ADVATE [Antihemophilic Factor (Recombinant), Plasma/Albumin- Free Method] Post-Authorization Safety Surveillance (PASS): Safety and Efficacy Following Product Switch in Routine Clinical Practice.

A prospective, non-interventional Post-Authorization Safety Surveillance (PASS) program was initiated in 2004 to document ADVATE safety and efficacy in routine clinical practice. More than 900 subjects newly prescribed ADVATE have been enrolled in the US, EU and Japan alone. Herein, we present final US and interim EU results comprising 506 treated subjects, 451 of which have completed the 1-year observation period and 20 ongoing. Age cohorts were as follows: 27 neonates/infants (0-<2 years), 128 children (2-<12 years), 54 adolescents (12-<16 years), and 285 adults (≥16 years); 12 with age unreported. At study entry, 61 patients were considered previously untreated (PUP) or minimally treated (MTPs) defined as ≤50 previous exposure days [EDs]); 437 subjects were considered previously treated patients (PTPs) (>50 previous EDs). Eight subjects had unknown exposure history. Twenty-nine PUPs/MTPs reported exact exposure history prior to ADVATE: 5 reported 0 ED; 7 reported 1 to 3 EDs; and 17 reported 4 to 50 EDs. Most study subjects had FVIII ≤2%; 46 of which were PUPs/MTPs and 389 were PTPs. Among PTPs with FVIII ≤2%, 331 had no known history of inhibitor; 58 reported having a history of inhibitor prior to receiving ADVATE. At enrollment, 58% of subjects were prescribed prophylaxis, while 42% were treated on-demand. A total of 4848 bleeds in 343 subjects were treated. The on-demand efficacy was rated only as excellent/good in 94% of subjects. Subjects who were prescribed ADVATE prophylaxis (N=291) received a mean of 3 infusions per week at 29 IU/kg/ infusion. The median annual bleed rate on prophylaxis was 2.4 bleeds per year. Prophylactic efficacy assessments were provided for 268 subjects; 92% received only excellent/good ratings. Similar efficacy results were seen for the various populations with or without history of inhibitor. No unusual or unexpected AEs were seen in the study. One de novo, low-titer (1.4 BU), transient inhibitor was reported in 331 PTPs with FVIII ≤2% and no prior inhibitor history, providing a de novo inhibitor incidence estimate of 0.3% (95% CI, 0.01% – 1.67%). Two recurrent, low-titer inhibitors (≤1.5 BU) were reported in PTPs with FVIII ≤2%. One de novo, high-titer and 1 de novo, low-titer inhibitor were reported in PTPs with FVIII >2%. Two high-titer inhibitors were reported among 61 PUPs/MTPs. Other SAEs included 1 headache, 2 allergic reactions, 1 ineffective drug response in a subject with inhibitor and ITI history, and 1 hemarthrosis secondary to trauma. Results from the US and EU PASS registries validate the ADVATE safety and efficacy profile in the general hemophilia A population, in real-world clinical settings. Consistent with the formal clinical study findings ADVATE continues to demonstrate low risk for inhibitor development in PTPs.