Abstract Body (Do not enter title and authors here): Hypothesis and Purpose: Obicetrapib, an orally-delivered cholesteryl ester transfer protein inhibitor, reduces concentrations of atherogenic lipid parameters and increases HDL-C when added to statins. BROOKLYN examined the efficacy, safety, and tolerability of obicetrapib 10 mg, as an adjunct to maximally tolerated lipid-modifying therapies, in patients with heterozygous familial hypercholesterolemia (HeFH) and suboptimal LDL-C control.
Study Design and Methods: This was a phase 3, randomized, double-blind, placebo-controlled trial with 1 year follow up.
Sample Size: 354 patients across 70 sites
Population Studied: Participants (n=354) with HeFH and fasting LDL-C >=70 mg/dL taking maximally tolerated lipid-modifying therapies
Intervention: Patients were randomly assigned to receive obicetrapib 10 mg or matching placebo orally daily for 52 weeks in a 2:1 ratio.
Power Calculations: Assuming 15% dropout rate, 285 evaluable participants would provide >90% power to detect a 30% reduction in LDL-C (standard deviation 15%) with obicetrapib compared to placebo with a 1-sided significance level of 0.025.
Primary End Point: Obicetrapib compared with placebo in LS mean percent change from baseline to week 12 in LDL-C.
Secondary End Points: Obicetrapib compared with placebo in percent changes from baseline in Apo B, non-HDL-C, HDL-C, total-C, Lp(a), and TG, and safety measures; Apo A1 was an exploratory endpoint.
Outcome: Mean baseline lipoprotein lipid levels for obicetrapib and placebo, respectively, were LDL-C: 123.4 and 119.9 mg/dL; ApoB: 107.2 and 105.3 mg/dL; non-HDL-C: 148.4 and 146.7 mg/dL; and HDL-C: 53.2 and 50.2 mg/dL. Obicetrapib, compared with placebo, significantly reduced mean LDL-C -36.3% at day 84 (P<0.0001) and -41.5% at day 365 (P<0.0001). On day 84 and day 365, obicetrapib, compared with placebo, significantly reduced mean ApoB -24.4%, -25.8%; non-HDL-C -34.5%, -37.5%; Lp(a) -45.9%, -54.3%; and increased HDL-C +138.7%, +121.4%, respectively. Obicetrapib was well tolerated with no serious adverse events or clinically significant changes in vital signs, electrocardiograms, or other clinical laboratory values.
Conclusions: Obicetrapib, as an adjunct to maximally tolerated lipid-modifying therapies, produced significant LDL-C lowering at day 84 with sustained effect through day 365 in patients with HeFH. Obicetrapib holds promise for patients with HeFH who are unable to attain their LDL-C treatment targets with available lipid-lowering agents.