patients from mean (SD) of 2.2 (0.49) at baseline to 3.3 (0.60) and 3.4 (0.53) mg/dL at week 40 and week 64.
In Study 2, CRYSVITA increased mean (SD) serum phosphorus levels from 2.5 (0.28) mg/dL at baseline to 3.5 (0.49) mg/dL at week 40.
Figure 1:Serum Phosphorus Levels (mg/dL) Over Time in Children 5-12 Years Receiving CRYSVITA Every 2 Weeks in Study 1a
Figure 1:Serum Phosphorus Levels (mg/dL) Over Time in Children 5-12 Years Receiving CRYSVITA Every 2 Weeks in Study 1a
Serum Phosphorus Level (mg/dL) (Mean ±SD) - Q2W. The dotted line represents the lower limit of normal (3.2 mg/dL) for patients in Study 1.
Radiographic eva luation of Rickets
Radiographs from 52 CRYSVITA-treated XLH patients in Study 1 and 13 patients in Study 2 were examined to assess XLH-related rickets using the 10-point Thacher Rickets Severity Score (RSS) and the 7-point Radiographic Global Impression of Change (RGI-C). The RSS score is assigned based on images of the wrist and knee from a single timepoint, with higher scores indicating greater rickets severity. The RGI-C score is assigned based on side-by-side comparisons of wrist and knee radiographs from two timepoints, with higher scores indicating greater improvement in radiographic evidence of rickets. A RGI-C score of +2.0 was defined as radiographic evidence of substantial healing.
In Study 1, baseline mean (SD) RSS total score was 1.9 (1.17) in patients receiving CRYSVITA every two weeks. After 40 weeks of treatment with CRYSVITA, mean total RSS decreased from 1.9 to 0.8 (see Table 6). After 40 weeks of treatment with CRYSVITA, the mean RGI-C Global score was +1.7 in patients receiving CRYSVITA every two weeks. Eighteen out of 26 patients achieved an RGI-C score of ≥ +2.0. These findings were maintained at week 64 as shown in Table 6.
In Study 2, baseline mean (SD) total RSS was 2.9 (1.37) in 13 patients. After 40 weeks of treatment with CRYSVITA, mean total RSS decreased from 2.9 to 1.2 and the mean (SE) RGI-C Global score was +2.3 (0.08). All 13 patients achieved a RGI-C global score ≥ +2.0. The mean (SE) lower limb deformity as assessed by RGI-C, using standing long leg radiographs, was +1.3 (0.14) (see Table 6).
Table 6: Rickets Response in Children 1-12 Years Receiving CRYSVITA Every 2 Weeks in Study 1 and Study 2
Endpoint
Timepoint CRYSVITA Every 2 Weeks
Study 1
(N=26) Study 2
(N=13)
RSS Total Score
Baseline Mean (SD) 1.9 (1.17) 2.9 (1.37)
LS Mean change from baseline in total scorea (reduction indicates improvement) with 95% CI
Week 40 -1.1 (-1.28, -0.85) -1.7 (-2.03, -1.44)
Week 64 -1.0 (-1.2, -0.79)
RGI-C Global Score
LS Mean scorea (positive indicates healing) with 95% CI
Week 40
+1.7 (+1.48, +1.84) +2.3 (+2.16, +2.51)
Week 64 +1. 6 (+1.34, +1.78)
The estimates of LS means and 95% CI (confidence interval) are from the generalized estimation equation model accounting for baseline RSS, visits and regimen and its interaction for Study 1 and from ANCOVA model accounting for age and baseline RSS for Study 2.
Serum Alkaline Phosphatase Activity
For Study 1, mean (SD) serum total alkaline phosphatase activity was 462 (110) U/L at baseline and decreased to 354 (73) U/L at Week 64 (-23%, p < 0.0001) in the patients who received CRYSVITA every 2 weeks.
For Study 2, mean (SD) serum total alkaline phosphatase activity was 549 (194) U/L at baseline and decreased to 335 (88) U/L at Week 40 (mean change: -36%).
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