Efficacy and safety of Nuwiq® in clinical trials with previously treated patients with severe hemophilia A
R. Klamroth1, J. Bichler2, M. Jansen3, L. Belyanskaya2, S. Knaub2, R. Liesner4, J. Oldenburg5, A. Tiede6, C. Kessler7 (1Berlin, Germany, 2Lachen, Switzerland, 3Vienna, Austria, 4London, United Kingdom, 5Bonn, Germany, 6Hannover, Germany, 7Washington DC, USA)
Bleeding disorders, coagulation and fibrinolytic factors
Time: 17:15 - 18:15
Objective: Nuwiq® is a recombinant FVIII concentrate without chemical modification or fusion with any other protein, which is produced in a human cell line that adds only human-specific post-translational modifications. It is approved for the treatment and prophylaxis of bleeding in patients with haemophilia A based on the results of 5 clinical studies in 135 adult and paediatric previously treated patients (PTPs) with severe haemophilia A.
Methods: Data from pre-authorisation studies were combined with those from two new studies, an extension study in 49 children and a pharmacokinetic (PK)-guided individualised prophylaxis study in 66 adults.
Results: The data comprise results on 201 PTPs (59 children, 142 adolescents/adults). 179 PTPs were treated prophylactically and 22 adolescents/adults were treated on-demand only. All were to be treated for >6 months and >50 Exposure Days. The mean half-life (one-stage assay) was 17.1±11.2 hours and 15.1±4.7 hours in two adult PK studies (22 and 66 patients), and 12.5±4.2 in 26 children. In the on-demand study, 986 BEs were treated. Efficacy was rated as excellent or good in 94.4% of cases and 97.4% were managed with 1 or 2 infusions. Standard prophylaxis (every other day in adults, every other day or 3-times per week in children) resulted in an annualized bleeding rate (ABR) of 2.3 and 4.0, respectively. In the PK-guided personalised prophylaxis, the ABR was 1.48. 73% of patients were bleed-free, the median dosing interval was extended to twice per week, and 58% of patients were treated with two or fewer injections per week. Median FVIII consumption decreased by nearly 10% compared to standard prophylaxis. In the children’s extension study the spontaneous ABR decreased from 1.36 to 0.67. Haemostatic efficacy was rated as excellent or good for 52 of the 53 surgeries occurring in all studies. Overall, 43,267 injections and >80 million IU of Nuwiq® were administered. Only 9 (0.02%) injections were connected with adverse drug reactions. No inhibitors were detected in any of the patients.
Conclusion: These results show excellent safety and efficacy in treatment of bleeding episodes, a low ABR in particular during personalised prophylaxis, an extended treatment interval under PK-guided personalised prophylaxis and no inhibitors in PTPs.