Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Real Life: One-Year Clinical and Economic Outcomes

Abstract

Background Recombinant factor VIII Fc fusion protein (rFVIIIFc) is the first extended half-life (EHL) recombinant clotting factor with marketing authorization; it has been available in France since October 2016. However, data and literature about rFVIIIFc in clinical practice are scarce. Objective We propose a 1-year clinical and economic outcome evaluation in patients with hemophilia A taking into consideration treatment adherence. Patients and methods We reviewed the diaries of all patients treated with rFVIIIFc at Marseille Hemophilia Center for 1 year. All the data were related to the patients' infusion (i.e., annual number of infusions, weekly dose/kg, and annual consumption) and bleeding reports. The clotting factor costs were considered, whereas additional costs (e.g., infusion devices and nurse intervention) were neglected. Results A total of 34 patients were evaluated. Their median age was 18 years (IQR = 18). Treatment adherence was observed in 62% for FVIII and 66% for rFVIIIFc. The analysis revealed a negligible decrease in the annual clotting factor consumption following the switch (− 2%, p = 0.7339). These data were combined with a significant reduction in the annual number of infusion (− 22.5%, median = 138.5, IQR = 65.8 for FVIII; median = 105, IQR = 24 for rFVIIIFc, p < 0.0001) and bleeding (− 50%, median = 5, IQR = 7.5 for FVIII; median = 1, IQR = 4 for rFVIIIFc, p < 0.0001). With regard to the cost, a decreasing trend was observed (− 8%, p = 0.1300). ConclusionThe analysis in a real-life setting revealed that the input of switches toward rFVIIIFc in different treatment (age of patients and regimen) patterns seems to corroborate previous studies. The results suggest that switches have a beneficial effect in terms of efficacy, clotting factor consumption, and cost.

rFVIII‐Fc in severe haemophilia A: The incentive switch in case of high risk of joint bleedings

“…In literature, there were large disparities in the impact on the rate of haemorrhagic episodes treated, ranging from an absent or minute difference 22–25 to decreases of up to two ABR points 8,9,20 . In France, Giraud et al described a 4.4 point drop of the median ABR 14 . Our study found a minimal decline of 0.7 points of the mean ABR for our entire cohort (all FVIII products combined); the decline appeared to be mainly due to the patients treated only with rFVIII‐Fc, who presented a meaningful decrease of 2.4 points between T1 and T2.…”

“…A 20%–30% decrease in FVIII consumption has also been observed in most cases in patients switched to rFVIII‐Fc 11–13 . Inversely, many medical teams failed to report a significant decrease in FVIII consumption post‐switch 10,14,15 …”

Efmoroctocog Alfa: A Review in Haemophilia A

“…A large number of retrospective real-world studies have confirmed the efficacy of efmoroctocog alfa in the prophylaxis of bleeding observed in phase III clinical trials. The following discussion, however, only focuses on those involving > 30 PTPs from one or more European countries [31,[36][37][38][39][40][41][42][43][44][47][48][49] or the USA [50][51][52].…”

“…Across the studies, changes in mean or median ABRs or bleed rates ranged from zero (i.e. no change) up to reductions of four (p ≤ 0.003 vs previous prophylaxis [40,41,47,49]); these were accompanied by reductions in the median number of weekly or yearly injections ranging from 22 to 33% (p < 0.001 vs previous prophylaxis [40,41,44,48,50]) and reductions in weekly, monthly or yearly FVIII consumption typically ranging from 10 to 40% (p ≤ 0.028 vs previous prophylaxis [31,40,44,49,50]) (Table 4).…”

“…No patients developed a neutralizing antibody to FVIII over the course of the A-LONG, Kids A-LONG or ASPIRE studies [6,[11][12][13]. A 25-year-old patient tested positive for a low-titre (0.73 BU/mL) inhibitor at week 14 in A-LONG, Table 4 Real-world effectiveness of switching to prophylaxis with efmoroctocog alfa from conventional FVIII products in patients with haemophilia A: results of before-after (within-patient) studies from Europe and the USA (A)BR (annualized) BR, (A)JBR (annualized) joint BR, BR bleeding rate, CFC clotting factor consumption, IF injection frequency, IU international unit, mo month, pt(s) patient(s), wk week, y year, ↑ increased, ↓ decreased *p ≤ 0.043, **p ≤ 0.004, ***p ≤ 0.0007 vs pre-switch a Mean (ABR [31,44,[47][48][49], IF [37,43], CFC [37,39,42,43]) or median (ABR [37,[40][41][42]50], BR [39], JBR [39], AJBR [40,50], IF [40-42, 44, 50], CFC [40,41,44,50]) value, where known b vs pre-switch value c Analysis includes an additional 11 pts who received on-demand efmoroctocog alfa d JBR [39] or AJBR [40,50] e n = 62 for ABR f n = 25 for ABR and CFC g Over a mean period of 10.6 mo [39] Study (no. of pts) but had negative results upon repeat testing 18 days later and thereafter [7].…”