Drugs. 2026 Jun 11. doi: 10.1007/s40265-026-02348-4. Online ahead of print.
ABSTRACT
Atherosclerotic cardiovascular disease (ASCVD) continues to be a leading cause of morbidity and mortality worldwide, with elevated low-density lipoprotein cholesterol (LDL-C) being a major modifiable risk factor. Despite the efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in LDL-C reduction, suboptimal adherence remains a significant challenge and may limit the cardiovascular benefits achievable with these therapies. Recaticimab, the first Fc-engineered anti-PCSK9 monoclonal antibody incorporating YTE mutation (M252Y/S254T/T256E), was specifically designed to prolong half-life through enhanced neonatal Fc receptor (FcRn) binding, thereby enabling ultra-long dosing intervals of up to 12 weeks. Results from three Phase III clinical trials demonstrated that recaticimab achieves potent and sustained LDL-C reductions, either as monotherapy or in combination with statins, with a favorable safety and tolerability profile. By integrating the YTE mutation-derived structural innovation with robust Phase III clinical evidence, recaticimab may help address some limitations of existing PCSK9 inhibitors, including frequent injections and suboptimal persistence in real-world use. However, whether these pharmacological advantages translate into improved cardiovascular outcomes remains to be established, particularly given that current clinical evidence is largely derived from studies conducted in Chinese populations, and thus requires further validation in broader populations. Future studies should evaluate its impact on real-world adherence, cardiovascular outcomes, and cost effectiveness.
PMID:42274993 | DOI:10.1007/s40265-026-02348-4