The Phase III BROOKLYN trial, presented at the American Heart Association (AHA) 2024 Annual Scientific Sessions, revealed that NewAmsterdam Pharma's obicetrapib, when used as an adjunct to maximally tolerated lipid-modifying therapies, significantly improved lipid profiles in patients with heterozygous familial hypercholesterolemia (HeFH). The study demonstrated notable reductions in LDL cholesterol and lipoprotein(a) [Lp(a)], addressing a critical unmet need in managing dyslipidemia and cardiovascular risk.
Obicetrapib's Mechanism and Trial Design
Obicetrapib functions as a selective inhibitor of cholesteryl ester transfer protein (CETP). By inhibiting CETP, the drug increases high-density lipoprotein (HDL) cholesterol and lowers triglyceride levels. The BROOKLYN trial (NCT05425745) randomly assigned patients in a 2:1 ratio to receive either obicetrapib 10mg or a matching placebo, administered orally once daily for 52 weeks. The primary endpoint of the trial was achieved, demonstrating a significant reduction in LDL cholesterol.
Significant Reductions in LDL Cholesterol and Lp(a)
Results from the BROOKLYN trial indicated substantial reductions in LDL cholesterol with obicetrapib treatment. Placebo-adjusted LDL cholesterol decreased by 36.3% at day 84 and 41.5% at day 365. Furthermore, 34% of patients treated with obicetrapib achieved LDL cholesterol reductions greater than 50%. Regarding treatment goals, 77% of patients reached the primary prevention target for familial hypercholesterolemia (FH) of 100mg/dL, 51% achieved the 70mg/dL target, and nearly 25% met the target of 55mg/dL for very high-risk FH patients.
In addition to LDL cholesterol reduction, obicetrapib demonstrated a placebo-adjusted reduction in Lp(a) of 54.3%. This is particularly significant as there are currently no therapies that directly target Lp(a), a known risk factor for cardiovascular diseases. Nuclear magnetic resonance (NMR) analysis revealed a 52.5% reduction in total LDL particle concentration and a 102.3% reduction in small atherogenic LDL particles at day 180.
Safety and Tolerability
Obicetrapib was reported to be well-tolerated, with no serious adverse events or clinically significant changes in vital signs, electrocardiograms, or other laboratory values. Unlike previous CETP inhibitors, obicetrapib did not show any changes in diastolic or systolic blood pressure throughout the study.
Market Potential and Future Directions
GlobalData forecasts that obicetrapib will generate the highest sales among pipeline drugs across the seven major markets, with projected sales reaching $1.40 billion by 2032. The longer-term effect of obicetrapib on cardiovascular outcomes is currently being evaluated in the PREVAIL trial. Future studies will also focus on evaluating the impact of obicetrapib in individuals with elevated Lp(a) levels to further validate its potential in reducing cardiovascular events.
