These results demonstrate that a dose of 25 IU kg(-1) pdFX is safe and efficacious for on-demand treatment and short-term prophylaxis in subjects with moderate or severe hereditary FX deficiency.

These results demonstrate the efficacy and safety of pdFX for treating children <12 years with moderate/severe hereditary FXD.

These data demonstrate that pdFX is safe and effective as replacement therapy in five subjects with mild-to-severe FX deficiency undergoing surgery on seven occasions.

To cite this article: Kulkarni R, James AH, Norton M, Shapiro A. Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in women and girls with hereditary factor X deficiency. J Thromb Haemost 2018; 16: 849-57. Essentials• Plasma-derived factor X concentrate (pdFX) is used to treat hereditary factor X deficiency.• pdFX pharmacokinetics, safety and efficacy were assessed in factor X-deficient women/girls. • Treatment success rate was 98%; only 6 adverse events in 2 subjects were possibly pdFX related.• On-demand pdFX 25 IU kg À1 was effective and safe in women/girls with factor X deficiency.Summary. Background: A high-purity, plasma-derived factor X concentrate (pdFX) has been approved for the treatment of hereditary FX deficiency, an autosomal recessive disorder. Objective: To perform post hoc assessments of pdFX pharmacokinetics, safety and efficacy in women and girls with hereditary FX deficiency. Patients/ Methods: Subjects aged ≥ 12 years with moderate/severe FX deficiency (plasma FX activity of < 5 IU dL À1 ) received on-demand or preventive pdFX (25 IU kg À1 ) for ≤ 2 years. Results: Of 16 enrolled subjects, 10 women and girls (aged 14-58 years [median, 25.5 years]) received 267 pdFX infusions. Mean monthly infusions per subject were higher among women and girls (2.48) than among men and boys (1.62). In women and girls, 132 assessable bleeding episodes (61 heavy menstrual bleeds, 47 joint bleeds, 15 muscle bleeds, and nine other bleeds) were treated with pdFX, with a 98% treatment success rate versus 100% in men and boys. Mean pdFX incremental recovery was similar in the two groups (2.05 IU dL À1 versus 1.91 IU dL À1 per IU kg À1 ), as was the mean half-life (29.3 h versus 29.5 h). Of 142 adverse events in women and girls, headache was the most common (12 events in six subjects). Six events (two infusion-site erythema, two fatigue, one back pain, one infusion-site pain) in two subjects were considered to be possibly pdFX-related. Following the trial, pdFX was used to successfully maintain hemostasis in two subjects undergoing obstetric delivery. Conclusions: pdFX was well tolerated and effective in women and girls with FX deficiency. Although women and girls had different bleeding symptoms and sites than men and boys, their pdFX pharmacokinetic profile was comparable.

This is the most comprehensive PK study to date in subjects with hereditary FX deficiency. These results are consistent with the observed haemostatic efficacy of pdFX and provide the PK data required for the treatment of hereditary FX deficiency using pdFX replacement therapy.

PurposeThis phase 3, multicenter, open-label, randomized, two-period, crossover bioequivalence trial evaluated the safety, tolerability, and pharmacokinetics of intravenous immunoglobulins (IVIGs) Gammaplex 5% and Gammaplex 10% in 33 adults and 15 children with primary immunodeficiency diseases (PIDs).MethodsEligible adults received five Gammaplex 5% infusions followed by five Gammaplex 10% infusions, or vice versa, stratified by a 21- or 28-day dosing regimen. Pediatric subjects received five Gammaplex 10% infusions only.ResultsThe primary objective, to demonstrate the bioequivalence of Gammaplex 10% and Gammaplex 5% at the 28-day dosing interval, was met based on the Gammaplex 10%/Gammaplex 5% ratio of area under the concentration versus time curve (AUC0–28) values. Throughout the study, total immunoglobulin G trough levels were well maintained, with total values generally ≥600 mg/dL (minimum level for study inclusion). At the dosing schedules and infusion rates used in this study, safety and tolerability were comparable and acceptable in adult and pediatric PID subjects treated with Gammaplex 10% and 5%.ConclusionsIn this study, the first direct comparison of 5% IVIG and 10% IVIG products in PID subjects, the pharmacokinetic analysis demonstrated bioequivalence of Gammaplex 10% and Gammaplex 5% at the 28-day dosing interval. The Gammaplex 10% formulation was safe and well tolerated in pediatric and adult PID subjects. Based on the results from this bridging study in PID subjects, Gammaplex 10% could be expected to have a therapeutic effect similar to the licensed Gammaplex 5%, which has demonstrated efficacy and tolerability in patients with PID and idiopathic thrombocytopenic purpura.Electronic supplementary materialThe online version of this article (doi:10.1007/s10875-017-0383-9) contains supplementary material, which is available to authorized users.

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Hereditary factor X (FX) deficiency is a rare bleeding disorder more prevalent in countries with high rates of consanguineous marriage. In a prospective, open-label, multicenter phase 3 study, 25 IU/kg plasma-derived factor X (pdFX) was administered as on-demand treatment or short-term prophylaxis for 6 months to 2 years. In Turkish subjects (n=6), 60.7% of bleeds were minor. A mean of 1.03 infusions were used to treat each bleed, and mean total dose per bleed was 25.38 IU/kg. Turkish subjects rated pdFX efficacy as excellent or good for all 84 assessable bleeds; investigators judged overall pdFX efficacy to be excellent or good for all subjects. Turkish subjects had 51 adverse events; 96% with known severity were mild/moderate, and 1 (infusion-site pain) was possibly pdFX-related. These results demonstrate that 25 IU/kg pdFX is safe and effective in this Turkish cohort (ClinicalTrials.gov identifier: NCT00930176).