Novo Nordisk Reports Concizumab Provided 86 Percent Reduction in Treated Bleeds in Hemophilia A or B with inhibitors

Novo Nordisk reported phase 3 results of its explorer7 study, assessing the efficacy and safety of prophylactic treatment with concizumab in people living with hemophilia A or B with inhibitors.

The results from the primary analysis were presented at the International Society of Thrombosis and Haemostasis Annual Congress (ISTH 2022) in London.

Hemophilia is a rare disease that impairs the body’s ability to make blood clots, a process needed to stop bleeding after a traumatic event. It is estimated to affect approximately 1,125,000 people worldwide. Hemophilia A and B are more common in males than in females, with approximately 88 percent of people diagnosed with hemophilia worldwide being male. Some people with hemophilia may also develop inhibitors, which are an immune system response to the clotting factors in replacement therapy that cause the treatment to stop working. Currently, it is estimated that 30 percent of people living with hemophilia A and 1 to 3 percent of people living with hemophilia B have inhibitors.

Concizumab is an anti-TFPI monoclonal antibody, designed to block a protein in the body that stops blood from clotting, called TFPI. By blocking TFPI, concizumab encourages the production of a blood clotting protein called thrombin, which helps to clot the blood and prevent bleeding. The pivotal explorer7 (hemophilia A or B with inhibitors) and explorer8 (hemophilia A or B without inhibitors) studies are currently ongoing. The use of concizumab in people with hemophilia A or B with or without inhibitors is investigational and not yet approved by regulatory authorities. Concizumab is also being evaluated in children living with hemophilia A and B, with and without inhibitors, in the investigational explorer10 pediatric study expected to complete in 2026.

Explorer7 is part of the ongoing explorer clinical trial program for concizumab, which aims to evaluate the efficacy and safety of concizumab for people living with hemophilia A or B with or without inhibitors. It is designed as a once-daily prophylactic treatment by administration under-the-skin with a ready-to-use, prefilled pen. In explorer7, 133 males (aged 12 years and over) were randomized 1:2 to either a no prophylaxis (arm one; ≥24 weeks) or concizumab prophylaxis (arm two; ≥32 weeks) or assigned to concizumab prophylaxis (arm three and four). The primary analysis compared number of treated spontaneous and traumatic bleeding episodes, measured as annualized bleeding rates (ABR), between arms one and two.

The results showed an 86 percent reduction in treated spontaneous and traumatic bleeds when on concizumab prophylaxis, with an estimated mean ABR of 1.7 compared to 11.8 with no prophylaxis, fulfilling the primary objective. The overall median ABR of concizumab was zero, compared to 9.8 for no prophylaxis. Twenty-one (63.6 percent) people on concizumab experienced no treated bleeds, compared to two (10.5 percent) on no prophylaxis. The safety and tolerability profile of concizumab in this study was within the expected range, with no thromboembolic events reported after treatment restart.

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

Novo Nordisk expects to submit concizumab for regulatory approval for the prophylactic treatment of hemophilia A or B with inhibitors in the second half of 2022 in the US and Japan, and in 2023 in the EU and the UK.

Author: Rare Daily Staff