Abstract Number: PB0956
Meeting: ISTH 2020 Congress
Background: 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 haemophilia B.
Aims: To evaluate the safety and efficacy of rFIXFc in PUPs.
Methods: In this open-label, multicentre, multinational, Phase 3 study (NCT02234310), male PUPs aged ˂18 years with haemophilia B (≤2 IU/dL endogenous FIX) were to receive prophylaxis with rFIXFc. Investigators could treat patients episodically prior to initiating prophylaxis. Primary endpoint was occurrence of inhibitor development. Secondary endpoints included annualized bleeding rate (ABR) and assessment of response to treatment of bleeding episodes with rFIXFc.
Results: Of 33 patients enrolled, 26 (79%) were ˂1-year old; 6 (18.2%) had a family history of inhibitors, 28 (84.8%) received prophylaxis (17 (51.5%) switched from episodic treatment); 5 (15.2%) received episodic treatment only. Twenty-seven (81.8%) patients completed the study. Twenty-one (63.6%), 26 (78.8%), 28 (84.8%) patients had ≥50, ≥20, ≥10 exposure days (EDs) to rFIXFc during the study, respectively. One patient on prophylaxis developed a low-titre 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). Median number of rFIXFc injections required to resolve a bleeding episode was 1 (Table). Response to bleeding episode treatment was rated as excellent/good for 100% of 22 injections in the episodic treatment group and 87.7% of 50 injections in the prophylaxis treatment group.
Conclusions: The study population was representative of PUPs with severe haemophilia 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 paediatric haemophilia population.
|Treatment||Episodic (n=22*)||Prophylactic (n=28*)|
|rFIXFc dosing||Median average weekly dose, IU/kg (range)||N/A||57.96 (47.0-233.9)|
|Median average dose interval, days (range)||N/A||7 (3.3-14.6)|
|Annualized bleeding rate (ABR)||Overall, median (IQR)||0.21 (0.00, 5.00)||1.24 (0.00, 2.49)|
|Spontaneous, median (IQR)||0.00 (0.00, 2.26)||0.00 (0.00, 0.00)|
|Spontaneous joint, median (IQR)||0.00 (0.00, 0.00)||0.00 (0.00, 0.00)|
|Number of injections required for resolution of a bleeding episode||Median (IQR)||1.0 (1.0, 1.0)||1.0 (1.0, 1.0)|
|ABR, annualized bleeding rate; IQR, interquartile range (25th, 75th percentile). ABR is the total number of bleeding episodes during the efficacy period extrapolated to a 1-year interval of time for all subjects in the efficacy period, regardless of duration in the efficacy period. *Number of patients with an efficacy period. Efficacy period reflects the sum of all intervals of time during which patients are treated with rFIXFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (>28 days). Patients are included in each treatment regimen they participated in for the duration of time on that regimen and as such may appear in more than one treatment regimen. The majority of bleeding episodes required ≤2 injections to resolve: 88.9% and 96.6% for the episodic and prophylactic regimens, respectively.|
[Annualized bleeding rate and number of injections required for resolution of a bleeding episode]
To cite this abstract in AMA style:Nolan B, Klukowska A, Shapiro A, Rauch A, Recht M, Ragni M, Curtin J, Gunawardena S, Poloskey S, Jayawardene D, Winding B, Fischer K, Liesner R. Final Results of PUPs B-LONG Study: Evaluating Safety and Efficacy of rFIXFc in Previously Untreated Patients with Haemophilia B [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/final-results-of-pups-b-long-study-evaluating-safety-and-efficacy-of-rfixfc-in-previously-untreated-patients-with-haemophilia-b/. Accessed November 29, 2023.
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