Abstract Number: OC 03.2
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: PUPs A-LONG is the first study evaluating an extended half-life (EHL), recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously untreated patients (PUPs) with haemophilia A.
Aims: To evaluate safety, including inhibitor development, and efficacy of rFVIIIFc in PUPs.
Methods: This open-label, multicentre, Phase 3 study (NCT02234323) enrolled male PUPs aged ˂6 years with haemophilia A (˂1 IU/dL endogenous FVIII) to receive rFVIIIFc. Primary endpoint was inhibitor development (incidence rate=number of patients with inhibitor/number of patients reaching ≥10 exposure days (ED) milestone or with inhibitor). A secondary endpoint was annualized bleeding rate (ABR).
Results: Of 103 patients receiving ≥1 dose; 80 (77.7%) were ˂1-year old; 20 (19.4%) had a family history of inhibitors, and 82 (79.6%) had a high-risk haemophilia genotype. Eighty-one patients started on episodic treatment; of these, 69 switched to prophylaxis. Twenty patients started on prophylaxis and 2 were not assigned a regimen. Eighty-seven (84.5%) patients completed the study. Eighty-seven (84.5%), 85 (82.5%), and 81 (78.6%), patients had ≥10, ≥20, ≥50 EDs to rFVIIIFc, respectively. Total and high-titre (≥5.00 BU/mL) inhibitor rate was 31.1% (28/90) and 15.6% (14/90), respectively, for patients with ≥10 EDs (3 inhibitor patients with ˂10 EDs included). Median time to inhibitor development was 9 EDs (range: 1-53). rFVIIIFc dosing and efficacy data in Table. Twenty-eight (27.2%) had rFVIIIFc treatment-related serious adverse events (TESAEs); FVIII inhibition, n=28; soft tissue haemorrhage, n=1; deep vein/CVAD-associated thromboses, n=2). There was 1 non-treatment-related death due to intracranial haemorrhage (onset during screening period prior to first rFVIIIFc dose).
Conclusions: This was the first prospective study of an EHL rFVIIIFc treatment for PUPs with severe haemophilia A. Overall inhibitor development was in the range that can be expected, although high-titre incidence was lower than that reported in the literature. The data demonstrate that rFVIIIFc was well tolerated and effective in this paediatric patient population.
| Treatment | Episodic (n=81*) | Prophylactic (n=89*) | |
| rFVIIIFc dose (n=88) | rFVIIIFc dose (n=88) | N/A | 101.44 (62.98, 138.68) |
| Average dosing interval, median (IQR), days | N/A | 3.87 (3.28-4.74) | |
| Number of weeks on rFVIIIFc | Median, (range) | 23.57 (0.4-107.8) | 43.97 (0-96.6) |
| Annualized bleeding rate (ABR) | Overall, median (IQR) | 2.24 (0.00, 5.94) | 1.49 (0.00, 4.40) |
| Spontaneous, median (IQR) | 0.00 (0.00, 1.41) | 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, 2.0) | 1.0 (1.0, 1.0) |
| Response to treatment | Injections assessed as ‘excellent/good’, n (%) | 102 (85%) | 163 (79.9%) |
| *Number of patients with an efficacy period. Full Analysis Set patients with an efficacy period: 101 (patients with ≥1 day of treatment for an episodic regimen or ≥2 prophylactic injections for prophylactic regimens). IQR, interquartile range (25th, 75th percentile). The annualized bleeding rate is the total number of bleeding episodes during the efficacy period extrapolated to a 1-year interval of time. Efficacy period reflects the sum of all intervals of time during which patients are treated with rFVIIIFc 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. | |||
[Annualized bleeding rate, number of injections required for resolution of a bleeding episode and response to treatment]
To cite this abstract in AMA style:
Königs C, Ozelo MC, Dunn A, Kulkarni R, Nolan B, Brown SA, Liesner R, Schiavulli M, Gunawardena S, Mukhopadhyay S, Jayawardene D, Winding B, Carcao M. Final Results of PUPs A-LONG Study: Evaluating Safety and Efficacy of rFVIIIFc in Previously Untreated Patients with Haemophilia A [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/final-results-of-pups-a-long-study-evaluating-safety-and-efficacy-of-rfviiifc-in-previously-untreated-patients-with-haemophilia-a/. Accessed November 29, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/final-results-of-pups-a-long-study-evaluating-safety-and-efficacy-of-rfviiifc-in-previously-untreated-patients-with-haemophilia-a/