Antisense Inhibition of Prekallikrein to Control Hereditary Angioedema.

Cohn, Danny M; Viney, Nicholas J; Fijen, Lauré M; Schneider, Eugene; Alexander, Veronica J; Xia, Shuting; Kaeser, Gwendolyn E; Nanavati, Charvi et al. · N Engl J Med · 2020

case_report · Level V

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Abstract

Hereditary angioedema is characterized by recurrent and unpredictable episodes of subcutaneous and mucosal swelling that can be life threatening. IONIS-PKK-L<sub>Rx</sub> is a ligand-conjugated antisense oligonucleotide designed for receptor-mediated delivery to hepatocytes. In a compassionate-use pilot study, two patients with severe bradykinin-mediated angioedema were initially administered weekly subcutaneous injections of the unconjugated parent drug, IONIS-PKK<sub>Rx</sub>, for 12 to 16 weeks, after which they received IONIS-PKK-L<sub>Rx</sub> at a dose of 80 mg every 3 to 4 weeks for 7 to 8 months. Treatment was accompanied by a reduction in the angioedema attack rate. (Funded by Amsterdam UMC.).

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