Indication: First drug approval for X-linked hypophosphatemia (XLH), a rare, inherited, progressive form of rickets.
Mechanism: Monoclonal IgG1 antibody that binds excess fibroblast growth factor 23 (FGF23). This action normalizes phosphorus levels, improves bone mineralization, improves rickets in children, and helps heal fractures in adults.
Adults: 1 mg/kg SC every 4 weeks; round dose to nearest 10 mg. Not to exceed 90 mg/dose.
Children aged 1 year or older: 0.8 mg/kg SC every 2 weeks; round dose to nearest 10 mg. Not to exceed 90 mg/dose.
Approval for children was based on 64-week, randomized, open-label study in 52 patients aged 5 to 12 years, which showed that treatment with burosumab improved rickets, increased serum phosphorus levels, decreased serum alkaline phosphatase activity, and increased growth. The indication is also supported by 40-week data from an open-label study in 13 patients aged 1 to 4 years. In these patients, burosumab improved rickets and lower-limb deformity, increased serum phosphorus levels, and decreased serum alkaline phosphatase activity.
Approval in adults with XLH (N=134) was supported by a randomized, double-blind, placebo-controlled study. Burosumab treatment resulted in a higher proportion of patients achieving serum phosphorus levels above the lower limit of normal compared with placebo (P<0.0001). A higher rate of complete healing of active fractures and pseudofractures was also observed compared with placebo. The adult indication is also supported by data from the 48-week, open-label, single-arm bone biopsy study in 14 adults, which showed healing of osteomalacia as demonstrated by decreases in osteoid volume/bone volume, osteoid thickness, and mineralization lag time.
Carpenter TO, Whyte MP, Imel EA, et al. Burosumab Therapy in Children with X-Linked Hypophosphatemia. N Engl J Med. 2018 May 24;378(21):1987-1998. https://www.nejm.org/doi/10.1056/NEJMoa1714641
Zhang X, Imel EA, Ruppe MD, et al. Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody (KRN23) in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia. J Clin Pharmacol. 2016 Feb. 56 (2):176-85. https://www.ncbi.nlm.nih.gov/pubmed/26073451
Zhang X, Peyret T, Gosselin NH, et al. Population pharmacokinetic and pharmacodynamic analyses from a 4-month intradose escalation and its subsequent 12-month dose titration studies for a human monoclonal anti-FGF23 antibody (KRN23) in adults with X-linked hypophosphatemia. J Clin Pharmacol. 2016 Apr. 56 (4):429-38. https://www.ncbi.nlm.nih.gov/pubmed/?term=26247790
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Cite this: Mary L Windle. FDA New Drug and Biologic Approvals, 2018 Midyear Review - Medscape - Aug 01, 2018.