Recaticimab in adult heterozygous familial hypercholesterolaemia (REMAIN-3): a multicentre, randomized, double-blind, placebo-controlled Phase 3 study

Abstract Aims Heterozygous familial hypercholesterolaemia (HeFH) is a genetic disorder, characterized by high plasma concentrations of low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the efficacy and safety of recaticimab, a new humanized anti-PCSK9 antibody capable of reducing LDL-C levels in patients with poorly controlled HeFH. Methods and results REMAIN-3 was a multicentre, randomized, double-blind, placebo-controlled Phase 3 study done at 25 sites in China. Patients with a genetic or clinical diagnosis of HeFH, who were on stable lipid-lowering therapy for ≥28 days, had fasting LDL-C ≥ 2.6 mmol/L (or ≥1.8 mmol/L for those with a history of atherosclerotic cardiovascular disease), and had fasting triglyceride ≤5.6 mmol/L, were randomly allocated in a 2:1 ratio to receive subcutaneous recaticimab at 150 mg or matching placebo every 4 weeks for 12 weeks. The primary endpoint was the percentage change in LDL-C from baseline to Week 12. Overall, 143 patients underwent randomization and received recaticimab (n = 95) or placebo (n = 48). At Week 12, the mean percentage change in LDL-C from baseline was −54.4% (95% CI, −57.9 to −50.8%) in the recaticimab group and −4.5% (95% CI, −9.4 to 0.3%) in the placebo group, with a treatment difference of −49.8% (95% CI, −55.8 to −43.9%; P < 0.0001). Recaticimab was superior to placebo in improving other lipid variables, including non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein a. Treatment-related adverse events (TRAEs) were comparable between groups (27.4% with recaticimab vs. 25.0% with placebo). The most common TRAEs occurring more frequently with recaticimab than placebo were injection site reaction (8.4% vs. 0%) and increased blood creatine phosphokinase (5.3% vs. 2.1%). Conclusion Recaticimab significantly lowered the LDL-C level compared with placebo, with an acceptable safety profile, providing a new effective treatment option for patients with inadequately controlled HeFH. Registration ClinicalTrials.gov Identifier: NCT04844125