Plasma Derived Factor X Concentrate Has Not Induced Inhibitor Development in the Clinical Setting

Background: Hereditary factor X deficiency (HFXD) is a rare autosomal recessive bleeding disorder caused by mutations in the F10 gene on chromosome 13. Historically, patients with HFXD were treated with nonspecific plasma formulations including fresh frozen plasma and prothrombin complex concentrates. Single factor concentrates are recommended by experts for treatment if available. Plasma derived factor X (pdFX) concentrate (Coagadex®, coagulation factor X, human, Bio Products Laboratory Ltd., Elstree, UK), has been granted a marketing license in both the US (2015) and EU (2016) for use in patients with HFXD. Inhibitor development with other factor concentrates has been a concern and is tracked in clinical trials and postmarketing use.

Objectives: Data from clinical trials and postmarketing surveillance were gathered to understand the occurrence of FX inhibitor development following treatment with pdFX. The total number of patients and overall exposure is estimated to provide a denominator for inhibitor development.

Methods: pdFX has been administered in two prospective clinical trials (TEN01 and TEN02) in the prophylactic and on-demand setting. Retrospective data were collected on 15 patients within the TEN05 protocol in the same setting. pdFX has been administered in the peri-operative setting in two studies (TEN03 and TEN06). All prospective clinical trials required inhibitor testing, at minimum once every 6 months, additionally following any significant bleeding, and at study completion. Postmarketing data are available from October 2015 to June 2022.

Results: Sixteen patients, aged ≥12 years, participated in the TEN01 study and received a total of 468 infusions of pdFX. Of these, 242 infusions were administered on demand and 184 prophylactically. The mean number of infusions per patient was 29 (range 5-115). Patients received pdFX treatment for up to two years.

In the TEN02 study, all nine patients were aged <9 years old and received pdFX prophylactically. Patients were treated for six months. 665 infusions were administered during the study with a mean of 74 infusions per patient (range 50-116).

Peri-operative use of pdFX was assessed in eight patients undergoing ten procedures in the TEN03 and TEN06 studies. Duration of dosing ranged from 1 to 15 days. Two-thirds of patients in the TEN06 study were receiving pdFX prophylaxis prior to study entry.

The TEN05 study was a retrospective data collection in fifteen patients who received pdFX on a compassionate use basis. 1366 infusions were administered during the data collection period with a mean of 91 infusions per patient (range 2-492).

First approval was granted in the United States on October 20, 2015. Following the first approval, pdFX was approved in the 27 European Union Member States and the United Kingdom (UK) on March 16, 2016. It is estimated there have been over 26,000 infusions with pdFX and no inhibitors have been reported.

Conclusion: To date, after over six years use in the postmarketing setting, there have been no reports of inhibitor development with pdFX.

Patel:Bio Products Laboratory, Ltd.: Current Employment. Norton:Bio Products Laboratory, Ltd.: Current Employment. Lewandowska:Genentecch: Other: Writing support; Agios: Consultancy, Other: Writing support; Spire: Other: Instructor; Octapharma: Speakers Bureau.