Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (RIX-FP) in Previously Treated Adolescents/Adults 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. 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 subjects ≥ 12 years of age with severe hemophilia B (ie, FIX activity of ≤ 2%) and investigates dosing intervals up to 21-days in selected subjects with successful treatment every 14 days.

Methods: Previously treated male patients (PTPs) who have completed the adult study CSL654_3001 received once every 7, 10, or 14 days prophylaxis and OD treatment for bleeding episodes. During study subjects could switch from one prophylaxis regimen to another at the discretion of the investigator. Subjects ≥ 18 years of age also had the option to administer rIX-FP once every 21 days. 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 59 PTPs ≥ 12 years of age were enrolled into the extension study; 58 (93.8%) subjects achieved ≥50 exposure days (EDs) and 54 (91.5%) ≥100 EDs. A total of 11 subjects have switched to a prophylaxis treatment interval of once every 21 days. The median (Q1, Q3) AsBR was 0.33 (0.00, 2.39), 0.00 (0.00, 0.68), 0.00 (0.00, 1.54), and 0.00 (0.00, 0.45) for once every 7, 10, 14 or 21 days prophylaxis, respectively. A total of 9 (42.9%), 11 (64.7%), 20 (50.0%) and 7 (63.6%) subjects on 7, 10, 14 and 21 days regimens experienced 0 spontaneous bleeding episodes, respectively. A total of 98.1% of bleeds were successfully treated with 1 or 2 injections of rIX-FP (95% CI: 92.9% to 99.5%) to achieve hemostasis. There were 3 related adverse events reported by 3 subjects, all of mild intensity (pain, gamma GTP increased, dizziness). No subjects developed inhibitors to FIX or antibodies to rIX-FP.

Conclusion: These Phase 3b interim results demonstrated a favorable long-term safety and tolerability profile of rIX-FP and its clinical efficacy for 7-, 10-, 14- or 21 days prophylaxis and treatment of bleeding episodes. None of the subjects developed inhibitors to FIX.