Awarded/Presented
Tags
Bleeding Disorders Conference
Clinical Research/Clinical Trials
Researchers
Anna Klukowska, MD, MedIcal University of Warsaw; Antoine Rauch, MD, PhD, Lille University Hospital Center (CHU) Lille; Amy Shapiro, MD, Indiana Hemophilia and Thrombosis Center; Bent Winding, MD, Swedish Orphan Biovitrum AB; Deepthi Jayawardene, MD, Sanofi; Beatrice Nolan, MD, Our Lady's Children's Hospital; Julie Curtin, MBBS, PhD, The Children's Hospital at Westmead; Kathelijn Fischer, MD, PhD, University Medical Center Utrecht; Margaret Ragni, MD, MPH, University of Pittsburgh Medical Center; Michael Recht, MD, PhD, Oregon Health and Science University; Raina Liesner, MD, Great Ormond Street Hospital; Sriya Gunawardene, MD, Sanofi; Stacey Poloskey, MD, Sanofi

Objective:

PUPs B-LONG aimed to evaluate the safety and efficacy of recombinant factor IX Fc fusion protein (rFIXFc) for prevention and treatment of bleeds in previously untreated patients (PUPs) with hemophilia B.

Methods:

In this open-label, multicenter, multinational, Phase 3 study (NCT02234310), male PUPs aged <18 years with hemophilia B (≤2 IU/dL endogenous FIX) were to receive prophylaxis with rFIXFc. Investigators could treat patients episodically before initiating prophylaxis. 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.

Summary:

Of 33 patients enrolled, 26 (79%) were <1 year old, 6 (18.2%) had a known family history of inhibitors, 28 (84.8%) received prophylaxis (17 [51.5%] switched from episodic treatment), and 5 (15.2%) received episodic 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 (EDs) to rFIXFc during the study, respectively. One patient on prophylaxis developed a low-titer inhibitor (<5.00 BU/mL) after 11 EDs; rate of inhibitor development was 3.0% (1/33 patients). Twenty-three (69.7%) patients had 58 treatment-emergent serious adverse events (TESAEs); 2 were assessed as treatment related (FIX 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 (Table 1). For infusions with an evaluation, subjects’ assessment of response to bleeding episode treatment was rated as excellent/good for 22/22 (100%) infusions in the episodic treatment group and 50/57 (87.7%) infusions in the prophylaxis treatment group.

Conclusions:

The study population was representative of PUPs with hemophilia B. Prophylaxis and treatment of bleeding episodes with rFIXFc were effective and generally well tolerated, without unanticipated safety findings. Type and incidence of TESAEs were similar to those expected for the pediatric hemophilia population.