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

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

Annualized Bleeding Rates in Severe Hemophilia on Prophylaxis in a Real-World Setting (ISTH 2022) - "We included all recorded infusions of adult patients with hemophilia A (HA) or B (HB) receiving prophylaxis with SHL or EHL (albutrepenonacog-alfa, damoctocog-alfa-pegol, efmoroctocog-alfa, eftrenonacog-alfa, lonoctocog-alfa, nonacog-beta-pegol, rurioctocog-alfa-pegol) for ≥6 months between 2018-01-01 and 2020-12-31. Fifty HA (median age 35 years; interquartile range 25-41) and 7 HB patients (42 years; 29-59) recorded a total of 31.3 million IU over 13,820 infusions for a median of 730 days (range 190-1,095). Median annualized bleeding rate (ABR) and joint ABR of the whole cohort was 4.74 (0.67-14.15) and 3.01 (0-8.36), respectively. Twenty-five patients were treated with EHL, eight of which documented a switch during the observation period."

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

AREA UNDER THE CURVE: INDIRECT PRODUCT COMPARISONS BETWEEN FACTOR VIII REPLACEMENT THERAPIES IN HAEMOPHILIA A (EAHAD 2022) - " The tool was created based on 11 identified crossover studies, presenting PK data for extended half-life (EHL) (Adynovi, Elocta, and Jivi) and standard half-life (SHL) products (Advate, Afstyla, Kogenate, Kovaltry, NovoEight, and ReFacto). Larger AUC for EHL compared to SHL products reflects higher FVIII over time after infusion, offering the option of longer injection intervals. In Scenarios 1 and 3, Jivi showed the largest AUC, and in Scenario 2, AUCs of EHLs Elocta and Adynovi were larger than Advate. This AUC tool may aid decision makers in comparing the relative value of FVIII concentrates in the absence of head-to-head trials."

Hematological Disorders • Hemophilia • Rare Diseases

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

Clinical • Enrollment closed • Hematological Disorders • Hemophilia • Rare Diseases

Monitoring of different factor VIII replacement products using a factor VIII one-stage clotting assay on cobas t 511/711 analysers. (PubMed, Haemophilia) - "These data allow the interpretation of FVIII activity results for different FVIII products using the Roche FVIII OSA on the cobas t 511/711 analysers."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Matching-Adjusted Indirect Comparison of Efficacy and Consumption of rVIII-SingleChain Versus Two Recombinant FVIII Products Used for Prophylactic Treatment of Adults/Adolescents with Severe Haemophilia A. (PubMed, Adv Ther) - "Although limited to published information for comparator trials, these results suggest that with an annualized rFVIII consumption comparable to rFVIIIFc, but significantly lower than rAHF-PFM, routine prophylaxis with rVIII-SingleChain is able to maintain a similar ABR and percentage of patients with zero bleeds, attesting to the long-acting nature of rVIII-SingleChain."

Clinical • Journal • Hematological Disorders • Hemophilia • Rare Diseases

Increased potency of recombinant VWF D'D3 albumin fusion proteins engineered for enhanced affinity for coagulation factor VIII. (PubMed, J Thromb Haemost) - "In summary, at potential clinical doses, the rD'D3-FP variants provide marked benefits with respect to dose levels and half-life extension of co-administered FVIII, supporting their development for use in the treatment of hemophilia A."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

[VIRTUAL] Joint Health Improvement Following a Switch to Prophylaxis with rVIII-SingleChain: A Patient Case (ISTH 2021) - "The patient is satisfied with his treatment and has not required any extra infusions despite an active lifestyle. Conclusions : This case report demonstrates an improvement in joint health following the switch to rVIII-SingleChain in a patient with severe hemophilia A and significant joint damage."

Clinical • Hematological Disorders • Hemophilia • Orthopedics • Rare Diseases • Rheumatology

SK Plasma enters the hemophilia treatment market with ‘AFSTYLA’ [Google translation] (Money Today Network (MTN)) - "SK Plasma announced on the 25th that it had signed an exclusive sales contract for CSL Behring Korea's long-acting recombinant factor 8 drug Afstyla (AFSTYLA, ingredient name: lonoctocog alpha)....CSLBehring will be in charge of production and import of Afstyla, and SK Plasma will be in charge of overall domestic marketing."

Licensing / partnership • Hemophilia

’Afstyla’ developed by Korea, insurance benefits applied from June 1st [Google translation] (Medipana) - "CSL Behring Korea is a gene-recombined single chain blood coagulation factor 8 drug 'AFSTYLA' It was announced that insurance benefits will be applied to IU items from June 1....With this insurance benefit, Afstyla can be administered at a single dose of 20-25 IU/kg for outpatients, and up to 30 IU/kg for moderate or severe bleeding. The number of administrations is allowed up to 4 doses at the first visit and 3 doses (severe 4 doses) at the second visit, and up to 7 doses (severe 8 doses) every 4 weeks. The upper limit is 625 won per IU."

Reimbursement • Hemophilia