Efficacy and safety of Donidalorsen in Hereditary Angioedema with C1 inhibitor deficiency: a systematic review and a meta analysis

Abstract

Hereditary angioedema with C1 inhibitor deficiency (HAE-C1-INH) is a rare disorder characterized by recurrent, potentially life-threatening swelling in various parts of the body, including the limbs, face, and airways Current treatments focus primarily on symptomatic relief and the management of acute attacks, without targeting the underlying genetic cause or the dysregulated bradykinin production. Donidalorsen, a novel antisense oligonucleotide, addresses a key driver of HAE-C1-INH by targeting prekallikrein (PKK) to reduce bradykinin levels. This meta-analysis evaluates the efficacy and safety of Donidalorsen versus placebo, focusing on two dosing regimens: 4-week and 8-week intervals. Data from two randomized controlled trials (110 patients) revealed that Donidalorsen significantly reduced the frequency of HAE-C1-INH attacks, with the 4-week regimen showing superior outcomes compared to the 8-week dosing. The 4-week group also experienced fewer moderate or severe attacks and a reduced need for on-demand therapy. Adverse events were comparable between the Donidalorsen and placebo groups. These findings suggest that more frequent dosing may optimize treatment outcomes in HAE-C1-INH.

Keywords: Attacks; Donidalorsen; Dosage; Hereditary Angioedema with C1 inhibitor deficiency; Placebo.