BAX326 is a recombinant factor IX (rFIX; nonacog gamma) manufactured without the addition of any materials of human or animal origin, and with two viral inactivation steps (solvent/detergent treatment and 15 nm nanofiltration). The aim of this prospective trial was to investigate the pharmacokinetics, haemostatic efficacy and safety of BAX326 in previously treated patients aged 12-65 years with severe or moderately severe haemophilia B. BAX326 was safe and well tolerated in all 73 treated subjects; adverse events considered related to treatment (2.7% incidence, all non-serious) were transient and mild, and no hypersensitivity reactions, inhibitor formation or thrombotic events were observed. Pharmacokinetic (PK) equivalence (n = 28) between BAX326 and a licensed rFIX was confirmed in terms of the ratio of geometric mean AUC(0-72) h per dose. Twice-weekly prophylaxis [mean duration 6.2 (±0.7) months; 1.8 (±0.1) infusions per week, 49.5 (±4.8) IU kg(-1) per infusion] was effective in preventing bleeding episodes, with a significantly lower (79%, P < 0.001) annualized bleed rate (4.2) compared to an on-demand treatment in a historical control group (20.0); 24 of 56 subjects on prophylaxis (43%) did not bleed throughout the study observation period. Of 249 total acute bleeds, 211 (84.7%) were controlled with one to two infusions of BAX326. Haemostatic efficacy at resolution of bleed was rated excellent or good in 96.0% of all treated bleeding episodes. The results of this study indicate that BAX326 is safe and efficacious in treating bleeds and routine prophylaxis in patients aged 12 years and older with haemophilia B.

The ability to switch between coagulation factors safely is of common interest to haemophilia patients and treating physicians. This is the first formal prospective comparative evaluation of safety, efficacy and incremental recovery of a plasma-derived FIX (pdFIX) and a recombinant FIX (rFIX) in the same haemophilia B patients following a switch from pdFIX Immunine® to a recently developed rFIX Bax326 product. Patients (aged <65 years) who completed a pretreatment study which prospectively documented the exposure to Immunine® and monitored FIX inhibitors while receiving prophylactic treatment were transitioned into pivotal (patients aged 12-65 years) and paediatric (patients aged <12 years) clinical studies investigating prophylaxis and treatment of bleeding episodes with Bax326. None of the 44 patients developed inhibitory or specific binding anti-FIX antibodies during the course of the studies. A total of 38 unrelated adverse events (AEs) were occurred in 20/44 (45.5%) subjects during the Immunine® study. Following a switch to Bax326, 51 AEs were reported in 25/44 (56.8%) subjects. The incidence of AEs related to Bax326 treatment (two episodes of dysgeusia in one patient) was low (2.3%); there were no serious adverse reactions. The comparison between Immunine® and Bax326 demonstrated analogous haemostatic characteristics and annualized bleeding rates. Overall, there is direct evidence indicating a safe and clinically effective transition from a pdFIX (Immunine®) to a newly developed rFIX (Bax326(1) ) for prophylaxis and treatment of bleeding in previously treated patients of all age cohorts with severe or moderately severe haemophilia B.

300 mg, a single 300-mg loading dose with subsequent 150-mg doses, or 450 mg; with inhibitors: 300 mg). Safety outcomes were treatment-emergent adverse events (TEAEs), injection site reactions, clinical and laboratory parameter changes. Efficacy was assessed by annualised bleeding rates (ABRs). Pharmacokinetics and pharmacodynamics (PD) were also evaluated. Among 26 treated participants [haemophilia A without inhibitor, n = 16 (61.5%); haemophilia A with inhibitor, n = 7 (26.9%); haemophilia B, n = 3 (11.5%)], 24 completed the study. Overall, 80.8% experienced TEAEs. ABR during treatment was significantly reduced versus an external ondemand control group (p < 0.0001) and versus pretreatment ABR (p < 0.0001), with significant reductions observed across all dose cohorts. Marstacimab exposure generally increased in a dose-related manner, with steady-state concentration reached by day 57. Changes in pharmacodynamic biomarkers occurred across all dose cohorts.Marstacimab was safe and well tolerated. Clinically meaningful reductions in ABR and treatment-related changes for all PD biomarkers indicated effective targeting of TFPI. (Clini caltr ials.gov identifier, NCT02974855). K E Y W O R D Sblood coagulation factors, drugs, investigational, haemorrhage, monoclonal antibodies, thrombin I N TRODUC T IONHaemophilia is an X-linked bleeding disorder caused by deficiencies in clotting factors VIII (FVIII) or IX (FIX). 1 For patients with severe haemophilia [factor activity levels <1% (<0.01 iu/ml) 2 ], intravenous prophylactic clotting factor replacement reduces bleeding and prevents or slows progression of joint disease. [3][4][5] frequent intravenous This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Haemophilia A (haemA) and B (haemB) are X-linked bleeding disorders characterised by deficiencies in coagulation clotting factors VIII (FVIII) and IX (FIX) respectively. 1 People with severe haemophilia (FVIII or FIX activity level <0.01 iu/ml or <1.0% of normal) experience frequent bleeding events, both spontaneous and post-traumatic, most often in the joints (haemarthrosis) and also in muscles and soft tissues. 1 Without treatment, patients with severe haemophilia will develop progressive and debilitating arthropathy with consequent joint dysfunction, pain, and poor quality of life. 2 Standard-of-care treatment for haemophilia has been based on intravenous (IV) prophylactic replacement with either

Livedoid vasculopathy is a rare condition which predominantly affects young women. It is characterized by intense painful purpuric maculae in the legs, ankles and feet, due to thrombosis of the small and medium-sized dermal vessels, in the absence of vasculitis. Livedoid vasculopathy has been frequently associated with hypercoagulable states and antiphospholipid syndrome. We describe a 34-year-old White woman suffering from systemic lupus erythematosus, livedo reticularis, haemolytic anaemia, severe thrombocytopenia and recurrent venous thrombosis who was admitted to the hospital for extremely painful purpuric lesions in her lower limbs. The clinical and histological findings were diagnostic of livedoid vasculopathy. Once the initial sub-therapeutic international normalized ratio levels were corrected, livedoid vasculopathy did not recur. Tests for antiphospholipid antibodies were repeatedly negative. This case, the first reported of livedoid vasculopathy in a patient with seronegative antiphospholipid syndrome and systemic lupus erythematosus, draws attention to livedoid vasculopathy, a thrombotic dermopathy that may be under-diagnosed in patients with antiphospholipid syndrome.