Safety and Efficacy of Turoctocog Alfa in the Prevention and Treatment of Bleeding Episodes in Previously Treated Patients from China with Severe Hemophilia A: Results from the Guardian 7 Trial

Abstract

Purpose: Hemophilia care in China is characterized by widespread use of on-demand regimens and low-dose prophylaxis. With a limited number of approved recombinant factor VIII (FVIII) products, the incidence of arthropathy and disability in hemophilia patients remains high in China. The purpose of this trial was to evaluate the safety and efficacy of turoctocog alfa for prophylaxis and treatment of bleeding episodes in patients from China with severe hemophilia A across all age groups.

Patients and methods: In this Phase 3, open-label trial, previously treated males of all ages with severe hemophilia A from China received turoctocog alfa for prophylaxis or on-demand treatment of bleeds. The primary endpoint was hemostatic effect for the treatment of bleeds during the main phase of the trial. Secondary endpoints included annualized bleeding rate during prophylaxis and the frequency of FVIII inhibitor development.

Results: Overall, 42 pediatric patients (age <12 years) and 26 adolescent/adult patients (≥12 years) were dosed with turoctocog alfa; 51 patients initiated treatment with prophylaxis, while 17 patients initiated on-demand treatment. During the main phase of the trial (6 months), hemostatic success was 95.1%. During the full trial (up to 24 months), hemostatic success was 95.4%; the overall median ABR was 1.18 bleeds/patient/year for prophylaxis patients; and 25 (51.0%) of 49 patients with target joints at baseline had all target joints resolved. No FVIII inhibitors (≥0.6 BU) were reported.

Conclusion: Turoctocog alfa was safe and effective for prophylaxis and treatment of bleeding episodes and for surgery in patients from China with severe hemophilia A across all ages.

Keywords: China; hemophilia A; prophylaxis; recombinant factor VIII; turoctocog alfa.

Figure 1

Participant flow. Notes: ^a3 screening failures: 1 patient did not meet the inclusion criteria (severe congenital hemophilia A with FVIII ≤1%) and 2 patients had inhibitors to FVIII (≥0.6 BU) at screening. ^b2 patients (one from each regimen) withdrew at will from the main phase. ^c2 patients in the prophylaxis regimen withdrew before starting the extension phase (1 due to refusal to participate in the extension and the other for personal reasons). ^d2 patients withdrew during the extension phase (1 due to medical insurance and the other for personal reasons) and the remaining 62 patients completed the extension period. A total of 5 patients were switched from their original prophylaxis dosing frequency during the trial: 1 small child, 1 older child and 1 adult switched from three times weekly to EOD, and 1 older child and 1 adult switched from EOD to three times weekly. Abbreviations: BU, Bethesda Units; EOD, every other day; PK, pharmacokinetics.

Figure 2

Mean FVIII activity profile following administration of turoctocog alfa, by age group. Notes: Chromogenic assay (linear scale), excluding outliers; bars show the standard error of the mean. A total of 17 patients were included in the PK assessment (small children, n=4; older children, n=6; adolescents, n=3; adults, n=4). Sampling frequency per patient for PK assessment varied between age groups (0–11 years, n=5 samples; ≥12 years, n=11 samples). Abbreviation: PK, pharmacokinetic.

Figure 3

Development of individual ABR over time for patients in the prophylaxis regimen. Notes: Only treatment-requiring bleeds and periods in which a patient was at risk are included. Results for the first month and periods where there are less than 10 patients on a regimen have been excluded for stability purposes. Abbreviations: ABR, annualized bleeding rate; n, number of patients.