Efficacy and Safety
Bleed control for when you need it—
Proven bleed control
of bleeds were successfully controlled with 1 or 2 infusions in a clinical study
Among 53 adults and adolescents who were treated on demand for 187 bleeding episodes:
- 71% of responses were rated excellent or good
- 24% of responses were rated moderate
- 3% were rated no response
- 3% were not rated
Rating scale: Excellent: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered. Good: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode. Moderate: Probable or slight improvement starting within 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode. No response: No improvement at all between infusions or during the 24-hour interval following an infusion, or condition worsens.
Study design: Open-label study of PTPs (mean age, 27.7 years; range, 12-60 years) with severe or moderately severe hemophilia A (factor VIII concentration [FVIII:C] ≤2%; ≥150 previous exposure days) given XYNTHA 3 times per week (30 ± 5 IU/kg; N=94) and on demand (investigator-determined dose; n=53 [187 bleeding episodes]). Results reported here for 3-times-per-week administration are based on 89 patients accruing ≥50 exposure days to XYNTHA.
Proven prophylactic bleed protection
In adolescents and adults on prophylaxis
of PTPs reported no bleeding (N=94)
- 1.9 median annualized bleeding rate (ABR) (interquartile range [IQR], 0.00-5.56)*
- Zero median ABR for patients who experienced spontaneous (IQR, 0.00-2.14) or traumatic (IQR, 0.00-2.14) bleeds
In children on prophylaxis
of PTPs reported no bleeding (N=8)
- 0.6 median ABR (IQR, 0.00-2.17)*
- Zero median ABR for patients who experienced spontaneous (IQR, 0.00-0.56) or traumatic (IQR, 0.00-1.79) bleeds
*IQR represents the middle 50% of ABRs when ordered from lowest to highest.
Study design: Two completed open-label studies compared the ABRs of 102 subjects (94 subjects ≥12 years of age and 8 subjects <12 years of age) who received XYNTHA for routine prophylaxis with those who used on-demand treatment alone. XYNTHA was administered for routine prophylaxis at a dose of 25 ± 5 IU/kg every other day (in subjects <12 years of age) or 30 ± 5 IU/kg administered 3 times weekly (in subjects 12 years of age or older), with provisions for dose escalation based on prespecified criteria (over a 4-week period, 2 spontaneous bleeds into a major joint and/or target joint, or 3 or more spontaneous bleeding episodes in any location). Among these 102 subjects, 7 dose escalations were prescribed for 6 subjects.
ACTIVE IS going to my daughter's field hockey game, doing some projects at home, and running soccer drills with my son this weekend.
Demonstrated bleed control during and after surgery
of bleed control ratings were excellent or good during and up to 1 hour after surgery
In the open-label clinical study of 30 adults and adolescents:
- 72% of responses were rated excellent
- 28% of responses were rated good
Surgical prophylaxis study: Open-label study (n=30) for surgical prophylaxis in PTPs with severe or moderately severe hemophilia A (FVlll:C ≤2%) undergoing major surgical procedures. Results reported here for 25 patients who received at least 1 dose of XYNTHA replacement therapy over at least 6 days post surgery.
Efficacy responses were assessed as follows: Excellent: Achieved hemostasis comparable to that expected after similar surgery in a patient without hemophilia; Good: Prolonged time to hemostasis, with somewhat increased bleeding compared with that expected after similar surgery in a patient without hemophilia; end of initial postoperative period was date of discharge or postoperative day 6, whichever occurred later.
ACTIVE IS swim practice on Saturday, kickball with my friends at recess, and riding my scooter after school.
Proven bleed control in adolescents and children
Bleed control in adolescents (12 to <17 years)
of bleeds were controlled with 1 or 2 on-demand infusions in a clinical study
In a clinical study, 66 bleeding episodes were treated on demand with XYNTHA:
- 58% of responses were rated excellent or good
- 36% of responses were rated moderate
- 6% were not rated
Study design: The open-label study of PTPs with severe or moderately severe hemophilia A (FVIII:C ≤2%; ≥150 previous exposure days) included 18 adolescents, 12 to <17 years of age, who received XYNTHA for on-demand and follow-up treatment. Results reported here for 10 patients (66 bleeding episodes). The median dose/infusion was 47 IU/kg.
Bleed control in children (<16 years)
of bleeds were controlled with 1 or 2 on-demand infusions of XYNTHA
In a clinical study, 562 bleeding episodes were treated on demand with XYNTHA:
- 94% of responses were rated excellent or good
- 5% of responses were rated moderate
- 0.4% were rated no response
- 0.2% were not rated
Study design: Children (n=50) <16 years of age with severe or moderately severe hemophilia A (FVIII:C ≤2% and with at least 20 prior exposure days) received XYNTHA for on-demand and follow-up treatment. Results reported here for 38 patients (562 bleeding episodes). The median dose/infusion was 28 IU/kg.
In comparison to the pharmacokinetic parameters reported in adults, children have shorter half-lives, larger volumes of distribution, and lower recovery of factor VIII after XYNTHA administration. Larger or more frequent doses may be required to account for the observed differences in pharmacokinetic parameters.
Demonstrated in clinical studies to have a low inhibitor rate
The development of factor VIII inhibitors was evaluated in 5 clinical studies of 167 adult and pediatric PTPs with ≥50 exposure days:
- Across all studies, 2 adult and 2 pediatric PTPs (2.4%) developed FVIII inhibitors
- In the surgical study of 30 patients, one low-titer, persistent inhibitor and one transient, false-positive inhibitor were without significance
- Results were not clinically significant, and these patients did not require treatment