[EFFICACY, PHARMACOKINETICS, PHARMACODYNAMICS, AND SAFETY OF INTRAVENOUS C1 INHIBITOR FOR LONG-TERM PROPHYLAXIS AND TREATMENT OF BREAKTHROUGH ATTACKS IN JAPANESE SUBJECTS WITH HEREDITARY ANGIOEDEMA: A PHASE 3 OPEN-LABEL STUDY]

Background: Hereditary angioedema (HAE) is associated with recurrent, painful, and potentially lifethreatening attacks characterized by swelling of subcutaneous or submucosal tissues.

Purpose: To investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of repeat-use C1 inhibitor (C1-INH) replacement therapy for long-term prophylaxis and treatment of breakthrough attacks in the management of Japanese patients with HAE type I or II.

Methods: An open-label, single-arm, Phase 3 study was conducted in Japanese patients with HAE (NCT02865720). For patients 6 years of age or older, 1000U were administered biweekly (by a healthcare professional or self-administered) via intravenous infusion.

Results: In 8 enrolled patients, the mean number of attacks normalized per month was lower during C1-INH treatment than during the 3 months prior (1.826 vs. 3.375). Clinically meaningful mean change from baseline in the angioedema-quality of life (AE-QoL) total score was shown during treatment with C1-INH. Pharmacokinetic data showed markedly higher and enduring post-baseline plasma levels of C1-INH functional activity and C1-INH antigen concentration, starting from 0.5h after first dose of C1-INH and lasting up to 72 hours. C1-INH was well tolerated with no new safety signals identified in this population of Japanese patients with HAE.

Conclusion: C1-INH was effective for long-term prophylaxis and treatment of breakthrough attacks with favourable safety profile in Japanese patients with HAE.