Safety and Efficacy of Monoclonal Antibody Purified Factor IX Concentrate in Previously Untreated Patients with Hemophilia B

Abstract

SummaryThe safety and efficacy of a monoclonal antibody purified factor IX concentrate were evaluated in two continuing trials of 32 previously untreated patients with mild, moderate, or severe hemophilia B. Patients were evaluated every 2 weeks for 24 weeks and every 3 months thereafter for at least 1 year. No patients became positive for human immunodeficiency virus antibody or hepatitis C virus antibody during the trial. Two patients developed a false-positive hepatitis B core antibody, one transiently, but neither had elevated levels of alanine aminotransferase (ALT). None of the 25 patients evaluable for non-A, non-B, non-C hepatitis by strict International Society of Thrombosis and Hemostasis criteria developed elevated levels of ALT indicative of posttransfusion infection. Anaphylaxis occurred in one subject who also developed an inhibitor to factor IX (19.3 Bethesda units). Five of the eight adverse events reported (63%) were mild in severity, and the relationship of three of these to therapy was considered remote. Hemostasis with monoclonal antibody purified factor IX concentrate was excellent in all patients.

The safety and efficacy of recombinant human blood coagulation factor IX in previously untreated patients with severe or moderately severe hemophilia B

“…5,[28][29][30] The development of inhibitors occurs in 1% to 3% of patients with hemophilia B, 29 but may be higher in individuals with severe disease. 29,31 In the current study, the incidence of FIX inhibitor was 2 of 63 (3%) patients, which is consistent with previous reports of hemophilia B patients treated with pdFIX products 9,32 or PTPs treated with rFIX. 20 Inhibitory antibodies occur most frequently in hemophilia B patients with major derangements of the F9 gene, due to large deletions, stop codons, and frame shift mutations.…”

“…Most responses to rFIX routine prophylaxis were rated "excellent" (91%), indicating that prophylaxis treatment during the preceding 3 months completely prevented spontaneous musculoskeletal bleeding episodes and that no change in rFIX regimen was necessary. These responses to rFIX for on-demand and prophylactic treatment regimens are similar to those reported in other studies of pdFIX in patients with hemophilia B 9,[23][24][25][26] and for rFIX in PTPs. 20 In the current study, the incidence of AEs related to rFIX treatment was low, occurring in 17% of patients, with most related AEs reported as mild or moderate in severity.…”

“…[4][5][6] In the past decade, the development of high-purity pdFIX preparations has reduced the thrombogenic risks associated with FIX replacement therapy. [7][8][9] In addition, the introduction of improved viral attenuation methods during manufacture has reduced the risk of viral transmission with pdFIX products. 10 Nevertheless, current viral attenuation methods may not eliminate nonenveloped viruses, including hepatitis A (HAV) and parvovirus, or bloodborne prions associated with transmissible spongiform encephalopathies, such as variant Creutzfeldt-Jacob disease.…”

Human recombinant factor IX: safety and efficacy studies in hemophilia B patients previously treated with plasma-derived factor IX concentrates

“…Although this was not a comparative study, hemostatic efficacy of rFIX was rated against participants' previous experience with pdFIX in "ondemand" and "secondary prophylaxis" regimens, and was reported as "excellent" or "good" in 90.9% to 98% of bleeding episodes, consistent with those reported in other studies that evaluated pdFIX in individuals with hemophilia B. [25][26][27][28][29][30] In addition, an analogous study testing rFVIII in PTPs with hemophilia A reported hemostatic efficacy as "excellent" or "good" in 91.2% of bleeding episodes, 31 similar to our results with rFIX in PTPs with hemophilia B.…”

Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial

“…6,[18][19][20][21] A recently approved long-acting FIX product, rFIXFc, demonstrated a terminal half-life of 82.1 hours when patients were dosed 50 IU/kg once weekly, whereas the steady state half-life of nonacog beta pegol was between 107 and 111 hours. 21 However, key differences between the trials for rFIXFc and nonacog beta pegol, namely prophylaxis regimes, dose adjustments, and pharmacokinetic analysis, make direct comparisons between these products difficult.…”