Brand Name



Fibroblast growth factor 23 (FBGF23) blocking antibody

FDA Indication

X-linked hypophosphatemia†,$


Burosumab is the first-in-class fibroblast growth factor 23 (FGF23)-blocking antibody. It is approved as a breakthrough therapy for the treatment of X-linked hypophosphatemia (XLH). FGF23 is one of 3 endocrine FGFs that act as hormones.62 FGF23 is produced and secreted in bone by osteocytes and regulates phosphate excretion, parathyroid hormone (PTH) secretion, and active vitamin D production by the kidney.63,64 FGF23 is known to bind to multiple FGF receptors, with binding to FGFR1c in the kidney and parathyroid glands thought to be the most important for phosphate homeostasis.64,65 FGF23 specifically lowers phosphate by downregulating sodium-dependent phosphate co-transport proteins, such as NaPi-2a and NaPi-2c.64,65 Blocking FGF23 with burosumab raises phosphate levels by reversing its wasting through the kidneys.

XLH is a rare inherited form of rickets characterized by excess levels of circulating FGF23.2 XLH is caused by mutations in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene that give rise to dysfunctional PHEX enzyme.66 Absent or deficient PHEX enzyme activity leads to errors in phosphate sensing and results in FGF23 overproduction.67 Excess FGF23 causes phosphate wasting through suppression of renal tubular reabsorption and inhibition of renal 1,25 dihydroxy vitamin D synthesis.66 Besides XLH, excess FGF23 activity is associated with other diseases including chronic kidney disease, cardiac hypertrophy, and tumor-induced osteomalacia.63 It is now thought that FGF23 has actions outside of the kidney and parathyroid gland, and that it can signal together with or independent of its FGF receptor cofactor, klotho.63,64 The role of FGF23 as either a confounder or mediator of inflammation, immunosuppression, and cardiovascular disease remains an area of intense research.63

XLH is a heterogenous disease associated with life-long disability from skeletal deformations, pain, fatigue, muscle weakness, and soft teeth. Mildly affected individuals may have hypophosphatemia without other signs and symptoms.68 Children may develop rickets, other skeletal deformities, gait abnormalities, and short stature.65 Manifestations in adults include osteomalacia, musculoskeletal pain and stiffness, and frequent dental abscesses.66 The conventional treatment of 3–5 times daily supplementation with oral phosphate and vitamin D is usually insufficient to counter all of the pathologic consequences of the disease.65,66

Burosumab is a recombinant IgG1 anti-FGF23-blocking monoclonal antibody produced in Chinese hamster ovary cells.2 Dosing is weight-based with a cap of 90 mg/dose. In patients with XLH (NCT02526160), twice-monthly subcutaneous administration to children, and monthly administration to adults, is proven to neutralize the biological activity of FGF23, improve renal phosphate reabsorption, and increase 1,25 dihydroxy vitamin D serum concentrations.2,66 Burosumab should not be given with supplemental oral phosphate or active vitamin D, and therapy requires frequent serum phosphate monitoring.2 Patients with severe or end-stage renal failure are not candidates for burosumab therapy due to premarket safety signals related to nephrocalcinosis and antibody-dependent cellular cytotoxicity (ADCC)-triggered renal tubule injury.2,69 Clinically observed adverse events of specific interest associated with burosumab include injection site reactions, hypersensitivity, hyperphosphatemia, ectopic mineralization (nephrocalcinosis), and treatment-emergent or worsening restless leg syndrome.2,69 Postmarket commitments for burosumab require collection of additional data related to renal safety and also spinal stenosis.69 Comprehensive reviews of the evidence for benefit and risk from burosumab administration have been published.70,71 The annual cost of therapy for XLH is estimated to be approximately $160,000–$200,000.72 The average wholesale price for 30 mg is $12,240.00.72

Further Reading in Goodman & Gilman’s