Concizumab in hemophilia with inhibitors: longer-term efficacy and safety results from the phase 3 explorer7 study

Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody intended for once-daily subcutaneous prophylactic treatment for people with hemophilia A or B with and without inhibitors. Results from the phase 3 explorer7 study confirmed superiority of concizumab prophylaxis over no prophylaxis in reducing the annualized bleeding rate (ABR) in people with hemophilia A or B with inhibitors (HAwI/HBwI). Male patients aged ≥12 years were randomized 1:2 to no prophylaxis (group 1) or concizumab prophylaxis (group 2), or nonrandomly allocated to concizumab prophylaxis (groups 3 and 4). After ≥24 weeks of treatment, patients in group 1 could switch to concizumab prophylaxis. At the 56-week cutoff (defined as when all patients in groups 2-4 had completed the visit at 56 weeks or permanently discontinued treatment), bleed-related efficacy, pharmacokinetics and pharmacodynamics, and safety were assessed. Of the 133 patients enrolled (HAwI, n = 80; HBwI, n = 53), 114 received concizumab prophylaxis (groups 2-4) and 19 were randomized to no prophylaxis (group 1). After ≥24 weeks, 13 patients from group 1 switched to concizumab. Median ABR for treated spontaneous and traumatic bleeding episodes in patients receiving concizumab was 0.8 (interquartile range [IQR], 0.0-3.2) at the 56-week cutoff, consistent with the low bleeding rates (median ABR, 0.0; IQR, 0.0-3.3) at the 32-week cutoff. Concizumab and free-TFPI concentration remained stable over time. No new safety concerns were reported. Longer-term (≥1 year) efficacy and safety results of concizumab prophylaxis for HAwI/HBwI were consistent with the 32-week cutoff results in explorer7. This trial was registered at www.clinicaltrials.gov as #NCT04083781.