Initiation of Prophylactic Treatment with Subcutaneous C1-Esterase Inhibitor (C1-INH [SC]) for Prevention of Hereditary Angioedema (HAE) Attacks and Onset of Effect: Findings from the Phase III COMPACT Study
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Huamin Henry Li, MD PhD FAAAAI, Marc A. Riedl, MD MS, Timothy Craig, DO, FAAAAI, AOA, Hilary J. Longhurst, MD, Marco Cicardi, MD, Bruce L. Zuraw, MD, Henrike Feuersenger, PhD
RATIONALE: Subcutaneous C1-INH (HAEGARDA®, CSL Behring, Marburg) at 60 IU/kg was recently approved by the US FDA as routine prophylaxis to prevent hereditary angioedema (HAE) attacks in adolescents and adults, based on the COMPACT study. This study demonstrated that the median attack rate was reduced by 95% with C1-INH relative to placebo. We explored the onset of the preventive effect of C1-INH (SC) after treatment initiation.

METHODS: In the COMPACT study, patients self-administered C1-INH (SC) or placebo twice weekly in a double-blind, crossover manner over two 16-week treatment periods. Per study design, the first 2 weeks of each treatment period were excluded in the primary analysis (time-normalized number of HAE attacks) to account for possible wash-in/wash-out effects, a methodological aspect of any crossover trial. In the present post-hoc analysis, we evaluated results from the first 2 weeks of treatment to determine how early the preventive effect of C1-INH (SC) can be observed.

RESULTS: In the first 2 weeks of treatment, 10/45 patients (22%) experienced attacks with 60 IU/kg versus 34/45 patients (76%) with placebo. A total of 14 attacks occurred (none severe) during the first 2 weeks with 60 IU/kg treatment versus 70 attacks with placebo (17 severe). Population pharmacokinetic models indicate that C1-INH functional activity exceeds the critical threshold of 40% after the second dose (Cmax=60.7%, Tmax=58.7 h, Ctrough=48%).

CONCLUSIONS: The preventive effect of C1-INH (SC) is already evident in the first 2 weeks of switching from on-demand treatment, as evidenced by less severe and fewer attacks during prophylaxis.