Key result
Obicetrapib 10 mg daily produced a placebo-adjusted reduction in Lp(a) of 37.3% (14.9 nmol/L) at 12 weeks in patients with HeFH or ASCVD.
Why the study?
The effects of the selective CETP inhibitor obicetrapib on Lp(a) levels in patients at high cardiovascular risk had not been fully elucidated.
Does obicetrapib 10 mg daily reduce Lp(a) levels in patients with HeFH or ASCVD?
Meta-Analysis (n=2,356)
Does obicetrapib 10 mg daily reduce Lp(a) levels in patients with HeFH or ASCVD?
Obicetrapib 10 mg daily significantly lowers Lp(a), LDL-C, and apoB levels in high cardiovascular risk patients, with similar absolute Lp(a) reductions across different baseline Lp(a) strata.
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Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The Lp(a) findings show an evolving story where we think this agent has the potential to lower both LDL and Lp(a).”
“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. But interestingly, there are a couple of other things as well: lipoprotein (a) went down somewhere between 35 and 48%.”
“We see the same LDL and Lp(a) lowering that we've seen previously in the programme. But it does give us some hope that the big outcome trial that we have ongoing may lead to cardiovascular benefit.”
Obicetrapib may be considered for Lp(a) lowering in HeFH or ASCVD; extends CETP inhibition to simultaneous, clinically relevant reductions in Lp(a), LDL-C, and apoB.
BACKGROUND AND AIMS: There is interest in developing lipoprotein(a) [Lp(a)] lowering therapies. Cholesteryl ester transfer protein inhibitors lower Lp(a), however the effects of the selective inhibitor obicetrapib on Lp(a) levels in high cardiovascular risk patients have not been fully elucidated. This analysis investigated the effect of obicetrapib on Lp(a). METHODS: A pooled analysis of trials evaluating the 12-week lipid effects of daily obicetrapib 10 mg compared with placebo in patients with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD) investigated the effect of obicetrapib on Lp(a) levels. RESULTS: In 2356 patients, the pooled cohort had a median age of 66 years, 36% were female with a history of ASCVD in 82%, HeFH in 27% and statin use in 91%. Median baseline lipid levels included low-density lipoprotein cholesterol (LDL-C) of 92 mg/dL, apolipoprotein B (apoB) of 87 mg/dL and Lp(a) of 42.9 nmol/L. Obicetrapib produced placebo-adjusted reductions in LDL-C of 37.0% and 35 mg/dL, in apoB of 21.3% and 20 mg/dL, and in Lp(a) of 37.3% and 14.9 nmol/L. In patients with baseline Lp(a) levels ≥50-<150 nmol/L, obicetrapib produced placebo-adjusted reductions in Lp(a) of 43.3% and 36.3 nmol/L. While patients with baseline Lp(a) ≥150 nmol/L demonstrated a lower percentage reduction in Lp(a) with obicetrapib than those with baseline levels ≥50-<150 nmol/L, the absolute reduction in Lp(a) was similar in both groups (-32.3 vs -36.3 nmol/L). CONCLUSIONS: Obicetrapib lowered LDL-C, apoB and Lp(a). The absolute reduction in Lp(a) with obicetrapib was similar in patients with mildly elevated Lp(a) levels, who are unlikely to qualify for administration of RNA-targeted Lp(a) lowering agents.
Nicholls et al. (2026) conducted a meta-analysis in Heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD) (n=2,356). Obicetrapib vs. Placebo was evaluated on Lipoprotein(a) [Lp(a)] levels (37.3% placebo-adjusted reduction). Obicetrapib 10 mg daily produced a placebo-adjusted reduction in Lp(a) of 37.3% (14.9 nmol/L) at 12 weeks in patients with HeFH or ASCVD.
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