Trial results for a Phase 3 study investigating obicetrapib in patients with heterozygous familial hypercholesterolemia (HeFH) were posted on ClinicalTrials.gov on 2025-06-11. The study showed that obicetrapib 10 mg significantly reduced low-density lipoprotein cholesterol (LDL-C) by -36.05% from baseline at Day 84, compared to a 0.25% increase with placebo.
Background
Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C), which increases the risk of early-onset cardiovascular disease. Obicetrapib is being investigated as a potential treatment to reduce these elevated cholesterol levels.
Trial design
The study (NCT05425745) was a Phase 3, placebo-controlled, double-blind, randomized trial designed to evaluate the efficacy, safety, and tolerability of obicetrapib. It enrolled 354 participants with heterozygous familial hypercholesterolemia (HeFH) who were already on maximum tolerated lipid-modifying therapies. Participants were randomized to receive either obicetrapib 10 mg or placebo.
Key results
The trial demonstrated that obicetrapib 10 mg significantly reduced LDL-C and Apolipoprotein B (ApoB) levels compared to placebo over one year.
- For the outcome "Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline":
- At Day 84, obicetrapib 10 mg showed a least squares mean reduction of -36.05% (Standard Error: 1.769), while placebo showed an increase of 0.25% (Standard Error: 2.480). An ANCOVA analysis indicated a least squares mean difference of -36.31 (95.0% CI: -42.22 to -30.39) with a p-value of 0.0001.
- At Day 180, obicetrapib 10 mg achieved a reduction of -31.80% (Standard Error: 2.054), compared to a 5.98% increase for placebo (Standard Error: 2.925). The ANCOVA analysis showed a least squares mean difference of -37.78 (95.0% CI: -44.79 to -30.78) with a p-value of 0.0001.
- At Day 365, obicetrapib 10 mg resulted in a reduction of -31.14% (Standard Error: 2.544), whereas placebo showed an increase of 10.30% (Standard Error: 4.222). An ANCOVA analysis reported a least squares mean difference of -41.45 (95.0% CI: -51.14 to -31.76) with a p-value of 0.0001.
- For the outcome "Percent Change in Apolipoprotein B (ApoB) From Baseline":
- At Day 84, obicetrapib 10 mg showed a reduction of -21.45% (Standard Error: 1.219), while placebo increased by 2.93% (Standard Error: 1.758). The ANCOVA analysis indicated a least squares mean difference of -24.39 (95.0% CI: -28.58 to -20.2) with a p-value of 0.0001.
- At Day 180, obicetrapib 10 mg achieved a reduction of -18.30% (Standard Error: 1.472), compared to a 6.02% increase for placebo (Standard Error: 2.127). The ANCOVA analysis showed a least squares mean difference of -24.32 (95.0% CI: -29.38 to -19.25) with a p-value of 0.0001.
- At Day 365, obicetrapib 10 mg resulted in a reduction of -17.62% (Standard Error: 1.663), whereas placebo showed an increase of 8.15% (Standard Error: 2.633). An ANCOVA analysis reported a least squares mean difference of -25.77 (95.0% CI: -31.88 to -19.67) with a p-value of 0.0001.
What this means
The consistent and statistically significant reductions in both LDL-C and ApoB observed with obicetrapib 10 mg over a 365-day period suggest its potential as an effective lipid-modifying therapy for patients with heterozygous familial hypercholesterolemia (HeFH). These results indicate that obicetrapib could offer a new therapeutic option for managing high cholesterol in this patient population, particularly when added to existing maximum tolerated lipid-modifying treatments.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05425745, titled "Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies," were posted on 2025-06-11 on clinicaltrials.gov.