1. Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A
by Barbara A. Konkle, Oleksandra Stasyshyn, Pratima Chowdary, David H. Bevan, Tim Mant, Midori Shima, Werner Engl, Jacqueline Dyck-Jones, Monika Fuerlinger, Lisa Patrone, Bruce Ewenstein, and Brigitt Abbuehl
Blood
Volume 126(9):
August 27, 2015
©2015 by American Society of Hematology

2. Both clinical studies were open label with no randomization.
Both clinical studies were open label with no randomization. In the phase 1 study (A), the sequence of treatment was Advate first, followed by BAX 855 for each subject in each cohort. Nine subjects in the 30 IU/kg group were treated first. After review of the data from the first cohort and approval by the Data Monitoring Committee, treatment of 10 subjects in the 60 IU/kg group commenced. Only 1 treated subject was excluded from the PK analysis set as a result of a bleeding episode within 4 days of infusion. In the pivotal study (B), treatment assignment depended on the subjects’ prior treatment: Subjects previously receiving prophylaxis were assigned to the prophylaxis group. The first 17 subjects who previously received on-demand treatment were assigned to the on-demand group, then additional subjects were assigned to the prophylaxis arm. The PK subset comprised 26 subjects in the prophylaxis group. Twelve subjects discontinued during prophylaxis: 1 for a surgical procedure, 1 because of screen failure, 2 because of discontinuation by the subject, 4 because of an adverse event, and 4 for protocol violation.
Barbara A. Konkle et al. Blood 2015;126:
©2015 by American Society of Hematology

3. In a descriptive analysis of 118 subjects in the PPAS, the median (Q1; Q3) and mean (SD) ABRs were computed for the prophylactic group vs the on-demand group, for all, joint and spontaneous bleeding episodes.
In a descriptive analysis of 118 subjects in the PPAS, the median (Q1; Q3) and mean (SD) ABRs were computed for the prophylactic group vs the on-demand group, for all, joint and spontaneous bleeding episodes.
Barbara A. Konkle et al. Blood 2015;126:
©2015 by American Society of Hematology

4. Mean annualized bleeding rates (ABRs) in subjects who received prophylactic treatment with BAX 855 are depicted by target joint status at screening.
Mean annualized bleeding rates (ABRs) in subjects who received prophylactic treatment with BAX 855 are depicted by target joint status at screening. There were 101 subjects in the PPAS, including 69 subjects with no target joints at screening and 32 subjects with target joints at screening. Median ABR values are also presented.
Barbara A. Konkle et al. Blood 2015;126:
©2015 by American Society of Hematology

5. The 1-stage clotting assay data shown represent median (Q1; Q3) FVIII plasma levels and the nominal sampling times as indicated on the linear x axis.
The 1-stage clotting assay data shown represent median (Q1; Q3) FVIII plasma levels and the nominal sampling times as indicated on the linear x axis. BAX 855 (dashed gray line) demonstrated an extended half-life compared with Advate (solid black line). The PK assessments shown were conducted in 26 subjects at their first exposure to BAX 855.
Barbara A. Konkle et al. Blood 2015;126:
©2015 by American Society of Hematology

6. Scatterplots and Spearman rank correlation analysis of T1/2 are displayed.
Scatterplots and Spearman rank correlation analysis of T1/2 are displayed. The T1/2 of BAX 855 was positively correlated to preinfusion VWF antigen plasma concentrations (A) and negatively correlated with ABR (B). The T1/2 values for these analyses were derived from PK assessments conducted in 26 subjects at their first exposure to BAX 855, using the 1-stage clotting assay. The circles represent individual subject values. An apparent outlier appears in A for a subject with a very low T1/2 and a high ABR; it is of note that no inhibitory antibodies to FVIII were detected in this subject.
Barbara A. Konkle et al. Blood 2015;126:
©2015 by American Society of Hematology