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Frovocimab (LY 3015014) is a humanized IgG4 monoclonal antibody (mAb) that neutralizes PCSK9. Frovocimab inhibits PCSK9 binding to LDL receptor (LDLR) while permitting the normal proteolytic cleavage of the bound intact PCSK9[1]. | [in vivo]
Frovocimab (LY 3015014; 10 mg/kg; i.v; once) causes significant PCSK9 accumulation, its duration of LDL lowering is reduced, and its clearance (CL) from serum is accelerated in mice expressing a noncleavable variant of human PCSK9[1].
Frovocimab (LY 3015014; 5 mg/kg; i.v; once) decreases LDL cholesterol in monkeys and, unlike other PCSK9 mAbs, does not cause an accumulation of intact PCSK9 in serum[1]. | Animal Model: | Male C57BL/6NTac mice injected with vector containing the NC R215A/R218A variant[1] | | Dosage: | 10 mg/kg | | Administration: | i.v; once | | Result: | Caused significant PCSK9 accumulation.
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| Animal Model: | Cynomolgus monkeys[1] | | Dosage: | 5 mg/kg | | Administration: | i.v; once | | Result: | Decreased LDL cholesterol in monkeys. |
| [References]
[1] Krista M Schroeder, et al. Proteolytic cleavage of antigen extends the durability of an anti-PCSK9 monoclonal antibody. J Lipid Res. 2015 Nov;56(11):2124-32. DOI:10.1194/jlr.M061903 |
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