Obicetrapib Shows Sustained LDL-C Reduction in HeFH Patients in Phase 3 Trial
核心洞察
Obicetrapib demonstrated a 36.3% reduction in LDL-C (搜索) compared to placebo at day 84, which was sustained at 41.5% at day 365 in HeFH patients.
The BROOKLYN trial also showed a significant reduction in lipoprotein(a) by 45.9% at day 84 compared to placebo in patients with HeFH.
NewAmsterdam Pharma's obicetrapib exhibited a safety profile comparable to placebo in the Phase 3 BROOKLYN trial, with good tolerability.
NewAmsterdam Pharma announced additional data from its Phase 3 BROOKLYN clinical trial, revealing that obicetrapib significantly reduced LDL-C (搜索) levels in patients with heterozygous familial hypercholesterolemia (搜索) (HeFH). The study, presented at the American Heart Association (AHA) Scientific Sessions, demonstrated a sustained reduction in LDL-C and other key lipid parameters over 52 weeks. These findings suggest obicetrapib could offer a valuable treatment option for HeFH patients whose LDL-C is not adequately controlled by existing therapies.
The BROOKLYN trial (NCT05425745) evaluated obicetrapib in adult patients with HeFH whose LDL-C (搜索) was not adequately controlled despite being on maximally tolerated lipid-lowering therapy. The trial met its primary endpoint, achieving a least squares (LS) mean reduction of 36.3% (p < 0.0001) in LDL-C compared to placebo at day 84. This effect was sustained at day 365, with an LS mean LDL-C reduction of 41.5% (p < 0.0001).
Significant Reductions in Lipoprotein(a) and Other Lipid Parameters
Beyond LDL-C (搜索), obicetrapib also demonstrated significant reductions in other atherogenic lipids. At day 84, lipoprotein(a) [Lp(a)] was reduced by 45.9% (p<0.0001) compared to placebo. Additional secondary endpoints, including apolipoprotein B (ApoB (搜索)), high-density lipoprotein cholesterol (HDL-C) and non-HDL-C, also met statistical significance (p < 0.0001).
Specifically, total LDL particle concentration was reduced by 52.5% and small LDL particle concentration was reduced by 102.4% at day 180. HDL-C increased by 138.7% compared to placebo at day 84.
Safety and Tolerability
Obicetrapib was observed to be well-tolerated, with a safety profile comparable to placebo. The treatment discontinuation rate in the obicetrapib arm was 7.6% versus 14.4% for placebo. There was no increase in blood pressure observed in the obicetrapib group.
Expert Commentary
Stephen Nicholls, M.B.B.S., Ph.D., Director, Monash Victorian Heart Institute and Professor of Cardiology, Monash University, stated, “We believe the additional data presented today underscore obicetrapib’s potential to significantly reduce not only LDL-C (搜索) but also Lp(a), LDL particles, both total and small, along with several other biomarkers in HeFH patients when compared to treatment with placebo...given the efficacy and safety profile observed to date, we believe obicetrapib has the potential, if approved, to provide physicians with a new tool to address unmet need in these patients.”
Trial Design and Patient Population
The BROOKLYN trial was a 52-week, global, Phase 3, randomized, double-blind, placebo-controlled, multicenter study. It enrolled 354 patients with HeFH whose LDL-C (搜索) was not adequately controlled. Patients were randomized 2:1 to receive 10 mg obicetrapib or placebo once daily, with or without food. The mean baseline LDL-C for patients in the obicetrapib arm was 123 mg/dL, despite approximately 79% being on high-intensity statins, 54% on ezetimibe, and 14% on PCSK9 inhibitors (搜索).
NewAmsterdam’s Phase 3 Program
NewAmsterdam Pharma has a comprehensive Phase 3 clinical development program for obicetrapib, consisting of four studies in over 12,250 patients. Topline data from the TANDEM and BROADWAY studies are expected in the fourth quarter of 2024. The PREVAIL cardiovascular outcomes trial, which completed enrollment in April 2024 with over 9,500 patients, is designed to assess obicetrapib’s potential to reduce major adverse cardiovascular events.