Kogenate FS liposome (octocog alfa (pegylated)) / Bayer - LARVOL DELTA

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

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

[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

Bayer sells a facility at its Wuppertal site to WuXi Biologics (Bayer Press Release) - "Bayer is selling a biologics substance facility at the Wuppertal site of its Pharmaceuticals Division to a German subsidiary of WuXi Biologics. Under the agreement the two companies announced on Monday, they will also enter into a long-term sublease agreement and a transitional service contract....The volume of the transaction, including the sublease agreement, amounts to approximately 150 million euros. The transaction, which is subject to regulatory approval, is expected to close in the first half of 2021. Bayer had originally planned to use the facility to produce recombinant factor VIII products."

Commercial • Hemophilia

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

Product discontinued (Firstwordpharma Press Release)

Discontinued • Hematological Malignancies • Hemophilia • Oncology

Patient characteristics that influence efficacy of prophylaxis with rFVIII-FS three times per week: A subgroup analysis of the LIPLONG study (Haemophilia) - P1, N=68; Sponsor: Bayer; NCT00629837; "The annualized median (range) number of bleeds was 2.2 (0.0–23) bleeds per year. The median (range) number of bleeds per year was significantly lower in patient subgroups without vs. with target joints [0.5 (0.0–17.1) vs. 4.2 (0.0–22.8); P = 0.02] and in those with ≤9 vs. >9 bleeds during the previous 6 months [1.1 (0.0–19.2) vs. 5.3 (0.0–22.8); P = 0.01]."

P1 data • Hemophilia

Population pharmacokinetic (PopPK) modelling indicates that patients switching to BAY 81-8973 from rFVIII-FS can continue their dosing schedule with improved protection. (PubMed, Haemophilia) - No abstract available

Clinical • Journal • PK/PD data

Intra‐individual across‐study comparison of pharmacokinetics of rFVIII‐FS, bay 81‐8973 and bay 94‐9027 in patients with severe haemophilia A (EAHAD 2020) - P2/3, P3; "In LEOPOLD I (NCT01029340), the PK profile of BAY 81-8973 (Kovaltry®; an unmodified, full-length rFVIII product manufactured using innovative technologies) was compared with that of rFVIII-FS (Kogenate®; a sucrose-formulated rFVIII product with the same amino acid sequence as BAY 81-8973) after a single 50 IU/kg infusion. A subset of these patients also participated in the PROTECT VIII trial (NCT01580293), in which the PK profile of BAY 94-9027 (Jivi®; a B-domain deleted rFVIII product site-specifically PEGylated to extend its half-life) was assessed after a single 60 IU/kg infusion... BAY 94-9027 demonstrated an extended half-life compared with both rFVIII-FS and BAY 81-8973 following a single infusion in patients with severe haemophilia A. In conclusion, switching treatment from either rFVIII-FS or BAY 81-8973 to BAY 94-9027 is expected to provide improved protection from bleeds and/or allow for less frequent infusions."

Clinical • PK/PD data

Increased branching and sialylation of N-linked glycans correlate with an improved pharmacokinetic profile for BAY 81-8973 compared with other full-length rFVIII products. (PubMed, Drug Des Devel Ther) - "Increased N-glycan branching and sialylation were seen for BAY 81-8973 vs rFVIII-FS and rAHF-PFM. Improved PK for BAY 81-8973 relative to rFVIII-FS and rAHF-PFM as seen in single-dose crossover PK studies might be related to this greater level of branching and sialylation, which can prolong the time BAY 81-8973 remains in the circulation."

Journal • PK/PD data

Kogenate: Patent expiry for formulation in Japan and Brazil in 2020 (Bayer AG) - Annual Report 2018

Patent