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

BACKGROUND: Recombinant 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. OBJECTIVE: To review the integrated efficacy data of rhC1INH for treatment of acute HAE attacks. METHODS: Efficacy 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. RESULTS: The 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. CONCLUSIONS: RhC1INH 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.