Kogenate FS (octocog alfa sucrose formulation) / CSL Behring, Bayer - LARVOL DELTA

Comparative Efficacy of Recombinant FVIII and Recombinant FVII Biosimilars in Severe Hemophilia A. (PubMed, Clin Appl Thromb Hemost) - "The only possible treatment for this bleeding condition is factor concentrate.AimThe aim of this study is to compare the effect of recombinant factor VIII (rFVIII) and recombinant factor VII (rFVII) on prothrombin time (PT), activated partial thromboplastin time (aPTT), FVIII and FVII in severe HA.MethodologyA mixing study was conducted on 30 samples of severe HA patients to assess the correction of PT, aPTT, FVIII, and FVII values using biosimilars of rFVIII (NovoEight and Kogenate FS) and rFVII (NovoSeven and AryoSeven) using a fully automated coagulation analyser 'Ceveron alpha'.ResultsAll the four drugs demonstrated a significant alteration for both PT (P < .0001) and aPTT (P < .0001) values. Two different groups of biosimilars were found to have a high potential to alter the PT and aPTT values. The FVIII biosimilars are efficient in increasing the FVIII levels."

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

The Influence of Coagulation Factor Biosimilars in Shortening the Activated Partial Thromboplastin Time in Patients with Hemophilia a (ASH 2024) - "Negative correlation was observed between PT and FVII values after adding Kogenate FS (r=-0.103, p<0.001), aPTT and FVIII values after adding Kogenate FS (r=-0.898, p<0.001), aPTT and FVIII values after adding NovoEight (r=-0.865, p<0.001), as well as aPTT and FVIII values after adding AryoSeven (r=-0.647, p<0.001).Conclusion : All the investigated drugs significantly shorten aPTT values and increase values of FVIII and FVII. In terms of efficacy, no difference exists between AryoSeven and NovoSeven, as well as between Kogenate FS and NovoEight only in altering PT."

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

Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review. (PubMed, Drugs R D) - P1 | "The PK of damoctocog alfa pegol was shown to be improved as compared with that of sucrose-formulated rFVIII (rFVIII-FS, Kogenate®), and was also demonstrated to be non-inferior to and, for some variables, more favorable than rFVIII-Fc fusion protein, efmoroctocog alfa (Elocta®; NCT03364998), rurioctocog alfa pegol (BAX 855, Adynovate®/Adynovi®; NCT04015492), and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, Advate®; NCT02483208). Efficacy for perioperative hemostasis has been demonstrated. Low bleeding rates were achieved across the studies, with twice weekly, every 5-day and every 7-day prophylaxis offering patients ≥ 12 years and their clinicians the chance to tailor treatment to individual needs and lifestyles, while maintaining long-term protection from bleeds and their consequences."

Journal • Review • Hematological Disorders • Hemophilia • Rare Diseases

Comparison of Coagulation Factor VIII Biosimilars (Kogenate FS Vs NovoEight) in Altering Prothrombin Time, activated Partial Thromboplastin Time, and levels of Factors VII and VIII in Hemophilia A (ISTH 2024) - "In a comparison of both of the investigational drugs to the original values of PT, aPTT and FVIII, among-group comparison with post-hoc pairwise comparisons showed a high statistically significant difference for aPTT and FVIII, compared to pre-treatment values (Table 1). A negative correlation was observed between PT and FVII values after adding Kogenate FS (r=-0.103, p< 0.001), aPTT and FVIII values after adding Kogenate FS (r=-0.898, p< 0.001), aPTT and FVIII values after adding NovoEight (r=-0.865, p< 0.001). Conclusion(s) : These investigated drugs significantly shorten aPTT values and increase values of FVIII and FVII."

Hematological Disorders • Hemophilia • Rare Diseases

Real-World Data on Hemophilia a Patients Transitioning from Bay 81-8973 to Bay 94-9027 and from Bay 14-2222 to Bay 81-8973 and then to Bay 94-9027 in the Athndataset (ASH 2023) - "Patients with Hemophilia A are transitioning more and more from standard half-life (SHL) products to extended half-life (EHL) recombinant factor VIII (rFVIII) productsObjective: To evaluate the effect of Hemophilia A patients transitioning from BAY 81-8973 (Kovaltry ®) to BAY 94-9027 (Jivi ®) and from BAY 14-2222 (Kogenate FS ®) to BAY 81-8973 and then to BAY 94-9027 in a real-world setting. The data show that hemophilia A patients who transitioned to BAY 94-9027 from BAY 81-8973, or those that transitioned from BAY 14-2222 to BAY 81-8973 and then to BAY 94-9027 did experience similar or decreased total annual bleed rates with a decrease in their prophylaxis regimen frequency when transitioning to BAY 94-9027 in the real world. The therapeutic burden of frequent infusions can be reduced when patients transition between rFVIII product classes (SHL to EHL), without change in their annual bleed rate. These data should be interpreted with caution owing to..."

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

Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials. (PubMed, J Blood Med) - P3 | "Previous clinical trials established the efficacy and safety of sucrose-formulated recombinant factor (F) VIII (rFVIII-FS/Kogenate FS®/Helixate FS®) and octocog alfa (BAY 81-8973/Kovaltry®; LEOPOLD trials). Octocog alfa was well tolerated, and no patients had drug-related serious AEs or inhibitors. Treatment with octocog alfa prophylaxis appeared to have a favorable risk-benefit profile compared with rFVIII-FS and thus could be an effective and improved alternative strategy for individualized treatment for children, adolescent and adult patients with severe hemophilia A currently on rFVIII-FS treatment."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Correlations between von Willebrand Factor Antigen Levels and Factor VIII Pharmacokinetics Are Similar across Different FVIII Products in Patients with Severe Hemophilia A (ASH 2019) - P1, P2, P2/3, P3; "The products were: PEGylated recombinant FVIII BAY 94-9027 (damoctocog alfa pegol, Jivi®); sucrose-formulated recombinant FVIII (rFVIII-FS; Kogenate®-FS); BAY 79-4980 (liposomal version of Kogenate®-FS); unmodified full-length recombinant FVIII BAY 81-8973 (Kovaltry); and recombinant antihemophilic factor plasma/albumin-free method rAHF-PFM (octocog alfa, Advate®). In this combined analysis across five FVIII products, FVIII PK parameters (t1/2, AUCnorm, and CL) were significantly correlated with endogenous VWF:Ag levels which were also correlated with age. Moreover, while there were differences in the average PK parameters between products (represented by the intercept for treatment), all five FVIII products demonstrated similar VWF-PK relationships. It is well known that a patient’s VWF:Ag level influences the PK of rFVIII, but this analysis suggests that the quantitative relationship between FVIII PK and VWF:Ag is similar for modified and

Clinical • PK/PD data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Enhanced pharmacokinetics and improved clinical outcomes in young hemophiliac boys after the switch to BAY 81-8973 from other standard half-life FVIII concentrates (ISTH 2022) - "Longer half-life time (t1/2)[Kogenate FS group:14.36±1.92 vs. 11.92±2.41h,P < 0.0001); Advate group(13.41±1.44 vs. 9.67±1.74h,P < 0.0001); GreenMono group(15.07±3.36 vs."

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

Enhanced pharmacokinetics and reduced bleeds in boys with hemophilia A after switching to Kovaltry from other standard half-life factor VIII concentrates. (PubMed, Res Pract Thromb Haemost) - "Participants who switched to Kovaltry from three other FVIII concentrates with the same dosing regimens obtained higher trough FVIII levels and better protection with reduced annualized bleeding rates. Compared with Kogenate FS, Advate, and GreenMono, Kovaltry showed enhanced PK profiles, which contributed to reduced bleeding rates."

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

[VIRTUAL] Chinese Real-world Experience of Product Switching in Severe Hemophilia Patients: from rFVIII-FS(Kogenate®) to BAY 81-8973 (Kovaltry®) (ISTH 2021) - "With no extra FVIII consumption needed, BAY 81-8973(Kovaltry®) showed optimal efficiency which may contributed to its superior pharmacokinetic profiles. Further studies focus on PK comparison of these two products in Chinese real-world setting are needed."

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

[VIRTUAL] Predicted FVIII Consumption of BAY 94-9027 Compared with Standard- and Extended-half-Life FVIII Products in Patients with Severe Hemophilia A (ISTH 2021) - "Aims : To use population PK (popPK) modeling of available H2H PK data to predict weekly FVIII consumption of different regimens of BAY 94-9027 (Jivi), compared with antihemophilic factor (recombinant) formulated with sucrose (Kogenate-FS), rFVIIIFc (Elocta) and BAX 855 (Adynovi). Other target thresholds and regimens will be presented. Conclusions : These dose predictions reveal the potential of BAY 94-9027 in reducing FVIII consumption compared with other rFVIII products, while maintaining the same FVIII trough level, and thereby similarly efficient protection from bleeds."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Pharmacokinetic variability of factor VIII concentrates in Chinese pediatric patients with moderate or severe hemophilia A. (PubMed, Pediatr Investig) - "Seventy-nine patients were enrolled (28 treated with Kogenate FS, 23 treated with Advate , and 28 treated with GreenMono™). VWF:Ag level and FVIII brand were associated with differences in FVIII PK. Thus, PK-guided dosing should be used to optimize individualized therapy in Chinese children."

Clinical • Journal • PK/PD data • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

Comparative pharmacokinetics of Kogenate FS and Kovaltry in 14 Chinese paediatric patients with haemophilia A: A single-centre study. (PubMed, Haemophilia) - No abstract available

Clinical • Journal • PK/PD data • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

Tailoring haemophilia A prophylaxis with BAY 81-8973: A case series. (PubMed, Transfus Apher Sci) - "BAY 81-8973 is an unmodified, full-length third generation recombinant factor VIII (rFVIII) which offers a more favorable pharmacokinetic (PK) profile, compared to its predecessor sucrose-formulated rFVIII (rFVIII-FS). We here report on a retrospective case series of nine patients affected by hemophilia A (HA), with variable disease severity, bleeding phenotype and comorbidities, to underline our clinical practice on prophylaxis with a recently introduced standard hall-life recombinant Factor VIII. The current case series highlights how the current clinical management of hemophilia is able to personalize treatment in several specific conditions like concomitant illnesses with thrombotic risk and allergic reactions."

Clinical • Journal • Allergy • Hematological Disorders • Hemophilia • Osteoarthritis • Rare Diseases

Bayer plays the long game with plans to double workforce at Berkeley biologics site (Fierce Pharma) - "Bayer has proposed a 30-year site development deal with the City of Berkeley that would see the company add about 1 million square feet of new work space and double its workforce there by hiring 1,000 more employees.'We’re building on a strong foundation in biologics development and biomanufacturing at this site and plan to diversify our operations,'...Currently, the Berkeley site is mainly responsible for making Bayer’s antihemophilic factor treatments—Kogenate, Kovaltry and Jivi..."

Commercial • Hemophilia

[VIRTUAL] Comparative Pharmacokinetics of Two Recombinant FVIII Concentrates in Chinese Pediatric Patients with Severe Hemophilia A: A Single-Center Study (ISTH 2020) - "Kovaltry showed better PK profiles and clinical outcomes comparing with Kogenate FS. Patients with higher VWF: Ag level or blood type non-O benefit more from the switch."

Clinical • PK/PD data • Gene Therapies • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

Impact of being overweight on factor VIII dosing in 72 children with severe hemophilia A treated with Advate, Kogenate FS or Refacto AF/Xyntha (ASH 2014) - Presentation time: Saturday, December 6, 2014, 5:30 PM-7:30 PM; Abstract #1498; P=NA, N=72; "The BMI-for-age emerged as the strongest predictor of FVIII recovery in children aged between 6 and 17, with a cut-off value at the 95th percentile...findings support that dose calculation of FVIII to reach a specific FVIII target level should be adapted in overweight children since only a small fraction of FVIII distributes outside the vascular system."

Retrospective data • Hemophilia

Comparison of post treatment monitoring of new and old factor VIII (FVIII) therapeutic products by one-stage clotting and chromogenic FVIII assays: Single centre experience (EAHAD 2016) - P=NA, N=135; "RefactoAF showed lowest % mean differences between OS FVIII assay and chromogenic factor VIII assay results for groups 2, 3 and 4 (<5 %mean difference) probably related to use of product specific standard whilst Advate, Kogenate and Helixate post infusion samples showed variable %mean differences across groups 1–5, on occasion related to small number of samples."

Clinical data • Hemophilia

Recombinant FVIII product type and the risk of inhibitor development in previously treated patients with hemophilia A: a systematic review and meta-analysis (EAHAD 2018) - "These data suggest that some rFVIII products are associated with increased immunogenicity as compared with Advate in severe and moderately severe PTPs with hemophilia A."

Retrospective data • Review • Biosimilar • Gene Therapies • Hematological Malignancies • Hemophilia

SPINART trial 3-year results with Bayer’s sucrose formulated recombinant factor VIII: Improved joint function and health-related quality of life in adults using prophylaxis (CiTH 2014) - Abstract #P13; P3, N=84; Study ID: SPINART (NCT00623480); Sponsor: Bayer; "LS mean change in CAJAS total score for the on-demand and prophylaxis groups was 0.19 and –0.46 at year 1 and 0.34 and  –0.57 at year 2, respectively. For HAEMO-QoL-A total score, LS  mean change from baseline to year 3 was –6.00 for on  demand and 3.98 for prophylaxis (LS mean difference, 9.98;  95% CI, 3.42 to 16.54)."

P3 data • Hemophilia

History of sucrose-formulated recombinant factor VIII (rFVIII-FS) use and reduction in bleeds following BAY 81-8973 prophylaxis in Leopold I (EAHAD 2016) - P2/3, N=62; Leopold I (NCT01029340); Sponsor: Bayer; "Patients had significantly fewer bleeds during treatment with BAY 81-8973 in the trial period than in the pre-trial period in both rFVIII-FS [n = 33, mean(SD): 6.0 (7.5) vs. 3.3 (4.3) bleeds; P < 0.01] and other FVIII [n = 26, 18.4 (19.7) vs. 4.9 (6.3);P < 0.01] groups. The rFVIII-FS group had fewer bleeds than the other FVIII group in the pre-trial period, and a smaller bleed reduction between periods [bleed reduction by group: rFVIII-FS: mean (SD): 2.7(6.0); other FVIII: 13.5 (19.4); P = 0.02]. A similar pattern was seen for joint bleeds but joint bleed reduction between periods was not significantly different between the two groups. All patients in the rFVIII-FS group and 15 patients in the other FVIII group received prophylaxis in the pre-trial period."

P2/3 data • Hemophilia

Bayer: Q1 2014 Results (Bayer AG) - Anticipated launch for hemophilia in 2016

Anticipated launch • Hemophilia

3-year analyses from SPINART: Patient- and joint-level changes in magnetic resonance imaging scores with Bayer’s sucrose formulated recombinant factor VIII (rFVIIIFS) in adolescents and adults previously treated on demand (EAHAD 2015) - Abstract #PP046; P3, N=84; SPINART (NCT00623480); Sponsor: Bayer; "Changes in eMRI total score at year 3 in SPINART were similar for the on-demand and prophylaxis groups. eMRI total scores worsened for ≥73% of patients treated with rFVIII-FS prophylaxis or on demand, but < 30% of individual joints worsened in each treatment group."

P3 data • Hemophilia

Bayer: Annual Report 2013 (Bayer AG) - Anticipated expiry of active ingredient patent in Canada in 2019; Anticipated expiry of formulation patents in Germany, France, UK, Italy and Spain in 2017; Anticipated expiry of formulation patent in Japan in 2017; Anticipated expiry of formulation patent in China in 2017; Anticipated expiry of formulation patent in US in 2017; Anticipated expiry of formulation patent in Canada in 2017; Anticipated expiry of active ingredient patent in US in 2014

Anticipated patent expiry • Hemophilia

3-Year results from SPINART: Prolonged reduction of bleeding with prophylaxis using Bayer’s sucrose-formulated recombinant factor VIII (CiTH 2014) - Abstract #O11; P3, N=84; Study ID: SPINART (NCT00623480); Sponsor: Bayer; "The total number of all bleeding episodes during the 3-year study was significantly lower with prophylaxis versus on demand (median, 2.0 vs 96.5, respectively; P<0.0001). Annualized number of all bleeding episodes (median [quartile 1; quartile 3], 0.7 [0; 1.6] vs 37.4 [24.1; 52.6]), total joint bleeding episodes (median, 1.0 vs 67.0), and joint bleeding episodes per year (median, 0.3 vs 27.3) were all lower with prophylaxis versus on demand."

P3 data • Hemophilia