Donidalorsen: a promising switch option in HAE care

Published online July 17, 2025

Hereditary angioedema (HAE) is a rare but serious genetic condition that causes unpredictable episodes of swelling, sometimes leading to life-threatening airway obstruction. Many patients rely on long-term prophylaxis (preventive treatment) to reduce the frequency and severity of attacks. Current options, such as C1 esterase inhibitor replacement therapy, lanadelumab, and berotralstat, have improved outcomes but can still be burdensome due to frequent dosing, side effects, or incomplete disease control. There remains a need for preventive therapies that are both effective and more convenient for patients.

In a new study published in The Journal of Allergy and Clinical Immunology: In Practice, Riedl et al. evaluated donidalorsen, an RNA-targeted therapy designed to reduce levels of plasma prekallikrein, a key driver of HAE attacks. Sixty-five patients who had been receiving long-term prophylaxis were enrolled in the open-label OASISplus Switch trial. Participants were transitioned to donidalorsen 80 mg injected subcutaneously (under the skin) once every four weeks, following a specific protocol for changing medications to minimize risk during the switch. Researchers assessed safety, frequency of HAE attacks, quality of life, disease control, and patient treatment preference at 16 weeks.

Results showed that donidalorsen was well tolerated, with most side effects being mild or moderate and unrelated to treatment. Importantly, as compared to baseline on their prior prophylactic agent, HAE attack rates dropped by an average of 62% by Week 16 after switching, and patients reported meaningful improvements in quality of life (assessed by the Angioedema Quality of Life questionnaire) and symptom control. By Week 16, 93% of patients had well-controlled disease, as measured by the Angioedema Control Test, compared with 67% before the switch. Strikingly, 84% of patients said they preferred donidalorsen over their prior treatment, citing fewer attacks, less injection pain, and greater convenience. These interim findings suggest donidalorsen may offer a valuable new option for patients with HAE, particularly those seeking improved disease control and reduced treatment burden. Longer-term results will clarify donidalorsen’s role in clinical practice.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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