ABSTRACT: Concizumab is a novel nonfactor replacement therapy for once-daily subcutaneous prophylactic treatment of hemophilia A/B (HA/HB) with and without inhibitors. Concizumab was superior to on-demand treatment in patients with HA/HB without inhibitors in the prospective, multicenter, open-label phase 3 explorer8 study. Here, longer-term efficacy and safety results from the start of the study up to the 56-week cutoff are presented. Males aged ≥12 years with HA/HB were randomized 1:2 to no prophylaxis (group 1) or concizumab (group 2) or allocated to concizumab (groups 3 and 4). Assessments at the 56-week cutoff included efficacy, pharmacokinetics/pharmacodynamics, and safety. The 56-week cutoff was defined as when all patients in groups 2 to 4 had completed the visit at 56 weeks or permanently discontinued treatment. Of 148 patients in the full analysis set, 21 were randomized to no prophylaxis (group 1: HA, n = 9; HB, n = 12), 42 to concizumab (group 2: HA, n = 18; HB, n = 24), and 85 to the nonrandomized concizumab groups (groups 3 and 4: HA, n = 55; HB, n = 30). After ≥24 weeks of treatment, 17 patients in group 1 switched to concizumab. Low median annualized bleeding rates for treated spontaneous and traumatic bleeding episodes were maintained at the 56-week cutoff in patients receiving concizumab (HA, 1.7 [interquartile range (IQR), 0.0-4.5]; HB, 2.8 [IQR, 0.0-6.4]), consistent with 32-week cutoff results. Concizumab plasma concentration remained stable, with no new safety concerns. Concizumab showed longer-term efficacy in patients with HA/HB at the 56-week cutoff and was considered safe and well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT04082429.
