Assessing prophylactic use and clinical outcomes in hemophilia A patients treated with rVIII-SingleChain and other common rFVIII products in Germany.

OBJECTIVE: To evaluate real-world outcomes with rVIII-SingleChain and other commonly used recombinant FVIII (rFVIII) products. METHODS: Hemophilia treatment centers in Germany (n = 21) contributed patient chart data. Inclusion criteria were prophylactic treatment with one of five rFVIII products for ≥8 weeks. RESULTS: Male patients (n = 225) were included: rVIII-SingleChain (n = 40), rFVIIIFc (n = 47), octocog alfa (rFVIII; n = 58), octocog alfa (BAY 81-8973; n = 40), or moroctocog alfa (n = 40). In patients with severe disease (n = 76), 66.6%, 70.0%, 20.0%, 7.7%, and 27.3% were dosed ≤2×/week, respectively. Irrespective of dosing frequency, mean annualized bleed rates (ABRs)/annualized spontaneous bleed rates (AsBRs) were 0.3/0.1, 0.8/0.4, 1.1/0.5, 1.5/0.8, and 1.4/0.6, and mean FVIII consumption (IU/kg/week) was 83.2, 97.2, 92.5, 104.0, and 102.1, respectively. Results for all patients were similar. Of the patients on prophylaxis with prior therapy and after switching to rVIII-SingleChain (n = 21), mean ABR/AsBRs were 0.7/0.3 and 0.2/0.0, respectively. After switching to rVIII-SingleChain, mean FVIII consumption reduced (109.4 vs 74.5 IU/kg/week), and percentage of patients dosed ≤2×/week increased (0% to 71.4%). CONCLUSIONS: rVIII-SingleChain prophylaxis provides excellent bleeding protection, with potentially lowest factor consumption among the products assessed. Patients who switched to rVIII-SingleChain prophylaxis reduced dosing frequency and consumption compared with prior treatment, with similar or potentially lower bleeding rates.

Real-World Utilisation and Bleed Rates in Patients with Haemophilia B Who Switched to Recombinant Factor IX Fusion Protein (rIX-FP): A Retrospective International Analysis.

INTRODUCTION: Despite the well-documented benefits of prophylaxis, treatment burden is still a barrier to adherence in patients with haemophilia. An extended half-life fusion protein linking recombinant FIX (rFIX) with human albumin (rIX-FP) has been developed for the treatment of patients with haemophilia B and is indicated for dosing up to every 14 days. This analysis evaluated real-world outcomes in patients switching to rIX-FP from the previous FIX product in Italy, Belgium and the UK. METHODS: Anonymised chart data were collected from the pre-existing medical records of patients with haemophilia B between May and September 2018. Patients were included in the analysis if they had been treated with rIX-FP for ≥ 8 weeks. Data were compared between rIX-FP and the patient's prior FIX product. RESULTS: Twenty-three HTCs from Italy (n = 13), Belgium (n = 3) and the UK (n = 7) provided data for 84 male patients, 92.8% of which had severe haemophilia B. The majority of patients were previously on prophylactic regimens with their prior FIX product (Italy, 44/49; Belgium, 7/10; UK, 22/25). The switch to prophylaxis with rIX-FP led to reductions in mean annualised bleeding rate of 94.3% in Italy, 93.9% in Belgium and 67.7% in the UK compared with prior FIX prophylaxis. Overall, 41% of patients experienced zero spontaneous bleeds prior to switching, compared with 88% following the switch to rIX-FP. The majority of patients had a reduction in dosing frequency following the switch, with 98.6% of patients dosing once weekly or less frequently compared with 9.6% of patients dosing at this frequency with their prior FIX. Mean weekly FIX consumption was reduced compared with prior FIX prophylaxis. CONCLUSION: This retrospective review of real-world evidence demonstrated that switching to rIX-FP from prior FIX was associated with improved haemostatic efficacy and reduced factor consumption in patients with haemophilia B from Italy, Belgium and the UK.

While clinical trials provide robust evidence as to the effectiveness and safety of a new drug, they are tightly controlled and so may not reflect some of the issues that may be discovered in clinical practice. Therefore, real-world analyses are important to determine how a product performs in patients in everyday settings. This study looked at the use of an extended half-life fusion protein linking recombinant FIX (rFIX) with human albumin (rIX-FP), which was designed to allow longer dosing intervals, in patients with haemophilia B in Italy, Belgium and the UK, and compared this with the patients' previous FIX product. Anonymous patient chart data were collected from participating centres and analysed in terms of bleeding rate, factor usage and dosing frequency for rIX-FP and previous FIX product. The results showed that after switching to rIX-FP, patients experienced lower bleeding rates, lower factor usage and less frequent dosing regimens compared with their previous FIX product. This is the first analysis to assess the real-world clinical benefits of switching to prophylaxis with rIX-FP from a prior FIX product in Italy, Belgium and the UK. This study further strengthens the results seen in clinical trials with rIX-FP, confirming that the effective bleeding prevention demonstrated in clinical trials is consistent with that seen in patients in real-world clinical practice.