Key takeaways
- Obicetrapib 10 mg significantly reduced plasma p-tau217 levels over 12 months in both the full analysis set and ApoE4 carriers, suggesting potential to slow Alzheimer’s disease progression.
- The BROADWAY sub-study enrolled over 1,700 participants, including 367 ApoE4 carriers, offering robust data on neurodegenerative biomarker trends within a cardiovascular trial population.
- These Alzheimer’s biomarker findings complement obicetrapib’s LDL-C lowering profile, supporting further evaluation of CETP inhibition for dual cardiovascular and neuroprotective benefit.
NewAmsterdam Pharma has shared positive data from the Phase III BROADWAY clinical trial (NCT05142722) evaluating the low-density lipoprotein cholesterol (LDL-C) lowering efficacy of obicetrapib, a CETP inhibitor. In a prespecified Alzheimer’s disease biomarker analysis, obicetrapib demonstrated a significantly significant reduction in absolute levels of plasma p-tau217, a key biomarker of Alzheimer’s pathology.1
p-tau217 levels decline in overall and ApoE4 patient groups
Further findings from this readout show:
- Daily treatment with obicetrapib 10 mg for 12 months led to a statistically significant reduction in plasma p-tau217 levels in both the overall analysis set (p=0.0019) and in ApoE4 carriers (p=0.0215).
- In APoE4/E4 carriers, the highest risk category for Alzheimer’s, obicetrapib lowered p-tau217 levels by 20.5% over 12 months, compared to placebo.
- Additional biomarkers, including neurofilament light chain, glial fibrillary acidic protein, p-tau181, and the Aβ42/40 ratio, also showed favorable trends.
- The most pronounced effects were observed in individuals with two copies of the ApoE4 allele.
ApoE4 is a known risk factor for both cardiovascular and Alzheimer’s disease, often associated with higher LDL-C, elevated Lp(a), and impaired cholesterol transport.
In a press release, Michael Davidson, MD, chief xecutive officer of NewAmsterdam Pharma, said: “Alzheimer’s disease remains a devastating global health challenge, with no effective preventive treatments available. Obicetrapib, our investigational once-daily oral therapy, shows promise by significantly slowing the progression of, and in some instances decreasing, plasma levels of p-tau217, a key Alzheimer’s biomarker, in this analysis. This is especially important in ApoE4 gene carriers—a group that represents over a quarter of the population and faces a heightened risk for this disease. Combined with its LDL-C lowering benefits observed in multiple clinical trials, obicetrapib may offer a unique opportunity to reduce both neurodegenerative and heart disease risks.”
June readout also showed significant biomarker improvements
These latest results from BROADWAY build on data from an earlier readout in June. Pre-specified analyses from the time revealed that treatment with obicetrapib led to statistically significant and clinically meaningful reductions in the primary outcome measure of Alzheimer’s disease biomarker in both the full ITT patient population (p<0.002) and in ApoE4 carriers (p=0.0215).2
In a press release from the time, Davidson said: “These findings strongly support a potential preventive strategy for Alzheimer's disease. In this study obicetrapib, a potent CETP inhibitor, improved the progression of key plasma biomarkers of AD pathology over a 12-month period in patients with ASCVD (atherosclerotic cardiovascular disease). These data further differentiate obicetrapib and underscore the critical role CETP inhibition may have in mitigating the risk of Alzheimer’s disease progression, alongside the significant cardiovascular benefits obicetrapib has shown in our pivotal Phase III trials.”
BROADWAY design and patient population overview
The BROADWAY trial is a 52-week, global, Phase III, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of obicetrapib 10 mg.
- The study enrolled 2,530 patients with ASCVD and/or heterozygous familial hypercholesterolemia whose LDL-C remained uncontrolled despite maximally tolerated lipid-lowering therapy.
- Participants were randomized 2:1 to receive obicetrapib 10 mg or placebo, taken once daily with or without food.
- Trial sites were located across North America, Europe, Asia, and Australia.
- The primary endpoint was the least squares mean percent change in LDL-C at day 84, which showed a 33% reduction with imputation in the obicetrapib arm.
- Secondary endpoints included percent change from baseline at day 84 in ApoB, Lp(a), ApoA1, HDL-C, non-HDL-C, total cholesterol, and triglycerides, as well as LDL-C at days 180 and 365.
- Exploratory measures included time to first major adverse cardiovascular event and assessment of safety and tolerability.
- In the pre-specified Alzheimer’s disease sub-study focused on plasma biomarkers, 1,727 patients were included, with 367 identified as ApoE4 carriers.
References
1. NewAmsterdam Pharma Presents Positive Data from BROADWAY Trial Demonstrating Statistically Significant Reductions in Key Alzheimer’s Disease Biomarkers at AAIC 2025. News release. NewAmsterdam Pharma. July 30, 2025. Accessed August 1, 2025. https://ir.newamsterdampharma.com/news-releases/news-release-details/newamsterdam-pharma-presents-positive-data-broadway-trial
2. NewAmsterdam Pharma Announces Positive Topline Alzheimer’s Disease Data from BROADWAY Clinical Trial. News release. NewAmsterdam Pharma. June 9, 2025. Accessed August 1, 2025. https://ir.newamsterdampharma.com/news-releases/news-release-details/newamsterdam-pharma-announces-positive-topline-alzheimers
