Introduction: Turoctocog alfa (NovoEight®) is a B?domain?truncated recombinant factor VIII (FVIII) product for the prevention and treatment of bleeding in patients (pts) with haemophilia A. Guardian 5 (NCT02035384) was a prospective, multinational, non?interventional, post?authorisation safety study investigating long?term safety and efficacy of turoctocog alfa in routine clinical practice.
Methods: Male previously treated pts (>150 exposure days [EDs]) of any age with severe/moderately severe haemophilia A (FVIII ? 2%) and a negative inhibitor test prior to first dosing were included to receive prophylaxis (PPX) or on?demand treatment. The primary endpoint was the incidence rate of FVIII inhibitors (?0.6 BU) after baseline visit, measured as per routine practice of each study site during clinic visits. Secondary endpoints included haemostatic effect (successful if rated Excellent or Good on a 4?point scale), annualised bleeding rate (ABR), and adverse reactions assessment. The study concluded when 50 pts reached a minimum of 100 EDs/pt.
Results: In total, 70 pts were screened and 68 exposed to turoctocog alfa (median [range] age: 26.5 [5–76] years). At inclusion, 63 (92.6%) pts were on a PPX regimen (<12 years, n = 14; ?12 years, n = 49), of which 55 had severe haemophilia and 8 moderately severe; 5 pts (?12 years with severe [n = 3], moderately severe [n = 1] haemophilia or FVIII level > 2% [n = 1]) were receiving on?demand treatment. Six (8.8%) pts reported a history of inhibitors. During the study, pts were exposed to turoctocog alfa for a mean (SD) of 131.9 (99.0) days/pt; 50 pts reached 100 EDs. No FVIII inhibitors were reported. Overall success rate of turoctocog alfa for treatment of 361 bleeds in 37 pts was 87.3% (excluding missing responses). Among PPX pts, median (range) ABR was 1.97 (0.0–25.5) bleeds/year; estimated ABR (negative binomial model) was 3.65 (95% CI: 2.53, 5.25). Overall, mean (SD) consumption of turoctocog alfa per month was 157.6 (137.9) IU/kg. One adverse drug reaction (angina pectoris), possibly study drug?related, was reported in a pt with cardiovascular risk factors who recovered and continued turoctocog alfa treatment.
Discussion/Conclusion: Turoctocog alfa was safe and efficacious for treatment in routine clinical practice. Results aligned with previous guardian trials.