Final results of pups a-long study: Evaluating safety and efficacy of rFVIIIFc in previously untreated patients with haemophilia A

Abstract

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 1. 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.L6335466442020-12-07 <br />