Antisense Inhibition of Prekallikrein to Control Hereditary Angioedema

N Engl J Med. 2020 Sep 24;383(13):1242-1247. doi: 10.1056/NEJMoa1915035. Epub 2020 Sep 2.

Abstract

Hereditary angioedema is characterized by recurrent and unpredictable episodes of subcutaneous and mucosal swelling that can be life threatening. IONIS-PKK-LRx 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-PKKRx, for 12 to 16 weeks, after which they received IONIS-PKK-LRx 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.).

Publication types

  • Case Reports
  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angioedemas, Hereditary / drug therapy*
  • Angioedemas, Hereditary / metabolism
  • Bradykinin / metabolism
  • Compassionate Use Trials
  • Female
  • Humans
  • Injections, Subcutaneous
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / therapeutic use*
  • Pilot Projects
  • Prekallikrein / antagonists & inhibitors*
  • Prekallikrein / metabolism

Substances

  • Oligonucleotides, Antisense
  • Prekallikrein
  • Bradykinin