Population Pharmacokinetic/Pharmacodynamic Modeling of Donidalorsen, an Antisense Oligonucleotide in Development for Prophylaxis of Hereditary Angioedema.

ABSTRACT: Hereditary angioedema (HAE) is a rare disorder linked to kallikrein-kinin system dysregulation, which leads to uncontrolled activation of plasma prekallikrein. Donidalorsen is an antisense oligonucleotide designed to selectively degrade prekallikrein messenger RNA and thereby reduce prekallikrein production. We aimed to develop population pharmacokinetic and pharmacokinetic/pharmacodynamic models of donidalorsen and evaluate the impact of potential intrinsic/extrinsic covariates on exposure and prekallikrein response. Plasma donidalorsen and prekallikrein data were obtained from phase 1 to 3 studies in healthy volunteers (NCT03263507, 721744-CS9) and adult and adolescent patients with HAE (NCT04030598, NCT05139810). The evaluated doses were 20, 40, 60, and 80 mg every 4 weeks (Q4W) and 80 

SUBMITTER: Diep JK 

PROVIDER: S-EPMC12862098 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature