Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (RIX-FP) in Previously Treated Children < 12 Years of Age with Hemophilia B: Long-Term Efficacy and Safety from an Ongoing Phase 3b Extension Clinical Trial

Introduction: A fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin (rIX-FP, Idelvion®) has been developed with a >5-fold longer half-life in comparison with standard FIX products, supporting a prophylaxis treatment interval of 7- to 14-days in adults. As part of the PROLONG-9FP clinical trial program, this phase 3b study aims to evaluate the long-term safety and efficacy of rIX-FP for routine prophylaxis and on-demand (OD) treatment of bleeding episodes in children <12 years of age with severe hemophilia B (ie, FIX activity of ≤ 2%), including the investigation of a dosing interval of every 14 days.

Methods: Previously treated male patients (PTPs) who have completed the pediatric study CSL654_3002 received once every 7, 10, or 14 days prophylaxis and OD treatment for bleeding episodes. During study subjects could switch between prophylaxis regimens at the discretion of the investigator. The primary endpoint was the number of subjects developing inhibitors against FIX. Annualized spontaneous bleeding rates (AsBR) were calculated based on data at the cut-off date 15 March 2017. Treatment efficacy was evaluated by number of injections to achieve hemostasis and Investigator assessment of hemostasis.

Results: A total of 24 PTPs <12 years of age were enrolled into the extension study; 24 (100%) subjects achieved ≥50EDS and 23 (95.8%) ≥100 EDs. A total of 8 subjects (33.3%) have switched to a prophylaxis treatment interval of once every 14-days. The median (Q1, Q3) AsBR was 0.00(0.00, 0.59), 0.00 (0.00, 3.06) and 0.75 (0.00, 2.86) for once every 7, 10, or 14 day prophylaxis, respectively. A total of 97% of bleeding episodes were treated with 1 or 2 injections of rIX-FP (95% CI: 90.7% to 99.1%). No PTPs developed inhibitors to FIX or antibodies to rIX-FP; there were no related adverse events.

Conclusion: These Phase 3b interim results demonstrated a favorable safety and tolerability profile of rIX-FP in children < 12 years of age. Clinical efficacy was shown for prophylactic treatment every 7-, 10- and 14- days and also for treatment of bleeding episodes. No subject developed inhibitors to FIX. These results are of significant clinical interest, especially for young children in whom regular venous access may be problematic.