Obicetrapib, alone or with ezetimibe, reduces atherogenic lipoprotein particles
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Key takeaways:
- Obicetrapib alone and in combination with ezetimibe lowered total, small and small-dense LDL particles compared with placebo.
- The results suggest obicetrapib/ezetimibe may be complementary to statin therapy.
ATLANTA — Obicetrapib, a novel cholesteryl ester transfer protein inhibitor, reduced atherogenic lipoprotein particles alone or in combination with ezetimibe, according to new data from the ROSE2 trial.
As Healio previously reported, in the main results of ROSE2, the combination of obicetrapib (NewAmsterdam Pharma) and ezetimibe further reduced LDL in statin-treated patients with dyslipidemia. Data on the effect on atherogenic lipoprotein particles were presented at the American College of Cardiology Scientific Session.
The researchers “wanted to look a little bit more at what’s happening with the particles,” Christie M. Ballantyne, MD, FACC, FACP, FAHA, FNLA, chief of the section of cardiovascular research and professor of medicine at Baylor College of Medicine, told Healio. “The particles carry cholesterol and are of different sizes and compositions. We particularly looked at small, dense LDL particles. There are two ways of measuring these. One is with [nuclear magnetic resonance] spectroscopy. The other is with an assay made by Denka Seiken [to analyze] the cholesterol in small, dense particles. The particles are smaller so they don’t contain as much cholesterol, but what was shown here was a very striking reduction in the small particles.”
The randomized double-blind, placebo-controlled analysis included 97 patients with LDL-C greater than 70 mg/dL despite taking high-intensity statin therapy who were randomly assigned to obicetrapib 10 mg; a combination of obicetrapib 10 mg and ezetimibe 10 mg; or placebo.
At 12 weeks, compared with the placebo group, the obicetrapib-alone group had greater reduction in total LDL particles (–54.8% vs. –5.7%; P < .0001), as did the obicetrapib/ezetimibe group (–72.1% vs. –5.7%; P < .0001). The same was true for small, dense LDL particles (placebo, –8.3%; obicetrapib, –92.7%; obicetrapib/ezetimibe, –95.4%; P for both comparisons < .0001), according to the researchers.
The amount of cholesterol in the small, dense LDL particles was reduced by –30.9% in the obicetrapib group and –44.4% in the obicetrapib/ezetimibe group compared with –3.7% in the placebo group (P for both comparisons < .001), Ballantyne and colleagues found.
“Statins do really well reducing the large particles, but we sometimes have an increased number of these small particles hanging around after statin therapy,” Ballantyne told Healio. “So [obicetrapib with or without ezetimibe] can work on a background of statins or in the statin-intolerant patient.”
Statins block cholesterol synthesis and ezetimibe blocks cholesterol absorption, “and how we think this works with a [cholesteryl ester transfer protein] like obicetrapib, is that you upregulate LDL receptors and end up having more cholesterol excretion into bile from the liver,” Ballantyne told Healio. “As the transintestinal cholesterol excretion is increasing, ezetimibe blocks the reuptake of cholesterol in the intestine. That transintestinal cholesterol excretion is increasing, and ezetimibe blocks the reuptake. The two are working together in a little bit different manner from the statin. It’s encouraging to see favorable benefits. In particular for people who are statin-intolerant, we want to have treatments that will get [LDL] down over 50%. The combination pill of obicetrapib and ezetimibe may be a very handy one.”
Four phase 3 trials of obicetrapib alone or in combination with ezetimibe, including the PREVAIL CV outcomes trial, are ongoing.
For more information:
Christie M. Ballantyne, MD, FACC, FACP, FAHA, FNLA, can be reached at cmb@bcm.edu; X (Twitter): @cballantynemd.
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Davidson MH, et al. Abstract 1433-211. Presented at: American College of Cardiology Scientific Session; April 6-8, 2024; Atlanta.
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