Donidalorsen Treatment of Hereditary Angioedema in Patients Previously on Long-Term Prophylaxis

Hereditary angioedema (HAE) is a rare, potentially life-threatening disorder characterized by episodes of tissue swelling. Donidalorsen, an investigational ligand-conjugated antisense oligonucleotide, reduces plasma prekallikrein production.

We report an interim analysis on safety, efficacy, quality of life (QoL), and treatment preference and satisfaction from an ongoing open-label phase 3 study (OASISplus Switch cohort, NCT05392114).

Patients with HAE receiving stable doses (≥12 weeks) of lanadelumab, complement protein 1 inhibitor, or berotralstat switched to donidalorsen 80 mg subcutaneously every 4 weeks, using a predefined algorithm. The primary end point was the incidence and severity of treatment-emergent adverse events. Other end points included change in HAE attack rate, angioedema-QoL score, disease control (≥10 points on the Angioedema Control Test), and treatment preference and satisfaction at week 16, compared with baseline on prior treatment.

A total of 65 patients were enrolled; 32 switched from lanadelumab, 22 from complement protein 1 inhibitor, and 11 from berotralstat. At cutoff, 58 were ongoing in the study (89%). Forty-five patients (70%) reported treatment-emergent adverse events; 62% were unrelated to donidalorsen. At week 16, total HAE attack rates had decreased by 62%. Hereditary angioedema attack rates decreased by 65%, 41%, and 73%, and mean angioedema-QoL scores improved by 8.4, 9.6, and 17.1 points for patients switching from lanadelumab, C1INH, and berotralstat, respectively. More patients reported well-controlled disease (93% vs 67%), and most patients preferred donidalorsen over their prior treatment, with improved treatment satisfaction.

Donidalorsen was well tolerated, decreased HAE attack rate, and improved QoL and disease control. Most patients preferred donidalorsen over their prior treatment. Further analyses are planned at week 52.