Alprolix (eftrenonacog alfa) / SOBI, Sanofi - LARVOL DELTA

Safety and efficacy of Fc fusion factor VIII and IX in major orthopedic surgery (ISTH 2025) - "Conclusion(s) rFVIIIFc and rFIXFc provide effective hemostasis during orthopedic surgery in hemophilia A and B, with a favorable safety profile...Tranexamic acid was administered in 93.3% (n=14) of cases for a median duration of 3 days (range:2–8)...Median hospital stay was 7 days (range:3–10). Table or Figure Upload"

Clinical • Surgery • Anemia • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Orthopedics • Rare Diseases

Real-World Study of Eftrenonacog alfa use in Hemophilia B at 8 Hemophilia Centers in Spain (ISTH 2025) - "The results are presented in the following table. Table or Figure Upload"

Clinical • Real-world • Real-world evidence • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases • Rheumatology

Real-World Effectiveness and Usage of Recombinant Factor IX Fc: Final Data from the B-MORE Study (ISTH 2025) - P | "An intrapatient comparison was conducted in 92 patients switching from prior standard half-life (SHL) FIX PPX to rFIXFc PPX (mean [range] duration: 11.5 [6.4–12.0] vs 40.6 [9.8–83.3] months). In these patients, median (IQR) change in ABR was 0.0 (-1.0–0.4), change in IF was -52.7 (-56.6– -38.4), and change in FC was -1,379.9 (-2,594.4– -264.3; n=91) IU/kg/year.Overall, most physicians (88.5%; 69/78) and patients (90.0%; 90/100) were satisfied/highly satisfied with rFIXFc PPX, at last assessment.No inhibitor development or serious adverse events related to rFIXFc were reported."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Association between FIX levels & bleeding rates in hemophilia B patients receiving rFIXFc or N9-GP (ISTH 2025) - "However, these estimates were highly imprecise and statistically non-significant. Table or Figure Upload"

Clinical • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Press Release: Q4 sales growth of 10.3%, 2024 business EPS guidance exceeded, and strong business EPS rebound expected in 2025 (GlobeNewswire) - "Lantus sales were €439 million and increased by 63.4%. US sales were €193 million...Toujeo sales were €290 million and increased by 6.5%, mainly driven by Europe (+10.1%) and Rest of World (+7.4%) where Toujeo continued to increase its basal insulin market share...Alprolix sales were €169 million and increased by 19.0%, benefiting from an increase in US market share and supply sales to Sobi. Myozyme/Lumizyme sales were €132 million and decreased by 17.0% due to the aforesaid shift to exviazyme/Nexviadyme. Thymoglobulin sales were €125 million and increased by 15.2%, reflecting increased sales in the US and in Rest of World.Praluent sales were €110 million and decreased by 6.8%, reflecting lower sales in Rest of World, specifically in China."

Sales • Aplastic Anemia • Familial Hypercholesterolemia • Hemophilia A • Hemophilia B • Pompe Disease • Type 2 Diabetes Mellitus

Real-world usage and effectiveness of recombinant factor IX Fc in haemophilia B from the B-SURE study in France. (PubMed, Ther Adv Hematol) - P | "Findings support the safety and effectiveness of rFIXFc, with reduced IF and FC while maintaining/improving bleed protection. Trial registration: NCT03655340."

Journal • Real-world evidence • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Investigating the Impact of FIX Fc Fusion on Its Extravascular Distribution and Hemostatic Properties (ASH 2024) - "A single dose of 50 IU/kg of recombinant FIX Fc fusion (rFIX-Fc; Alprolix) was administered retro-orbitally to each mouse...In sum, our data demonstrates the localization of rFIX-Fc in seemingly identical spatial regions as Col IV, and this appears to be the result of a specific interaction between these two proteins as confirmed in vitro in our binding assay. Overall, this suggests that the extension of FIX half-life via Fc-fusion technology does not impair its extravascular distribution and Col IV binding."

Hematological Disorders • Hemophilia • Hemophilia B • Musculoskeletal Diseases • Rare Diseases

ORPHEE: A Real-World Study on rIX-FP Prophylaxis Use in Adolescent/Adult Patients With Hemophilia B. (PubMed, Eur J Haematol) - "This analysis confirmed that switching to rIX-FP allows for reducing injection frequency and FIX consumption while maintaining good bleed protection."

Journal • Real-world • Real-world evidence • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Intracranial hemorrhage in an infant leads to the diagnosis and treatment of severe hemophilia B: a case report. (PubMed, Ital J Pediatr) - "This is an uncommon case in which rFIXFc was continued despite the appearance of an allergic reaction and the development of FIX inhibitors. Subsequent allergic reactions were prevented with a combination of oral oxatomide and intravenous hydrocortisone given prior to prophylactic rFIXFc. Further studies are recommended to determine the usefulness of this combination with rFIX therapy."

Journal • Allergy • Cerebral Hemorrhage • CNS Disorders • Dermatology • Glomerulonephritis • Hematological Disorders • Hemophilia • Hemophilia B • Immunology • Musculoskeletal Diseases • Nephrology • Orthopedics • Rare Diseases • Renal Disease

B-MORE: An International Study to Evaluate the Real-world Effectiveness and Usage of Alprolix in Patients With Haemophilia B (clinicaltrials.gov) - P=N/A | N=151 | Completed | Sponsor: Swedish Orphan Biovitrum | Active, not recruiting ➔ Completed | Trial completion date: Jul 2024 ➔ Mar 2024 | Trial primary completion date: Jul 2024 ➔ Mar 2024

Real-world • Real-world effectiveness • Real-world evidence • Trial completion • Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

PBPK modeling of recombinant factor IX Fc fusion protein (rFIXFc) and rFIX to characterize the binding to type 4 collagen in the extravascular space. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "This suggests that rFIXFc present in the extravascular compartment may play an important role in achieving hemostasis after rFIXFc administration. Further studies on extravascular distribution of rFIXFc and the distribution profile of other EHL-FIX concentrates are needed to evaluate the predictions of our PBPK model and to investigate its clinical relevance."

Journal • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Pharmacokinetic model-based assessment of factor IX prophylaxis treatment regimens in severe hemophilia B. (PubMed, Sci Rep) - "A population pharmacokinetic (popPK) model-based assessment comparing the performance of FIX products (rFIX, rIX-FP, rFIXFc, N9-GP) was developed. N9-GP use in adolescents and adults was associated with lower consumption compared with rIX-FP. Insights from this study may be utilized by clinicians to inform decision-making, by considering the model-generated estimated optimal posologies alongside multiple clinical factors and patient preferences."

Journal • PK/PD data • Hematological Disorders • Hemophilia • Rare Diseases

Real-world usage and effectiveness of recombinant factor VIII/factor IX Fc in hemophilia A/B: final data from the 24-month, prospective, noninterventional PREVENT study in Germany. (PubMed, Res Pract Thromb Haemost) - P=N/A | "Compared with previous FVIII, ABR was considerably reduced with rFVIIIFc, with stable annualized FC. For rFIXFc, bleed protection was maintained vs previous FIX while reducing annualized IF."

Journal • Real-world • Real-world evidence • Hematological Disorders • Hemophilia • Rare Diseases

Long-term Clinical Outcomes of Prophylaxis With a rFVIIIFc or rFIXFc in Adults 50+ Years of Age With Hemophilia A or B. (PubMed, Blood Adv) - P3 | "Positive impacts on health-related quality of life were observed in individuals on either rFVIIIFc or rFIXFc prophylaxis. The results for the older subgroups were consistent with the overall study populations, demonstrating that prophylaxis with rFVIIIFc or rFIXFc provides long-term clinical benefits irrespective of age and presence of target joints in patients with severe hemophilia."

Clinical data • Journal • Hematological Disorders • Hemophilia • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Rare Diseases • Rheumatology

Prophylaxis with recombinant factor IX Fc fusion protein reduces the risk of bleeding and delays time to first spontaneous bleed event in previously untreated patients with haemophilia B: A post hoc analysis of the PUPs B-LONG study. (PubMed, Eur J Haematol) - P3 | "rFIXFc prophylaxis, particularly starting early, reduced the risk of bleeding and delayed time to first spontaneous bleed compared with rFIXFc OD. Hence, initial treatment regimens impact bleed patterns in paediatric PUPs."

Journal • Retrospective data • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

Dominant negative effects of Gln50Arg mutation in the EGF-1 domain of factor IX causes severe Hemophilia B affecting factor IX replacement therapy (ISTH 2024) - "Plasma was in vitro spiked with Alprolix, Rixubis, Benefix or FEIBA. Hemostatic screening revealed normal platelet aggregation and coagulation factor activities, except for FIX activity levels of 5 IU/dL in both brothers and a FXI activity of 39 IU/dL in one boy. FIX antigen concentrations were in the normal range in both boys and their mother, FIX inhibitor screening was negative (Figure 1). After bolus infusion of Alprolix, FIX activity in vivo recovery was within expected range, but thrombin generation indicated weak response to FIX substitution therapies."

Hematological Disorders • Hemophilia • Rare Diseases • EGF

FIX Post infusion monitoring surveys: Results and analysis from the updated UK NEQAS BC Haemophilia programmes 2024 (ISTH 2024) - "Data was returned from 47 centres. Centres performed either one stage assays (OSA), chromogenic assays (CA) or both. OSA Alprolix Median value, 40 IU/dL with CV = 8.7%; Benefix Median value, 14.3 IU/dL with CV = 13.6%; Idelvion Median value, 20.4 IU/dL with CV = 14.5% and Refixia Median value, 15.4 IU/dL with CV = 18.2% CA Alprolix Median value, 35.7 IU/dL; Benefix Median value, 11.7 IU/dL; Idelvion Median value, 24.8 IU/dL and Refixia Median value, 13.4 IU/dL."

Hematological Disorders • Hemophilia • Rare Diseases

FIX is localised in the vessel wall and can generate thrombin when in complex with collagen IV in human synovial tissues (ISTH 2024) - "On surfaces with the FIX-collagen complex present, FIX-DP generated a peak thrombin concentration comparable to PNP. FIX binding was confirmed by a chromogenic activity assay and a dose-dependent effect of FIX coating concentration was observed. Collagen plates coated with extended half-life concentrates, Alprolix and Idelvion, generated a significant increase in the endogenous thrombin potential (ETP), when compared to short-acting concentrate, Replenine and Benefix (* p < 0.01)."

Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis

Prophylaxis in Non Severe haemophilia: Experience from Spanish Hemonorte Working Group (ISTH 2024) - "Of patients performing switch, they were on prophylaxis, mainly with Efmoroctocog Alfa® (32%), significantly reducing infusion frequency and weekly factor consumption...In NS-HB patients (average age 39 y, 8 moderate and 2 mild), we found a similar impact of switch to EHL-FIX (mainly Eftrenonacog Alpha®, 50%), with reduction in infusion frequency and weekly factor consumption, leading to significant decrease in total, spontaneous, and joint ABR (Table 1-2)... We included 36 NS patients (25 HA and 11 HB) without history of inhibitors. 76 % HA patients are moderate and 46,1%, suffer hemophilic arthropathy, with average age of 34.3 years (y). 88% of patients were on previous prophylaxis, mostly with Standard Hal life FVIII, three times a week (50 %)."

Hematological Disorders • Hemophilia • Rare Diseases • Rheumatology

Real-world outcomes of prophylaxis with extended half-life factor IX products for hemophilia B: a pooled analysis of medical chart data from Germany and Italy (ISTH 2024) - "Overall, 225 PwHB were included (mean age 34.1 years; 66% with severe hemophilia B; Table 1). Pooled results for consumption and bleeding rates are presented in Table 2. PwHB treated with rIX-FP prophylaxis had significantly lower FIX consumption compared to those treated with rFIXFc: mean 42.4 IU/kg/week vs."

Real-world • Real-world evidence • Retrospective data • Hematological Disorders • Hemophilia • Rare Diseases

Haemostatic Management of a Moderate Haemophilia B (MHB) Patient with respiratory failure through VV-Extracorporeal Membrane Oxygenation (ECMO) (ISTH 2024) - "FIX concentrate (Alprolix) was initially administered as a bolus dose pre-ECMO (levels 50-100IU/dL) and UFH was started (targeting an anti-Xa 0.3-0.5U/mL). The ECMO run was 32 days, during which he also required bilateral chest drain insertion for bilateral pneumothoraces and an abdominal drain for an intra-abdominal collection. He received daily FIX replacement, on average 5000 iu daily (weight 97 kg) maintaining a mean trough of 49 IU/L and a mean peak of 82IU/L."

Clinical • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hemophilia • Infectious Disease • Pneumonia • Rare Diseases • Respiratory Diseases • Thrombosis

Assessing factor consumption and bleeding outcomes of prophylaxis with three commonly prescribed factor IX products for hemophilia B: a retrospective medical chart analysis in the United States (ISTH 2024) - "Overall, 213 PwHB (53% with severe HB) were included, with a mean age [range] of 32.7 [12-84] years (Table 1). Results for consumption and bleeding rates are presented in Table 2. PwHB treated with rIX-FP prophylaxis had significantly lower mean FIX consumption compared to those treated with the other two products: rIX-FP (45.8 IU/kg/week) vs."

Retrospective data • Hematological Disorders • Hemophilia • Rare Diseases

Audit of comprehensive care of haemophilia B against World Federation of Haemophilia guidelines (BSH 2024) - "5/5 switched prophylaxis from standard to extended half-life products (Alprolix, Refixia or Idelvion) due to breakthrough bleeds (4/5) or compliance (1/5). Fifty-six patients with haemophilia B were identified. Data collection included 19 patients: 7 mild, 5 moderate, 5 severe and 2 carriers from 2018 to 2023. Prophylaxis: Hundred percent of patients with severe haemophilia B were on prophylaxis."

Hematological Disorders • Hemophilia • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Rare Diseases

Factor VIII moiety of recombinant Factor VIII Fc fusion protein impacts Fc effector function and CD16+ NK cell activation. (PubMed, Front Immunol) - "Based on our results we propose that FVIII light chain-mediated membrane binding results in tethering of the fusion protein to the cell surface, and this, together with increased binding affinity for CD16, allows for Fc-CD16 interactions to proceed, resulting in NK cellular activation. Our working model may explain our previous results where we observed that rFVIIIFc activated NK cells via CD16, whereas rFIXFc did not despite having identical IgG1 Fc domains."

Journal • Hematological Disorders • Hemophilia • Rare Diseases • IFNG

Cost-Effectiveness of Recombinant Factor IX Fc Prophylaxis and Recombinant Factor IX On-Demand Treatment in Patients with Haemophilia B Without Inhibitors. (PubMed, Adv Ther) - "rFIXFc prophylaxis provides improved health outcomes and lower costs, and represents a cost-effective treatment option compared with rFIX on-demand for adolescent and adult male patients with haemophilia B. This comparative assessment of cost-effectiveness should help to inform both clinicians and healthcare policy makers when making treatment decisions for patients with haemophilia B."

Cost effectiveness • HEOR • Journal • Hematological Disorders • Hemophilia • Rare Diseases