ESC Congress 2026 Abstract · Oct 26, 2026

Ticalicibart monthly as add-on therapy to statins for nonfamilial hypercholesterolemia: the randomized, phase 3 TIMER trial

By Xu C, Li T, Wu Y et al.

Background: Existing anti-PCSK9 monoclonal antibodies (mAbs) reduce low-density lipoprotein cholesterol (LDL-C) effectively. However, these mAbs require frequent dosing. SAL003 is a novel fully human IgG2 anti-PCSK9 mAb engineered for an extended half-life (~45 days), which allows once-monthly dosing. Objectives: To evaluate the efficacy and safety of SAL003 140 mg every 4 weeks (Q4W) added to stable statin therapy in adults with nonfamilial hypercholesterolemia and residual cardiovascular risk. Methods: TIMER was a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial conducted at 64 sites in China. After a 4-week statin run-in, patients with LDL-C ≥1.8 mmol/L and atherosclerotic cardiovascular disease (ASCVD), or ≥2.6 mmol/L without ASCVD, despite moderate- or high-intensity statin were randomized 2:1 to SAL003 140 mg or matching placebo Q4W for 24 weeks (double-blind), followed by an open-label extension to 52 weeks where all participants received SAL003. Results: Between December 2023 and June 2025, 729 patients were randomized (SAL003 n = 484; placebo n = 245). Mean age was 58.3 ± 9.8 years, 59 % were male, 56 % had ASCVD, and baseline LDL-C was 3.22 ± 1.01 mmol/L. At week 24, SAL003 reduced LDL-C by a least-squares mean of −65.9% compared with −15.1% with placebo (between-group difference −50.9%; 95% CI −53.8 to −47.9). The proportion achieving target LDL-C (< 1.8 mmol/L ASCVD; < 2.6 mmol/L non-ASCVD) was 89.4 % vs 14.0 % (p < 0.001). Absolute LDL-C reduction was –2.22 mmol/L versus –0.64 mmol/L (p < 0.001). Consistent benefits were observed across all pre-specified subgroups, including age ≥ 65 years, diabetes, chronic kidney disease.Non-HDL-C fell by –57.9 %, ApoB by –56.6 %, and Lp(a) by –21.6 % with SAL003 versus –10.1 %, –9.4 %, and +17.6 % with placebo, respectively (all p < 0.001). During the open-label extension (weeks 25–52), LDL-C reductions were sustained (–55.5 % from baseline) and patients crossing over from placebo achieved comparable LDL-C lowering (−59.5%) without evidence of attenuation. Treatment-emergent adverse events (TEAEs) occurred in 61.0 % of SAL003 and 65.2 % of placebo recipients during the double-blind phase; most were mild. Injection-site reactions were infrequent (1.1 % vs 2.5 %). Serious adverse events were balanced (6.0 % vs 4.1 %); no treatment-related deaths occurred. Anti-drug antibodies developed in 3.0 % of patients and did not appear to affect efficacy. Conclusions: Once-monthly SAL003 140 mg added to statin therapy produced rapid, potent, and durable LDL-C reduction with high target attainment and an acceptable safety profile. The extended-dosing interval offers a practical advantage over existing shorter-acting PCSK9 mAbs and may enhance real-world adherence for long-term cardiovascular risk reduction.

doi.org/10.1093/eurheartj/ehag785.4168Open accessInterventions