donidalorsen for preventing recurrent attacks of hereditary angioedema

Donidalorsen is a liver-targeted antisense oligonucleotide (ASO) conjugate that binds to prekallikrein (PKK) mRNA, leading to its RNase H1-mediated degradation

• this process decreases the production of PKK protein, reducing plasma kallikrein activity and preventing the overproduction of bradykinin responsible for hereditary angioedema (HAE) attacks
• the Phase III OASIS-HAE trial (1) found that donidalorsen significantly reduces swelling attacks and improves quality of life in patients with hereditary angioedema
  • administered subcutaneously, the drug showed an 81% reduction in attack rates at 4-week intervals compared to placebo
  • the most common adverse events were erythema at the injection site, headache, and nasopharyngitis; 98% of adverse events were mild or moderate in severity

NICE state (2):

Donidalorsen can be used as an option to prevent recurrent attacks of hereditary angioedema (HAE) in people 12 years and over, only if:

• they have 2 or more attacks a month, and
• the company provides it according to the commercial arrangement

Reference:

1. Riedl MA et al, Efficacy and Safety of Donidalorsen for Hereditary Angioedema. ,N Engl J Med 2024;391:21-31.
2. NICE (August 2026). Donidalorsen for preventing recurrent attacks of hereditary angioedema in people 12 years and over.