Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial
Elena Santagostino, Uri Martinowitz, Toshko Lissitchkov, Brigitte Pan-Petesch, Hideji Hanabusa, Johannes Oldenburg, Lisa Boggio, Claude Negrier, Ingrid Pabinger, Mario von Depka Prondzinski, Carmen Altisent, Giancarlo Castaman, Koji Yamamoto, Maria-Teresa Álvarez-Roman, Christine Voigt, Nicole Blackman, Iris Jacobs, PROLONG-9FP Investigators Study Group, Chantal Rothschild, Thierry Lambert, Reinhard Schneppenheim, Günter Auerswald, Christine Heller, Annarita Tagliaferri, Maria Elisa Mancuso, Aaron Lubetsky, Katsuyuki Fukutake, Masashi Taki, Keiji Nogami, Michio Sakai, Tatiana Chernova, Maria Fernanda López-Fernández, Joan C Gill, Amy Shapiro, Patrick Fogarty, Elena Santagostino, Uri Martinowitz, Toshko Lissitchkov, Brigitte Pan-Petesch, Hideji Hanabusa, Johannes Oldenburg, Lisa Boggio, Claude Negrier, Ingrid Pabinger, Mario von Depka Prondzinski, Carmen Altisent, Giancarlo Castaman, Koji Yamamoto, Maria-Teresa Álvarez-Roman, Christine Voigt, Nicole Blackman, Iris Jacobs, PROLONG-9FP Investigators Study Group, Chantal Rothschild, Thierry Lambert, Reinhard Schneppenheim, Günter Auerswald, Christine Heller, Annarita Tagliaferri, Maria Elisa Mancuso, Aaron Lubetsky, Katsuyuki Fukutake, Masashi Taki, Keiji Nogami, Michio Sakai, Tatiana Chernova, Maria Fernanda López-Fernández, Joan C Gill, Amy Shapiro, Patrick Fogarty
Abstract
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 #NCT0101496274.
Trial registration: ClinicalTrials.gov NCT01496274.
© 2016 by The American Society of Hematology.
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Source: PubMed