Long-term prophylactic treatment with deucrictibant for angioedema due to acquired C1-inhibitor deficiency

Background: Angioedema due to acquired C1-inhibitor deficiency (AAE-C1INH) is a rare disorder characterized by recurrent episodes of angioedema due to excessive bradykinin release. Deucrictibant, an oral B2 receptor antagonist, is currently under development for long-term prophylactic and on-demand treatment in hereditary angioedema. In a recent small double-blind, placebo-controlled crossover trial (EudraCT no. 2021-000720-36), all 3 participants with AAE-C1INH had complete control of angioedema during 8 weeks of treatment with deucrictibant immediate-release capsule. Objective: We investigated the long-term efficacy and safety of deucrictibant extended-release tablet as prophylactic treatment in patients with AAE-C1INH. Methods: In this open-label, single-arm study, patients with AAE-C1INH received deucrictibant 40 mg extended-release tablet once daily. The primary end point was the time-normalized number of investigator-confirmed angioedema attacks per 28 days of exposure to deucrictibant compared to baseline. Results: Four patients with AAE-C1INH were enrolled, 3 of whom were rolled over from the randomized controlled trial of immediate-release deucrictibant. The on-treatment follow-up duration in this study ranged from 563 to 612 days. The mean monthly attack rates at baseline were 1.2, 1.2, 0.9, and 2.1, respectively (mean, 1.35). One mild abdominal attack was reported by one patient 2 days after initiation of deucrictibant treatment; the remaining patients were attack-free during the treatment period. The mean monthly angioedema attack rate for all patients was 0.01. No treatment-related adverse events were reported. Conclusion: Deucrictibant extended-release tablet effectively prevented angioedema attacks in patients with AAE-C1INH, with no safety concerns.