Nuwiq (simoctocog alfa) / Octapharma - LARVOL DELTA

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

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

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

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

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

Factor VIII is a regulator of angiogenesis and a promoter of endothelial barrier stability (ISTH 2024) - "HA BOECs were treated in vitro with simoctocog alfa, efmoroctocog alfa, rurioctocog alfa pegol, damoctocog alfa pegol, or octocog alfa. Impaired tubulogenesis, migration and permeability of HA ECs vs healthy ECs were observed. A significant enhancement of EC functionality was demonstrated by treating HA BOECs with rFVIII products, with a higher positive effect for simoctocog alfa. Moreover, in NSG-HA mice treated with different rFVIII concentrates, and subsequently injected with Evans Blue dye, we showed a significant reduction of dye extravasation with a complete correction in mice treated with simoctocog alfa compared with other rFVIII products."

Hematological Disorders • Hemophilia • Rare Diseases

Impact of differential binding of recombinant factor VIII concentrates to platelets on platelet clotting functionality (ISTH 2024) - "rFVIII (simoctocog alfa) exhibited significantly higher binding to platelets than other rFVIII molecules. Through a time-course analysis, we found that rFVIII interaction occurs already in proaggregatory platelets. This early interaction upregulates the intracellular signalling cascade leading to an increased shift from proaggregatory to procoagulant phenotype."

Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis

Simoctocog alfa (Nuwiq®) in children: early steps in life's journey for people with severe hemophilia A. (PubMed, Ther Adv Hematol) - "Optimal care of children should consider several factors, including minimization of inhibitor development risk, maintaining tolerance to FVIII, highly effective bleed prevention and treatment, safety, and impact on long-term outcomes such as bone and joint health. In this context we review the pediatric clinical data and ongoing studies with simoctocog alfa."

Journal • Review • Cardiovascular • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases • Rheumatology

INDIRECT COMPARISON OF PROPHYLAXIS EFFICACY BETWEEN SIMOCTOCOG ALFA AND EFANESOCTOCOG ALFA IN SEVERE HEMOPHILIA A AND THEIR COST IN THE UNITED STATES (THSNA 2024) - "Based on MAIC, prophylaxis with simoctocog alfa resulted in similar zero bleed rates and total ABR as with efanesoctocog alfa, albeit with a higher weekly dose. Despite higher dosing, simoctocog alfa endured an estimated 29% lower cost burden than efanesoctocog alfa."

Clinical • Hematological Disorders • Hemophilia • 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 | Not yet recruiting ➔ Recruiting | Initiation date: Oct 2023 ➔ Feb 2024

Enrollment open • Trial initiation date • Hematological Disorders • Hemophilia • 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 | Not yet recruiting | Sponsor: Octapharma | Initiation date: Oct 2023 ➔ Feb 2024

Surgery • Trial initiation date • Hematological Disorders • Hemophilia • Rare Diseases

Personalised prophylaxis with simoctocog alfa versus standard emicizumab prophylaxis in haemophilia A, a matching- adjusted indirect comparison (EAHAD 2024) - No abstract available

Hematological Disorders • Hemophilia • Rare Diseases

Personalised prophylaxis with simoctocog alfa versus standard prophylaxis with efanesoctocog alfa in haemophilia A, a matching-adjusted indirect comparison (EAHAD 2024) - No abstract available

Hematological Disorders • Hemophilia • Rare Diseases

REAL WORLD USE OF SIMOCTOCOG ALFA IN PERSONS WITH HAEMOPHILIA A (PwHA) IN SPAIN (EAHAD 2024) - No abstract available

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

The Atlanta Study: Emicizumab PUPs and Nuwiq ITI Study (clinicaltrials.gov) - P3 | N=0 | Withdrawn | Sponsor: Emory University | Terminated ➔ Withdrawn

Trial withdrawal • Hematological Disorders • Hemophilia • Rare Diseases