CETP Inhibition With Obicetrapib: Implications for Cardiovascular Event Prevention

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Welcome to DataPulse from ESC 2025 on ReachMD. This activity, titled “CETP Inhibition with Obicetrapib: Implications for Cardiovascular Event Prevention” is provided by Medcon International.

Dr. Nichols: 
Hi, my name is Steve Nichols. I’m professor of cardiology at Monash University in Melbourne, Australia. I’m also the study chair of the obicetrapib development program, and I’m here at the ESC meeting in Madrid where we’ve presented data looking at MACE outcomes for obicetrapib, the CETP inhibitor, looking at a pooling of phase 3 clinical trials. 

For many years, there’s been interest in developing CETP inhibitors. Their ability to raise HDL, lower LDL, and whether that will translate to cardiovascular risk reduction. Obicetrapib is a highly selective CETP inhibitor, and in early studies, we’ve demonstrated that obicetrapib effectively lowers LDL cholesterol and lipoprotein A on top of maximally tolerated statin therapy. 

At the ESC meeting, we presented MACE data from 2 pooled clinical trials: one study called BROADWAY, which enrolled more than 2,500 patients with ASCVD with or without FH, and the BROOKLYN study of 354 patients, all of whom had heterozygous FH. In those studies, patients were treated for 12 months with either obicetrapib 10 mg or placebo. We previously reported the effects of obicetrapib in terms of LDL reductions in the order of 35% to 40%, LPA reductions somewhere in the order of 35% to 40% as well. 

And at the ESC meeting, we purported that there’s a reduction in MACE. When we look at the composite of coronary heart disease death, myocardial infarction, or coronary revascularization, we see a 32% reduction in that risk. It is relatively small studies, relatively short studies. It’s early in the development program, but it’s a really positive finding for the therapy. 

We then subsequently looked at the effect of obicetrapib on cardiovascular events in the first 6 months and the second 6 months of those studies. In the first 6 months, there was no separation of the curves. In the second 6 months, there was actually quite a comprehensive reduction in cardiovascular risk. And in fact, the hazard ratio between month 6 and month 12 was 0.45, suggesting that there was a more than 50% reduction in risk. 

Now, that’s unlikely to be what we’ll see in the pivotal, large cardiovascular outcome trial, PREVAIL, which has enrolled 9,500 high-risk patients with high LDL cholesterol; that is ongoing. That will give the definitive answer for whether obicetrapib reduces cardiovascular risk. But these findings that we report at the ESC meeting give us more energy and more enthusiasm to suggest that the lowering of LDL and lowering of LPA that we see with obicetrapib looks like it is translating to cardiovascular benefit. PREVAIL will give us the definitive answer in the next few years. 

What this all means is that we have another effective agent for lowering atherogenic lipid levels. Another tool in the toolbox for the patient in the prevention clinic and a more effective way to get patients to LDL goal and lower their cardiovascular risk. 

I hope you found this useful.

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