Phase 3 Study Results of Obicetrapib on Alzheimer Disease Biomarker Progression: Philip Scheltens, MD, PhD

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“We had a very significant influence of obicetrapib on the p-tau217 evolution over time. In the placebo group, it increased and in the obicetrapib group, it decreased. So, a very significant result that shows us that obicetrapib is able to influence AD biomarkers, and that may offer a potential for prevention in the future."

Researchers assessed the investigational cholesteryl ester transfer protein (CETP) inhibitor obicetrapib (NewAmsterdam Pharma) in the phase 3 BROADWAY study (NCT05142722) in atherosclerosis cardiovascular disease. BROADWAY is a phase 3, double-blind, placebo-controlled trial that randomized participants (n = 1,727; mean age, 65 years; women, 33%) 2:1 to receive 10-mg daily versus placebo over 12 months. Results from trial revealed that obicetrapib significantly slowed the progression of Alzheimer disease (AD) biomarkers over 1 year, with most pronounced effects observed in older carriers of the APOE4 allele.¹

In the study, obicetrapib significantly lowered low-density lipoprotein by 33% and increased high-density lipoprotein by 125% in comparison with placebo. Notably, obicetrapib displayed significant attenuation of increase in the median plasma p-tau217 (obicetrapib, 1.1%; placebo, 4.8%; P = .01) and p-tau217/Aβ42:Aβ40 ratio (obicetrapib, 2.7%; placebo, 6.5%; P = .006). At baseline, p-tau217 levels were higher in ApoE4 carriers (n = 367) compared with noncarriers (0.47 pg/ml vs 0.39 pg/ml; P <0.0001). ApoE4 carriers also demonstrated greater benefit compared with placebo, with obicetrapib stabilizing p-tau217 levels (0% increase vs. 5.7%; P = .03) and limiting increases in the p-tau217/Aβ42:Aβ40 ratio (2.1% vs. 10.2%; P = .005).

Primary investigator Philip Scheltens, MD, PhD, presented these findings at the recently concluded 2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada. During the conference, Scheltens, Emeritus Professor of Cognitive Neurology at VU University Medical Center, had a brief discussion with NeurologyLive^® on the recently presented results of the BROADWAY study. In the conversation, Scheltens, who also serves as the head of the EQT Life Sciences Dementia Fund, highlighted that these data may support the dual therapeutic potential of obicetrapib to treat both cardiovascular and neurodegenerative diseases.

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REFERENCES
1. Davidson M, Szarek M, Nicholls S, et al. Effects of Obicetrapib, a Potent Oral CETP Inhibitor, on Alzheimer's Disease Biomarkers in 1727 Patients with cardiovascular disease. Presented at: 2025 Alzheimer’s Association International Conference; July 27-31; Toronto, Canada. Abstract 108443.