Population Pharmacokinetics and Pharmacodynamics of Burosumab in Adult and Pediatric Patients With X‐linked Hypophosphatemia

• Published in: Journal of clinical pharmacology 2022-01, Vol.62 (1), p.87-98
• Main Authors: Lee, Sun Ku, Gosselin, Nathalie H., Taylor, Julie, Roberts, Mary Scott, McKeever, Kathleen, Shi, Jack
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Factors; Aged; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Body Weight; burosumab; Child; Child, Preschool; Dose-Response Relationship, Drug; Familial Hypophosphatemic Rickets - drug therapy; Female; Fibroblast growth factor 23; Fibroblast Growth Factors - immunology; Humans; Hypophosphatemia; Infant; Injections, Subcutaneous; Male; Middle Aged; Models, Biological; Monoclonal antibodies; Patients; Pediatrics; Pharmacodynamics; Pharmacokinetics; Pharmacometrics; Phosphorus; Phosphorus - blood; serum phosphorus; X‐linked hypophosphatemia; Young Adult
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1002/jcph.1950

Burosumab is a fully human monoclonal antibody against fibroblast growth factor 23, which has been approved to treat X‐linked hypophosphatemia (XLH) in adult and pediatric patients. The present work describes the pharmacokinetics (PK) of burosumab and the pharmacokinetic‐pharmacodynamic (PK‐PD) relationship between burosumab and serum phosphorus in adult and pediatric patients with XLH. A total of 2844 measurable serum concentrations of burosumab and 6047 measurable serum concentrations of phosphorus in 277 subjects from 9 clinical studies were included in the population PK and PK‐PD modeling. The serum concentration of burosumab following a subcutaneous administration was well described by a population PK model comprising a first‐order absorption, 1‐compartmental distribution, and a linear elimination. The relationship between serum burosumab and serum phosphorus was adequately described by a sigmoid maximal efficacy model. Body weight was the only covariate associated with PK and PK‐PD parameters. No other intrinsic factors affected PK or PK‐PD relationship in adult and pediatric patients with XLH. Further simulations helped to guide the dosing regimen of burosumab in adult and pediatric patients with XLH including age groups with no clinical data.