An evaluation of recaticimab for the treatment of hypercholesterolemia

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, by preventing the degradation of LDL receptors, either through interference in the binding of PCSK9 to LDL receptors or through silencing of PCSK9 at a molecular level, have revolutionized lipid-lowering treatment and offer the opportunity to further improve clinical outcomes for patients with hypercholesterolemia. We discuss the role of PCSK9 as a therapeutic target for hypercholesterolemia, describe the pharmacodynamics, pharmacokinetics, and metabolism of recaticimab, and report the recent clinical trials with this 'humanized' IgG1 monoclonal antibody (mAb) against PCSK9. Recaticimab has high affinity for PCSK9 that confers a prolonged duration of action. Recaticimab durably decreases LDL-cholesterol, non-HDL-cholesterol and apoB, but can also lower Lp(a). Recaticimab may offer advantages over current mAbs in clinical use in terms of its long half-life, dosing interval of up to 12 weeks, and potentially a lower cost, however, long-term concerns regarding immunogenicity remain. Longer-term studies in a variety of more diverse patient cohorts will be needed to further evaluate the efficacy, safety, and durability of recaticimab and to ascertain the best dosing schedule for cardiovascular outcome studies.