Patient Reported Outcomes Favor Concizumab Prophylaxis in Hemophilia A or B

Huyen Tran

Credit: Alfred Health

Patient-reported outcomes (PROs) in the Phase 3 explorer7 study, including health-related quality of life (HRQoL) and treatment burden, favored concizumab prophylaxis over no prophylaxis among individuals with Hemophilia A or B with inhibitors.¹

Among individuals with hemophilia, the burden from the disease and its treatment can impact overall HRQoL, centering PROs as an opportunity to directly evaluate a patient’s outlook and function, particularly on how a novel treatment affects the patient experience.

“The exploratory patient-reported endpoint results provided herein give information from the patient’s perspective of the potential benefits of daily subcutaneous concizumab prophylaxis, compared with no prophylaxis, in the context of HRQoL and treatment experience,” wrote the investigative team, led by Huyen Tran, director of the Ronald Sawers Haemophilia Centre at The Alfred Hospital and professor at Monash University.

Hemophilia complicated by inhibitors can notably increase the treatment burden. Prophylaxis with bypassing agents in patients with hemophilia B with inhibitors can be inconsistent, with a need for frequent intravenous administration.² Changing the route of administration to subcutaneous injection has represented a major advancement for patients with Hemophilia A with inhibitors.³

Concizumab is a humanized, monoclonal anti-tissue factor pathway inhibitor antibody developed as a daily subcutaneous prophylaxis for patients with Hemophilia A or B with or without inhibitors.¹ The explorer7 study is a prospective, multicenter, open-label Phase 3 study evaluating the safety and efficacy of once-daily subcutaneous concizumab prophylaxis in males aged ≥12 years with Hemophilia A or B with inhibitors.

At the primary analysis cutoff, once-daily subcutaneous concizumab prophylaxis reduced the estimated mean annualized bleeding rate (ABR) compared with no prophylaxis (ABR, 1.7 vs. 11.8, respectively; P <.001) in patients with Hemophilia A or B with inhibitors.⁴

The study also evaluated the impact of once-daily concizumab prophylaxis on HRQoL, treatment burden, and treatment preference in patients with Hemophilia A or B, using results from 8 PRO questionnaires.¹

These questionnaires included a hemophilia-specific questionnaire to assess QoL (Hemophilia Quality of Life Questionnaire for Adults) and the burden of hemophilia treatment (Hemophilia Treatment Experience Measure) using a 5-point Likert scale. The Hemophilia Patient Preference Questionnaire evaluated various aspects of a patient’s treatment-related preferences.

In explorer7, 133 patients were enrolled – patients were randomized into 2 arms (no prophylaxis; concizumab prophylaxis) or allocated to nonrandomized arms (concizumab prophylaxis in both). PRO responses were obtained from baseline to Week 24.

Upon analysis, the estimated treatment difference in the Hemophilia Quality of Life Questionnaire for Adults scores between patients receiving concizumab prophylaxis or no prophylaxis was –22.6 points for the total score (95% CI, –42.5 to –2.7) and –15.7 points (95% CI, –51.8 to 20.5) for physical health, directionally favoring concizumab prophylaxis.

Moreover, the estimated treatment difference directionally favored concizumab prophylaxis in the domains of “feeling,” “treatment,” “view of yourself,” and “sport and leisure.”

In the Hemophilia Treatment Experience Measure questionnaire, the estimated treatment difference was –19.9 points (95% CI, –34.3 to –5.6) for “total score,” supporting concizumab over no prophylaxis. In other analyzed domains, concizumab was supported in “injection difficulties,” “interference,” and “emotional impact.”

Treatment preference was assessed in 83 participants after 16 did not respond to the questionnaire. Of the respondents, 77 preferred concizumab, while 5 reported no preference and 1 preferred their previous treatment. The most common reasons indicated for concizumab preference included “fewer bleeds” (75%), “require less time” (43%), and “less painful to inject” (33%).

“Despite the questionnaire completion rate being lower than anticipated, the PRO data collected in this study directionally favored concizumab prophylaxis vs no prophylaxis in some areas of HRQoL,” Tran and colleagues wrote.

References

1. _{Tran H, von Mackensen S, Abraham A, et al. Concizumab prophylaxis in persons with hemophilia A or B with inhibitors: patient-reported outcome results from the phase 3 explorer7 study. Res Pract Thromb Haemost. 2024;8(4):102476. Published 2024 Jun 17. doi:10.1016/j.rpth.2024.102476}
2. _{Brod M, Bushnell DM, Neergaard JS, Waldman LT, Busk AK. Understanding treatment burden in hemophilia: development and validation of the Hemophilia Treatment Experience Measure (Hemo-TEM). J Patient Rep Outcomes. 2023;7(1):17. Published 2023 Feb 23. doi:10.1186/s41687-023-00550-6}
3. _{Fletcher S, Jenner K, Holland M, Khair K. The lived experience of a novel disruptive therapy in a group of men and boys with haemophilia A with inhibitors: Emi & Me. Health Expect. 2022;25(1):443-454. doi:10.1111/hex.13404}
4. _{Matsushita T, Shapiro A, Abraham A, et al. Phase 3 Trial of Concizumab in Hemophilia with Inhibitors. N Engl J Med. 2023;389(9):783-794. doi:10.1056/NEJMoa2216455}