Research Studies

Dr. Laura Sommerville graduated cum laude from Messiah College and then obtained her MS and PhD degrees in cellular and molecular biology from Temple University. Her graduate work and doctoral dissertation produced several awards and publications in peer reviewed publications. She has been a postdoctoral fellow in the laboratory of Dr. Maureane Hoffman at Duke University since July 2014. Dr. Sommerville's 2015 JGP research fellowship award project is on understanding the loss of perivascular tissue factor during angiogenesis in hemophilia.

Background:

A high-purity plasma-derived FX concentrate (pdFX) has been developed for treatment of hereditary FX deficiency, an autosomal recessive disorder.

Aim:

This post hoc analysis describes the pharmacokinetics, safety, and efficacy of pdFX in 10 women and girls with hereditary FX deficiency.

Methods:

In this open-label study, subjects (10 women/girls, 6 men/boys) aged ≥12 years with moderate or severe FX deficiency (basal plasma FX activity ≤5 IU/dL) were enrolled and received 25 IU/kg pdFX for on-demand treatment of bleeding episodes or preventative use for up to 2 years. All subjects provided informed consent and the protocol was approved by appropriate independent ethics committees.

Results:

Nine women and girls had severe and 1 had moderate FX deficiency, were aged 25.5 (median; range 14–58) y, and received a total of 267 pdFX infusions (178 for on-demand and 89 for preventative treatment). Men and boys (5 severe and 1 moderate FX deficiency) received a total of 159 pdFX infusions (64 on-demand; 95 preventative). The mean number of infusions per subject per month was higher among women and girls (2.48) than males (1.62). The mean pdFX incremental recovery was similar between women/girls and men/boys (2.05 vs 1.91 IU/dL per IU/kg, respectively), as was mean half-life (29.3 and 29.5 h, respectively). Among women and girls, 132 assessable bleeding episodes (61 heavy menstrual bleeding, 47 joint, 15 muscle, and 9 other) were treated with pdFX. Women and girls reported a treatment success rate (ie, subject rating of “excellent” or “good” response to pdFX) of 98%, comparable to the 100% treatment success rate among men and boys. After study completion, 2 subjects received pdFX for hemostatic cover during obstetric delivery. Additional infusion, bleed, and safety data will be presented.

Conclusion:

These results show that, in women and girls with moderate or severe hereditary FX deficiency, who experience reproductive tract and other bleeding events, pdFX was safe and effective. The pharmacokinetic profile of pdFX in women and girls was similar to that of men and boys.

Funding: Bio Products Laboratory

Objectives:

Contemporary real-world data on units dispensed and expenditures associated with use of standard half-life (SHL) and extended half-life (EHL) factor VIII replacement products in U.S. patients with hemophilia A are limited. This exploratory analysis of real-world administrative data was conducted to determine units dispensed and factor replacement product-related direct expenditures associated with currently marketed recombinant SHL and EHL FVIII products, and to examine inter-product switches.

Methods:

De-identified claims data from the commercially available Truven Health MarketScan® Research US claims database were used to identify direct expenditures and number of international units (IUs) dispensed for all patients with a diagnosis code of ICD-9 286.0/ICD-10 D66 who used SHL (SHL group) and/or EHL (EHL group) during the study period from Aug 1, 2014 to Jan 31, 2017. Data on switching from an SHL to an EHL factor VIII replacement product were captured in patients with continuous pharmacy enrollment for whom claims data were available for at least 1 calendar quarter and up to 1 year before and after the index date of a product switch. Descriptive statistics were used to analyze results.

Summary:

Cross-sectional analysis.
The SHL group comprised 415 patients, among whom six distinct SHL FVIII products had been dispensed, and the EHL group included 91 patients, among whom two EHL FVIII products had been dispensed. The age distribution of the two groups was similar (p =0.57), although the proportion of patients under 18 years of age was somewhat higher in the SHL group than in the EHL group (46.9% vs 36.2%). The median FVIII product dispensation per calendar quarter was 46,409 IU (IQR, 12,760-87,670 IU) (SHL) versus 67,375 IU (IQR, 50,524-98,264 IU) (EHL). Median expenditures per calendar quarter were substantially higher for EHL ($135,519; IQR, $100,320-186,557) than for SHL ($61,152; IQR, $18,593-115,845).

Switching analysis.
Of the patients in the EHL group, 29 had switched from one of three SHL FVIII products to one of two EHL FVIII products during the study period. The total median IU dispensation per calendar quarter increased following the switch from 58,598 IU (pre-switch, SHL) to 68,036 IU (post-switch, EHL; 16% increase), as did the factor-related expenditure ($76,553, SHL, versus $141,101, EHL; 84% increase).

Conclusion:

Real-world data derived from a large claims database, unadjusted for treatment regimen or hemophilia severity, reveal marked differences in metric units and expenditures among hemophilia A patients to whom SHL and/or EHL products were dispensed. Switching from an SHL to an EHL FVIII replacement product was associated with a substantial increase in units dispensed and factor expenditures. Further analyses, incorporating essential clinical characteristics, should be explored.