Hypercholesterolemia is clinically defined by the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and the 2020 National Lipid Association (NLA) guidelines as total cholesterol levels ≥200 mg/dL (5.2 mmol/L), non-high-density lipoprotein cholesterol (non-HDL-C) ≥160 mg/dL (4.1 mmol/L), or low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL (3.4 mmol/L), owing to their predictive value for atherosclerotic cardiovascular disease (ASCVD) (1,2). The 2016 Chinese Society of Cardiology (CSC) guidelines further define hypercholesterolemia within the local clinical framework, setting thresholds of total cholesterol ≥6.2 mmol/L (240 mg/dL) or LDL-C ≥4.1 mmol/L (160 mg/dL), which are particularly relevant given the approval of Ongericimab in China (3). Primary isolated hypercholesterolemia is characterized by LDL-C ≥190 mg/dL (5 mmol/L) with triglycerides (TGs) (<150 mg/dL or 1.7 mmol/L), while combined hyperlipidemia is defined by triglycerides ≥150 mg/dL (1.7 mmol/L) and high non-HDL-C, according to European Atherosclerosis Society (EAS) guidelines (4,5). In familial hypercholesterolemia, which represents the genetic form of the disease, mutations in the low-density lipid receptor genes lead to impaired hepatic LDL clearance (6). The liver is responsible for metabolizing approximately 66% of circulating LDL, and defects in LDL receptor function or expression contribute to persistently elevated blood LDL-C levels (6).

Globally, familial hypercholesterolemia is present in almost 0.32% (1 in 313 individuals) of the population. This figure rises to 3.2% in patients with ischemic heart disease (IHD) and to 6.7% in those with premature (5,7). In China, the prevalence of hypercholesterolemia has risen nearly fourfold (1.6% to 6.0%) in ten years (2002-2012) (8). In the United States, the CDC reported high total cholesterol to be prevalent in 11.3% of Americans from August 2021 to August 2023. Furthermore, these values are comparable between both genders (9). Although statins are considered the best cholesterol-lowering drugs for treating hypercholesterolemia, around 9.1% of individuals are affected by statin-associated intolerance, and some are contraindicated for statins due to clinical reasons (10,11). This highlights the need for novel therapies targeting hepatic catabolism of apoB-containing lipoproteins (11). According to recent studies, Ongericimab (JS002) is one of those novel, long-acting monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) (12). PCSK9 acts on LDL-receptors present on hepatocytes by promoting their degradation and inhibiting their recycling. Consequently, the uptake of LDL-cholesterol by the hepatocytes is reduced (12). Ongericimab acts as a selective inhibitor of PCSK9, promoting recycling of LDL receptors and limiting their degradation by PCSK9. This leads to increased clearance of LDL-C by hepatocytes. Subsequently, a marked reduction in plasma low-density lipid cholesterol levels is observed. Hence, the Ongericimab can serve as a core therapeutic agent in Atherosclerotic Cardiovascular Disease (ASCVD) prevention (12).

Recent clinical trials have demonstrated promising outcomes for Ongericimab in lowering LDL-C and improving lipid profiles. A randomized controlled trial reported significant LDL-C reductions in patients with primary hypercholesterolemia and mixed hyperlipidemia upon the subcutaneous administration of Ongericimab (13). In a recent phase 3 trial with 139 participants, Ongericimab reduced LDL-C by 66.2% on a least-squares mean basis when compared to a placebo from baseline to week 12, and the effect persisted until week 52. It also resulted in notable decreases in Lipoprotein(a) [Lp(a)], total cholesterol, ApoB, and non-HDL-C (14). Additional evidence from a study on Chinese patients with heterozygous familial hypercholesterolemia showed that Ongericimab led to a marked decrease in low-density lipid-cholesterol at week 24 (15).

Despite multiple recent RCTs conducted in China, no meta-analysis has yet synthesized these findings. Given the rising prevalence of hypercholesterolemia globally and regionally, a systematic evaluation of Ongericimab’s efficacy and safety is both timely and clinically necessary. The present study is, to our knowledge, the first meta-analysis to pool available RCT data on Ongericimab, thereby providing clinicians with a comprehensive, evidence-based assessment of its therapeutic potential.