Bone Abstracts

Objectives: XLH features renal phosphate (Pi) wasting, hypophosphatemia, rickets, and skeletal deformities from elevated circulating levels of fibroblast growth factor 23 (FGF23). KRN23, an investigational fully human monoclonal antibody, binds FGF23 and inhibits its action. Our Phase 2 study of KRN23 in XLH children (ages 5–12 years) is demonstrating improvements in serum Pi and rickets. Here we present our Phase 2 trial evaluating the efficacy and safety of KRN23 in younger children with XLH.

Methods: In an ongoing, open-label, multicenter trial, children 1–4 years old with XLH received KRN23 at an initial dose of 0.8 mg/kg subcutaneously every 2 weeks. We evaluated serum Pi, alkaline phosphatase (ALP), 1,25(OH)₂D, and KRN23 concentrations and safety. This, our initial report, includes BL data for the first 10 children enrolled, and up to 4 weeks of treatment data for the first five subjects.

Results: At BL (N=10), the mean age was 3.0 years and 70% were boys. The median standing height percentile was 9.1%. Complications of XLH included gait disturbance (60%), tibial torsion (60%), knee deformity (40%), and skull malformation (40%). At BL, all had low serum Pi levels (mean (SE) =0.83 (0.025) mmol/l) (Normal (Nl): 1.03–1.97 mmol/l) while ALP was elevated in 8 of 10 subjects. Mean serum Pi increased after KRN23 treatment by 0.41 (0.030) mmol/l at Week 1 and 0.36 (0.070) mmol/l at Week 4. Normal Pi levels were achieved in 100 and 80% of subjects at Weeks 1 and 4, respectively. Mean (SE) serum 1,25(OH)₂D levels increased from 118 (17) pmol/l at BL to 256 (38) pmol/l at Week 1 (Nl: 60–220 pmol/l). Serum KRN23 concentrations at Weeks 1 and 4 resembled the values observed in the Phase 2 study in older children. All adverse events (AEs) were mild, and except for upper respiratory tract infections (n=2), all other AEs occurred in 1 subject each. No serious AEs occurred.

Conclusions: Initial results in 1 to 4 year-old children with XLH suggest KRN23 pharmacodynamic responses are similar to those of older children. The study is ongoing and will evaluate changes in rickets severity and growth.

Disclosure
Imel: travel and consulting fees from Ultragenyx; Carpenter: grant support and travel from Ultragenyx; Mao, Skrinar, San Martin: employees of Ultragenyx; Whyte: research grant support, honoraria, and travel from Ultragenyx and Alexion.