Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial

Abstract

• rIX-FP maintains mean trough of 20 and 12 IU/dL FIX activity with 40 IU/kg weekly and 75 IU/kg every 2 weeks prophylaxis, respectively. • Weekly and 14-day prophylaxis regimens with rIX-FP were well tolerated and provided low bleeding rates and target joint improvement.A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity £2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P < .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as

Albutrepenonacog alfa (Idelvion®) for the treatment of Italian patients with hemophilia B: a budget impact model

“…In the clinical development program (PROLONG-9FP), which included previously treated adult and pediatric patients with severe hemophilia B (FIX ≤ 2%), Idelvion ® demonstrated a favorable pharmacokinetics profile, which allows for a prolonged period between two doses in the prophylactic setting, maintaining an adequate FIX level, and fewer infusions at lower dose to stop bleeding per hemorrhagic episode [9][10][11][12]. This improvement could mean a reduction of costs associated with fewer infusions.…”

“…The enhanced PK profile shown by Idelvion ® , a recombinant human coagulation FIX generated by the fusion with albumin, compared to existing FIX therapies, allows prolonged period between two doses in the prophylactic setting, maintaining an adequate FIX level, and fewer infusions at lower dose to stop bleeding per hemorrhagic episode [9][10][11][12]18,19]. The results from the pivotal studies [11,12] support the dosing interval up to 14 and 7 days in adult/ adolescent and pediatric population since both dosages demonstrated to keep trough FIX level > 1-2 IU/dl which is the commonly recommended target [4].…”

“…The study of Santagostino et al [11] is a prospective, non-randomized, multinational, open-label phase 3 study, designed to evaluate pharmacokinetics (PK), efficacy and safety of Idelvion ® for prophylactic and on-demand treatment of previously treated patients (adult/ adolescent, age: 12-65 years) with severe or moderate hemophilia B (FIX ≤ 2 IU/dl).…”

“…Idelvion ® is indicated for the treatment and prophylaxis of bleeding in all age groups of patients with hemophilia B [14]. In February 2010, Idelvion ® has received orphan designation by the European Commission [15], which has been maintained [16] after the marketing authorization released on May 2016 [17], basing on the results of two pivotal studies conducted in adult/adolescent [11] and pediatric population [12].…”

“…A total of 83 patients were enrolled (52 from [11], 24 from [12] and 7 who started prophylaxis following major surgery). In adult/adolescent population 45 (87%) patients ≥ 12 years switched from 7-day to 10-or 14-day regimen and 10 patients ≥ 18 years switched from 14-to 21-day interval.…”