Concizumab prophylaxis reduces bleeds in hemophilia population ‘with complex treatment needs’
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Key takeaways:
- Patients who received prophylactic concizumab had a mean overall annualized bleeding rate of zero compared with 9.8 among those who did not receive prophylactic therapy.
- 63.6% of patients in the concizumab group did not experience a bleeding event during the first 24 weeks of the study compared with 10.5% in the nonprophylaxis group.
Prophylactic concizumab conferred an 86% reduction in treated spontaneous and traumatic bleeds among patients with hemophilia A or B with inhibitors, data from a randomized phase 3 trial showed.
A primary analysis of the explorer7 study results — presented at International Society on Thrombosis and Haemostasis 2022 Congress — revealed that nearly two-thirds of patients who remained on prophylactic concizumab (Novo Nordisk) throughout the study experienced no bleeding episodes that required treatment.
Background
The World Federation of Hemophilia considers factor VIII and factor IX prophylaxis the standard of care for patients with severe hemophilia A or B, according to Stephanie Seremetis, MD, chief medical officer of rare blood disorders at Novo Nordisk.
“Research shows that earlier initiation of prophylaxis minimizes the likelihood of bleeds, thereby minimizing the risk [for] long-term joint damage and other long-term complications,” she told Healio.
However, development of inhibitors represents “one of the most crucial complications in the treatment of hemophilia” and requires alternative therapeutic strategies, Seremetis said. This is especially true for patients with hemophilia B who develop inhibitors, for whom “severely” limited options are available, Seremetis said.
The explorer7 study aimed to evaluate the efficacy and safety of prophylactic concizumab — a high-affinity, anti-tissue factor pathway inhibitor monoclonal antibody — in patients with hemophilia A or B with inhibitors.
The investigational therapy is for all hemophilia subtypes and acts independent of factor VIII and factor IX. It is designed to enhance the body’s ability to generate adequate amounts of factor Xa, which allows for increased thrombin generation to achieve effective hemostasis.
Methodology
Study investigators randomly assigned 133 patients previously treated on-demand in a 1:2 ratio to one of two study arms. Arm 1 included patients who received no prophylaxis whereas arm 2 included those receiving prophylactic concizumab. The study also included two extension arms as part of a phase 2 trial.
The trial restarted following a pause due to treatment-related thromboembolic events, and the treatment protocol was amended to provide patients with a 1 mg/kg concizumab loading dose, followed by an initial once-daily dose of 0.2 mg/kg concizumab.
The comparative number of treated spontaneous and traumatic bleeding episodes, expressed as the estimated mean annualized bleeding rate, between treatment arms 1 and 2 served as the study’s primary endpoint. Secondary endpoints comprised quality-of-life measurements, including changes in SF-36 questionnaires for bodily pain and physical function.
The study’s primary analysis included 33 patients randomly assigned to treatment arm 2 (concizumab prophylaxis) and 19 patients assigned to treatment arm 1 (no prophylaxis).
Key findings
The explorer7 study achieved its primary endpoint by significantly reducing the number of bleeding events among the study population.
Results showed a mean overall annualized bleeding rate of zero for patients who received prophylactic concizumab compared with 9.8 among those who did not receive prophylactic therapy.
Researchers noted a mean annualized bleeding rate of 11.8 (95% CI, 7-19.9) for those who did not receive prophylactic therapy compared with 1.7 (95% CI, 1-2.9) among patients who received prophylactic concizumab.
Twenty-one patients (63.6%) in the concizumab group did not experience a bleeding event during the first 24 weeks of the study period compared with two patients (10.5%) in the nonprophylaxis group (OR = 23.42; 95% CI, 2.63-208.87).
Severe treatment-related adverse events occurred in 15.8% of patients in the nonprophylaxis group compared with 18.2% in the concizumab group.
No treatment-related thromboembolic events occurred after the trial restarted.
Clinical implications
Seremetis characterized results from explorer7 as “encouraging for people living with hemophilia A or B with inhibitors,” in addition to being promising news for clinicians who treat these patients.
“Based on the results of explorer7, concizumab offers the potential of everyday protection for people living with hemophilia A and B, regardless of inhibitor status,” she told Healio. “The [results] demonstrate the potential of concizumab to prevent bleeds in a population with complex treatment needs, and potentially help to address the significant challenge of inhibitors in hemophilia A and B.”
Novo Nordisk expects to apply to the FDA in the second half of 2022 for regulatory approval of concizumab for the prophylactic treatment of hemophilia A or B with inhibitors, according to a company-issued press release.
References:
- Jiménez Yuste V, et al. Abstract LB 01.2. Presented at: International Society on Thrombosis and Haemostasis 2022 Congress; July 9-13, 2022; London.
- Novo Nordisk. Phase 3 data for concizumab show 86% reduction in treated bleeds in haemophilia A or B with inhibitors (press release). Available at: www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=124149. Published July 10, 2022. Accessed July 10, 2022.
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Jiménez Yuste V, et al. Abstract LB 01.2. Presented at: International Society on Thrombosis and Haemostasis 2022 Congress; July 9-13, 2022; London.
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