denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 322. Disorders of Coagulation or Fibrinolysis: Poster I
Hematology Disease Topics & Pathways:
Anemias, Bleeding Disorders, Biological, Diseases, Bleeding and Clotting, Therapies, Clinically relevant
This is the first study of recombinant factor IX Fc fusion protein (rFIXFc) for prevention and treatment of bleeds in previously untreated patients (PUPs) with hemophilia B. We evaluated the safety and efficacy of rFIXFc in PUPs.
Methods
In this open-label, multicenter, multinational, Phase 3 study (NCT02234310), male PUPs <18 years of age with hemophilia B (≤2 IU/dL endogenous factor IX) were to receive prophylaxis with rFIXFc. Investigators could treat patients on demand prior to initiating prophylaxis. The primary endpoint was occurrence of inhibitor development. Secondary endpoints included annualized bleed rate (ABR) and assessment of response to treatment of bleeding episodes with rFIXFc.
Results
Of 33 patients enrolled, 26 (79%) were <1 year of age, 6 (18.2%) had a family history of inhibitors, 28 (84.8%) received prophylaxis (17 [51.5%] switched from on-demand treatment), and 5 (15.2%) received on-demand treatment only. Twenty-seven (81.8%) patients completed the study. Twenty-one (63.6%), 26 (78.8%), and 28 (84.8%) patients had ≥50, ≥20, and ≥10 exposure days (ED) to rFIXFc during the study, respectively. One patient on prophylaxis developed a low-titer inhibitor (<5.00 BU/mL) after 11 EDs; the rate of inhibitor development was 3.0% (1/33 patients). Twenty-three (69.7%) patients had 58 treatment-emergent serious adverse events (TESAE); 2 were assessed as treatment related (factor IX inhibition and hypersensitivity in 1 patient, resulting in withdrawal). Median ABR (prophylaxis) was 1.2 (Table 1). Median number of rFIXFc infusions required to resolve a bleeding episode was 1 in both the prophylactic and on-demand groups (Table 1). Response to bleeding episode treatment was rated as excellent/good for 100% of 22 infusions in the on-demand treatment group and 87.7% of 50 infusions in the prophylaxis treatment group.
Conclusions
The study population was representative of PUPs with severe hemophilia B. Prophylaxis and treatment of bleeding episodes with rFIXFc was highly effective and generally well tolerated, without unanticipated safety findings; type and incidence of TESAEs were similar to those expected for the pediatric hemophilia population.
Disclosures: Nolan: Sobi: Other: personal fees; Bayer, CSL Behring, and Sanofi.: Other: sponsorship; Sanofi: Other: PI for sponsor-(Sanofi-) led clinical trial. Klukowska: Takeda, Roche, Novo Nordisk, and Sobi: Other: personal fees; Takeda, Roche, and Sobi: Membership on an entity's Board of Directors or advisory committees; Takeda and Novo Nordisk: Other: lecturer. Shapiro: Glover Blood Therapeutics: Research Funding; Octapharma: Research Funding; OPKO: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Research Funding; Kedrion Biopharma: Research Funding; Pfizer: Research Funding; ProMetic Bio Therapeutics: Consultancy, Research Funding; Sangamo: Research Funding; Sigilon: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk Hemophilia Foundation: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding; Catalyst BioSciences: Membership on an entity's Board of Directors or advisory committees; Bioverativ: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioMarin: Research Funding; Agios: Research Funding. Rauch: Sobi: Other: advisory boards (these fees were paid to the institution), and received travel expenses for attending medical meetings. Recht: Pfizer: Consultancy, Other: personal fees, Research Funding; Genentech: Consultancy, Other: personal fees, Research Funding; Takeda: Consultancy, Other: personal fees, Research Funding; BioMarin: Research Funding; Spark: Research Funding; Bayer: Research Funding; Grifols: Research Funding; Hema Biologics: Consultancy, Research Funding; LFB: Research Funding; Octapharma: Research Funding; Catalyst Biosciences: Consultancy; Kedrion: Consultancy; Sanofi: Consultancy, Research Funding; Novo Nordisk: Consultancy, Other: personal fees, Research Funding; uniQure: Consultancy, Other: personal fees, Research Funding; CSL Behring: Consultancy, Other: personal fees. Ragni: Baxalta/Takeda, CSL Behring, Genentech, a member of the Roche Group, OPKO Biologics, and Vascular Medicine Institute: Research Funding; American Thrombosis Hemostasis Network: Other: Committee work; Alnylam Pharmaceuticals Inc., Baxalta/Takeda, BioMarin, Bioverativ, and Spark Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sangamo: Consultancy, Research Funding; Takeda: Research Funding; Bioverativ: Consultancy, Research Funding; Spark: Consultancy, Research Funding; BioMarin: Consultancy, Research Funding; Alnylam/Sanofi, ATHN, BioMarin, Bioverativ, Sangamo, Spark: Research Funding; Alnylam/Sanofi, BioMarin, Bioverativ, Spark: Consultancy. Curtin: Bioverativ Inc/Sanofi, CSL Behring, Pfizer, and Roche: Other: personal fees; Bioverativ (paid to her institute): Other: Sponsorship; CSL Behring and Shire/Takeda: Research Funding; Pfizer: Other: received hemophilia treatment center funding and equipment support; BioMarin, CSL Behring, Freeline (paid to institute), Roche, and Shire/Takeda: Membership on an entity's Board of Directors or advisory committees. Gunawardena: Sanofi: Current Employment. Poloskey: Sanofi: Current Employment. Jayawardene: Sanofi: Current Employment. Winding: Sobi AB: Current Employment. Fischer: Bayer, Baxter/Shire, SOBI/Biogen, CSL Behring, Octapharma, Pfizer, NovoNordisk: Research Funding; Bayer, Baxter, Biogen, CSL Behring, Freeline, Novo Nordisk, Pfizer, Roche, and Sobi: Consultancy; Bayer, Biogen, Pfizer, Baxter/Shire, and Novo Nordisk: Research Funding. Liesner: Sobi, Octapharma, CSL Behring, Grifols, Shire/Takeda, Novo Nordisk, Bayer, and Roche.: Other: personal fees.
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