85 Clinical Efficacy of Recombinant Human C1 Inhibitor in Patients with Acute Hereditary Angioedema Attacks

Abstract

BackgroundRecombinant human C1 Inhibitor (rhC1INH) has been approved in Europe for the treatment of acute hereditary angioedema attacks. The efficacy of rhC1INH was demonstrated in 2 randomized-controlled trials. Open-label extension studies, where patients could be treated for subsequent HAE attacks, demonstrated continued efficacy for repeated rhC1INH treatments.ObjectiveTo review the integrated efficacy data of rhC1INH for treatment of acute HAE attacks.MethodsEfficacy was assessed using patient-reported HAE-specific visual analog scales. The primary endpoint was time to onset of relief of symptoms (VAS decrease ≥20 mm), and the secondary efficacy endpoint was time to minimal symptoms (VAS <20 mm at all locations). Other endpoints included clinical response (relief achieved within 4 hours) and relapse (recurrence of symptoms within 24 hours following initial improvement). Subgroup analyses by attack location were also performed.ResultsThe dataset included 141 HAE patients treated for 403 attacks. Median times to the onset of symptom relief for attacks treated with 100 U/kg, 50 U/kg and 2100 U rhC1INH were 66, 60, and 61 minutes, respectively, compared to 495 minutes in the placebo-treated group. Median times for time to minimal symptoms were 266, 240 and 241 minutes for the 100 U/kg, 50 U/kg, and 2100 U rhC1INH-treated attacks respectively compared to 1210 minutes for the placebo-treated attacks. High clinical response rates were observed for the rhC1INH-treated groups (93, 96 and 88% for the 100 U/kg, 50U/kg, and 2100 U respectively) compared to the placebo group (41%). None of the rhC1INH-treated attacks relapsed. Subgroup analysis by attack location showed that abdominal attacks had the fastest median time to onset of symptom relief (50, 36 and 60 minutes for 100 U/kg, 50 U/kg and 2100 U doses respectively), followed by oro-facial-pharyngeal-laryngeal attacks (70, 65 and 120 minutes), and peripheral attacks (75, 84 and 121 minutes). No drug-related serious adverse events or hypersensitivity reactions were observed.ConclusionsRhC1INH has demonstrated efficacy for the treatment of repeated HAE attacks for all doses tested (100 U/kg, 50 U/kg and 2100 U). Controlled studies did not show additional benefit with doses greater than 50 U/kg. RhC1INH was generally safe and well tolerated.