Objective:
Report results of an open-label international study that collected retrospective data on compassionate use of high-purity plasma-derived FX concentrate (pdFX) in subjects with hereditary factor X (FX) deficiency (FXD).
Methods:
This study included subjects with hereditary FXD (irrespective of severity) who received compassionate use pdFX as routine prophylaxis (RP), on-demand (OD) treatment, short-term prevention, and/or perisurgical hemostatic cover. Dosing was at the investigator’s discretion and tailored to each patient. Data from date of first compassionate use dose until data cutoff (31 December 2015) were collected retrospectively.
Summary:
All 15 enrolled subjects from 12 study centers received ≥1 pdFX dose for compassionate use. Of these, 13 subjects were aged ≥12 years (mean, 22.8 years) and 2 were aged <12 years, 8 (53.3%) were female, 12 (80.0%) were white, 3 (20.0%) were Asian. All subjects had moderate or severe FXD (FX activity [FX:C] <5 IU/dL).Of the 15 patients, 7 received only RP, 7 received only OD, and 1 alternated between OD and RP. The 8 subjects on RP received a total of 1239 RP infusions (mean, 154.9 infusions/subject, range 39–492), with a mean dose/infusion/subject of 32.5 IU/kg. The 2 subjects aged <12 years received larger RP doses than the 6 older subjects (mean doses/infusion/subject of 51.1 vs 26.3 IU/kg).Twelve subjects (8 OD, 4 RP; all aged ≥12 years) reported 88 bleeds (34 minor, 7 major, and 47 not rated); 37 bleeds were menorrhagic, 28 were traumatic, 17 were spontaneous, 4 were other, and 2 had unknown cause. pdFX efficacy was rated as effective for the 79 bleeds (including 1 subdural hematoma) treated with OD pdFX. Mean pdFX dose was 22.2 IU/kg/infusion/subject, with a mean of 9.5 infusions/subject to treat a bleed. More bleeds occurred in the OD than in the RP population.Two subjects underwent 1 dental procedure each, with only 1 presurgical pdFX dose required per patient; a third surgery, a portacath insertion, required 6 infusions to prevent postoperative bleeding. Two successful pregnancies/childbirths were also reported, with no abnormal bleeding complications or efficacy/safety concerns reported.The mean duration of compassionate use was 87.6 weeks for the 15 subjects, with a range of 15–211 weeks (0.3–4.0 years). Over the 1373 infusions administered across 25.2 subject-years, investigators rated overall pdFX efficacy as excellent in 14 (93.3%) subjects and good in 1 (6.7%) subject. No adverse drug reactions, safety concerns, infusion site reactions, tolerability issues, or inhibitor development were reported during pdFX compassionate use.
Conclusions:
The higher bleed rate in OD versus RP use and the treatment duration (up to 4 years) support the efficacy and safety of pdFX demonstrated in prospective clinical studies and its continued use in the treatment of subjects with hereditary FXD.