NewAmsterdam Pharma Reports Positive Alzheimer’s Data from BROADWAY Trial

NewAmsterdam Pharma, a company focused on developing non-statin, oral medications for patients with cardiovascular disease, has announced promising results from its Phase 3 BROADWAY clinical trial. The study primarily aimed to evaluate the efficacy of obicetrapib, a CETP inhibitor, in reducing low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who have not achieved adequate LDL-C control despite using maximally tolerated lipid-lowering therapies.

In addition to assessing LDL-C reduction, the BROADWAY trial included a pre-specified sub-study focusing on the potential effects of obicetrapib on Alzheimer's disease (AD) biomarkers. This aspect of the study is particularly significant given the emerging interest in the link between cholesterol metabolism and AD pathology. The findings from this sub-study indicate that obicetrapib treatment results in significant and clinically meaningful reductions in key biomarkers associated with AD, such as p-tau217, in the full study population and specifically among ApoE4 carriers.

These findings suggest that obicetrapib might offer a dual benefit by addressing both cardiovascular and neurodegenerative risks. Michael Davidson, CEO of NewAmsterdam Pharma, highlighted the potential of obicetrapib to serve as a preventive strategy for Alzheimer's, emphasizing its role in slowing the progression of AD biomarkers over a year-long period in patients with ASCVD.

The results build upon a foundation of genetic studies, Mendelian randomization, and earlier clinical data from NewAmsterdam's proof-of-concept Phase 2a trial. The implications of these findings are particularly relevant for individuals carrying the ApoE4 gene, which is associated with a heightened risk of AD, as there are currently no FDA-approved preventive options for this population. Philip Scheltens, a professor emeritus at Amsterdam University Medical Center, noted the significance of these findings in potentially altering the disease trajectory for ApoE4 carriers, delaying or preventing the onset of AD symptoms.

John Kastelein, Chief Scientific Officer of NewAmsterdam, pointed out that approximately two-thirds of Alzheimer's patients carry the ApoE4 risk isoform, highlighting the potential of CETP inhibition as a novel approach to reducing AD risk. The study's findings are supported by the broader body of evidence demonstrating obicetrapib's efficacy in lowering LDL-C and other key biomarkers related to chronic diseases.

The BROADWAY trial was a 52-week, global, randomized, double-blind, placebo-controlled study involving 2,530 patients from diverse regions, including North America, Europe, Asia, and Australia. Participants were randomly assigned to receive either 10 mg of obicetrapib or a placebo in addition to their existing lipid-lowering therapies. The primary endpoint focused on the percentage change in LDL-C levels, while secondary endpoints included changes in other cholesterol-related measures and time to major adverse cardiovascular events (MACE).

The Alzheimer's sub-study, involving 1,727 patients with a significant proportion of ApoE4 carriers, assessed changes in plasma AD biomarkers over a 12-month period. The data revealed a statistically significant reduction in p-tau217 levels in both the overall intent-to-treat population and among ApoE4 carriers.

These results underscore obicetrapib's potential as a comprehensive therapy addressing both cardiovascular and neurodegenerative concerns. NewAmsterdam plans to present the full findings at the Alzheimer's Association International Conference in Toronto, further highlighting the therapeutic promise of obicetrapib in addressing unmet needs in patient populations at risk of cardiovascular and neurodegenerative diseases.