Authors of an article published recently in the Journal of Thrombosis and Haemostasis (JTH) looked at the treatment of individuals with factor X deficiency (FX) with a human plasma-derived concentrate (pdFX). FX is one of the rarer bleeding disorders with an estimated incidence of 1 in 500,000 to 1 in a million and though they represent a very small patient population the symptoms associated with FX are no less problematic, especially if not properly treated.
Individuals with FX can experience any number of symptoms depending on the disease severity, including nose bleeds, easy bruising, bleeding after trauma or surgery, joint bleeds, excessive umbilical cord bleeding, intramuscular bleeds and a high risk for intracranial hemorrhaging in infants. On top of this, females with FX often encounter additional symptoms and complications including menorrhagia (heavy menstrual bleeding), first trimester miscarriage and post-partum hemorrhaging. The authors of the JTH article, led by Roshni Kulkarni, MD, were therefore particularly interested in affected females.
Dr. Kulkarni is Professor Emerita of Pediatric Hematology/Oncology in the Department of Pediatrics and Human Development at Michigan State University. She is also the Director of the Center for Bleeding and Clotting Disorders in East Lansing, MI. Kulkarni and her fellow authors focused on pdFX efficacy, safety and pharmacokinetics (PKs), which indicate the concentration and duration of a drug’s effect in the body.
Historically, available FX treatment options were limited to fresh-frozen plasma or plasma-derived prothrombin complex concentrates, which are plasma products containing a combination of vitamin K-dependent proteins. This changed in October 2015 when the U.S. Food and Drug Administration (FDA) approved a high purity pdFX for individuals aged 12 and older with hereditary FX for on-demand treatment and control of bleeding episodes, and for perioperative management of bleeding in patients with mild hereditary FX.
The FDA approval was based on a successful multi-center and multinational phase 3 clinical study which enrolled 16 participants, 10 of which were females who manifested severe and frequent symptoms – the authors conducted a “post hoc” assessment of this group. Post hoc assessments are not pre-planned, rather they are considered an additional/supplementary analysis of study results.
The study included 10 females between the ages 14-58 years who, in sum, received 267 pdFX infusions. Investigators observed that monthly infusions per subject were higher among women and girls (2.48) than among men and boys (1.62). Female participants were treated with pdFX for 132 “assessable” bleeding episodes including 61 heavy menstrual bleeds, 47 joint bleeds, 15 muscle bleeds, and nine other bleeds. The results showed a comparable 98% treatment success rate in females, versus 100% in males. PK also compared favorably when compared to the males enrolled. Study data also showed that pdFX was used to effectively sustain hemostasis in two participants who had undergone obstetric delivery. Of 142 adverse events (AE) in females, the majority (95.1%) were reported as mild or moderate. Headache was the most common AE.
Despite the study’s modest size investigators emphasized the value of clinical data demonstrating efficacy of a targeted therapy in this group. “Because this disorder is rare in the general population, this post hoc analysis is limited by a small sample size of patients with severe FX deficiency; however, this analysis remains important, as it provides valuable information on the symptoms and required treatment for this vulnerable population,” noted the authors.
Kulkarni R, James, 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. Journal of Thrombosis and Haemostasis. 2018 May; 16(5): 849-857.