On-demand treatment in adolescents and adults
Ninety-four (94) subjects, 12 years of age and older received XYNTHA in a routine prophylaxis treatment regimen with on-demand treatment administered as clinically indicated. All 94 subjects were treated with at least one dose and all are included in the intent-to-treat (ITT) population. Eighty-nine (89) subjects accrued ≥50 EDs. Median age for the 94 treated subjects was 24 years (mean 28 and min-max: 12–60 years).
Of these 94 subjects, 30 evaluable subjects participated in a randomized crossover pharmacokinetics substudy. Twenty-five (25/30) of these subjects with FVIII:C ≤1% completed both the first (PK1) and the second (PK2) pharmacokinetic assessments [see Clinical Pharmacology (12.3)].16
Fifty-three subjects (53/94) received XYNTHA on-demand treatment for a total of 187 bleeding episodes. Seven of these bleeding episodes occurred in subjects prior to switching to a prophylaxis treatment regimen. One hundred ten of 180 bleeds (110/180 or 61%) occurred ≤48 hours after the last dose and 39% (70/180 bleeds) occurred >48 hours after the last dose. The majority of bleeds reported to occur ≤48 hours after the last prophylaxis dose were traumatic (64/110 bleeds or 58%). Forty-two bleeds (42/70 or 60%) reported to occur >48 hours after the last prophylaxis dose were spontaneous. The on-demand treatment dosing regimen was determined by the investigator. The median dose for on-demand treatment was 31 IU/kg (min-max: 6–74 IU/kg) and the median exposure per subject was 3 days (min-max: 1–26).
The majority of bleeding episodes (173/187 or 93%) resolved with 1 or 2 infusions (Table 5). One hundred thirty-two of 187 bleeding episodes (132/187 or 71%) treated with XYNTHA were rated excellent or good in their response to initial treatment, 45 (24%) were rated moderate. Five (3%) were rated no response, and 5 (3%) were not rated.
Table 5: Summary of Response to Infusions to Treat New Bleeding Episode by Number of Infusions Needed for ResolutionResponse to 1st Infusion | Number of Infusions (%) 1 | Number of Infusions (%) 2 | Number of Infusions (%) 3 | Number of Infusions (%) 4 | Number of Infusions (%) >4 | Total Number of Bleeds |
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|
Excellent* | 42 (95.5) | 2 (4.5) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 44 |
Good† | 69 (78.4) | 16 (18.2) | 3 (3.4) | 0 (0.0) | 0 (0.0) | 88 |
Moderate‡ | 24 (53.3) | 16 (35.6) | 2 (4.4) | 0 (0.0) | 3 (6.7) | 45 |
No Response§ | 0 (0.0) | 0 (0.0) | 2 (40.0) | 2 (40.0) | 1 (20.0) | 5 |
Not Assessed | 4 (80.0) | 0 (0.0) | 0 (0.0) | 1 (20.0) | 0 (0.0) | 5¶ |
Total | 139 (74.3) | 34 (18.2) | 7 (3.7) | 3 (1.6) | 4 (2.1) | 187 |
Of the 94 subjects described above, in the first completed open-label safety and efficacy study of XYNTHA, 18 were adolescent subjects 12 to <17 years of age with severe to moderately severe hemophilia A (FVIII:C ≤2%). Ten (10) of these adolescent subjects, received XYNTHA for the on-demand treatment of 66 bleeding episodes, with the majority of the bleeding episodes (63/66 or 95%) resolving with 1 or 2 infusions. The response to infusion was rated on a pre-specified 4 point hemostatic efficacy scale. Thirty-eight (38) of 66 bleeding episodes (58%) were rated excellent or good in their response to initial treatment, 24 (36%) were rated as moderate, and 4 (6%) were not rated. The median dose per on demand infusion was 47 IU/kg (min-max: 24–74).
On-demand treatment in children
Additional data for 50 subjects are available from a second safety and efficacy study of XYNTHA in children (≤12 years of age) with severe to moderately severe hemophilia A (FVIII:C ≤2%). Of the 50 subjects, 38 subjects received XYNTHA for on-demand and follow-up treatment of 562 bleeding episodes with the majority of the bleeding episodes (518/562 or 92%) resolving with 1 or 2 infusions. Of 559 bleeding episodes treated with XYNTHA with response assessments to the first infusion, 526 (94%) were rated excellent or good in their response to initial treatment and 27 (5%) were rated as moderate. The median dose per on-demand infusion was 28 IU/kg (min-max: 10–92).