Prepared by Bhuvana Sunil, MD and Ambika Ashraf, MD
Burosumab twza (Crysvita – Ultragenyx pharmaceuticals) is an injectable recombinant IgG1 human monoclonal antibody preparation neutralizing fibroblast growth factor 23 (FGF-23). It was approved by FDA for children ≥ 1 year and adults for the treatment of X-linked hypophosphatemia (XLH) in April 2018 and expanded to ≥ 6 months in September 2019, and more recently, in June 2020, for children ≥ 2 years and adults for the treatment of tumor induced osteomalacia (TIO). For TIO, the suggested dosing is 0.4 to 0.5 mg/kg once every 4 weeks to be rounded to the nearest 1 mg with a maximum dose of 2 mg/kg (not to exceed 180 mg) every 2 weeks. For TIO, FDA approval was based on data from two single-arm Phase 2 studies in adults. Mean serum phosphorus increased from baseline by approximately 1.60 mg/dL and was maintained after titration, from Week (W) 22 (2.85 mg/dL, dosing cycle midpoint) to W144 (2.56 mg/dL, dosing cycle endpoint, p<0.0001). Serum TmP/GFR and 1,25(OH)2D also increased with burosumab. Increases in overall osteoid volume and thickness, improvements in physical functioning, fatigue, pain, and quality of life were seen. Most common adverse reactions in TIO patients (>10%) are: tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache.