Nuwiq (simoctocog alfa) / Octapharma - LARVOL DELTA

Osteoblasts differentiated from FVIII-deficient mice exhibit impaired mineralization capacity and promote excessive in vitro osteoclastogenesis (ASH 2025) - "During osteoblastdifferentiation, cells were treated with varying concentrations of simoctocog alfa (recombinant FVIII[rFVIII]), FIX, or hirudin (an inhibitor of thrombin activity)...These findings suggest that FVIII replacement therapy in HApatients may offer benefits beyond hemostatic control, potentially enhancing bone health and reducingfracture risk. Further investigation into the molecular mechanisms linking FVIII to bone homeostasiscould inform new strategies for managing hemophilia-associated comorbidities."

Preclinical • Hematological Disorders • Hemophilia • Hemophilia A • Musculoskeletal Diseases • Orthopedics • Rare Diseases • CSF1 • TRAP

Impact of secondary FVIII prophylaxis on joint bleeding and arthropathy in a Hemophilia A mouse model lacking inhibitor response (ASH 2025) - "However, this mouse model has not been suitable to study the effects of FVIII prophylaxisas mice develop anti-FVIII antibodies following repeated injections.Aims: To study effects of secondary FVIII prophylaxis after joint bleeding, we developed a novel HAmouse model that lacks inhibitor formation (F8-/- Ighm-/-, or DKO). DKO mice were randomized into 3 experimental groups (Gr.): 1) no treatment, 2) single rFVIIIinjection (simoctocog alfa, 200 IU/kg, day 0), 3) initial rFVIII injection (200 IU/kg, day 0), followed bysecondary prophylaxis with 100 IU/kg for 3 weeks (daily on days 1-4 and then 3 times per week)... Mice receiving secondary rFVIII prophylaxis (Gr.3) exhibited increased thrombin generationcompared to no treatment (Gr.1) or single rFVIII treatment (Gr.2), despite FVIII trough levels being nearthe detection limit in all groups. Prophylaxis prevented swelling of the injured knee on days 4, 11, and 21and preserved normal running behavior.µCT analysis..."

Preclinical • Hematological Disorders • Hemophilia • Hemophilia A • Immunology • Inflammation • Osteoarthritis • Rare Diseases • Rheumatology • Systemic Inflammatory Response Syndrome

Matching-Adjusted Indirect Comparison between Personalized Prophylaxis with Simoctocog Alfa Versus Standard Prophylaxis with Emicizumab in Adults with Hemophilia a (ASH 2023) - "Indirect comparisons demonstrated that PK-guided, personalized prophylaxis with simoctocog alfa can lead to statistically significantly higher zero bleed rates and decreased ABRs compared with standard emicizumab prophylaxis. This MAIC analysis provides important comparative efficacy and utilization data, which can help guide patients and physicians in making decisions regarding product choice for prophylaxis regimens."

Clinical • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Matching-Adjusted Indirect Comparison of Personalized Prophylaxis with Simoctocog Alfa Versus Standard Prophylaxis with Efanesoctocog Alfa in Adults with Severe Hemophilia a (ASH 2023) - "An indirect comparison analysis demonstrated that a PK-guided, personalized prophylaxis with simoctocog alfa in adult PTPs resulted in zero bleed rates and ABRs that are not statistically different from those with efanesoctocog alfa. The higher total weekly dose observed with simoctocog alfa is to be expected based on the dosing recommendations for each respective FVIII replacement product. This MAIC analysis provides important comparative efficacy and utilization data, which can help guide patients and physicians in making decisions regarding product choice for prophylaxis regimens."

Clinical • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Factor VIII Is an Endothelial Factor That Promotes Vessel Stability (ASH 2023) - "HA BOECs were treated in vitro with B-domain deleted (BDD; simoctocog alfa) or full-length (FL) rFVIII products, and EC functionality was evaluated by tubulogenic, migration, permeability and proliferation assays... In conclusion, information about the possible extra-coagulative role of FVIII may be crucial to understand the key molecular targets missing in HA patients at the cellular level that impair EC functionality. Knowledge of the possible effect of different rFVIII products on ECs functionality can lead to new therapeutic approaches potentially resulting in safer and more efficient treatment of HA."

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

Design of an Observational Study (PROVE) to Assess the Long-Term Effects of Prophylaxis with Simoctocog Alfa or Emicizumab on Joint and Bone Health in Hemophilia a Patients (ASH 2023) - "The PROVE study aims to generate real-world data on the long-term effects of prophylaxis with simoctocog alfa or emicizumab on joint and bone health in hemophilia A."

Clinical • Observational data • Hematological Disorders • Hemophilia • Hemophilia A • Musculoskeletal Diseases • Orthopedics • Rare Diseases • Rheumatology

Impact of Recombinant Factor VIII and Platelet Interaction on Platelet Functionality and Hemophilia a Treatment (ASH 2023) - "Simoctocog alfa demonstrated higher binding to activated platelets in vitro compared with efmoroctocog alfa, rurioctocog alfa pegol or damoctocog alfa pegol, resulting in an increased phenotype shift of platelets from the pro-aggregatory to the pro-coagulant state. The increased binding of simoctocog alfa was associated with a phenotypic shift in platelets as evidenced by increased exposure of PS on the platelet membranes. The binding of simoctocog alfa to platelets was disrupted when integrin αIIbβ3 activation was inhibited, suggesting a role of integrin αIIbβ3 signaling following binding of FVIII to platelets."

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

Transcriptomic Profiling to Understand Inhibitor Development in Previously Untreated Patients with Severe Hemophilia a (ASH 2023) - P3 | "Aims: To evaluate peripheral blood transcriptomic profiles prior to and during early FVIII treatment in severe hemophilia A patients who did or did not develop inhibitors to simoctocog alfa in the prospective NuProtect study... Differential transcriptomic profiles were seen in severe hemophilia A patients who developed inhibitors compared with those who do not, even before commencing FVIII treatment. Inhibitor patients demonstrated alterations in ribosomal protein expression that could disrupt protein synthesis efficiency, protein folding and quality control processes, and trigger cellular stress responses. Inhibitor patients also showed an upregulation of B-cell mediated factors involved in adaptive immune mechanisms."

Clinical • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • CD20 • F8 • RPS8

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

Role of Factor VIII in Angiogenesis, Vessel Stability and the Regulation of Extracellular Matrix Proteins (ASH 2024) - "Recombinant (r)FVIII (Nuwiq®, simoctocog alfa) was added to both in vitro and in vivo experiments to investigate the influence of exogenous FVIII treatment on EC function...These results further support the use of exogenous FVIII in HA. Overall, our findings suggest that, in addition to coagulation, FVIII plays an important role in the regulation of EC function and vessel stability."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • F8 • NID2

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

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

Preventing Bleeds in Pediatric Patients With Hemophilia A: Which Factor Replacement Therapy Offers the Best Protection and at What Cost? (ISPOR-EU 2025) - "Second lowest number of bleeds was achieved with efanesoctocog alfa (Altuviiio/Altuvoct) with 3.90 bleeds, following Efmoroctocog alfa (Elocta), turoctocog alfa pegol (Esperoct), turoctocog alfa (NovoEight), simoctocog alfa (Nuwiq), octocog alfa (Kovaltry), Afstyla (lonoctocog alfa) and octocog alfa (Advate) with 9.80, 9.85, 9.85, 11.85, 16.85, 18.45 and 18.75 bleeds, respectively. Prevention of bleeds is of utmost importance when treating pediatric patients with hemophilia A. Choosing a treatment with the lowest possible bleeding rates can support the physical development of the patient. This analysis showed that the lowest number of bleeds and lowest costs are estimated to be reached by damoctocog alfa pegol (Jivi)."

Clinical • Hematological Disorders • Hemophilia • Hemophilia A • Pediatrics • Rare Diseases

NuPOWER (Nuwiq for Perioperative management Of patients With haemophilia A on Emicizumab Regular prophylaxis): protocol for an open-label, single-arm, multicentre study. (PubMed, BMJ Open) - P4 | "This work will be disseminated by publication of peer-reviewed manuscripts and presentations at scientific meetings. CT EU 2022-502060-21-00; NCT05935358."

Clinical protocol • Journal • Hematological Disorders • Hemophilia • Hemophilia A • Pediatrics • Rare Diseases

Influence of recombinant factor VIII binding to platelets on fibrin clot formation and stability (ISTH 2025) - "Activated platelets were incubated with rFVIII (simoctocog alfa)...Light sheet microscopy microstructural analysis highlights the importance of rFVIII-platelet interactions in the context of blood clot stability (Figure 2). Table or Figure Upload"

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

Role of FVIII in regulating endothelial cell function and extracellular matrix protein expression (ISTH 2025) - "This impaired phenotype was reverted by LV-FVIII transduction or by recombinant FVIII (rFVIII) treatment (simoctocog alfa) demonstrating HA BOECs function enhancement...The transcriptomic and proteomic profiles of BOECs revealed that FVIII regulates the expression of endothelial basement membrane and extracellular matrix genes. Nidogen2 was identified as one of the main FVIII-regulated genes and exogenous expression restored the extracellular matrix integrity and EC function of HA ECs."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • NID2

Role of factor VIII as a regulator of angiogenesis and promoter of endothelial barrier stability (ISTH 2025) - "HA BOECs were treated in vitro with simoctocog alfa, efmoroctocog alfa, rurioctocog alfa pegol, damoctocog alfa pegol, octocog alfa, efanesoctocog alfa or non-factor therapy, emicizumab. Furthermore, simoctocog alfa in vivo rescue was greater compared to efmoroctocog alfa or efanesoctocog alfa. These effects on ECs may be mediated by the binding and signaling of simoctocog alfa to the ECs surface."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

NuPOWER: Nuwiq for Perioperative Management Of Patients With Haemophilia A on Emicizumab Regular Prophylaxis Study (clinicaltrials.gov) - P4 | N=28 | Recruiting | Sponsor: Octapharma | Trial completion date: Dec 2025 ➔ Aug 2026 | Trial primary completion date: Dec 2025 ➔ Aug 2026

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

Nuwiq Dosing and Outcomes In the ManagEment of Women/Girls With Haemophilia A Needing FVIII Treatment for Surgery (clinicaltrials.gov) - P4 | N=28 | Recruiting | Sponsor: Octapharma | Trial completion date: Dec 2025 ➔ Feb 2027 | Trial primary completion date: Dec 2025 ➔ Feb 2027

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

Design of an international, phase IV, open-label study of simoctocog alfa in women/girls with hemophilia A undergoing surgery (NuDIMENSION). (PubMed, Ther Adv Hematol) - P4 | "Data from NuDIMENSION will generate much-needed evidence on surgical management of women/girls with hemophilia A, which will help to enable the development of treatment guidelines specific for such patients. CT EU 2022-502061-17-00; NCT05936580."

Journal • P4 data • Surgery • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

PREVAIL: Immune Tolerance Induction in Haemophilia A Patients Using Wilate or Nuwiq (clinicaltrials.gov) - P=N/A | N=14 | Terminated | Sponsor: Octapharma | N=80 ➔ 14

Enrollment change • Hematological Disorders • Hemophilia • Rare Diseases

Deciphering the circulating microRNA signature of hemophilic arthropathy. (PubMed, Thromb Res) - "In this proof of concept study we identified a signature of 5 circulating miRNAs associated with Hart with potential as diagnosis tools for HArt. These miRNAs are potential negative regulators of gene expression, suggesting their activity in HArt by interfering with osteoblastic (miR- 208a-3p) and osteoclastic (miR-506-3p) differentiation to impair bone mineralization and remodeling processes, or regulating chondrogenesis (miR-335-5p). miRNAs associated with earlier stages of HArt will be further investigated in a sub-study of the prospective clinical trial PROVE, which will investigate the effects of long-term prophylaxis with simoctocog alfa versus emicizumab in adults with hemophilia A."

Journal • Hematological Disorders • Hemophilia • Rare Diseases • Rheumatology • MIR335 • MIR506

Nuwiq Dosing and Outcomes In the ManagEment of Women/Girls With Haemophilia A Needing FVIII Treatment for Surgery (clinicaltrials.gov) - P4 | N=28 | Recruiting | Sponsor: Octapharma | Not yet recruiting ➔ Recruiting

Enrollment open • Surgery • Hematological Disorders • Hemophilia • Rare Diseases

miRNA expression profiles as a potential biomarker of joint and bone health in haemophilia A (ISTH 2024) - "The pilot study identified 2 miRNAs differentially expressed in patients with HArt (Pettersson score ≥1), after adjusting for the false discovery rate (FDR). The validation study evaluated these 2 miRNAs. The results demonstrated that two miRNAs (miR- 208a-3p and 524-3p) were significantly underexpressed in plasma of patients with HArt compared to patients without arthropathy, with FDR < 0.05 (Figure 1)."

Biomarker • Hematological Disorders • Hemophilia • Rare Diseases • Rheumatology • MIR208A • MIR335 • MIR506

Indirect comparison of prophylaxis efficacy between simoctocog alfa and efanesoctocog alfa in severe hemophilia A and their cost in the United States (ISTH 2024) - "After matching, the percentage of patients with zero bleeds and mean total ABR were similar between the 2 regimens (Figure 1). The mean weekly dose was significantly higher in patients treated with simoctocog alfa versus efanesoctocog alfa (98.3 IU/kg vs 52.2 IU/kg; p< 0.001). The median dosing interval in the NuPreviq study was 3.5 days; patients in the XTEND-1 study were treated once-weekly."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases