Individualized prophylaxis with Nuwiq® (Human-cl rhFVIII) in adult PTPs with severe hemophilia A

J. Bichler1, C. Kessler2, K. Meijer3, A. Armstrong4, S. Knaub1, G. Pezeshki5, M. Wang6 (1Lachen, Switzerland, 2Washington DC, USA, 3Groningen, The Netherlands, 4Helsinki, Finland, 5Hoboken, NJ, USA, 6Aurora, CO, USA)

Bleeding disorders, coagulation and fibrinolytic factors
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: Pharmacokinetic (PK)-guided personalized prophylaxis with Nuwiq® was assessed in the GENA-21 study in 66 previously treated adult patients (PTPs) with severe haemophilia who were predominantly treated on-demand prior to study entry. In this study, the median half-life was 15.1 hours, the median dosing interval was extended to 3.5 days, 58% of patients were treated with two or fewer infusions per week and 73% of patients were bleed-free. The prolonged dosing interval was achieved with 7% less FVIII consumption per week when compared to regular prophylaxis. The objective of the present study (GENA-21b) is to confirm the data of GENA-21 and to assess the benefit of PK-guided individualized prophylaxis in patients who were predominantly on regular routine prophylactic treatment prior to study start.

Methods: The ongoing prospective, open-label, multicenter phase 3b study will enroll 55 adult PTPs with severe haemophilia A from USA, Canada, Europe, and Japan. Each patient will receive Nuwiq® for PK evaluation (single dose of 60 ± 5 IU/kg) followed by 1-3 months of routine prophylaxis (i.e. 30-40 IU/kg every other day or 3 times per week, Phase I). Individual PK data are analyzed by one-stage clotting assay to determine the dose and injection interval which would theoretically result in a trough FVIII level of ≥1%. Thereafter, prophylaxis will continue for 6 months based on the individually recommended treatment schedule (Phase II).

Results: Snap shot data will be presented at the GTH. So far 22 patients underwent PK with a median half-life of 15.2 hours. The median treatment interval in Phase I standard prophylaxis is 2.3 days, with a median single dose of 34.0 IU/kg and a median weekly dose of 105.0 IU/kg. During individualized prophylaxis, the recommended median treatment interval is 3.5 days, the median dose/infusion 36.3 IU/kg resulting in a median weekly dose of 84.9 IU/kg. FVIII half-life relationship with von Willebrand factor antigen and blood group will be analyzed.

Conclusion: So far, the available data confirm the favorable results of the GENA-21 study with an even lower weekly consumption of FVIII during personalized compared to routine prophylaxis (84.9 vs. 105.0 IU/kg).