The Menarini Group announced positive topline data from the Phase 3 BROOKLYN clinical trial evaluating obicetrapib in patients with heterozygous familial hypercholesterolemia (HeFH). The trial, sponsored by NewAmsterdam Pharma, assessed the efficacy and safety of obicetrapib in adults with HeFH whose LDL-C levels are not adequately controlled despite being on maximally tolerated lipid-lowering therapy.
The BROOKLYN trial met its primary endpoint, demonstrating a statistically significant least squares (LS) mean reduction of 36.3% in LDL-C compared to placebo at week 12 (p < 0.0001). This reduction was sustained at 52 weeks, with an LS mean LDL-C reduction of 41.5% (p < 0.0001). Notably, over 50% of patients achieved an LDL-C level below 70 mg/dL.
Additional Biomarker Reductions
The study also reported statistically significant reductions in other key biomarkers, including non-HDL-C, ApoB, and Lp(a), consistent with findings from prior studies. These results further support the potential of obicetrapib to improve the lipid profile in HeFH patients.
Safety and Tolerability
Obicetrapib demonstrated a favorable safety profile in the trial. Treatment-emergent adverse events related to the study drug occurred in 4.3% of patients in the obicetrapib arm compared to 6.8% in the placebo arm. No study drug-related treatment-emergent serious adverse events were reported in either treatment arm. The treatment discontinuation rate for obicetrapib was 7.6% versus 14.4% for placebo.
Expert Commentary
Stephen Nicholls, M.B.B.S., Ph.D., Director, Monash Victorian Heart Institute and Professor of Cardiology, Monash University, and principal investigator of the obicetrapib development program, stated, "BROOKLYN data has confirmed obicetrapib’s ability to significantly reduce LDL-C in HeFH patients, a population already on multiple lipid-lowering therapies. I am incredibly encouraged by these results, which suggest we may have a new, high-efficacy, oral option for a difficult-to-treat patient population."
About the BROOKLYN Trial
The Phase 3 BROOKLYN trial was a 52-week, global, randomized, double-blind, placebo-controlled, multicenter study. It evaluated the efficacy and safety of 10 mg obicetrapib compared to placebo as an adjunct to maximally tolerated lipid-lowering therapies in patients with HeFH whose LDL-C is not adequately controlled. A total of 354 patients were randomized 2:1 to receive 10 mg obicetrapib or placebo dosed as a once-daily oral treatment. The mean baseline LDL-C for enrolled patients in the obicetrapib arm was 123 mg/dL, with approximately 79% of patients reporting high-intensity statin use during screening.
The primary objective was to evaluate the effect of obicetrapib on LDL-C levels. Secondary objectives included evaluating the effect of obicetrapib on non-HDL-C, ApoB, and lipoprotein (a), as well as assessing the safety and tolerability profile of the drug.
Implications for HeFH Treatment
Heterozygous Familial Hypercholesterolemia affects approximately 1 in 250 people worldwide and increases the risk of major adverse cardiovascular events. Katherine Wilemon, Founder and CEO of the Family Heart Foundation, noted, "HeFH patients are difficult to treat, often requiring multiple therapies to control their LDL-C levels. We are highly encouraged with these results and the potential to have another efficacious oral option."
Obicetrapib's Phase 3 Program
Obicetrapib is currently being evaluated in a global Phase 3 clinical development program consisting of four studies involving over 12,250 patients. These studies include BROOKLYN (HeFH patients), BROADWAY (ASCVD and/or HeFH patients), TANDEM (fixed-dose combination with ezetimibe), and PREVAIL (cardiovascular outcomes trial in ASCVD patients).
