Obicetrapib Achieves Robust LDL-C Reductions in Phase 3 ASCVD Trials

NewAmsterdam Pharma has announced new Phase 3 data showing once-daily oral obicetrapib, as an adjunct to statins, significantly reduced low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) who do not respond sufficiently to standard therapy.1

Presented as late-breaking research at the European Atherosclerosis Society (EAS) Congress 2025, on May 7, 2025 and simultaneously published in The New England Journal of Medicine and The Lancet, the BROADWAY and TANDEM trials found that obicetrapib cut LDL-C by more than 30% as monotherapy and nearly 50% when combined with ezetimibe.

“We believe the additional data presented today further supports obicetrapib as a meaningful advancement in the development of an oral medication to be used adjunctively to statins,” said Michael Davidson, MD, chief executive officer of NewAmsterdam Pharma.1 “These results will support global regulatory filings and reinforce our belief that obicetrapib has the potential to be an effective, once-daily, oral treatment that significantly reduces LDL-C.”

BROADWAY

In the multinational, randomized, placebo-controlled BROADWAY trial, assessing the effect of obicetrapib in patients with ASCVD and/or heterozygous familial hypercholesterolemia (HeFH), results were positive at Day 84. Compared with placebo, obicetrapib achieved a 33% reduction in LDL-C on top of maximally tolerated lipid-lowering therapies (P <.0001).2

An exploratory analysis showed a 21% relative reduction in major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.79; 95% CI, 0.54-1.15), including heart disease death, non-fatal heart attack or stroke, and revascularization. Safety and improvements in biomarkers, including high-density lipoprotein cholesterol (HDL-C), non-HDL-C, lipoprotein (a) [Lp(a)], apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1), aligned with earlier findings.

“Despite broad availability of lipid-lowering medications, many patients are unable to reach their LDL-C goals, and CVD-related mortality rates continue to rise,” said Stephen Nicholls, MBBS, PhD, director of the Monash Victorian Heart Institute and professor of cardiology at Monash University.1 “The additional data presented today further supports the potential of obicetrapib.”

TANDEM

Key data from the randomized, double-blind TANDEM trial found a fixed-dose combination (FDC) of obicetrapib 10 mg and ezetimibe 10 mg met all co-primary endpoints for LDL-C reduction on top of maximally tolerated lipid-modifying therapies in patients with ASCVD or ASCVD risk factors and/or HeFH. Compared with placebo or monotherapy, the obicetrapib and ezetimibe FDC significantly lowered LDL-C by 48.6% at Day 84 (P <.001).3

Further analysis showed more than 60% of patients on the FDC lowered LDL-C by more than 50%, and more than 70% hit levels below 55 mg/dL by Day 84. Safety results were comparable to placebo and remained tolerable in patients with ASCVD and/or HeFH.

“The TANDEM data presented today are highly encouraging, demonstrating obicetrapib in combination with ezetimibe delivering a roughly 50% LDL-C reduction and improvements across other lipid parameters,” said Ashish Sarraju, MD, cardiovascular medicine at the Cleveland Clinic.1 ““Simple and effective oral therapies like this are needed alongside maximally tolerated statins in the current CVD treatment paradigm.”

Pooled Phase 3 Data

Pooled data on Lp(a) from the Phase 3 BROADWAY, TANDEM, and BROOKLYN trials assessed changes in patients with levels spanning 50 to 150 nmol/L at baseline. Among this population, obicetrapib produced a median placebo-adjusted reduction of 45% in Lp(a) across 12 weeks.1

“Understanding residual risk is important for the overall treatment of ASCVD,” said John Kastelein, MD, PhD, chief scientific officer of NewAmsterdam.1 “Obicetrapib has shown clinically relevant reductions across multiple biomarkers of risk, including Lp(a) and LDL particles, and we believe obicetrapib could help change the definition of what an effective cardiometabolic therapy provides for patients.”

NewAmsterdam Pharma commenced the Phase 3 PREVAIL cardiovascular outcomes trial in March 2022, designed to assess the potential of obicetrapib to reduce MACE. Enrollment of PREVAIL was completed in April 2024, and more than 9500 patients were randomized.

References

1. Newamsterdam Pharma announces late-breaking data from Broadway and Tandem Pivotal Studies published in leading medical journals and presented at the European Atherosclerosis Society (EAS) Congress 2025. NewAmsterdam Pharma. May 7, 2025. Accessed May 7, 2025. https://ir.newamsterdampharma.com/news-releases/news-release-details/newamsterdam-pharma-announces-late-breaking-data-broadway-and.

2. Nicholls SJ, Nelson AJ, Ditmarsch M. Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk. NEJM. May 7, 2025. Accessed May 7, 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2415820.

3. Sarraju A, Brennan D, Hayden K. Fixed-dose combination of obicetrapib and ezetimibe for LDL cholesterol reduction (TANDEM): a phase 3, randomised, double-blind, placebo-controlled trial. The Lancet. May 7, 2025. Accessed May 7, 2025. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00721-4/abstract.