Nuwiq (simoctocog alfa) / Octapharma - LARVOL DELTA

Evaluating Costs and Efficacy of rFVIII Prophylaxis Using Matching-Adjusted Indirect Comparisons in Hemophilia A. (PubMed, TH Open) - "Methods Matching-adjusted indirect comparisons (MAICs) were performed to compare simoctocog alfa with efanesoctocog alfa (ALTUVIIIO) and turoctocog alfa pegol (Esperoct), and results were integrated with a previously published MAIC comparing simoctocog alfa with efmoroctocog alfa (ELOCTATE), damoctocog alfa pegol (JIVI), and rurioctocog alfa pegol (ADYNOVATE). In comparison with efanesoctocog alfa (Group A), no significant differences were observed in the proportion of individuals with zero bleeds, whereas treated total annualized bleeding rate (ABR) and treated spontaneous ABR favored efanesoctocog alfa. Conclusion This indirect comparison suggests that personalized prophylaxis with simoctocog alfa may offer economic advantages versus EHL rFVIII products in individuals with severe hemophilia A. Clinical outcomes were broadly comparable across comparators, although treated total and spontaneous ABRs were significantly lower with efanesoctocog alfa (Group A)."

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

Surgical prophylaxis with simoctocog alfa in people with severe haemophilia A on emicizumab prophylaxis: The NuPOWER study (ISTH 2026) - P4 | "FVIII levels during simoctocog alfa surgical prophylaxis in a 51-year-old male undergoing total knee replacement. DOI*10.1016/j.rpth.2026.104835"

Hematological Disorders • Hemophilia • Hemophilia A • Musculoskeletal Diseases • Orthopedics • Rare Diseases

Protect-NOW: Real-world treatment of previously untreated and minimally treated patients with severe haemophilia A (ISTH 2026) - P | "The efficacy, safety and immunogenicity of the human cell line-derived recombinant FVIII simoctocog alfa, plasma-derived (pd)FVIII/VWF (0.4:1) and pdVWF/FVIII (1:1) have been demonstrated in prospective clinical trials in PUPs with severe haemophilia A. Aims To investigate the long-term effectiveness, safety and utilisation of simoctocog alfa, 0.4:1 pdFVIII/VWF and 1:1 pdVWF/FVIII in PUPs and minimally treated patients (MTPs, <5 FVIII EDs) with severe haemophilia A in a real-world setting...32 patients received emicizumab, of whom 16 received concomitant FVIII...Protect-NOW study design. Page 2 DOI*10.1016/j.rpth.2026.104875"

Clinical • HEOR • Real-world • Real-world evidence • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • F8

AFSTYLA® (rVIII-SingleChain) demonstrates high adherence, effective bleed control,and superior weight-adjusted cost efficiency in prophylaxis for hemophilia A in realworldclinical practice (ISTH 2026) - "Methods A retrospective analysis was conducted in 29 patients with moderate or severe hemophilia A receiving prophylactic treatment with AFSTYLA, ADYNOVI, ELOCTA, ESPEROCT, REFACTO, or NUWIQ. Conclusions In real-world clinical practice, AFSTYLA® shows excellent adherence, effective bleed control, and the best weight-adjusted cost–efficiency profile among the evaluated FVIII products. These findings support AFSTYLA as a solid, effective, and sustainable long-term prophylactic option for patients with hemophilia A. Table or Figure Upload (1) No Table or Figure Upload (2) No DOI*10.1016/j.rpth.2026.105746"

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

Time in Hemostatic Range (TIHR) Provides Harmonized Regimen-Level Assessment of FVIII Prophylaxis in Real-World Hemophilia A cohort (ISTH 2026) - "Methods Retrospective single-center analysis of 15 hemophilia A patients (11 severe, 4 moderate) receiving prophylaxis with seven FVIII products: efanesoctocog (n=6), simoctocog (n=3), efmoroctocog (n=2), Turoctocog (n=1), rurioctocog (n=1), fandhi (n=1), and octanate (n=1). AI-assisted transparent workflow demonstrates reproducible pharmacometric methodology. Table or Figure Upload (1) Table 1 Page 2 Table or Figure Upload (2) Table 2 Page 3 DOI*10.1016/j.rpth.2026.105835"

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

High factor VIII concentrations modulate interactions between platelets and von Willebrand factor in vitro (ISTH 2026) - "Experiments used B-domain-deleted recombinant FVIII (simoctocog alfa). Eptifibatide was present during ristocetin ‑ or VWF ‑ activating ‑ nanobody induced platelet agglutination to block integrin-VWF interactions...JTH. https://doi.org/10.1016/j.jtha.2023.09.004 #Platelets #FVIII #VWF #GPIb DOI*10.1016/j.rpth.2026.105208"

Preclinical

Real-World Pharmacokinetic Profiles of Recombinant and Plasma-Derived Factor VIII in Haemophilia A Using WAPPS-HEMO in a Single Centre in Chile (ISTH 2026) - "PK parameters for rFVIII (Nuwiq ® ) and pdFVIII (Octanate ® or Alphanate ® ). Page 2 DOI*10.1016/j.rpth.2026.104908"

Clinical • PK/PD data • Real-world • Real-world evidence • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

rFVIII restores structured fibrin architecture and promotes a procoagulant platelet phenotype in Hemophilia A plasma-derived blood clots (ISTH 2026) - "Methods Platelet-rich plasma from healthy donors and individuals with severe HA was activated with tissue factor and collagen-related peptide in the presence or absence of rFVIIIa (simoctocog alfa)...Without rFVIIIa, fibrin forms thick, sparsely interconnected fibers, while addition of rFVIIIa results in a thinner fibrin network with spatial association to platelet clusters containing proaggregatory (green) and procoagulant (purple) platelets embedded within the fibrin network (red). DOI*10.1016/j.rpth.2026.105184"

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

Real-world use of simoctocog alfa prophylaxis in severe haemophilia A: preliminary results from the Hungarian Long-Term Non-Interventional Investigation (Nuwiq NIS) (ISTH 2026) - "ABR during the last 12 months of prophylaxis. Page 3 DOI*10.1016/j.rpth.2026.104884"

Clinical • Real-world • Real-world evidence • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • F8

FVIII Deficiency Compromises In Vitro Osteoblasts Mineralization and Their Secretome Profile (ISTH 2026) - "During differentiation, the cultures were supplemented with increasing concentrations of recombinant FVIII (Nuwiq®), vWF, or the FVIII/vWF combination...These findings support a direct, non-hemostatic role for FVIII in osteoblast biology and indicate that VWF may modulate osteoblast activity under conditions of FVIII deficiency, Collectively, these data suggest that FVIII replacement therapy may contribute to improved bone integrity in patients with HA. DOI*10.1016/j.rpth.2026.103541"

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

A Rare Case With Severe and Refractory Emicizumab Hypersensitivity (ASPHO 2026) - "Despite premedication with diphenhydramine, famotidine, and hydrocortisone, severe delayed reactions occurred, necessitating permanent discontinuation. Bleeding episodes were managed with bypassing agents (anti-inhibitor coagulant complex, recombinant activated factor VII). ITI with simoctocog alfa achieved suboptimal response (peak inhibitor 84 BU; FVIII recovery 10%–25%) and was complicated by MRSA bacteremia, requiring discontinuation. Efanesoctocog alfa provided partial control with persistent high-titer inhibitors... This case documents rare severe emicizumab hypersensitivity refractory to premedication in a pediatric patient with high-responding inhibitor. When first-line non-factor therapies fail and ITI is unsuccessful, concizumab demonstrated substantial efficacy as alternative prophylaxis. Further investigation is needed to characterize risk factors for severe emicizumab reactions and establish management algorithms when standard therapies are not tolerated in..."

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

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