OR29-01 Long-Term Safety in Adults with X-Linked Hypophosphatemia (XLH) Treated with Burosumab, a Fully Human Monoclonal Antibody Against FGF23: Final Results of a Phase 3 Trial
Bibliographic record
Abstract
Abstract Burosumab, a fully human IgG1 monoclonal antibody to FGF23, is approved in Canada and Brazil to treat XLH in patients ≥1 year of age and in the US to treat XLH in patients ≥6 months of age. Burosumab has also received conditional marketing authorization in Europe to treat XLH with radiographic evidence of bone disease in children ≥1 year of age and in adolescents with growing skeletons. Burosumab significantly improved serum phosphorus, fracture/pseudofracture healing, stiffness, and physical functioning in a phase 3, double-blind, multicenter study (CL303, NCT02526160). In this trial, subjects were randomized 1:1 to receive burosumab or placebo subcutaneously every 4 weeks. At Week 24, subjects in the placebo group crossed over to receive burosumab (total duration ≥96 weeks). Here, we report final long-term safety results from this trial. Most (119/134, 89%) subjects completed 96 weeks and received 1 mg/kg burosumab; protocol-specified dose reductions were required for 11/134 (8.2%) subjects to effectively manage hyperphosphatemia (all mild [Grade 1]). Mean (±SE) baseline serum phosphorus was 1.98 (±0.03) mg/dL and was 2.97 (±0.05) mg/dL at Week 94 (midpoint of dose interval). Mean (±SE) iPTH level was 96 (±3.8) pg/mL at baseline and progressively declined to 79 (±3.3) pg/mL at Week 96. Nephrocalcinosis score at Week 96 changed by 0 in 101 subjects, -1 in 9 subjects, +1 in 10 subjects (14 subjects not available). There were no meaningful changes in ectopic mineralization. There were no neutralizing antibodies. No treatment-emergent adverse events led to study or treatment withdrawal. Serum phosphorus was maintained with long-term burosumab treatment, with no evidence of loss of effect in adults with XLH. Burosumab dose reductions effectively managed mild hyperphosphatemia. Frequency, severity, and types of AEs reported were consistent with previous burosumab trials.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".