Afstyla (lonoctocog alfa) / CSL Behring, SK Bio - LARVOL DELTA

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

rVIII-SingleChain Prophylaxis in Spanish Hemophilia A: A Real-World Economic Evaluation (ISTH 2026) - "Afstyla scenario was projected using Olivieri et al...Conclusions rVIII-SingleChain prophylaxis achieves clinical non-inferiority with significantly lower factor consumption (33%), nearly doubled zero bleeds rate (60% vs 33%), and substantial cost savings (98.4% probability). This represents economic dominance: improved clinical outcomes with lower costs, offering high value to healthcare systems while enhancing patient quality of life.More studies with larger cohort are necessary to confirm this results Table or Figure Upload (1) Table 1 Page 2 Table or Figure Upload (2) Table 2 Page 3 DOI*10.1016/j.rpth.2026.105838"

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

Bleeding outcomes and quality of life: A sub-analysis of a non-interventional study of rVIII-SingleChain prophylactic treatment for haemophilia A (ISTH 2026) - "Background Clinical trials and real-world studies in patients with haemophilia A (HA) have demonstrated the efficacy of rVIII-SingleChain (AFSTYLA ® ) for the treatment and prevention of bleeding episodes...Conclusions This study of rVIII-SingleChain prophylaxis and on-demand treatment reported positive clinical outcomes (factor consumption and patients with zero bleeds) and QoL measures in participants of all ages and disease severities with HA. DOI*10.1016/j.rpth.2026.104860"

Clinical • HEOR • Observational data • Hematological Disorders • Hemophilia • Hemophilia A • Infectious Disease • Novel Coronavirus Disease • Rare Diseases

Thrombin generation assay in patients with hemophilia A on different FVIII concentrates and efanesoctocog alfa (ISTH 2026) - "Lonoctocog alfa shows the largest discrepancy between FVIII and TGA kinetics, which could indicate good effectiveness even with lower FVIII levels. Samples were measured up to 48 hours after application, or 72 hours for efanesoctocog alfa. Page 2 DOI*10.1016/j.rpth.2026.104818"

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

Comparison of Coagulation and Chromogeic Methods in Pharmacokinetics with Extended Half-life Factor VIII (ISTH 2026) - "Chromogenic substrate assays (CSA) with Coamatic FactorVIII Results A sufficient number to compare results between methods was reached only for the pharmacokinetics with 4 concentrates: 3 FVIII-EHL (Efmoroctocog Alfa (Elocta) - Turoctocog Alfa (Esperoct) - Damoctocog Alfa Pegol (Jivi), all B domain deleted) and a single-chain FVIII (Lonoctocog Alfa (Afstyla). Table or Figure Upload (2) Figure2. DOI*10.1016/j.rpth.2026.104886"

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

Recombinant Single-chain Factor VIII (rVIII-SingleChain) in Chinese Participants With Hemophilia A Previously Treated With FVIII Products (clinicaltrials.gov) - P3 | N=60 | Active, not recruiting | Sponsor: CSL Behring | Trial completion date: Jun 2026 ➔ Oct 2026 | Trial primary completion date: Jun 2026 ➔ Oct 2026 | Recruiting ➔ Active, not recruiting

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

Performance of Factor VIII Extended Half-Life Product Measurements in External Quality Assessment Programmes. (PubMed, Int J Lab Hematol) - "The FVIII results submitted by participants showed that currently available OSA and CA do not provide consistent results in some products with both an under- and over-estimation of the expected recovery based on potency at either concentration level. Results for Afstyla Lonoctocog alfa suggest that centres were not clear on whether OSA results were before or after application of the correction factor (multiplication of initial result by 2)."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • 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

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

AFEEL: Low Dose Emicizumab vs Low Dose Factor VIII in Prophylaxis in Hemophilia A Patients (clinicaltrials.gov) - P2/3 | N=20 | Not yet recruiting | Sponsor: Dhaka Medical College

New P2/3 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Recombinant Single-chain Factor VIII (rVIII-SingleChain) in Chinese Participants With Hemophilia A Previously Treated With FVIII Products (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: CSL Behring | Not yet recruiting ➔ Recruiting | Trial completion date: Feb 2026 ➔ Jun 2026 | Trial primary completion date: Feb 2026 ➔ Jun 2026

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

OPERA: Register of Patients With haEmophilia A tReated With Afstyla® (clinicaltrials.gov) - P=N/A | N=62 | Completed | Sponsor: CSL Behring | Active, not recruiting ➔ Completed

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

Recombinant single-chain factor VIII (rVIII-SingleChain) in Chinese participants with hemophilia A previously treated with FVIII products (clinicaltrialsregister.eu) - P3 | N=60 | Sponsor: CSL Behring

New P3 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Recombinant Single-chain Factor VIII (rVIII-SingleChain) in Chinese Participants With Hemophilia A Previously Treated With FVIII Products (clinicaltrials.gov) - P3 | N=60 | Not yet recruiting | Sponsor: CSL Behring

New P3 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Switching hemophilia A patients to rVIII-SingleChain: The Iberian experience. (PubMed, Medicine (Baltimore)) - "The real-world outcomes of lonoctocog alfa (rVIII-SingleChain), a long-acting factor VIII (FVIII) with a favorable safety and efficacy profile in trials, were assessed in patients with hemophilia A in Iberian (Spain and Portugal)...No safety concerns were reported. Patients who switched to rVIII-SingleChain prophylaxis had excellent bleeding control and reduced infusion frequency in regular clinical practice, with the subsequent increase in quality-of-life."

Journal • Observational data • Retrospective data • Hematological Disorders • Hemophilia • Rare Diseases

Comprehensive laboratory assessment of lonoctocog alfa versus octocog alfa in severe haemophilia A. (PubMed, Haemophilia) - "Lonoctocog alfa and octocog alfa showed comparable recovery and safety in vivo as well as similar impacts on TG in vitro. Observed assay discrepancies on lonoctocog alfa demonstrated variability of results also between different FVIII CSAs."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

A Generative and Causal Pharmacokinetic Model for Factor VIII in Hemophilia A: A Machine Learning Framework for Continuous Model Refinement. (PubMed, Clin Pharmacol Ther) - "The hybrid ML-PK model was trained on chromogenic assay data of lonoctocog alfa and predictive performance was then evaluated on an external data set of patients who received octocog alfa with FVIII levels measured using the one-stage assay. In conclusion, the proposed approach introduces interesting new possibilities for model development. In the context of rare disease, the introduction of generative models facilitates sharing of synthetic data, enabling the iterative improvement of population PK models."

Journal • Machine learning • PK/PD data • Hematological Disorders • Hemophilia • Rare Diseases

Inhibitor recurrence following immune tolerance induction in a hemophilia A patient with inhibitor post COVID-19 infection (ISTH 2023) - "Patient received ITI (at start titer, 3.4 BU) with Nuwiq 100 iu/kg/day for 2 years and shift to afstyla 50 iu/kg/day for year then tapping to 35 iu/kg/biw on prophylaxis therapy later. This case was successful ITI under rFVIII but inhibitor recurrent was noticed post COVID-19 infection. He would be received rescue ITI with haemate-P and emicizumab.Conclusion(s): Management of HA patients with inhibitor is still a challenge until now. As a break of COVID-19 infection or vaccination, clinician and laboratory should be aware of this potential adverse event."

Clinical • Hematological Disorders • Hemophilia • Hepatitis C • Infectious Disease • Novel Coronavirus Disease • Rare Diseases

Value of Hemophilia Drug Treatment Using Analysis of the Area Under the Curve (ISTH 2023) - "Estimated AUCs for all products compared with octocog alfa (Advate) in base-case analysis are shown in Figure 1 and Table 1. Damoctocog alfa pegol (Jivi) and efmoroctocog alfa (Elocta) had the largest AUCs compared with Advate (+71%–90% and +66%–73%, respectively) depending on min/max range. Among all SHLs, lonoctocog alfa (Afstyla) had a larger AUC compared with Advate (+18%–27%)."

Hematological Disorders • Hemophilia • Rare Diseases

Post-infusion monitoring of Afstyla FVIII replacement therapy – data from the UK National External Quality assessment for Blood Coagulation (UK NEQAS BC) programme 2022. (ISTH 2023) - "The overall CV of 20.7% for sample 22:02 by OSA in this survey should encourage laboratories to perform Chromogenic assays for Afstyla measurement.Conclusion(s): Manufacturer recommends doubling one stage assay results for Aftsyla. Applying this multiplication step to the raw median results in table 1 would result in a 94% recovery of one stage assay level compared to the chromogenic assay level. From the data returned and applying the multiplication step to one stage assay results recoveries of between 84% and 126% compared to the chromogenic assay results were achieved.There is a risk that laboratories may not be aware of the extended half-life (EHL) being prescribed."

Hematological Disorders • Hemophilia • Rare Diseases

Altuviiio - a longer-acting factor VIII product for hemophilia A. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Relationship between factor VIII levels and bleeding for rFVIII-SingleChain in severe hemophilia A: A repeated time-to-event analysis. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Our objective was to examine the relationship between the dose, factor VIII (FVIII) levels and bleeding for rFVIII-SingleChain (lonoctocog alfa, Afstyla). In conclusion, the developed PK-RTTE model adequately described the relationship between dose, FVIII levels and bleeds for rFVIII-SingleChain. The obtained estimates were in agreement with those published for the FVIII concentrates BAY 81-8973 (octocog alfa) and BAY 94-9027 (damoctocog alfa pegol), indicating similar efficacy to reduce bleeding."

Journal • Hematological Disorders • Hemophilia • Mood Disorders • 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

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

Performance of FVIII deficient plasma with VWF in the activity measurement of FVIII replacement products in plasma samples using an OSC assay. (ISTH 2022) - "Using acceptance criteria of 100 ± 25% recovery, 5 out of 6 products across all levels were assayed accurately. Mean FVIII% recoveries across all levels of Advate, Eloctate, Jivi, Novoeight and Wilate were 93, 95, 101, 113 and 95% respectively. The percent recoveries of Afstyla, after x2 conversion, fell within the acceptance criteria for levels of ≥ 0.1 IU/mL but over-estimated at 149.76% at the lowest level of 0.05 IU/mL."

Hematological Disorders • Hemophilia • Rare Diseases