The Peter Attia Drive

#384 - Special episode — Obicetrapib: The CETP inhibitor with cardiovascular benefits and potential Alzheimer's prevention

53 min

Peter Attia discusses Obicetrapib, a novel CETP inhibitor, highlighting its significant potential for both cardiovascular disease and Alzheimer's prevention. The drug has shown robust reductions in LDL-C, APOB, and Lp(a), while also demonstrating a remarkable attenuation of Alzheimer's-related plasma biomarkers, particularly P-Tau 217, with a profound effect observed in ApoE4/E4 carriers. Despite a complex history of previous CETP inhibitors, Obicetrapib's unique profile and promising early data generate cautious optimism for its future impact.

Summarized by Podsumo

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✨ Key Takeaways

1

Obicetrapib, a CETP inhibitor, has shown significant reductions in LDL cholesterol (up to 50%+), APOB (30%), and Lp(a) (33%), positioning it as a powerful tool for cardiovascular risk reduction.
2

The drug demonstrated a remarkable attenuation of P-Tau 217, a key Alzheimer's biomarker, across all participants in the Broadway study, with an even more striking effect in ApoE4 carriers.
3

In the small but highly significant subgroup of ApoE4/E4 individuals, Obicetrapib led to an almost 8% reduction in P-Tau 217 over 12 months, contrasting with a nearly 13% increase in the placebo group, creating a 20% difference.
4

Unlike previous CETP inhibitors that failed due to off-target toxicities (e.g., blood pressure increase with Torsetropib) or insufficient lipid lowering, Obicetrapib appears to be safe and highly effective at reducing atherogenic lipoproteins.
5

The drug also shows metabolic neutrality or even potential benefits regarding incident diabetes, which could be an advantage over statins, and its mechanism in the brain for ApoE4 carriers is biologically plausible, involving enhanced cholesterol efflux and antioxidant availability.

💬 Notable Quotes

"I haven't been as excited about any drug in the market or a drug that's about to enter the market as I am with respect to this drug."
"Do not assume that because a person has high HDL cholesterol or low LDL cholesterol, that they're necessarily safe."
"The most interesting finding for me, and I think anybody who would look at the paper, is what happened in the admittedly small subset, 29 people of E4, E4s of NEH."