Concizumab as a Subcutaneous Prophylactic Treatment Option for Patients with Hemophilia A or B: A Review of the Evidence and Patient’s Perspectives

Abstract

Concizumab is a monoclonal, humanized IgG4 antibody specific for the Kunitz-2 domain of Tissue Factor Pathway Inhibitor (TFPI). Preclinical studies in vitro or on animal models and in vivo have demonstrated the ability of concizumab to restore thrombin generation, promoting the establishment of a procoagulant action; all these results were subsequently confirmed in the studies of EXPLORER program. Concizumab may represent a new opportunity for the treatment of persons with hemophilia, so there is much anticipation for the results of the ongoing trials still. This review retraces all the studies on concizumab published to date, with a brief discussion about the patient’ perspectives.

Relationship between plasma tissue Factor Pathway Inhibitor (TFPI) levels, thrombin generation and clinical risk of bleeding in patients with severe haemophilia A or B

“…It may also have reflected the difficulties encountered in determining bleeding rates, as noted above and emphasised in a recent review 22 . The impact of TFPI on bleeding tendency in haemophilia patients is reflected by the clinical efficacy of anti‐TFPI therapies in controlling bleeding in haemophilia animal models 24,25 and in haemophilic patients 20,26–28 . As the results of TG assay in haemophilia patients are affected by fTFPI levels, this assay could be used to monitor anti‐TFPI therapy, especially if performed in PRP, in which case both plasma and platelet TFPI are taken into account.…”

Exploring nonreplacement therapies’ impact on hemophilia and other rare bleeding disorders

“…However, clinical development was briefly halted in 2020 due to 3 nonfatal thrombotic events in the phase 3 trials. Following a risk mitigation plan with a new reduced dosing regimen of drug to mitigate the thromboembolic risk, phase 3 studies of the Explorer program were resumed [ 52 ]. In addition, updated indications for the management of mild and moderate breakthrough bleeding episodes have been proposed.…”

Hemophilia throughout the life cycle

“…It is administered subcutaneously and has a long half-life 55 . Preliminary data on other subcutaneous drugs for the treatment of hemophilia A and B, such as concizumab and marstacimab, anti-TFPI (Tissue Factor Pathway Inhibitor) antibodies, as well as fitusiran, an antithrombin inhibitor, are encouraging, although results of ongoing trials are awaited 56 .…”