BeneFix (nonacog alfa) / Pfizer - LARVOL DELTA

Cost-Savings Analysis of Fitusiran Prophylaxis: Reducing Breakthrough Bleeding Treatment Expenditure in the Kingdom of Saudi Arabia (ISPOR-EU 2025) - P3 | "For people with haemophilia (PwH) A without inhibitors, episodic treatments comprised octocog alfa, efmoroctocog alfa and rurioctocog alfa pegol for PwH A and nonacog alfa, albutrepenonacog alfa and eftrenonacog alfa for PwH B. Treatments included for PwH with inhibitors were factor VIII inhibitor bypassing activity (FEIBA) and eptacog alfa. In the KSA, fitusiran AT-DR prophylaxis may considerably reduce breakthrough bleed management costs in PwH versus CFC/BPA prophylaxis. Cost savings are predicted to be more substantial in PwH with inhibitors than in those without inhibitors."

HEOR • Hematological Disorders • Hemophilia • Rare Diseases

Cost-Savings Assessment of Fitusiran Prophylaxis in Minimizing Breakthrough Bleeding Treatment Expenses in the United Arab Emirates (ISPOR-EU 2025) - P3 | "The episodic treatments included were efmoroctocog alfa, octocog alfa and rurioctocog alfa pegol for people with haemophilia (PwH) A without inhibitors and albutrepenonacog alfa, nonacog alfa and eftrenonacog alfa for PwH B without inhibitors...A scenario analysis examined the impact of vial sharing. Among PwH without inhibitors, fitusiran AT-DR enabled per-bleed savings ranging from UAE Dirham (AED) 4,625 (efmoroctocog alfa) to AED 11,521 (rurioctocog alfa pegol) in PwH A and from AED 8,935 (nonacog alfa) to AED 30,053 (albutrepenonacog alfa) in PwH B. In PwH with inhibitors, fitusiran AT-DR usage generated per-bleed savings of AED 71,846 (FEIBA) to AED 90,761 (eptacog alfa). In the UAE, fitusiran AT-DR prophylaxis may considerably reduce costs associated with episodic treatments for breakthrough bleeds in PwH compared with CFC/BPA prophylaxis. PwH with inhibitors might have larger cost savings than those without inhibitors."

HEOR • Hematological Disorders • Hemophilia • Rare Diseases

Patient and Clinical Experience on Concizumab Clinical Trial: A Case Study (ASH 2024) - P=N/A, P3 | "The maintenance dose was initiated on week 4 based on a concizumab exposure of 97.9 ng/mL.Prior to explorer8, the patient was intensely treated with daily BeneFIX® and Rebinyn® prophylaxis during explorer6, but both FIX standard and extended half-life treatment failed to prevent bleeding episodes.Key Clinical Question : What factors should be considered when determining whether a patient should be withdrawn from a clinical trial?Clinical Approach : Throughout the clinical trial, the investigator discussed withdrawal from the study because of an increase in the number of bleeding episodes; however, the patient remained in the clinical trial as the patient and their family preferred concizumab over previous prophylaxis regimens. This case demonstrates that we may have more to learn from our patients on why they choose to participate and/or stay on clinical trials.Disclaimer : Novo Nordisk had no influence on the content of the ABSTRACT . The studies..."

Case study • Clinical • Hematological Disorders • Hemophilia • Hemophilia B • Infectious Disease • Novel Coronavirus Disease • Rare Diseases

Population Modeling of Factor IX Activity Following Administration of Fidanacogene Elaparvovec Gene Therapy in Participants with Hemophilia B. (PubMed, Clin Pharmacokinet) - P2, P3 | "Model-based estimates showed that a single dose of fidanacogene elaparvovec elicited long-lasting elevations in FIX activity, suggesting most individuals would not require prophylactic FIX replacement for at least 15 years post-infusion."

Journal • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

REAL-WORLD EXPERIENCE WITH NONACOG BETA PEGOL IN HEMOPHILIA B AFTER 30 MONTHS OF FOLLOW-UP (EHA 2025) - "A retrospective review of the medical records of two patients who switched from SHL to EHL FIX was conducted to assess their clinical outcomes and therapeutic response.Patient 1 (46 years old, 72 kg): Previously on prophylaxis with Nonacog Alfa (SHL) at 4,000 IU twice weekly. Prophylactic therapy is highly effective in reducing bleeding episodes and their long-term complications, especially in patients with severe factor deficiency or a bleeding phenotype.Treatment should be individualized, considering the risk/benefit ratio alongside patient values and preferences, to determine the optimal timing and choice of prophylaxis.Recombinant factor products are a safe and effective treatment option for patients with .The availability of extended half-life factor IX products offers substantial prolongation of half-life, improving patient quality of life, reducing infusion frequency, and enhancing treatment adherence.Significant economic impact is observed, with a reduction in..."

Clinical • Real-world • Real-world evidence • Cerebral Hemorrhage • CNS Disorders • Gastroenterology • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Osteoarthritis • Rare Diseases

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

Dominant negative effects of Gln50Arg mutation in the EGF-1 domain of factor IX causes severe Hemophilia B affecting factor IX replacement therapy (ISTH 2024) - "Plasma was in vitro spiked with Alprolix, Rixubis, Benefix or FEIBA. Hemostatic screening revealed normal platelet aggregation and coagulation factor activities, except for FIX activity levels of 5 IU/dL in both brothers and a FXI activity of 39 IU/dL in one boy. FIX antigen concentrations were in the normal range in both boys and their mother, FIX inhibitor screening was negative (Figure 1). After bolus infusion of Alprolix, FIX activity in vivo recovery was within expected range, but thrombin generation indicated weak response to FIX substitution therapies."

Hematological Disorders • Hemophilia • Rare Diseases • EGF

FIX Post infusion monitoring surveys: Results and analysis from the updated UK NEQAS BC Haemophilia programmes 2024 (ISTH 2024) - "Data was returned from 47 centres. Centres performed either one stage assays (OSA), chromogenic assays (CA) or both. OSA Alprolix Median value, 40 IU/dL with CV = 8.7%; Benefix Median value, 14.3 IU/dL with CV = 13.6%; Idelvion Median value, 20.4 IU/dL with CV = 14.5% and Refixia Median value, 15.4 IU/dL with CV = 18.2% CA Alprolix Median value, 35.7 IU/dL; Benefix Median value, 11.7 IU/dL; Idelvion Median value, 24.8 IU/dL and Refixia Median value, 13.4 IU/dL."

Hematological Disorders • Hemophilia • Rare Diseases

FIX is localised in the vessel wall and can generate thrombin when in complex with collagen IV in human synovial tissues (ISTH 2024) - "On surfaces with the FIX-collagen complex present, FIX-DP generated a peak thrombin concentration comparable to PNP. FIX binding was confirmed by a chromogenic activity assay and a dose-dependent effect of FIX coating concentration was observed. Collagen plates coated with extended half-life concentrates, Alprolix and Idelvion, generated a significant increase in the endogenous thrombin potential (ETP), when compared to short-acting concentrate, Replenine and Benefix (* p < 0.01)."

Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis

Evaluation of recovery of factor IX replacement therapy with HemosIL Chromogenic Factor IX (ISLH 2024) - "HemosIL Chromogenic Factor IX demonstrated the ability to correctly measure FIX activity in plasma pools with 3 FIX replacement therapies: Alpha Nine SD, BeneFIX, and REBINYN. Results with albutrepenonacog alpha (recombinant FIX fused with recombinant human albumin; Idelvion) demonstrated over recovery of 59% when compared to the theoretical value based on the potency assignment by the manufacturer. In 2019 Rosén et al."

Hematological Disorders • Hemophilia • Rare Diseases

Pattern of use and clinical outcomes with rIX-FP in pediatric/adolescent patients with haemophilia B in Italy: Results from IDEAL real-world study. (PubMed, Eur J Haematol) - "The results in this pediatric/adolescent subgroup support rIX-FP prophylaxis may reduce infusion frequency, while providing high FIX trough levels, stable annualized bleeding rate and a good safety profile."

Clinical data • Journal • Real-world • Real-world evidence • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

Nonacog Alfa for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Patients with Moderately Severe or Severe Hemophilia B in India. (PubMed, Indian J Hematol Blood Transfus) - "The mean (SD) annualized total factor consumption (TFC) per patient was 224,582 (75,527) IU; the mean (SD) annualized TFC by weight per patient was 3639 (573) IU/kg. Nonacog alfa was safe and effective for the prevention of hemorrhagic episodes in Indian males with congenital, severe hemophilia B. No participants developed FIX inhibitors, and no new safety signals were reported."

Journal • Hematological Disorders • Hemophilia • Immunology • Rare Diseases

Real-World Evidence Study on Hemophilia B Treatment with Factor IX and Corresponding Treatment Costs in Finland (ISPOR-EU 2023) - "In Finland, four different FIX replacement products are available, i.e., human coagulation factor IX, nonacog alfa, eftrenonacog alfa, and nonacog beta pegol. FIX product costs are the main driver for the high economic burden for HB treatment. Annual FIX treatment costs varied depending on age group and treatment regimen."

Clinical • HEOR • Real-world • Real-world evidence • Treatment costs • Hematological Disorders • Hemophilia • Rare Diseases

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

Budget Impact Analysis (BIA) of the Use of Nonacog Beta Pegol in Patients with Haemophilia B in the Colombian Health System (ISPOR 2023) - " An Excel BIA model was b uilt to estimate the economic impact of the progressive inclusion of nonacog beta pegol in the Colombia n institutional health market for the p rophylactic treatment of haemophilia B. The model was developed and populated with local data from The National Administrative Department of Statistics (DANE) and epidemiological data from the public and official records of the High-Cost Account (CAC) of 113 patients with h a emophilia B in 2021 ; C linical information including dosage, treatment schemes and annual bleeding rates were obtained from the published clinical trial of nanocog beta pegol and nonacog alfa. The inclusion of nonacog beta pegol in the Colombian health system for the treatment of patients with h a emophilia B in prophylaxis can result in savings of up to USD1,748,603 over a 3-year horizon."

Clinical • HEOR • Hematological Disorders • Hemophilia • Rare Diseases

Treatment switch to nonacog beta pegol factor IX in hemophilia B: A Canadian cost-consequence analysis based on real-world factor IX consumption and clinical outcomes. (PubMed, Res Pract Thromb Haemost) - "Overall, annual treatment costs were 9.4% and 10.5% lower after the switch to N9-GP from nonacog alfa and eftrenonacog alfa, respectively. N9-GP improves clinical outcomes and may be cost-saving vs nonacog alfa and eftrenonacog alfa."

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

TAWAM HOSPITAL, AL AIN, UAE EXPERIENCE WITH SWITCHING FROM STANDARD HALF-LIFE RECOMBINANT COAGULATION FACTOR IX TO EXTEND HALF-LIFE RECOMBINANT COAGULATION FACTOR IX, FC FUSION PROTEIN IN PATIENTS WITH SEVERE HEMOPHILIA B (EAHAD 2023) - "After switching patients to ALPROLIX® (Extend Half-life Coagulation FIX, Recombinant, Fc Fusion Protein), Patients showed a better outcome in term of surgeries, target joint, bleeding tendency, FIX trough levels and hospitalization in last 12 months."

Clinical • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

CLINICAL APPLICATION OF EXTENDED HALF-LIFE PRODUCT ALBUTREPENONACOG ALFA (RIX-FP) IN CHILDREN WITH HAEMOPHILIA B (EAHAD 2023) - "All patients had been previously treated with recombinant FIX concentrates [Benefix (Nonacog alfa, Pfizer) and Rixubis (Nonacog gamma, Baxalta) for more than 50 (patients on demand) or 100 EDs (Exposure Days). This study demonstrates the successful transition of CWH B from SHL to rIX-FP."

Clinical • Hematological Disorders • Hemophilia • Ischemic stroke • Rare Diseases

RETROSPECTIVE STUDY OF THE EFFECTIVENESS AND SAFETY OF THE USE OF RIX-FP IN PATIENTS WITH HAEMOPHILIA B. EXPERIENCE OF FOUR CENTRES IN THE REGION OF CASTILLA Y LEÓN (C&L) (EAHAD 2023) - "In the previous treatment, all on FIX-SHL prophylaxis: 6 BeneFIX®, 1 RIXubis®; and 1 Inmunine®. This study in adult/adolescent and paediatric HB patients appears to show that prophylaxis with rIX-FP achieves a better PK profile than previous treatment, prolonging the administration schedule and with greater convenience and better adherence for the patient. It improves haemostatic effectiveness and controls traumatic bleeding events that occur in routine clinical practice."

Retrospective data • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases • Rheumatology

DETECTION OF FACTOR IX MOLECULES IN LIVER AND PAWS OF HEMOPHILIA-B MICE (EAHAD 2023) - "Introduction: FIX bound to type IV collagen in the endothelial basement membrane may provide haemostatic protection.However, its potential role in the protection against joint bleeds has not been demonstrated yet.Type I collagen is the most common form of collagen into muscle and joints where extravascular FIX might play a key role. Immunohistochemistry,protein engineering Our in-vitro experiments showed that plasma-derived FIX (pdFIX, Mononine®) had 4-fold better binding capacity to type I and IV collagen compared to recombinant FIX (rFIX).Post-translational modifications,mainly present into the activation peptide (AP),may influence FIX binding capacity to collagens and therefore its ability to reach extravascular compartment.To better understand the role of the AP in collagen binding, we have generated a rFIX molecule containing two APs.A bioengineered functional recombinant FIX produced by a human hepatoma cell-line,had full procoagulant activity and bound more..."

Preclinical • Gastrointestinal Cancer • Hematological Disorders • Hemophilia • Hepatocellular Cancer • Liver Cancer • Rare Diseases • Solid Tumor

WAPPS-Hemo as a tool for optimizing prophylaxis with extended half-life FIX in patients with severe or moderate hemophilia B (ISTH 2022) - "Aims: The impact of switching from standard half-life (SHL) rFIX product (Nonacog alfa, Benefix) to extended half-life (EHL) rFIX-Fc (Eftrenonacog alfa, Alprolix) or N9-GP (Nonacog beta pegol, Refixia) was evaluated on FIX pharmacokinetics (PK), weekly dosage and prophylactic infusion frequency. Thirteen patients with hemophilia B were switched to EHL-FIX, six to rFIX-Fc (2 severe and 4 moderate phenotypes; median age 25.5 y, range 18-60 y) and seven to N9-GP (3 severe and 4 moderate; median age 53 y, range 40-74 y). Median dose of FIX concentrate for the PK analysis was 46 IU/kg for rFIX-Fc and 52 IU/kg for N9-GP. The median half-life was extended to 124-125 hours for both FIX-Fc and N9-GP compared with 22-38 h using rFIX (Benefix)."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Performance of a Chromogenic Factor IX Activity Assay in the Recovery of Factor IX Replacement Therapies (ISTH 2022) - "Aims: To evaluate the recovered activity of seven FIX replacement products including AlphaNine SD, Alprolix, BeneFIX, Idelvion, Rebinyn, Ixinity and Rixubis by a new chromogenic FIX assay. Using acceptance criteria of 100 ± 25 percent recovery, the Chromogenic Factor IX assay accurately quantified 6/7 products across all levels including AlphaNine, Alprolix, BeneFIX, Rebinyn, Ixinity and Rixubis. The mean FIX recovery was 96, 116, 93, 82, 117 and 102% respectively, relative to the theoretical target across all tested levels. There was an over-recovery of Idelvion (albumin fusion recombinant FIX) with a mean recovery of 153%."

Hematological Disorders • Hemophilia • Rare Diseases

Impact of inhibitors on the procoagulant efficacy of bypass agents or hemostatic factors in combination with emicizumab (ISTH 2022) - " Blood from 21 emicizumab-treated patients, 8 with inhibitor, was collected in CTI.Therapeutic doses of rFVIII (100IU/dl octacog-alfa), BPAs (1µg/ml rFVIIa, 5IU/dl aPCC) or 100IU/dl of plasma-derived FIX (pFIX), two standard-half-life-rFIX (Nonacog-alfa and Nonacog-gamma), and extended-half-life-rFIX (albutrepenonacog-alfa) were tested.Clotting time (CT) was evaluated by Rotational Thromboelastometry (ROTEM) and Thrombin Peak by thrombin generation test (TGT) using low tissue factor concentration. Emizicumab-treated samples showed prolonged CT (Fig-1A) and lower thrombin peak values (Fig-1B) than healthy controls and no significant differences were observed between samples with and without inhibitors.Addition of 100IU/dl of all FIX products normalized the CT values similarly to the same dose of rFVIII. Nonacog-alfa was more efficient producing similar effects than the addition of 1μg/ml rFVIIa. aPCC response was stronger."

Clinical • Combination therapy • Hematological Disorders • Hemophilia • Rare Diseases

IN VITRO ANALYSIS OF THE IMPACT OF INHIBITORS ON THE PROCOAGULANT EFFECTS OF BYPASS AGENTS OR HEMOSTATIC FACTORS IN COMBINATION WITH EMICIZUMAB (EHA 2022) - "Spiking with therapeutic doses of 100 IU/dl octocog-alfa (rFVIII), BPAs [1 µg/ml eptacog alfa activated (rFVIIa); 5 U/dl activated prothrombin complex concentrate (aPCC)] or 100 IU/dl of plasma-derived FIX (pFIX), two standard-half-life (SHL) rFIX (nonacog-alfa and nonacog-gamma), and one extended-half-life (EHL) rFIX (albutrepenonacog-alfa) were tested. Conclusion Procoagulant effect of BPAs with emicizumab was similar with or without inhibitors whereas thrombin generation increment produced by rFIX was enhanced in the presence of inhibitors. These results provide a rationale for investigating the concomitant use of rFIX and emicizumab in PwHA with inhibitor in breakthrough bleeding and surgery."

Combination therapy • Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

A quantitative systems pharmacology (QSP) model to compare the non-clinical biodistribution and efficacy between recombinant factor IX (rIX) therapies (WFH 2022) - "Model calibration utilized mouse studies of radiolabeled rIX-Fc (Alprolix®), rIX-WT (BeneFIX®), and rIX-FP (Idelvion®). The mouse QSP model showed plasma and tissue biodistribution of rIX variants cannot be explained without a BP, and it is plausible to assume that different rIX variants have different BPs. The correlation between levels of bound rIX and coagulation endpoints suggests that vascular-bound rIX may be the pharmacologically active pool for hemostasis. Extravasation and sequestration of rIX-WT and rIX-Fc into tissues may explain the decreased vascular exposure, and reduced efficacy at later timepoints."

Clinical