Abstract
Abstract 1190
The goal of this study was to evaluate the efficacy and safety of two prophylaxis regimens of reformulated recombinant coagulation factor IX (rFIX-R), 100 IU/kg once weekly and 50 IU/kg twice weekly, compared with on-demand treatment in subjects with severe hemophilia B.
Pharmacokinetic data were collected for 47 subjects aged 6 to 64 years with severe hemophilia B. Factor IX activity (FIX:C) measurements were made immediately before rFIX-R administration and at 0.5 hours post-administration of either 100 IU/kg or 50 IU/kg doses, to assess recovery before the initiation of each weekly regimen. Another FIX:C sample was collected at least 72 hours after dosing during each regimen. All samples were analyzed at local laboratories.
The mean prophylactic doses of rFIX-R administered were 86 ± 29 IU/kg in the 100 IU/kg once-weekly group and 53 ± 14 IU/kg in the 50 IU/kg twice-weekly group. The treatment comparison between the two prophylaxis regimens for annualized bleeding rate was not significant (LS mean = 2.0; 95% CI, −1.2 – 5.2; n=43), although both were significantly different from the on-demand treatment period (both, P<.0001). The number of new bleeding events in each group was 51 and 35, respectively, with only 12/51 new hemorrhages occurring within 72 hours of dosing in the 100 IU/kg once-weekly group compared with 29/35 in the 50 IU/kg twice-weekly group. The pharmacokinetic results are shown in the Table.
| C0hr(IU/dL) | C0.5hr(IU/dL) | Recovery (IU/dL/IU/kg) | Ctrough(IU/dL) | |
|---|---|---|---|---|
| 50 IU/kg (n=41) | ||||
| Mean | 3.57 | 49.9 | 0.93 | 6.38 |
| SD | 3.11 | 16.1 | 0.31 | 4.63 |
| Min | 0 | 0.6 | 0.002 | 0.3 |
| Median | 3.0 | 49.9 | 0.9 | 5.0 |
| Max | 14.0 | 83.0 | 1.51 | 27.0 |
| 100 IU/kg (n=43) | ||||
| Mean | 3.10 | 91.5 | 0.91 | 6.31 |
| SD | 2.19 | 28.9 | 0.35 | 5.41 |
| Min | 0 | 1.12 | 0.011 | 0.04 |
| Median | 2.7 | 95.1 | 0.93 | 4.9 |
| Max | 10.0 | 146 | 2.32 | 24.0 |
| C0hr(IU/dL) | C0.5hr(IU/dL) | Recovery (IU/dL/IU/kg) | Ctrough(IU/dL) | |
|---|---|---|---|---|
| 50 IU/kg (n=41) | ||||
| Mean | 3.57 | 49.9 | 0.93 | 6.38 |
| SD | 3.11 | 16.1 | 0.31 | 4.63 |
| Min | 0 | 0.6 | 0.002 | 0.3 |
| Median | 3.0 | 49.9 | 0.9 | 5.0 |
| Max | 14.0 | 83.0 | 1.51 | 27.0 |
| 100 IU/kg (n=43) | ||||
| Mean | 3.10 | 91.5 | 0.91 | 6.31 |
| SD | 2.19 | 28.9 | 0.35 | 5.41 |
| Min | 0 | 1.12 | 0.011 | 0.04 |
| Median | 2.7 | 95.1 | 0.93 | 4.9 |
| Max | 10.0 | 146 | 2.32 | 24.0 |
C indicates plasma concentration.
The number (%) of observed trough plasma concentrations (Ctrough) that fell into the mild (>5%) range for hemophilia were 18 (45%) and 19 (48%) for the r-FIX-R 100 IU/kg once-weekly and 50 IU/kg twice-weekly groups, respectively. However, the severe phenotype was observed in 4 (10%) and 3 (7%) subjects, respectively.
The pharmacokinetics of r-FIX-R are dose proportional. The C0.5hr increased in proportion to the dose administered. Recovery was consistent between the two prophylaxis regimens. Both regimens provided similar therapeutic results for Ctrough. The apparent difference in time after dose of new bleeding events between the 2 regimens is intriguing and deserves further study.
Korth-Bradley:Pfizer Inc: Employment. Valentino:Inspiration Bioscience: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; CSL Behring: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center; Pfizer: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center; NovoNordisk: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; GTC Biotherapeutics: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; Bayer Healthcare: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; Baxter Bioscience: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center, Honoraria; Biogen: Educational Grants on behalf of Dr. Valentino for Rush University Medical Center; Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees, Past-President. Rendo:Pfizer Inc: Employment. Shafer:Pfizer Inc: Employment. Smith:Pfizer Inc: Employment. Baumann:Pfizer Inc: Employment. Charnigo:Pfizer Inc: Employment.
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