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 a 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 optimal dosing schedule for cardiovascular outcome studies.