Eloctate (efraloctocog alfa) / UCB, Sanofi, SOBI - LARVOL DELTA

Hematopoietic stem cell transplantation in a newborn suffering from severe combined immunodeficiency and severe hemophilia A: a case report and review of the literature. (PubMed, Res Pract Thromb Haemost) - "Prophylactic factor (F)VIII substitution during HSCT was performed with an extended half-life FVIII product (efmoroctocog alfa)...No bleeding complications or FVIII inhibitors occurred during this individualized management. This is the first case report of a newborn suffering from both SCID and severe hemophilia A. HSCT is feasible in this situation without bleeding complications if an individual substitution regimen with FVIII is applied."

Journal • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Immunology • Primary Immunodeficiency • Rare Diseases • Transplantation

Immune Tolerance Induction With a Recombinant Factor VIII Fc in Haemophilia A: Data From a Chart Review Study. (PubMed, Eur J Haematol) - P | "ITI with rFVIIIFc is likely to be successful in first-time ITI patients and is an effective option for those who have previously experienced ITI failure."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

FVIII half-life products: A real-world experience. (PubMed, Thromb Res) - "EHL FVIII products offer significant clinical benefits, reducing the burden of frequent infusions and improving adherence while maintaining effective bleeding control. Despite these advancements, comprehensive evaluations of cost, safety, and long-term outcomes are essential to optimize their integration into haemophilia care."

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

Regulation of immune responses to therapeutic factor VIII by transplacental delivery of Fc-fused immunodominant factor VIII domains or peptides. (PubMed, Haematologica) - "Here, we evaluated whether the transplacental delivery of Fc-fused FVIII (rFVIIIFc) induces complete immune tolerance towards FVIII...Conversely, the transplacental delivery of Fc-fused A2 and C2 immunodominant domains of FVIII, as well as of Fc-fused molecules containing seven different immunodominant FVIII-derived peptides decreased the levels of anti-FVIII antibodies following FVIII replacement therapy in the offspring. Our study paves the way towards the development of engineered Fc-fused molecules able to efficiently cross the placenta and confer potent and long-lasting immune tolerance to protein therapeutics."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

POCUS: Hemostatic Potential and Joint Health in Patients With Severe Hemophilia A on Novel Replacement Therapies (clinicaltrials.gov) - P4 | N=28 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Trial completion date: Jul 2025 ➔ Jul 2027 | Trial primary completion date: Jul 2025 ➔ Jul 2027

Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

In vitro combined haemostatic efficacy of emicizumab and extended half-life factor VIII compounds. (PubMed, Haemophilia) - "TGA can be used to monitor combined treatment with emicizumab and either efmoroctocog alfa or efanesoctocog alfa, which is not possible with currently available FVIII reagents for the latter. As expected, there is no synergistic effect between the mimetic and FVIII at therapeutical doses. Both efmoroctocog alfa and efanesoctocog alfa show similar in vitro procoagulant activity in terms of thrombin generation."

Journal • Preclinical • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

A randomized, two-armed, double-blind, single-dose, cross-over, bioequivalence clinical trial to compare pharmacokinetic parameters and safety of recombinant human factor VIII with Fc fusion produced by AryoGen Pharmed Company versus Elocta® (reference product) in previously treated patients with severe haemophilia A. (PubMed, Ann Hematol) - P3 | "In conclusion, the rFVIII-Fc product is bioequivalent to Elocta® with a similar safety profile, offering an effective alternative for severe haemophilia A patients. This trial was registered in ClinicalTrials.gov (NCT06137092)."

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

Press Release: Q4 sales growth of 10.3%, 2024 business EPS guidance exceeded, and strong business EPS rebound expected in 2025 (GlobeNewswire) - "ALTUVIIIO (hemophilia A) sales were €230 million of which more than 85% were in the US...Nexviazyme/Nexviadyme (Pompe disease) sales were €184 million and increased by 42.0%, driven by Europe (+68.6%) and Rest of World (+55.0%). In the US (+26.3%)...Rezurock (chronic graft-versus-host disease) sales were €132 million and increased by 53.5%, driven by the US (+43.4%) and by launches in Europe (sales of €8 million) and in Rest of World (sales of €5 million)...Cablivi (acquired thrombotic thrombocytopenic purpura) sales were €73 million and increased by 24.1%, driven by an increased number of patients being identified for appropriate treatment, in the US and from launches in Europe and in Rest of World...Eloctate sales were €81 million and decreased by 21.4%, mainly due to patients converting to ALTUVIIIO in the US and in Japan. Aubagio sales were €78 million and decreased by 35.5%..."

Sales • Chronic Graft versus Host Disease • Hemophilia A • Multiple Sclerosis • Pompe Disease • Thrombocytopenic Purpura

Can surgery be performed without any bleeding with one extra dose of rFVIIIFc between prophylaxis days? (EAHAD 2025) - No abstract available

Surgery

Indirect Comparison of the Efficacy and Therapy-Related Costs of a Pharmacokinetic and Individualized Prophylaxis Regimen with Simoctocog Alfa Versus Other Extended-Half Life Factor VIII Concentrates (ASH 2024) - "For comparison, aggregated data was obtained from the following trials with EHL concentrates : pathfinder2 (turoctocog alfa pegol, N = 175), A-LONG (efmoroctocog alfa, N = 117), PROTECT FVIII (damoctocog alfa pegol, N = 110), PROPEL (rurioctocog alfa pegol 1–3% and 8–12%; N = 57 and 58), and XTEND-1 (efanesoctocog alfa, Group A, N = 133). Conclusion : Albeit at a generally higher weekly dose, a PK-guided, individualized prophylaxis regimen with simoctocog alfa offered comparable or significantly improved zero bleed rates and significantly lower or comparable ABRs than prophylactic regimens with EHL rFVIII concentrates. Nevertheless, the estimated annual cost of a simoctocog alfa-based regimen is 20–55% lower than with the other concentrates."

Clinical • PK/PD data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Binding of therapeutic Fc-fused factor VIII to the neonatal Fc receptor at neutral pH associates with poor half-life extension. (PubMed, Haematologica) - "Here we compared the binding behaviour to FcRn of Fc-fused FVIII, Fc-fused FIX and two human monoclonal HIV-1 broadly-neutralizing IgG1, m66.6 and VRC01 with identical Fc. Accordingly, mutations of key positively charged amino-acids in the FVIII C1C2 domains decreased the binding of the protein to FcRn at pH 7.4 in vitro and increased the half-life of rFVIIIFc in VWFKO mice. Our findings suggest that the removal of positively charged patches on Fc-fused proteins to ameliorate FcRn recycling without affecting therapeutic efficacy, may improve their pharmacokinetic properties."

Journal • Human Immunodeficiency Virus • Infectious Disease

Role of Factor VIII As a Regulator of Angiogenesis and Promoter of Endothelial Barrier Stability (ASH 2024) - "HA BOECs were treated in vitro with the rFVIII products simoctocog alfa (Nuwiq®), efmoroctocog alfa (Elocta®), rurioctocog alfa pegol (Adynovate®), damoctocog alfa pegol (Jivi®), octocog alfa (Advate®), or emicizumab (Hemlibra®). Investigating the potential extra-coagulative role of FVIII could be crucial to understanding the key molecular targets at the cellular level which impair EC function in patients with HA. Knowledge of the possible effect of different rFVIII products and non-factor therapies on EC function can be used to optimize therapeutic approaches, which in turn may result in safer and more efficient treatment of HA."

Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Osteoarthritis • Rare Diseases

Cost Comparison of Efanesoctocog Alfa with Existing Factor VIII Replacement Therapies for Major Surgeries in People with Severe Hemophilia a (ASH 2024) - P2/3, P3 | "Objective To estimate total costs associated with perioperative hemostatic management in patients with severe HA treated with SHL (octocog alfa), EHL (rurioctocog alfa pegol and efmoroctocog alfa), and high-sustained (efanesoctocog alfa) FVIII replacement therapies. This is attributed to its high-sustained factor activity and reduced factor consumption during the reported perioperative period. The major limitations of the study were : the types of major surgeries varied among studies; the perioperative period data of octocog alfa were not found."

HEOR • Reimbursement • Surgery • US reimbursement • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Factor VIII (FVIII) Trough Levels of Real-World Severe-Type People with Hemophilia a (PwHA) on rFVIII-Fc Prophylaxis: Clinical Correlates and Effects on Perceivable Bleeding Outcomes (ASH 2024) - "Conclusion : Our study showed that for real-world PwHA on rFVIIIFc prophylaxis, trough levels variated hugely, and that trough levels were significantly higher in PwHA with non-O group and longer rFVIIIFc half life, and significantly correlated to endogenous VWF levels, age, and BMI. Meanwhile, our data indicated that between PwHA with non-zero and zero bleeding, the proportion of trough <1% was not significantly different; meanwhile, trough level was not correlated to perceivable bleeding frequency, including ABR and AJBR."

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

Influencing Factors and Predictors for Bleeding Outcomes in Severe-Type People with Hemophilia a (PwHA) on Extended Half-Life rFVIII-Fc Prophylaxis (ASH 2024) - "Introduction : In the past, we had ever reported that real-world severe-type people with hemophilia A (PwHA) got improved bleeding outcomes when they shifted to extended half-life (EHL) recombinant FVIII with Fc-fusion protein (rFVIIIFc) prophylaxis...Many clinical factors, dosing regimen, and pharmacokinetic factors were proved to be unable to independently influence bleeding outcomes. Only ratio of VWF : activity/VWF : Ag was proved as a predictor for ABR."

Hematological Disorders • Hemophilia • Hemophilia A • Hepatitis C • Infectious Disease • Rare Diseases • Rheumatology

Impact of Variable Recombinant Factor VIII Binding on Platelet Functions (ASH 2024) - "rFVIII-platelet binding : Activated platelets were incubated with simoctocog alfa (Nuwiq®), efmoroctocog alfa (Elocta®), rurioctocog alfa pegol (Adynovate®) or damoctocog alfa pegol (Jivi®). The rFVIII products explored in this study bound to platelets with varying strength, with simoctocog alfa demonstrating the highest amount of platelet binding, as well as the highest interaction with pro-aggregatory platelets. These findings indicate that variations in platelet binding may influence the efficacy of rFVIII products in the treatment of HA."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • ANXA5

Efanesoctocog Alfa versus Standard and Extended Half-Life Factor VIII Prophylaxis in Adolescent and Adult Patients with Haemophilia A without Inhibitors. (PubMed, Adv Ther) - P3 | "Efanesoctocog alfa was associated with significantly lower ABRs (any, spontaneous and joint) compared with EHL or SHL prophylaxis therapies. Patients had, on average, 2.2 and 3.6 fewer bleeds per year versus EHL and SHL therapies, respectively."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Rescue immune tolerance induction with a recombinant factor Fc-fused VIII: prospective ReITIrate study of clinical, humoral and cellular immune responses. (PubMed, Ther Adv Hematol) - P4 | "This study demonstrates that ITI with rFVIIIFc given within a limited timeframe has potential benefit in a difficult-to-treat inhibitor haemophilia population who failed previous ITI attempts. NCT03103542."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • CD4 • IL2RA • IL7R

Superior Prophylactic Effectiveness of a Recombinant FVIIIFc Over Standard Half-Life FVIII in Hemophilia A: A-SURE Study. (PubMed, Eur J Haematol) - "rFVIIIFc has superior prophylactic effectiveness versus SHL FVIII, providing higher bleed protection with fewer injections and lower factor consumption."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Real-world insights into the management of hemophilia A in Italy: treatment patterns and healthcare resource utilization. (PubMed, Blood Res) - "These findings revealed an extensive use of EHL FVIII products, suggesting growing efforts from clinicians to optimize prophylactic strategies and achieve better bleeding protection."

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

Pharmacokinetics of Efmoroctocog alfa by Two-Compartment Model Highlights Hemophilia A Patients with Biphasic Decay, Long Mean Residence Time, and Beta Half-Life. (PubMed, J Clin Med) - "The TCM only fits two-thirds of the PKs, highlighting their biphasic decay and a long Beta half-life. In these patients, the TCM would be preferable to properly evaluate individual PK features."

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

Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review. (PubMed, Drugs R D) - P1 | "The PK of damoctocog alfa pegol was shown to be improved as compared with that of sucrose-formulated rFVIII (rFVIII-FS, Kogenate®), and was also demonstrated to be non-inferior to and, for some variables, more favorable than rFVIII-Fc fusion protein, efmoroctocog alfa (Elocta®; NCT03364998), rurioctocog alfa pegol (BAX 855, Adynovate®/Adynovi®; NCT04015492), and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, Advate®; NCT02483208). Efficacy for perioperative hemostasis has been demonstrated. Low bleeding rates were achieved across the studies, with twice weekly, every 5-day and every 7-day prophylaxis offering patients ≥ 12 years and their clinicians the chance to tailor treatment to individual needs and lifestyles, while maintaining long-term protection from bleeds and their consequences."

Journal • Review • 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 efmoroctocog alfa prophylaxis improves perceived pain, mental, and physical health in patients with hemophilia A: post hoc analysis of phase III trials using patient-reported outcomes. (PubMed, Ther Adv Hematol) - P3 | "Long-term efmoroctocog alfa prophylaxis reduces pain and improves HRQoL in adult and adolescent patients with hemophilia A. In pediatric patients, it reduces perceived pain and maintains satisfaction levels. NCT01458106, NCT01181128, NCT01454739."

Journal • P3 data • Patient reported outcomes • Retrospective data • Hematological Disorders • Hemophilia • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Pediatrics • 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