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

Obicetrapib, a CETP inhibitor, is examined for its potential in reducing LDL cholesterol and its possible implications for Alzheimer's disease, particularly in individuals carrying the APOE4 allele. The history of CETP inhibitors, including failed drugs like torcetrapib and dalcetrapib, is revisited, emphasizing how obicetrapib differs with its robust LDL-lowering response and lack of off-target toxicity. The Broadway study, a phase 3 trial, revealed that obicetrapib significantly attenuated the increase in Ptau 217, a key biomarker for Alzheimer's, especially in APOE4 carriers. This effect is attributed to the drug's ability to enhance ApoA1 availability in the CNS, potentially offsetting impaired lipid trafficking associated with the APOE4 gene.