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 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.