Xyntha (moroctocog alfa) / Pfizer - LARVOL DELTA

Site-Specific Insertion of Factor VIII Gene Results in Durable Factor VIII Expression in Nonhuman Primates (ASH 2024) - "Plasma was collected starting 14 days post LNP dosing and assayed for safety parameters and/or activity of the transgene derived cFVIII-F2196K using a commercial chromogenic FVIII activity assay with a recombinant human FVIII-BDD protein (Xyntha) as the standard...To date, no verified off target editing has been observed. Collectively, these results suggest that gene editing may provide a curative approach to hemophilia A patients."

Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • ALB

Neutralizing antibodies to emicizumab in a pediatric patient with hemophilia A with inhibitors (ISTH 2025) - "Aims We present the case of a 3 years and 10 months old boy, diagnosed in our Clinic with severe Hemophilia A, who was under on-demand treatment with moroctocog alfa from 4 months of age until 1 year and 1 month, then he continued with prophylaxis (25-50 IU/Kg/day x 2-3 days/week).Two months later, high-titre anti-FVIII antibodies (60 BU) developed. The patient’s FVIII activity was below 1% in the chromogenic method with bovine reagent, and anti-FVIII inhibitor titer was 3.5 BU. The child is currently under on-demand and short course prophylactic treatment with rFVIIa, but continuous prophylaxis with APCC is planned."

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

Miniaturized Activated Partial Thromboplastin Time (APTT) Assay for Analysis of Small Sample Volumes (ISTH 2025) - "APTT correlated with FVIII activity measured by CA (r: -0.72 to -0.77, R2: 0.51 to 0.59, log-log scale). Notably, TG in mouse plasma correlated with activity of Lonoctocog alfa and Moroctocog alfa in plasma, but not with Efanesoctocog alfa (r=0.52, R2= 0.27)."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Impact of Extended Half-Life Factor VIII on Pharmacokinetics and Bleeding Rates in Hemophilia A (ISTH 2025) - "Patients initially treated with SHL FVIII (Beriate®, Immunate®, Octanate®, Advate®, Novoeight®, Hemophil M®, Xyntha®) and later switched to EHL FVIII (Adynovate®, Jivi®) were included. A weak, non-significant negative correlation existed between spontaneous bleeding and T1/2 for both SHL (r=-0.23, IC 95% -0.51 to 0.09, p>0.05) and EHL (r=-0.24, IC 95% -0.49 to 0.05, p>0.05). A significant positive correlation was observed between AUC and T1/2 (r=0.79, IC 95% 0.7 to 0.86, p<0.05) Table or Figure Upload"

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

Advancing Hemophilia A Management with the Portability of Turoctocog Alfa Pegol (N8-GP) (ISTH 2025) - "Results Six patients (mean age: 33.7 years, range 27–43) included three with moderate and three with severe hemophilia A. Before switching to N8-GP, half were treated with rurioctocog alfa pegol, while the rest used damoctocog alfa pegol, moroctocog alfa, or plasma-derived FVIII equally. The results of the satisfaction survey are presented in Figures 1 and 2. Table or Figure Upload"

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • Rheumatology

Activated factor X delivered by adeno-associated virus significantly inhibited bleeding and alleviated hemophilic synovitis in hemophilic mice. (PubMed, Gene Ther) - "AAV-FXaop could be stably expressed in vivo and showed the best immediate and prolonged hemostatic effects, similar to those of commercial drugs (Xyntha and Benefix). In addition, FXa expression in joints significantly alleviated the occurrence of hemophilic synovitis. AAV-delivered FXa may be a novel target for treating hemophilic and hemophilic synovitis."

Journal • Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

COMPARATIVE EVALUATION OF QUALITY OF LIFE IN HEMOPHILIA A PATIENTS UNDER PROPHYLAXIS: A 4-YEAR PERSPECTIVE (EHA 2024) - "Consequently, 20 patients previously under prophylaxis with standard half-life (SHL) products (INN-octocog alfa, octocog alfa, moroctocog alfa), transitioned to prophylactic treatment utilizing extended half-life(EHL) products (rurioctocog alfa pegol, efmoroctocog alfa, damoctocog alfa pegol), while 4 remained on SHL. A comprehensive analysis of 4 years' worth of data reveals a significant improvement across all quality-of-lifedimensions, underscoring the imperative for improved and personalized prophylactic interventions to achieveoptimal efficacy. Tailoring treatment regimens to align with the emotional and physical well-being of patientsholds promise for the implementation of more successful clinical approaches."

Clinical • HEOR • CNS Disorders • Depression • Hematological Disorders • Hemophilia • Pain • Psychiatry • Rare Diseases • Sexual Disorders

The Impact of Suboptimal Adherence to Factor Replacement Therapy on Time Spent Below Target Factor Trough Levels: Simulations Using Population Pharmacokinetic Modeling (ISTH 2023) - "Individual PK parameters were randomly sampled from normal distributions defined by previous population PK models, derived from nonacog alfa (FIX-SHL), eftrenonacog alfa (FIX-EHL), moroctocog alfa (FVIII-SHL), or efmoroctocog alfa (FVIII-EHL). Adherence simulations (Table, Figure) estimated that with conventional target trough levels (eg, 3–5%), suboptimal adherence (1 or 2 missed doses) increased median time spent below trough level. The impact of suboptimal adherence was not mitigated when modeling EHL vs SHL therapies. Even with perfect adherence (ie, 0 missed doses), and regardless of use of SHL or EHL, most modeled individuals' time was spent below a factor activity of 20%.Conclusion(s): These data illustrate the potential impact of suboptimal adherence to prophylaxis on time spent below FVIII and FIX trough levels."

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

Development of AAV Transduction and Potency Assays to Evaluate Quality Attributes of ASC618, a Second Generation AAV8-Based Hemophilia A Gene Therapy (ASGCT 2023) - P1/2 | "The potency of ASC618 GMP lots relative to that of a reference standard (ASC618 Engineering Lot), which is evaluated by two assays that we have developed: a Potency-ELISA assay and a Potency-Activity assay, which XYNTHA® Antihemophilic Factor VIII (Recombinant) was used to generate standard curves for both assays. By using the transduction, Potency-ELISA, and Potency-Activity assays, three independent batches of ASC618 drug substance (DS) or drug product (DP) have been tested. The relative transduction confirmed high consistency with the relative potency in both ELISA and Activity assays."

Gene therapy • Gastrointestinal Cancer • Gene Therapies • Hematological Disorders • Hemophilia • Hepatology • Liver Cancer • Oncology • Rare Diseases • Solid Tumor

Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII. (PubMed, Clin Appl Thromb Hemost) - "In inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AF is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding Kovaltry might have contributed to inhibitor development."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Chemosensitization of carboplatin by NOX66: Pharmacokinetics and safety (ESMO 2017) - P2a; "...This first-in-human study will look at the ability of NOX66 to deliver relatively high levels of idronoxil in a bio-active form, investigating (a) PK and (b) safety of NOX66 administration both as a monotherapy and in combination with carboplatin...Patients included have end stage, refactory solid tumours, and no further therapy options available...Subject to safety review, standard dose (AUC6) carboplatin is administered for cycles 4-6. Safety assessment is continued throughout the study, with measures to identify efficacy signals (CT scan, ECOG) performed at baseline and after Cycles 3 and 6."

Ovarian Cancer

CLINICAL APPLICATION OF LONG ACTING FACTOR VIII PRODUCT LONOCTOCOG IN CHILDREN WITH HAEMOPHILIA A (EAHAD 2023) - "All patients (apart from one with mild haemophilia) had been previously treated with recombinant FVIII concentrates [SHL: Advate (Takeda), Kovaltry (Bayer) and Refacto (Pfizer)] for more than 100 EDs (Exposure Days). This study demonstrates the successful transition of CWH A from SHL to Lonoctocog."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Comparison of Activated Clotting Time to Hepcon Protamine Titration for Anticoagulation Management during Cardiopulmonary Bypass Surgery in a Patient with Severe Hemophilia a on Emicizumab Prophylaxis (ASH 2022) - "This 54-year-old male has a complex medical profile including Child Pugh B cirrhosis (baseline INR 1.5, platelets 100), Hepatitis C (treated), HIV on antiretroviral therapy (undetectable viral load), and remote portal vein thrombosis in the context of FEIBA and tranexamic acid use for a gastrointestinal bleed...Preop FVIII replacement with moroctocog alfa (Xyntha®) (60 U/kg) was administered to target a ~120% FVIII level...Therefore, the results may reflect derangements in one or more of these variables. We need further preclinical and clinical studies to better characterize the effect of emicizumab on ACT and identify the safest intraoperative monitoring strategy for patients on emicizumab requiring CPB surgery."

Clinical • Anesthesia • Cardiovascular • Critical care • Fibrosis • Gastrointestinal Disorder • Hematological Disorders • Hemophilia • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Rare Diseases • Thrombosis • Venous Thromboembolism

Biological activity of a new recombinant human coagulation factor VIII and its efficacy in a small animal model. (PubMed, Biochem Biophys Res Commun) - "In vitro, commercially available recombinant FVIII (Xyntha) and pdFVIII were used as controls, and there were no statistical differences between rFVIII and commercial FVIII preparations, which demonstrates the satisfactory efficacy and potency of rFVIII...Moreover, different batches of rFVIII were comparable. Overall, our results demonstrate the potential of rFVIII as an effective strategy for the treatment of FVIII deficiency."

Journal • Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

Moroctocog Alfa (AF-CC) for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Patients with Hemophilia A in India. (PubMed, Indian J Hematol Blood Transfus) - "Moroctocog alfa was well tolerated with no reported treatment-emergent adverse event-related dose reductions, discontinuations, or serious adverse events. Moroctocog alfa was safe, effective, and well tolerated in Indian participants with congenital moderate to severe hemophilia A. No participant developed FVIII inhibitors during the study."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Area under the curve: Comparing the value of factor VIII replacement therapies in haemophilia A. (PubMed, Haemophilia) - "This analysis concludes that EHL products differ in relative AUC, have a larger AUC compared with standard half-life, and thus, different FVIII levels over time after infusion. This model may aid decision makers in the absence of head-to-head data."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Oral Anti-CD3 and Bioencapsulated FVIII Therapy Exhibit Distinct Mechanisms That Suppress Inhibitor Formation in Hemophilia a (ASH 2022) - "Concurrently, mice received 5 weekly IV injections of 1.5 international units (IU) of human FVIII (Xyntha)...Canonical nTreg markers such as FoxP3, CD25, and GITR were significantly downregulated in LAP Tregs. LAP expression highly correlated with expression of TGFb1 and IL-10 cytokines, increased expression of chemokine receptors and their ligands and of integrin family members, and showed an inflammation-induced profile characterized by upregulation of IL1B, granzymes, Jun Fos pathway, among others.We conclude that LAP Tregs are a phenotypically distinct cell subset with a unique gene signature, allowing us to identify correlates of suppression in this population."

IO biomarker • Cholera • Hematological Disorders • Hemophilia • Immune Modulation • Immunology • Inflammation • Rare Diseases • CD4 • CD69 • CTLA4 • FOXP3 • ICOS • IL10 • IL1B • IL2RA • PD-1 • TGFB1 • TIGIT

Cost-Minimization Analysis of Damoctocog Alfa Pegol With the Treatment of Hemophilia A in Turkey (ISPOR-EU 2022) - "OBJECTIVES: To compare the lifetime consumption and cost of an extended-half liferecombinant factor VIII (rFVIII), the damoctocog alfa pegol, with reimbursed standard half life (SHL) factors (octocog alfa, moroctocog alfa, turoctocog alfa) for the treatment of haemophilia A (HemA) in patients with age ≥ 12 years in Turkey, from the public payer perspective. From the perspective of the public payer, damoctocog alfa pegol demonstrated good efficacy while being the lowest cost-generating option for the treatment of HemA patients in Turkey, when compared to existing reimbursed SHLs."

HEOR • Hematological Disorders • Hemophilia • Rare Diseases

NOX66 plus carboplatin - a phase 1 signalling study (ESMO Asia 2017) - P2a; "Patients (16) with end stage, refactory solid tumours, and no further therapy options available, were allocated to one of two treatment cohorts, receiving NOX66 at a dose of 400mg or 800mg of idronoxil daily. NOX66 in combination with carboplatin is well tolerated, with efficacy data for patients receiving low dose-low dose combination therapy providing evidence to suggest that NOX66 may sensitize end stage solid tumours to chemotherapy."

Combination therapy • Late-breaking abstract • P1 data • Solid Tumor

A Cost Minimization Model of Afsteyela® (Lonoctocog-Alfa) for the Prophylactic Treatment of Pediatric Patients With Haemophilia A, in Mexico (ISPOR-EU 2022) - " A cost-minimization model (fo anual costs) was developed to estimate the treatment cost associated with lonoctocog-alfa, compared to turoctocog-alfa, moroctocog-alfa, octocog-alfa and simoctocog-alfa in pediatric patients with severe Haemophilia-A. For the treatment of patients with severe Haemophilia-A in Mexico, lonoctocog-alfa was a cost-saving option compared to existing rFVII in Mexico from the public payer perspective."

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

Efficacy, safety and bioequivalence of the human-derived B-domain-deleted recombinant factor VIII TQG202 for prophylaxis in severe haemophilia A patients. (PubMed, Haemophilia) - "TQG202 shows bioequivalence with Xyntha. The promising efficacy and tolerability in the severe haemophilia A prophylaxis support the use of TQG202in clinical practice."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Hemophilia A developing cerebral infarction after surgical treatment of giant hemophilic pseudotumor: a case report. (PubMed, BMC Surg) - "For the treatment of I-BZI caused by acute anemia from Hemophilia A, volume expansion, red blood cell supplement and continuous improvement of coagulation with suitable dose of factor VIII (FVIII) should be considered to improve prognosis."

Journal • CNS Disorders • Hematological Disorders • Hemophilia • Oncology • Rare Diseases

Laboratory evaluation of extendend-half-life recombinant FVIII products (EHL-FVIIIs): one stage coagulation assay or chromogenic assay? (ISTH 2022) - "Similar discrepancies were observed in patients receiving ReFacto® (B-domain-deleted FVIII) a decade ago and has been resolved with the use of specific ReFacto Laboratory Standard... The EHL-FVIII products tested were: Damoctocog alpha-pegol, Rurioctocog alpha-pegol, Turoctocog alpha-pegol and Efmoroctocog alfa... The classical OSA assay could show significant discrepancies between the nominal and real EHL-FVIII concentrations. The determination of Efmoroctocog alfa by OSA provides a value two-fold higher than the expected level. The calibrated-OSA assay is very accurate in determining the values of all EHL-FVIIIs, showing in the spiked experiments a drug recovery from 92% to 101%."

Assay of modified factor VIII is modulated by von Willebrand factor. What should we measure ? (ISTH 2022) - "For Advate and Beriate activities were similar in both assays. For normal plasma FVIII and Advate, clotting activity of free and complexed FVIII is similar. However, for modified FVIII (Refacto, Eloctate, Adynovi) added VWF (Wilfactin) inhibits their coagulation activities. For Eloctate and Refacto this concerns a maximal inhibition of 74 and 52%."

"Sobi to cease ReFacto manufacturing in the first quarter of 2024 https://t.co/WNMOrjutxY" (@CisionNews)