• Obicetrapib significantly reduces LDL cholesterol levels in high-risk individuals, even when added to existing lipid-lowering therapies.
• A combination of obicetrapib and ezetimibe shows even greater LDL cholesterol reduction, offering a potential new treatment option.
• Inclisiran, administered twice yearly, effectively lowers LDL cholesterol in lower-risk individuals, offering better compliance and potential benefits as monotherapy.

Recent clinical trials have highlighted the potential of obicetrapib, a CETP inhibitor, in significantly reducing LDL cholesterol levels. The BROADWAY trial demonstrated substantial improvements in LDL, HDL, apoB, and Lp(a) in high-risk individuals. The TANDEM trial showed that a combination of obicetrapib and ezetimibe reduced LDL cholesterol by nearly 50%. Another trial, VICTORION-Mono, focused on inclisiran as a monotherapy option. These developments offer new hope for patients struggling to manage their cholesterol levels and reduce cardiovascular risk.

• What: Obicetrapib is a CETP inhibitor under investigation for its ability to lower LDL cholesterol levels. Inclisiran is being investigated as monotherapy to also lower LDL Cholesterol.
• Who: Key individuals involved include Stephen Nicholls (Victorian Heart Institute), Ashish Sarraju (Cleveland Clinic), R. Scott Wright (Mayo Clinic), Pam Taub (University of California San Diego), and researchers from NewAmsterdam Pharma and Novartis.
• When: The research was presented at the European Atherosclerosis Society Annual Congress in May 2025. The BROADWAY and TANDEM trials results were published in the New England Journal of Medicine and The Lancet, respectively.
• Where: The BROADWAY trial was conducted at 188 sites in China, Europe, Japan, and the U.S. The TANDEM trial involved 48 U.S. sites.

The studies on obicetrapib and inclisiran indicate significant advancements in LDL cholesterol management. Obicetrapib, particularly in combination with ezetimibe, demonstrates substantial LDL reduction, potentially offering a new option for high-risk patients. However, the discontinuation rate in the BROADWAY trial and the lack of long-term data are concerns. Inclisiran offers a novel approach with its twice-yearly administration, potentially improving compliance, although cost remains a significant barrier. The ongoing PREVAIL and ORION-4 trials are crucial for determining the long-term cardiovascular benefits of these therapies.

"These findings suggest that obicetrapib may be a useful adjunct to lipid lowering in patients at high risk for cardiovascular events,"

"We need to give patients and their doctors all the options we can to try to get LDL under control if they are at risk for, or already have, cardiovascular disease."

"Many experts now recommend starting treatment with combination therapies rather than try a single medication and adding additional therapies later. This strategy gets more patients to goal more quickly and makes good sense for high-risk patients."

"Statin therapy has really improved outcomes in atherosclerotic cardiovascular disease, but what we continue to see in practice is that a growing number of patients are statin-hesitant."

Obicetrapib, as a monotherapy or combined with ezetimibe, demonstrates significant promise in reducing LDL cholesterol and potentially lowering cardiovascular risk. The ongoing PREVAIL trial is crucial for providing data on long-term cardiovascular outcomes and will evaluate obicetrapib's effect on major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, stroke, and non-elective coronary revascularization. Obicetrapib has also exhibited a favorable safety profile in trials. Inclisiran emerges as a potential monotherapy option with a convenient twice-yearly injection schedule and has shown sustained LDL-C reduction over several years. Studies like ORION-3 have confirmed long-term efficacy and safety. While inclisiran has demonstrated effectiveness in lowering LDL-C, its impact on long-term cardiovascular outcomes is still being investigated. Cost-effectiveness remains a key consideration for both therapies.