Obicetrapib May Predict and Prevent Cardiovascular Disease, with Kausik Ray, FMedSci

At the 9th Annual Heart in Diabetes Conference in Philadelphia, PA, Kausik Ray, FMedSci, the immediate past president of the European Atherosclerosis Society, director of the Imperial Centre for Cardiovascular Disease Prevention and the Imperial Clinical Trials Unit-Global, and professor of public health and honorary consultant cardiologist at the Imperial College London, presented recent research on cholesteryl ester transfer protein (CETP) inhibitors and where they could be applied clinically.1

Obicetrapib, the latest CETP inhibitor and the first that may advance to clinical practice, has 3 predecessors that were cancelled in production due to insufficient efficacy or poor safety responses. Designed to raise high-density lipoprotein (HDL) and control the increase of lipoprotein (a) (LP(a)) to prevent atherosclerotic cardiovascular disease and ischemic stroke, CETP inhibitors also exhibited the effect of reducing low-density lipoprotein (LDL). This has led to a general shift in perception to identify LP(a) as the core indicator behind cardiovascular risk.2

Ray spoke on the difficult history of CETP inhibitors, acknowledging the shortcomings of the potentially life-changing medication in the past.

“There was a whole sort of history with this where the first drug actually tested had an off-target effect of increasing blood pressure,” Ray told HCPLive. “The second of the class, dalcetrapib, didn’t change LDL or APOB and raised HDL modestly; it didn’t have any benefit on outcomes. The third of these showed a modest change in LDL and a large increase in HDL but was probably terminated prematurely.”

Obicetrapib, the most recent CETP inhibitor in the pipeline, is still currently in development; however, recent trials have suggested that it may also be the first to enter clinical practice. Ray also noted the results from the recent BROADWAY study, which investigated patients simultaneously taking a high-intensity statin and obicetrapib.

“It reduced LDL cholesterol by around 33% and APOB by around 24%. So, it’s actually changing all the things that you want it to,” Ray said. “But interestingly, there are a couple of other things as well: lipoprotein (a) went down somewhere between 35 and 48%.”

A later trial on which Ray presented data, called TANDEM, utilized a fixed-dose combination of ezetimibe and obicetrapib. Ray expounded on these results and the optimism that they inspired in investigators.

“The two together gave you 48% lowering of LDL. More patients got to goal on a background of statin therapy; 70% of patients were getting to these really low targets that we now aim for below 55 in our patients,” Ray told HCPLive. “And we also saw LP(a) reductions as well with no safety signal.”

Despite the difficult history surrounding CETP inhibitors, Ray anticipates little to no uncertainty in clinicians utilizing obicetrapib should it be approved for cardiovascular disease prevention.

“I think that this has been approved by the FDA and the European Medicines Agency for LDL lowering based on a whole host of background data from genetics on target reduction,” Ray said. “You’ve got to provide enough safety data, which we have seen. I think that if clinicians know about LDL lowering, they know about the unmet need.”

Additionally, with no other CETP inhibitors in the pipeline or on the horizon, Ray anticipates obicetrapib becoming the first and only CEPT treatment accepted for clinical use in treating cardiovascular disease.

“It’s potentially twice as powerful as bempedoic acid in that regard, so that’s why I think it will be really much more interesting for our physicians and patients,” Ray said.

Ray reports the following disclosures: Amgen, Abbott Laboratories, Astra Zeneca, Esperion, Kowa, Regeneron, Sanofi, and others.

References

1. Ray K. CETP Inhibition – Where Might They Fit in Clinical Practice. Presented at the 9th Annual Heart in Diabetes Conference in Philadelphia, PA, June 6-8, 2025.

2. Averna M, Cefalù AB. LP(a): The new marker of high cardiovascular risk. Nutr Metab Cardiovasc Dis. 2025;35(3):103845. doi:10.1016/j.numecd.2024.103845