Berotralstat effectiveness and safety in patients with hereditary angioedema with normal C1 inhibitor.

Background: Hereditary angioedema (HAE) with normal C1 inhibitor (nC1-INH) is the least common endotype of HAE, a rare disorder with localized, intermittent attacks of soft tissue swelling. Prophylactic treatments are available across HAE endotypes, including berotralstat, a once-daily oral inhibitor of plasma kallikrein. Objective: This European multicenter case series aimed to report treatment-related outcomes with berotralstat in patients with HAE-nC1-INH. Methods: A retrospective case series analysis including observational data from patients in United Kingdom and French centers was performed. Patients were included if they had a genetic assay demonstrating a known HAE-nC1-INH-associated variant; or had a family history of angioedema and normal C1-INH level and function, no response to antihistamine treatment, met predefined diagnostic criteria for HAE-nC1-INH, and had been prescribed berotralstat 150 mg daily for at least 6 months. Data were collected from the patients' records using a standardized form. Results: Four female and 2 male patients with HAE-nC1-INH were included from 4 centers in France and the United Kingdom. Duration of berotralstat treatment at analysis ranged from 6 to 23 months. Five patients showed a response to berotralstat, observed as a 29-100% reduction in attack rates. Three patients experienced a reduction in attack severity from moderate to minor or mild. One patient reported adverse events during berotralstat initiation: nausea and diarrhea. Conclusion: Long-term prophylactic berotralstat was effective in reducing HAE attacks for 5 of 6 patients with HAE-nC1-INH. No significant safety signals were noted.