Trial results for the fixed-dose combination (FDC) of obicetrapib 10mg and ezetimibe 10mg were posted on ClinicalTrials.gov on 2025-10-08. The Phase 3 study demonstrated that the FDC significantly reduced low-density lipoprotein cholesterol (LDL-C) by -45.58% from baseline, compared to a 3.03% increase for placebo. This trial evaluated the FDC as an adjunct to diet and maximally tolerated lipid-lowering therapy in participants with heterozygous familial hypercholesterolemia (HeFH) and/or atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors.
Background
The study investigated obicetrapib 10mg and ezetimibe 10mg fixed dose combination. It was designed for participants diagnosed with dyslipidemias, hypercholesterolemia, familial hypercholesterolemia, ASCVD, or high cholesterol, aiming to provide additional lipid-lowering benefits beyond existing maximally tolerated therapies.
Trial design
The study (NCT06005597) was a Phase 3, placebo-controlled, double-blind, randomized trial that enrolled 407 participants. The conditions investigated included heterozygous familial hypercholesterolemia (HeFH) and/or atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors. Participants were randomized to receive one of the following interventions: combination therapy (obicetrapib 10mg and ezetimibe 10mg FDC), monotherapy obicetrapib, monotherapy ezetimibe, or placebo.
Key results
The trial results showed significant reductions in lipid parameters across various treatment arms. For the outcome of "Effect of Fixed-Dose Combination (FDC) Compared to Placebo on LDL-C":
- The Fixed Dose Combination group showed a least squares mean percent change from baseline of -45.58% (Standard Error: 3.465).
- The Placebo group showed a least squares mean percent change from baseline of 3.03% (Standard Error: 3.564).
An ANCOVA analysis for this comparison yielded a least squares mean difference of -48.61 (95.0% CI: -58.33 to -38.89) with a p-value of 0.0001.
Comparing the FDC to monotherapies for LDL-C:
- Against Ezetimibe Monotherapy, the FDC showed a least squares mean percent change of -45.58% versus -17.63% (Standard Error: 3.497) for ezetimibe alone. The ANCOVA difference was -27.94 (95.0% CI: -37.53 to -18.35) with a p-value of 0.0001.
- Against Obicetrapib Monotherapy, the FDC showed a least squares mean percent change of -45.58% versus -28.82% (Standard Error: 3.484) for obicetrapib alone. The ANCOVA difference was -16.76 (95.0% CI: -26.4 to -7.12) with a p-value of 0.0007.
Additionally, Obicetrapib Monotherapy compared to Placebo for LDL-C showed a least squares mean percent change of -28.82% (Standard Error: 3.484) versus 3.03% (Standard Error: 3.564). The ANCOVA difference was -31.85 (95.0% CI: -41.64 to -22.07) with a p-value of 0.0001.
Other key lipid outcomes included:
- For "Effect of Fixed Dose Combination (FDC) Compared to Placebo on Non-HDL-C": The FDC showed a least squares mean percent change of -42.42% (Standard Error: 2.977) versus 2.71% (Standard Error: 3.017) for placebo. The ANCOVA difference was -45.13 (95.0% CI: -53.43 to -36.84) with a p-value of 0.0001.
- For "Effect of Fixed Dose Combination (FDC) Compared to Placebo on Apolipoprotein B (ApoB)": The FDC showed a least squares mean percent change of -26.91% (Standard Error: 2.425) versus 2.28% (Standard Error: 2.466) for placebo. The ANCOVA difference was -29.19 (95.0% CI: -35.99 to -22.4) with a p-value of 0.0001.
What this means
The results from this Phase 3 trial indicate that the fixed-dose combination of obicetrapib and ezetimibe demonstrated superior efficacy in reducing LDL-C, Non-HDL-C, and Apolipoprotein B compared to placebo. Furthermore, the FDC achieved greater lipid reductions than either obicetrapib or ezetimibe administered as monotherapy. These findings suggest that the FDC could be a valuable therapeutic option for patients with dyslipidemias, including those with HeFH and ASCVD, who require further lipid-lowering treatment beyond maximally tolerated standard therapies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT06005597, titled "Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies," were posted on 2025-10-08 on clinicaltrials.gov.