Table 3.
Changes from baseline in primary and selected secondary pharmacodynamic outcomes in open-label phase 2 trials of subcutaneous burosumab in pediatric patients aged 1–4 or 5–12 years with X-linked hypophosphatemia
| Outcome | Burosumab every 2 wks in pts aged 1–4 years (n = 13) [5, 9, 16] | Dose-finding trial in pts aged 5–12 years [5, 8] | |
|---|---|---|---|
| Burosumab every 2 wks (n = 26) | Burosumab every 4 wks (n = 26) | ||
| Thacher Rickets Severity Score a (primary endpoint) | |||
| Mean score at BL (range) | 2.9 | 1.9 (0–4.5) | 1.7 (0–3.0) |
| Mean score at wk 40 (LSM change from BL; 95% CI) | 1.2 (− 1.7; − 2.0 to − 1.4)*** | 0.8 (− 1.1; − 1.3 to − 0.9)** | 1.1 (− 0.7)** |
| Mean score at wk 64 (LSM change from BL; 95% CI) | 0.8 (− 1.0; –1.2 to − 0.79) | 0.9 (− 0.8) | |
| Radiographic Global Impression of Change global score b | |||
| LSM change from BL in score at wk 40 (95% CI) | 2.3 (2.2–2.5)** | 1.7 (1.5–1.8) | 1.5 |
| LSM change from BL in score at wk 64 (95% CI) | 1.6 (1.4–1.8) | 1.6 | |
| Fasting serum phosphorus level (LLN 3.2 mg/dL) | |||
| Mean at BL (mg/dL) | 2.5 | 2.4 | 2.3 |
| Mean at wk 40 (mg/dL) | 3.5 | 3.4** | 2.8**c |
| Fasting TmP/GFR (LLN 3.42 mg/dL) | |||
| Mean at BL (mg/dL) | 2.2 | 2.0 | |
| Mean at wk 40 (mg/dL) | 3.3** | 3.0**c | |
| Fasting serum 1,25-dihydroxyvitamin D levels (LLN 43 pg/mL) | |||
| Mean at BL (pg/mL) | 41.3 | 41.4 | |
| Mean at wk 40 (pg/mL) | 70**c | 60**c | |
| Fasting serum total ALP activity (ULN 385 U/L) | |||
| Mean at BL (U/L) | 549 | 462 | 456 |
| Mean at wk 40 (U/L) | 335*** | 380c | 405c |
| Mean at wk 64 (U/L) | 354** | 385*c | |
ALP alkaline phosphatase, BL baseline, LLN lower limit of normal, LSM least-squares mean (estimated using models that accounted for Rickets Severity Score and other variables at BL), TmP/GFR maximum rate of tubular phosphate reabsorption/glomerular filtrate rate, ULN upper limit of normal, wk week
*p = 0.002, **p < 0.001, ***p < 0.0001 vs BL
aScores range from 0 to 10, with higher scores indicating more severe disease (blinded assessment of prespecified radiographic abnormalities at the wrist and knee at a single timepoint)
bScores range from − 3 to + 3, with negative scores indicating worsening, 0 no change, and positive scores healing (blinded side-by-side assessment of radiographs of the wrist and knee obtained at two timepoints)
cValue estimated from a figure