Donidalorsen is an antisense oligonucleotide targeted against plasma prekallikrein used for the prevention of attacks of hereditary angioedema. Hereditary angioedema (HAE) is a rare genetic disease characterized by recurrent episodes of severe swelling induced by excessive production of bradykinin.
- Mechanism
- Curator reviewed · 4 references
Donidalorsen is a prekallikrein-directed antisense oligonucleotide (ASO) which is covalently linked to a ligand containing three N-acetyl galactosamine (GalNAc) residues to facilitate its delivery to hepatocytes. Donidalorsen binds to plasma prekallikrein (PKK) mRNA, resulting in ribonuclease H1 (RNase H1)-mediated degradation of the PKK mRNA and a subsequent reduction in the production of PKK protein, a pro-enzyme for plasma kallikrein.
In patients with HAE, C1-inhibitor deficiency or dysfunction leads to excessive plasma kallikrein activity and bradykinin generation, which causes angioedema attacks. By lowering PKK concentration, donidalorsen prevents excessive kallikrein-induced bradykinin production in patients with HAE.
- Primary indication
- Donidalorsen is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older.Curator reviewed · 1 structured indication
- First approval
- United States, 2025 · European Union, 2026
- Also known as
- DNA, D((2'-O-(2-METHOXYETHYL))M5RU-SP-(2'-O-(2-METHOXYETHYL))RG-SP-(2'-O-(2-METHOXYETHYL))M5RC-(2'-O-(2-METHOXYETHYL))RA-(2'-O-(2-METHOXYETHYL))RA-SP-G-SP-T-SP-M5C-SP-T-SP-M5C-SP-T-SP-T-SP-G-SP-G-SP-M5C-SP-(2'-O-(2-METHOXYETHYL))RA-(2'-O-(2-METHOXYETHYL)
- Code names
- ISIS-721744 FREE ACID
- Brand names
Resolves to
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