Obicetrapib

Obicetrapib is an investigational, highly selective cholesteryl ester transfer protein (CETP) inhibitor being studied for the treatment of elevated levels of low-density lipoprotein cholesterol (LDL-C).1

In preclinical studies, inhibiting CETP with obicetrapib reduced LDL-C levels by decreasing hepatic cholesterol, which led to an upregulation of LDL receptor expression and increased LDL clearance.2

A close-up of blood cellsA close-up of blood cells

Mechanism Of Action

Obicetrapib is currently being studied as a potential treatment to lower LDL-C as an
adjunct to maximally tolerated lipid-lowering therapies in patients with atherosclerotic
cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) in
three pivotal Phase 3 trials: BROADWAY, BROOKLYN, and PREVAIL.3-5

Clinical programs

Registrational Studies

PHASE 1

PHASE 2

PHASE 3

Cardiovascular Disease

BROADWAY
PHASE 3

BROADWAY (NCT05142722) is a Phase 3, placebo-controlled, double-blind, randomized study in patients with ASCVD and/or HeFH to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy.3

Primary objective: Evaluate the effect of obicetrapib on LDL-C levels.

Secondary objectives: Evaluate the effect of obicetrapib on apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), lipoprotein(a) (Lp(a)), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol, and triglycerides.

BROOKLYN
PHASE 3

BROOKLYN (NCT05425745) is a Phase 3, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy in participants with a history of HeFH.4

Primary objective: Evaluate the effect of obicetrapib on LDL-C levels.

Secondary objectives: Evaluate the effect of obicetrapib on Lp(a), ApoB, and non-HDL-C.

Topline results: Observed an LS mean LDL-C reduction of 36.3% (p < 0.0001) compared with placebo at day 84, which was sustained at day 365 with an LS mean LDL-C reduction of 41.5% (p < 0.0001).

PREVAIL
PHASE 3

PREVAIL (NCT05202509) is a Phase 3, placebo-controlled, double-blind, randomized study in participants with ASCVD who are not adequately controlled despite maximally tolerated lipid-lowering therapy.5

Primary objective: Evaluate the effect of obicetrapib on the risk of major adverse cardiovascular events (MACE).

Secondary objectives: Evaluate the effect of obicetrapib on all-cause mortality, total cardiovascular events, new-onset diabetes, and change in LDL-C, non-HDL-C, and ApoB.

Completed Programs

PHASE 1

PHASE 2

PHASE 3

Cardiovascular Disease

ROSE
PHASE 2

ROSE (NCT04753606) was designed as a placebo-controlled, double-blind, randomized, Phase 2, dose-finding study evaluating the efficacy, safety, and tolerability of obicetrapib used along with high-intensity statin therapy.6

Topline results: Patients treated for 8 weeks with 10 mg of obicetrapib achieved an LS mean LDL-C reduction of 40.1% (p < 0.0001) compared with placebo. Additionally, results found no serious adverse events (AEs) in the two obicetrapib cohorts, and two serious AEs in the placebo arm.

Obicetrapib as an Adjunct to Stable Statin Therapy in Japanese Patients
PHASE 2

This Phase 2b study (NCT05421078) was a placebo-controlled, double-blind, randomized, dose-finding trial to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to stable statin therapy in Japanese patients.7

Topline results: Patients treated for 8 weeks with 10 mg of obicetrapib achieved an LS mean LDL-C reduction of 36.8% (p < 0.0001) compared with placebo.

Other Lipid-Related Conditions

PHASE 2A ALZHEIMER’S TRIAL
PHASE 2

This proof-of-concept Phase 2a trial (NCT05161715) was designed to explore the pharmacodynamics, cognitive effects, pharmacokinetics, safety, and tolerability of obicetrapib in early Alzheimer’s disease (AD) patients who are ApoE4 carriers.8

Topline Results: We observed reductions of 11% and 12% in 24- and 27-hydroxycholesterol in cerebrospinal fluid (CSF), respectively, indicating potential improvement of cholesterol metabolism in the brain, and observed 8% increase in Aβ42/40 ratio, a key biomarker of AD risk, suggesting improvement in disease pathology.

1. Ford J, Lawson M, Fowler D, et al. Tolerability, pharmacokinetics and pharmacodynamics of TA-8995, a selective cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Br J Clin Pharmacol. 2014;78(3):498-508. doi:10.1111/bcp.12380 2. Inia J, Keijzer N, Worms N, et al. Obicetrapib alone and in combination with ezetimibe reduces non-HDL-cholesterol by enhanced LDL-receptor-mediated VLDL clearance and increased net fecal sterol excretion in apoe*3-leiden.cetp mice. Atherosclerosis. 2024;395,suppl1. 3. ClinicalTrials.gov. Randomized study to evaluate the effect of obicetrapib on top of maximum tolerated lipid-modifying therapies (BROADWAY). NCT05142722. Updated September 18, 2023. Accessed March 7, 2024. https://clinicaltrials.gov/study/NCT05142722 4. ClinicalTrials.gov. Evaluate the effect of obicetrapib in patients with HeFH on top of maximum tolerated lipid-modifying therapies. (BROOKLYN). NCT05425745. Last updated January 23, 2024. Accessed March 7, 2024. https://clinicaltrials.gov/study/NCT05425745 5. ClinicalTrials.gov. Cardiovascular outcome study to evaluate the effect of obicetrapib in patients with cardiovascular disease (PREVAIL). NCT05202509. Last updated March 7, 2024. Accessed May 5, 2024. https://clinicaltrials.gov/study/NCT05202509 6. ClinicalTrials.gov. Randomized study of obicetrapib as an adjunct to statin therapy (ROSE). NCT04753606. Last updated July 12, 2024. Accessed July 21, 2024. https://clinicaltrials.gov/study/NCT04753606 7. ClinicalTrials.gov. A Dose-Finding Study in Japanese Patients to Evaluate the Effect of Obicetrapib as an Adjunct to Stable Statin Therapy. Last updated September 27, 2024. Accessed September 27, 2024. https://clinicaltrials.gov/study/NCT05421078 8. ClinicalTrials.gov. Proof-of-concept, open-label study in patients with early Alzheimer’s disease. NCT05161715. Last updated May 4, 2024. Accessed July 21, 2024. https://clinicaltrials.gov/study/NCT05161715