Table 4.
Changes from baseline in key secondary and other outcomes with subcutaneous burosumab 1.0 mg/kg every 4 weeks (n = 68) vs placebo (n = 66) in adults with X-linked hypophosphatemia in a 48-week study (double-blind and extension phases)
| Outcome | Double-blind phase (wks 0–24) [5, 13] | Open-label extension phase (wks 25–48) [19, 20] | |
|---|---|---|---|
| Burosumab vs placebo | Continuous burosumab | Placebo → burosumab | |
| BPI worst pain a | |||
| LSM change from BL in score at wk 24 | − 0.79 vs − 0.32 (LSM TD − 0.46) | ||
| LSM change from BL in score at wk 48 | − 1.1†† | − 1.5†† | |
| WOMAC physical function subscale score b | |||
| LSM change from BL in score at wk 24 | − 3.11 vs 1.79 (LSM TD − 4.90) | ||
| LSM change from BL in score at wk 48 | − 7.8† | − 6.4† | |
| WOMAC stiffness subscale score c | |||
| LSM change from BL in score at wk 24 | − 7.87 vs 0.25 (LSM TD − 8.12*) | ||
| LSM change from BL in score at wk 48 | − 16.0†† | − 15.3†† | |
| Fx/PFx healing | |||
| % of pts with active Fx/PFx at BL (no. of Fx/PFx) | 47.1 vs 57.6 (65 vs 91) | ||
| % of Fx/PFx fully healed at wk 24 | 43.1 vs 7.7 (OR 16.8**) | ||
| % of Fx/PFx fully healed at wk 48 | 63 | 35 | |
| Fasting serum phosphate (normal range 2.5–4.5 mg/dL) | |||
| Mean at BL (mg/dL) | 2.0 vs 1.9 | ||
| Mean at midpoint of dose interval (wks 2–22) [mg/dL] | 3.2 vs 2.1 | ||
| Mean at end of the dosing interval (wks 4–24) [mg/dL] | 2.7 vs 2.0 | ||
| Mean at midpoint of dose interval at wk 46 (mg/dL) | 3.0 | 3.0 | |
| Mean at end of dose interval at wk 48 (mg/dL) | 2.4 | 2.5 | |
| Fasting TmP/GFR (normal range 2.5–4.2 mg/dL) | |||
| Mean at BL (mg/dL) | 1.7 vs 1.6 | ||
| Mean at wk 22 (peak effect) [mg/dL] | 2.7 vs 1.7 | ||
| Mean at wk 24 (trough effect) [mg/dL] | 2.2 vs 1.7 (LSM TD 0.43**) | ||
| Fasting serum 1,25-dihydroxyvitamin D levels (normal range 18–72 pg/mL) | |||
| Mean at BL (pg/mL) | 32.4 vs 33.5 | ||
| Mean at wk 22 (peak effect) [pg/mL] | 57.0 vs 34.9 (LSM TD 22.7**) | ||
BL baseline, BPI Short-Form Brief Pain Inventory, F/PF fracture/pseudofracture, LSM least-squares mean, OR odds ratio, pts patients, Placebo → burosumab, switch from placebo in double-blind phase to burosumab in extension phase (24 wks treatment with burosumab), TD treatment difference, mP/GFR maximum rate of tubular phosphate reabsorption/glomerular filtrate rate, wk week, WOMAC Western Ontario and McMaster Osteoarthritis Index
*p = 0.0012, **p < 0.001 vs placebo; † p < 0.001, †† p < 0.0001 vs BL
aScores range from 0 to 10, with a decrease from BL indicating less pain
bScore ranges from 0 to 68, with a decrease from BL indicating better physical function
cScores range from 0 to 8, with a decrease from BL indicating less stiffness