NewAmsterdam Pharma's obicetrapib has demonstrated positive topline results in the Phase 3 BROADWAY clinical trial, offering a potential new therapeutic option for patients with atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH). The trial, which evaluated obicetrapib in adult patients whose LDL-C was not adequately controlled despite being on maximally tolerated lipid-lowering therapy, met its primary endpoint with a statistically significant reduction in LDL-C.
Primary Endpoint Achieved
The BROADWAY trial achieved its primary endpoint, demonstrating a 33% reduction (p<0.0001) in LDL-C from baseline to day 84 in patients treated with obicetrapib 10 mg compared to placebo. This significant reduction was observed on top of maximally tolerated lipid-modifying therapies, highlighting the potential of obicetrapib to further lower LDL-C levels in high-risk patients.
Reduction in Major Adverse Cardiovascular Events
In an exploratory analysis, a 21% reduction in major adverse cardiovascular events (MACE) was observed in the obicetrapib arm compared to placebo at one year. While MACE was not a primary or secondary endpoint of the trial, this finding suggests that obicetrapib may offer cardiovascular risk reductions beyond LDL-C lowering.
Safety and Tolerability
Obicetrapib was observed to be well-tolerated, with a safety profile comparable to placebo. The treatment discontinuation rate for the obicetrapib arm was 11.1% versus 12.4% for placebo. Key adverse events of special interest, including glycemic control and renal function, favored obicetrapib.
Biomarker Changes
The observed changes in other biomarkers, including high-density lipoprotein cholesterol (HDL-C), non-HDL-C, lipoprotein(a) (Lp(a)), apolipoprotein B (ApoB), and Apolipoprotein A1 (ApoA1), were consistent with data reported in the Company’s prior clinical trials.
Expert Commentary
"The BROADWAY clinical trial highlights the transformative potential of obicetrapib — a powerful, well-tolerated, and convenient treatment option for millions with dyslipidemia, if approved, could help them reach their LDL-C goals and significantly reduce the risk of life-threatening cardiovascular events," said Stephen Nicholls, M.B.B.S., Ph.D., Director, Monash Victorian Heart Institute and Professor of Cardiology, Monash University.
Trial Design
The Phase 3 BROADWAY 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 ASCVD and/or HeFH whose LDL-C is not adequately controlled. The trial randomized 2,530 patients 2:1 to receive 10 mg obicetrapib or placebo dosed as a once-daily oral treatment.
Next Steps
NewAmsterdam plans to present additional results from BROADWAY at an upcoming medical conference and to publish the data in a major medical journal. The company also intends to discuss regulatory filings for obicetrapib with authorities in 2025.
