Concizumab Reduces Treated Bleeds in Hemophilia A or B with Inhibitors

Víctor Jiménez-Yuste, MD

The Explorer7 study assessed the efficacy and safety of prophylactic treatment with concizumab in individuals living with hemophilia A or B with inhibitors and found that the safety and tolerability of the drug was within the expected range and no thromboembolic events were reported.

The anti-tissue factor pathway inhibitor (TFPI) antibody is in development and not yet approved by regulatory authorities to provide patients with once-daily prophylactic treatment. It's administered subcutaneously for all hemophilia types.

Those with hemophilia can experience "bleeds" as a result of the body's inability to produce blood clots due to the bleeding disorder and need to be treated with medication, especially following a traumatic event.

However, in some individuals, the immune system develops inhibitors that can block these replacement therapies that are used to allow proper clotting. It's estimated that 30% of those with hemophilia A and 1-3% of hemophilia B have inhibitors.

The Phase 3 Data

According to the phase 3 data presented at the International Society of Thrombosis and Haemostasis Annual Congress (ISTH 2022) in London, UK, investigators observed an 86% reduction in treated spontaneous and traumatic bleeds when patients with inhibitors were on concizumab prophylaxis.

“One of the most critical complications in the treatment of haemophilia is the development of inhibitors, as they render standard replacement therapy ineffective and severely limit treatment options for haemophilia B,” lead investigator Victor Jiménez-Yuste, MD, Haematology Department, La Paz University Hospital, said in a statement.

The estimated mean ABR of 1.7 in the treated population compared with 11.8 in those without prophylaxis demonstrated that the study fulfilled its primary objective. The overall median ABR of concizumab was 0 and 9.8 for no prophylaxis. No treated bleeds occurred in 21, or 63.6%, of individuals on concizumab while in the control group only 10.5%, or 2 people, had an absence of treated bleeds throughout the study.

“Based on the results of the explorer7 study, there is a potential for concizumab to become a new treatment option for people living with haemophilia A or B with inhibitors," Jiménez-Yuste said.

The Explorer Clinical Trial Program

The Explorer7 study primary analysis compared the number of treated spontaneous and traumatic bleeding episodes, measured as ABR, between arms 1 and 2 of the ongoing clinical trial program for concizumab. For the evaluation, 133 males (aged 12 years and over) were randomised 1:2 to either a no prophylaxis (arm 1; ≥24 weeks) or concizumab prophylaxis (arm 2; ≥32 weeks) or assigned to concizumab prophylaxis (arm 3 and 4).

A regulatory approval for the prophylactic treatment of hemophilia A or B with inhibitors is expected to be submitted by the developing company Novo Nordisk during the second half of 2022 in the US and Japan, and during 2023 in the EU and UK.

“The treatment of haemophilia is complex and no one treatment fits all,” Martin Lange, executive vice president and head of Development at Novo Nordisk said. “Concizumab offers the potential for everyday protection for people living with haemophilia and provides an important potential addition to our haemophilia offering, especially in the haemophilia B with inhibitor population who currently have limited treatment options.”