NAARDEN, Netherlands– NewAmsterdam Pharma (NAP), a clinical-stage company focused on the research and development of transformative therapies for metabolic diseases, today announced the publication of a new review article in the European Society of Cardiology (ESC) publication Cardiovascular Research examining cholesteryl ester transfer protein (CETP) inhibition as a potentially high-impact therapeutic target for reducing major adverse cardiovascular events (MACE) such as heart attack and stroke by lowering both low density lipoprotein cholesterol (LDL-c) and apolipoprotein B (ApoB). The work was co-authored by NewAmsterdam’s chief scientific officer, John Kastelein, M.D., Ph.D., NewAmsterdam’s vice president of research and development Marc Ditmarsch, M.D., as well as Nick Nurmohamed, M.D., of Amsterdam University Medical Center.
Blocking CETP can have two major effects on a patients’ lipid profile depending on the characteristics of the CETP inhibitor: it can lower LDL-c and ApoB, and increase HDL-c. First generation CETP inhibitors focused on increasing HDL-c to reduce MACE. It is now well-understood in the cardiovascular medicine community that increasing HDL-c levels does not reduce MACE risk, but rather lowering LDL-c is the axiom for MACE reduction.
A recently published analysis of the long-term follow up of the Phase 3 cardiovascular outcome trial, REVEAL, showed that LDL-c and ApoB reduction by a CETP inhibitor results in MACE risk reduction to the same degree as any other LDL-lowering therapy, including statins.1 This observed outcome confirms findings shown in recent large Mendelian randomization studies that people with CETP loss-of-function genes have the same decreased cardiovascular outcome risk as people with mutations in the genes targeted by currently used LDL-lowering drugs.2 NewAmsterdam’s next generation CETP inhibitor, obicetrapib, is intended to lower LDL-c and ApoB, showing a 51% LDL-c reduction in patients treated with high intensity statin dosages in its Phase 2 trial, ROSE.3 Obicetrapib could become a simple, low-dose, cost-effective treatment for reducing MACE by optimizing the lipid profile of patients with atherosclerosis.
“NewAmsterdam Pharma has been working diligently to deliver an LDL-c lowering therapy that is low-dose, cost effective, once daily, and more targeted to reducing LDL-c, ApoB and the significant health risks associated with ASCVD,” said NewAmsterdam’s chief scientific officer and founder Dr. John Kastelein. “CETP loss-of-function is considered a longevity gene, and those with CETP loss-of-function are significantly less likely to develop cardiometabolic diseases, and are at less of a risk for major adverse cardiac events (MACE). This genetic validation is at the core of our research into obicetrapib, and, we believe, is one of the main reasons for its effectiveness in clinical trials.”
More than 100 million people globally are not achieving LDL-c goals despite the current available standard of care. Current lipid lowering therapies come in the form of statin therapy, ezetimibe and proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9). PCSK9 and statin therapies also come with statin intolerance and discontinuation, as well as showing a likelihood of developing new-onset diabetes in patients. CETP inhibitors, however, have proven to be effective in lowering the risk of new-onset diabetes, and improve glucose tolerance and insulin sensitivity. These reasons highlight why there continues to be a significant unmet need for future lipid-lowering therapies.
This paper examines how a CETP inhibitor like obicetrapib, which is now entering Phase 3 trials, has the potential to provide an effective, simple, low dose, once daily, cost-effective treatment for lowering cholesterol and reducing the risk for cardiovascular events.
