Key Points:
- BROOKLYN was a phase III trial that assessed the safety and effectiveness of obicetrapib as an adjunct to maximally tolerated lipid-modifying therapies, in patients with heterozygous familial hypercholesterolemia (HeFH).
- Obicetrapib reduced LDL-C levels by 36.3% at day 84, reaching 41.5% at day 365.
- Obicetrapib also demonstrated a 54.3% reduction in lipoprotein(a) levels, addressing a key cardiovascular risk factor.
- Adverse events were comparable between groups, with no significant differences in serious adverse events or cardiovascular deaths.
- Obicetrapib also improved non-HDL cholesterol and apolipoprotein B levels, enhancing lipid management.
Heterozygous familial hypercholesterolemia (HeFH) is a genetic condition that increases the risk of premature cardiovascular disease due to elevated LDL-C levels. Obicetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, offers a novel approach to further reduce LDL-C and address additional lipid abnormalities in patients who remain above target levels despite intensive statin therapy.
On 18 November, at the American Heart Association (AHA) 2024 Annual Scientific Sessions the results of the BROOKLYN trial were presented. BROOKLYN trial was a Phase III clinical trial (NCT05425745) evaluating the safety and effectiveness of obicetrapib as an adjunct to maximally tolerated lipid-modifying therapies, in patients with heterozygous familial hypercholesterolemia (HeFH). Patients were randomly assigned in a 2:1 ratio to receive either obicetrapib 10mg or a matching placebo, orally, once daily for 52 weeks.
In this randomized, placebo-controlled trial, obicetrapib significantly reduced LDL-C levels by 36.3% at day 84 and 41.5% at day 365. Furthermore, 34% of patients achieved over 50% LDL-C reduction. The drug also lowered lipoprotein(a) by 54.3%, a critical improvement given its role as an independent cardiovascular risk factor. Improvements in non-HDL cholesterol and apolipoprotein B further highlighted its comprehensive lipid-lowering effects.
Obicetrapib demonstrated a favorable safety profile, with similar rates of adverse events between treatment and placebo groups. Influenza, hypertension, and nasopharyngitis were the most commonly reported events, but there were no significant differences in serious adverse events or cardiovascular deaths. Importantly, obicetrapib did not lead to increases in blood pressure, a concern with other CETP inhibitors.
These findings highlight obicetrapib’s potential as an effective and well-tolerated therapy for HeFH, addressing both LDL-C and other lipid abnormalities. While the trial duration was relatively short, ongoing studies, including the PREVAIL trial, aim to further evaluate its long-term cardiovascular benefits. For patients struggling to achieve lipid targets, obicetrapib offers a promising new option to enhance cardiovascular risk management.