Literature Review Indicates Efficacy of Obicetrapib in Treating Hyperlipidemia

According to a recent systematic review and meta-analysis of previous phase 2/3 trials, obicetrapib improves the lipoprotein profile by lowering atherogenic lipids and increasing HDL markers, establishing it as a potential adjunct in hyperlipidemia therapy.1

A highly selective cholesteryl ester transfer protein inhibitor that reduces low-density lipoprotein cholesterol (LDL-C) levels, obicetrapib’s safety data have only recently been characterized. Recent trials, such as BROADWAY and TANDEM, have provided substantial data regarding obicetrapib’s LDL-lowering efficacy. Investigators posited that the inclusion of these and similar trials will reinforce the evidence base of obicetrapib’s safety and efficacy.1,2

“Hence, a PRISMA-compliant meta-analysis encompassing all recent randomized controlled trials on obicetrapib is warranted,” wrote Shariq Ahmad Wani, MBBS, department of internal medicine, Wayne State University, and colleagues. “Such an updated quantitative synthesis will elucidate the extent of obicetrapib’s impact on LDL-C, ApoB, non-HDL-C, HDL-C, triglycerides, and Lp(a), thus addressing previous limitations related to sample size and informing its potential clinical role.”1

Studies were included if they examined obicetrapib (or TA-8995), involved patients with hyperlipidemia, and included summary statistics for the mean difference before and after the intervention was available. Studies were excluded if they were animal or preclinical studies, lacked a control or placebo comparator, had inadequate data to compute effect estimates, or had intervention periods shorter than 4 weeks.1

The team determined the lipid-lowering effects of obicetrapib by calculating the mean differences in lipid parameters before and after treatment. The primary meta-analysis included all treatment arms, including 5 mg and 10 mg monotherapy, as well as 10 mg combined with ezetimibe. Subgroup analyses were conducted to evaluate each arm separately.1

Ultimately, 7 randomized controlled trials (RCTs) were included in the study, comprising 3681 participants. Most of these trials were parallel-group, double-blind phase 2/3 studies, which were conducted between 2014 and 2025. Sample sizes ran from 61 to 2530 with follow-up durations between 2 and 52 weeks. The mean age of participants was roughly 65 years. Median body mass index (BMI) was recorded as 28 kg/m2.1

Baseline low-density lipoprotein cholesterol (LDL-C) averaged roughly 105 mg/dL-1, with a range of 88 to 139 mg/dL-1, regardless of administration of maximally tolerated lipid-lowering therapy. Over 70% of participants were receiving concurrent statin treatment.1

Pooling 1948 participants receiving obicetrapib and 1130 participants receiving placebo resulted in a mean LDL-C reduction of -25.82 mg/dL (95% CI, -33.52 to -18.12; P <.00001), with a percentage change of roughly -24.8% from baseline 88 mg/dL. After conducting subgroup analyses by dosage, investigators found a magnitude effect of -22.7 mg/dL (95% CI, -36.49 to -8.91; P = .001) for a dosage of 5 mg, -24.01 mg/dL (95% CI, -33.66 to -14.35; P <.00001) for a dosage of 10 mg, and -45 mg/dL (95% CI, -54.06 to -35.94; P <.01) for a dosage of 10 mg combined with ezetimibe.1

Another 13 trial arms (n = 2172 obicetrapib, n = 1350 placebo) examined high-density lipoprotein cholesterol (HDL-C). A 5 mg dose of obicetrapib resulted in a mean difference (MD) of 132.9 mg/dL (95% CI, 110.6 to 155.2; P <.01), a dose of 10 mg saw an MD of 149.1 mg/dL (95% CI, 129.5 to 168.8; P <.01), and a 10 mg combination with ezetimibe resulted in an MD of 132.6 mg/dL (95% CI, 120.6 to 144.6; P <.01).1

Additionally, investigators found a substantial rise in apolipoprotein A1 (MD 141.9 mg/dL), while triglycerides remained stable (MD 1 mg/dL) and very low-density lipoprotein (VLDL) decreased modestly at the lowest dose (MD -3.8 mg/dL).1

“Long-term follow-up is crucial to confirm sustained efficacy, monitor for rare adverse events (e.g., age-related macular degeneration as suggested in preclinical CETP models), and establish real-world tolerability,” Ahmad Wani and colleagues wrote. “Collectively, these future pathways will be critical in transitioning obicetrapib from a potent lipid-lowering agent to a fully validated, outcome-proven cardiovascular therapy.”1

References

1. Ahmad Wani S, Naveed MA, Ali A, et al. Updated meta-analysis of the lipid-lowering efficacy of Obicetrapib: A comprehensive review of Randomized Controlled Trials. Journal of Clinical Lipidology. Published online August 6, 2025. doi:10.1016/j.jacl.2025.08.002

2. Nicholls SJ, Nelson AJ, Ditmarsch M, et al. Safety and efficacy of Obicetrapib in patients at high cardiovascular risk. New England Journal of Medicine. 2025;393(1):51-61. doi:10.1056/nejmoa2415820