Interim Analysis of an Open-Label, Ascending-Dose, Phase 1 Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Doses of the Subcutaneously Administered Human Monoclonal Antibody Pozelimab in Combination with Single Doses of the Subcutaneously Administered siRNA Cemdisiran in Healthy Volunteers

Introduction. Pozelimab (REGN3918) and cemdisiran (ALN-CC5) are C5 inhibitors under development for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), myasthenia gravis (MG), and other diseases in which tissue damage is mediated by terminal complement pathway activity. Pozelimab is a fully human monoclonal immunoglobulin G4P (IgG4P) antibody directed against C5, and cemdisiran is a synthetic small interfering RNA (siRNA) targeting C5 mRNA. Both agents can be administered via subcutaneous (SC) injection. Pharmacokinetic (PK)/pharmacodynamic (PD) modeling based on observed data from both pozelimab and cemdisiran healthy volunteer studies (NCT03115996, NCT02352493) suggests that, by combining cemdisiran and pozelimab, the dose of both agents may be significantly reduced and the interval for SC dosing of pozelimab may be significantly increased.