Endocrine Abstracts

Hypophosphatemia due to excess urinary phosphate losses and rachitic bone disease occur in several related disorders. The most common form of the heritable hypophosphatemic disorders, X-linked hypophosphatemia (XLH, estimated incidence: 1/10 000–1/20 000), is due to loss-of-function mutations of the osteocyte/osteoblast protein, PHEX. Associated elevations in circulating FGF23 lead to reduced abundance of phosphate transporters on the luminal surface of renal tubular cell...

Familial hypophosphatemic rickets was recognized in the 1950s, when hypophosphatemia due to renal phosphate wasting was identified in individuals with rickets unresponsive to vitamin D therapy. X-linked dominant inheritance was evident in many cases, and the most common form of the disease is known as X-linked hypophosphatemia (XLH). A description of vitamin D-refractory rickets likely represents the first report of XLH (Albright F et al., Am J Dis Children 1937)...

In XLH, high circulating FGF23 causes hypophosphatemia, rickets, and short stature. In our Phase 2 study, 52 XLH children (ages 5–12 years, ≤Tanner 2) were randomized to receive KRN23 subcutaneously biweekly (Q2W) or monthly (Q4W). Serum phosphate (Pi) was measured biweekly. KRN23 dose was titrated (maximum 2 mg/kg) targeting age-appropriate serum Pi concentrations.The first 36 subjects had a mean 6.6 years of standard-of-care treatment before...

UX023-CL303 is an ongoing, Phase 3, double-blind, multicenter study examining the efficacy and safety of burosumab, a fully human monoclonal antibody against FGF23, in adults with XLH. Eligible subjects had serum phosphorus levels <0.81 mmol/l and skeletal pain (BPI – Worst Pain ≥4). Subjects (N=134) were randomized 1:1 to receive burosumab 1 mg/kg or placebo subcutaneously every 4 weeks. After 24 weeks, subjects in the placebo group crossed-over to rec...