SAFETY AND EFFICACY OF LONG-TERM SUBCUTANEOUS C1-INHIBITOR REPLACEMENT THERAPY FOR PREVENTION OF HEREDITARY ANGIOEDEMA ATTACKS

Abstract

Introduction Subcutaneous human C1-inhibitor [C1-INH(SC)] is approved for prevention of angioedema attacks based on the Phase 3 COMPACT trial results. This extension study provides long-term data on efficacy and safety of C1-INH(SC). Methods This open-label, multicenter, randomized, parallel-arm study enrolled patients diagnosed with hereditary angioedema (HAE) type I/II with ≥4 HAE attacks over 2 consecutive months within 3 months prior to screening. Patients (n=126) were randomized 1:1 to receive 40 or 60 IU/kg C1-INH(SC) twice-weekly, with up-titration to 60 IU/kg or 80 IU/kg to optimize prophylaxis. Endpoints were long-term safety, HAE attack rate and rescue medication use. Results Mean duration of exposure for both doses of C1-INH(SC) was 1.5 years (maximum 2.7 years). Median annualized attack rate was 1.0 and 1.3 for 60 and 40 IU/kg, respectively. Median annualized rescue medication use was 0.0 and 0.2 for 60 and 40 IU/ kg, respectively. 23 patients receiving 60 IU/kg had >2 years of exposure (mean 2.3 years); 83% of these patients were attack free and 87% used no rescue medications during Months 25–30. C1-INH functional activity increased dose dependently to a median of 63% and 48% with 60 and 40 IU/kg, respectively. Incidence of adverse events was low: 8.5 and 11.3 per patient-year for 60 and 40 IU/kg, respectively. The safety profile remained favorable and consistent with the placebo-controlled Phase 3 COMPACT study during long-term routine use. Conclusions Long-term replacement therapy with C1-INH(SC) 60 IU/kg twice-weekly in patients with frequent HAE attacks provides safe, sustained and profoundly effective prophylaxis.