Clinical Development of Obicetrapib (TA-8995)
Randomized Study of Obicetrapib as an Adjunct to Statin Therapy (ROSE)
ROSE (NCT04753606) was designed as a placebo-controlled, double-blind, randomized, Phase 2 dose-finding study to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to high-intensity statin therapy. A total of 120 patients were randomized to placebo, 5-mg obicetrapib, or 10-mg obicetrapib for an 8-week treatment period. The primary end point was met for both doses. In the 10-mg dose group, obicetrapib lowered median LDL by 51% (primary endpoint least squares mean LDL-C decreased 44%, P < .0001; Shapiro-Wilk Normality Test, P = .0001, median LDL-C decreased by 51%). Following the treatment period, patients continued for a 4-week safety follow up and a 15-week PK follow up. Overall, obicetrapib was well tolerated compared to placebo.
Top-line results of the ROSE study show the effects of CETP inhibition on LDL-C reduction and HDL-C increase attributed to orally administered obicetrapib. Results included reduction of median LDL-C levels by greater than 50% (primary endpoint LS mean LDL-C decreased 44%, P < .0001; Shapiro-Wilk Normality Test, P = .0001, median LDL-C decreased by 51%). Notably, median baseline LDL-C for participants in the study was 52 mg/dL at day 56 of the study, compared with median LDL-C 94 mg/dL at baseline.
Randomized Study to Evaluate the Effect of Obicetrapib in Addition to Maximum Tolerated Lipid-Modifying Therapies (BROADWAY)
BROADWAY (NCT05142722) is a placebo-controlled, double-blind, randomized study to evaluate the effect of obicetrapib in addition to maximally tolerated lipid-lowering therapy in patients with established atherosclerotic cardiovascular disease who require additional lowering of low‑density lipoprotein cholesterol (LDL-C). A total of 2,400 patients will be randomized to placebo or 10 mg obicetrapib dosed as a once-daily oral treatment for a 52-week treatment period. The primary objective of the BROADWAY trial is to evaluate the effect of obicetrapib on LDL-C levels after 12 weeks of treatment. Secondary endpoints include the evaluation of obicetrapib on lipoprotein(a), apolipoprotein B, non-HDL-C, HDL-C, total cholesterol, triglycerides, MACE (major adverse cardiovascular effects such as cardiovascular death, myocardial infarction, stroke, or non-elective coronary revascularization), and safety. Initial data is expected to be reported in 2024.
Evaluate the Effect of Obicetrapib in Patients With Hypercholesterolemia in Addition to Maximum Tolerated Lipid-Modifying Therapies (BROOKLYN)
BROOKLYN (NCT05425745) is a placebo-controlled, double-blind, randomized, Phase 3 trial to evaluate the effect of obicetrapib on LDL-C levels in patients with heterozygous familial hypercholesterolemia (HeFH) as an adjunct to maximally tolerated lipid-lowering therapy. Approximately 300 patients on maximally tolerated lipid-modifying therapies with a history of HeFH, an inherited genetic disorder that causes high cholesterol levels, and who have a baseline LDL-C of at least 70 mg/dL will be randomized to placebo or 10 mg of obicetrapib dosed as a once-daily oral treatment for a 52-week treatment period. Additional measures will be recorded throughout the study to evaluate the effect of obicetrapib on fasting lipoprotein(a), apolipoprotein B, non-HDL-C, HDL-C and safety. Initial data is expected to be reported in 2024.
Cardiovascular Outcome Study to Evaluate the Effect of Obicetrapib in Patients With Cardiovascular Disease (PREVAIL)
PREVAIL (NCT05202509) is a placebo-controlled, double-blind, randomized study in patients with a history of atherosclerotic cardiovascular disease who do not have adequate control of their LDL-C despite being on maximally tolerated lipid-modifying therapies. The primary objective of the PREVAIL trial is to evaluate the effect of obicetrapib on the risk of major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or non-elective coronary revascularization. Secondary endpoints include the evaluation of obicetrapib to lower LDL-C and prevent new cases of type 2 diabetes and long-term safety. A total of 9,000 patients will be randomized to placebo or 10 mg of obicetrapib dosed as a once-daily oral treatment. Initial data is expected to be reported in 2026.