The ‘All prticipants’ graph shows that those on obi saw a 1.99% increase in p-Tau217 levels, whereas the placebo group saw a 4.98% increase. Hence a 2.99% reduction for obi vs. placebo
The ApoE4 subset saw a 1.45% increase on obi vs. 7.19% increase for E4’s on placebo. Hence 5.74% reduction.
E4/E4 saw a 7.81% DECREASE vs. 12.67% increase for E4/E4’s on placebo. Hence 20.48% reduction.
https://ir.newamsterdampharma.com/events/event-details/newamsterdam-conference-call-aaic-2025
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Ergo the legend was reversed as suspected. Interesting that E4/E4 is worst case untreated but best response treated.
Assuming equal randomization to placebo and obi in both the whole study population and the ε4 carriers, that would be roughly 2.16% vs. 4.27% increase in the noncarriers. Not shabby, though it would have been nice to see even a slight a decrease like in the ε4 homozygotes.
adssx
#166
Reminder: in MR, CETPi seems useless for AD (but beneficial for LBD and PDD): Obicetrapib (CETP inhibitor for dyslipidemia) - #135 by adssx
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adssx
#167
Obicetrapib significantly increases plasma and high-density lipoprotein (HDL) levels of lipophilic antioxidants 2025
Results: Obicetrapib 10 mg/day increased HDL by 159%. In the HDL fraction, obicetrapib 2.5mg significantly increased all antioxidants at V3 with lutein and α-tocopherol increases (48.44% and 48.50%) maintained at V5. Obicetrapib 5mg significantly increased lutein, zeaxanthin, β-cryptoxanthin, γ-tocopherol, and α-tocopherol at V3, by 25.02%, 35.03%, 99.08%, 49.15% and 47.94%, with more marked increases at V5. Obicetrapib 10mg significantly increased lutein, zeaxanthin, β-cryptoxanthin, β-carotene, γ-tocopherol and α-tocopherol at V3, by 38.16%, 37.43%, 109.67%, 86.99%, 42.10% and 57.73% with more marked increases at V5 in lutein, zeaxanthin, β-cryptoxanthin, β-carotene, and α-tocopherol. Obicetrapib 10 mg/day decreased non-HDL-C by 30.3%. In the non-HDL fraction at V5, obicetrapib 2.5mg significantly decreased lutein, zeaxanthin, γ-tocopherol, and α-tocopherol. At V5, obicetrapib 5mg significantly decreased γ-tocopherol and α-tocopherol. At V5, obicetrapib 10mg significantly decreased lutein, zeaxanthin, γ-tocopherol, and α-tocopherol. Obicetrapib 2.5mg, 5mg, and 10mg significantly decreased plasma oxLDL at V3 by 21.03%, 26.38%, and 22.00% and at V5 by 12.04%, 19.38%, and 18.85%.
Conclusions: Across doses, obicetrapib robustly increased lipophilic antioxidant levels. Despite a decrease in lipophilic antioxidants in non-HDL on par with LDL-C reduction, obicetrapib decreased oxLDL. These data reflect obicetrapib’s effect on non-HDL-C and support that, in fact, HDL protects against LDL oxidation.
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Bicep
#168
I don’t understand the mechanism here. Where do the antioxidants come from? I understand the HDL is protective, so antioxidants are spared?
Well, since lutein and the like are not produced endogenously, presumably they must come from diet or supplementation. Not necessarily immediately, but from stores in tissues. Lipophilic antioxidants accumulate, so there’s something to draw upon.
It tells you in the abstract: they were shifted from the LDL and wider non-HDL cholesterol to the HDL-C (but still lowered oxLDL).
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