The efficacy of tafolecimab in lipoprotein(a) reductions in hypercholesterolaemic patients: a pooled analysis of three phase 3 trials

Background High levels of lipoprotein(a) [Lp(a)] are recognised as an independent risk factor for arteriosclerotic cardiovascular disease, particularly with Lp(a) levels >50 mg/dL. The CREDIT phase 3 trials have demonstrated that tafolecimab effectively reduces levels of low-density lipoprotein cholesterol (LDL-C) and Lp(a) in Chinese patients with hypercholesterolaemia. However, its efficacy on lowering Lp(a) among patients with very high baseline Lp(a) levels is not well defined. Purpose This study evaluated the efficacy of tafolecimab on Lp(a) in patients with hypercholesterolaemia by pooling data from three phase 3 trials. Methods This pooled analysis included 734 hypercholesterolaemic participants from three multicentre, double-blind, phase 3 randomised controlled trials, with 494 participants receiving tafolecimab 450 mg every four weeks (Q4W) and 240 participants receiving placebo Q4W. The primary efficacy endpoint was the percentage reduction in Lp(a) levels from baseline at 12 weeks. According to the 2022 European Atherosclerotic Society Lp(a) consensus statement, the baseline Lp(a) levels were categorised as: <30 mg/dL, ≥30 mg/dL but <50 mg/dL, and ≥50 mg/dL. Results At baseline, the mean Lp(a) levels were comparable between the tafolecimab and placebo groups (22.9 mg/dL vs. 23.4 mg/dL, P > 0.05). By week 12, tafolecimab significantly reduced Lp(a) levels compared to placebo (-10 mg/dL vs. -1 mg/dL, P < 0.0001). A significantly greater proportion of participants treated with tafolecimab achieved a >50% reduction in Lp(a) levels than the placebo group (36.5% vs 6.7%, P < 0.0001). Additionally, for participants with baseline Lp(a) levels <30 mg/dL and Lp(a) ≥50 mg/dL, tafolecimab induced significant reductions in Lp(a) compared with placebo at week 12 [Lp(a) <30 mg/dL: mean difference=-33.82%, 95% CI: -39.77%, -27.87%; Lp(a) ≥50 mg/dL: mean difference=-33.66%, 95% CI: -43.55%, -23.76%]. Those with baseline Lp(a) levels between 30 and 50 mg/dL experienced a more potent reduction of Lp(a) levels (mean difference=-41.38%, 95% CI: -53.91%, -28.84%). Conclusions Tafolecimab 450 mg Q4W offers greater reductions in Lp(a) levels in hypercholesterolaemic patients with higher initial Lp(a) levels, which provides a novel therapeutic option for improving Lp(a) and preventing cardiovascular risks for this patient population.