Patients with genetic predisposition to extreme cholesterol levels may finally have access to more effective treatment options, as traditional statin therapy often proves insufficient for managing their cardiovascular risk. This development could transform outcomes for the estimated one in 250 people worldwide carrying defective cholesterol-processing genes.
The BROOKLYN trial demonstrated that obicetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, achieved substantial LDL cholesterol reductions of 36.3% compared to placebo in 354 patients with heterozygous familial hypercholesterolemia already receiving maximum tolerated lipid-lowering medications. The drug targets CETP, an enzyme that transfers cholesterol between lipoproteins, effectively redirecting cholesterol metabolism to favor beneficial HDL particles while reducing harmful LDL levels. Treatment was well-tolerated across the study population, addressing previous concerns about CETP inhibitor safety profiles.
This finding represents a significant advancement for familial hypercholesterolemia management, where patients often struggle to reach target cholesterol levels despite aggressive statin therapy, PCSK9 inhibitors, and lifestyle modifications. The 36% reduction magnitude approaches what clinicians typically observe with high-intensity statins in average patients, making it particularly valuable for this treatment-resistant population. However, the study's relatively short duration and focus on cholesterol metrics rather than cardiovascular outcomes warrant cautious interpretation. Long-term safety data and evidence of actual heart attack or stroke prevention will determine whether obicetrapib joins the standard therapeutic arsenal. For adults with genetic hypercholesterolemia, this represents potential hope for better cholesterol control, though real-world efficacy and cost-effectiveness remain to be established through broader clinical experience.