Concizumab in patients with hemophilia A or B without inhibitors: 56-week cut-off results of the phase 3 explorer8 study

Concizumab is a novel non-factor-replacement therapy intended for once-daily subcutaneous prophylactic treatment of hemophilia A/B with and without inhibitors. Superiority was confirmed for concizumab compared with on-demand treatment in patients with hemophilia A/B without inhibitors (HA/HB) 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 cut-off 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 3/4). Assessments at the 56-week cut-off included measures of efficacy, pharmacokinetics/pharmacodynamics, and safety. The 56-week cut-off was defined as when all patients in group 2-4 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 were assigned to the non-randomized concizumab groups 3/4 (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 cut-off in patients receiving concizumab (HA: 1.7 [interquartile range, 0.0; 4.5]; HB: 2.8 [0.0; 6.4]), consistent with 32‑week cut‑off results. Concizumab plasma concentration remained stable over time and no new safety concerns were reported. Concizumab showed longer-term efficacy in patients with HA/HB at the 56-week cut-off and was considered safe and well tolerated. ClinicalTrials.gov; NCT04082429.