Currently Enrolling Trials
Crysvita (burosumab-twza) is a fibroblast growth factor 23 (FGF23) blocking antibody.
Crysvita is specifically indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 1 year of age and older.
Crysvita ishttps://admin-centerwatch.epublishing.com/admin/directory/general/load?listingId=3360# specifically indicated for fibroblast growth factor 23 (FGF23)-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older.
Crysvita is supplied as a subcutaneous injection.
XLH: The recommended starting dose for pediatrics is 0.8 mg/kg of body weight, rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg. After initiation of treatment with Crysvita, measure fasting serum phosphorus every 4 weeks for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is above the lower limit of the reference range for age and below 5 mg/dL, continue treatment with the same dose. Follow dose adjustment schedule per the drug label. The recommended dose regimen in adults is 1 mg/kg body weight, rounded to the nearest 10 mg up to a maximum dose of 90 mg, administered every four weeks. After initiation of treatment with Crysvita, assess fasting serum phosphorus on a monthly basis, measured 2 weeks post-dose, for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is within the normal range, continue with the same dose. See drug label for specific dose adjustments.
TIO: The recommended starting dose for pediatrics (2 years to 18 years of age) is 0.4 mg/kg body weight administered every 2 weeks, rounded to the nearest 10mg, up to a maximum dose of 2 mg/kg not to exceed 180mg, administered every 2 weeks. The recommended starting dose for adults is 0.5 mg/kg body weight administered every 4 weeks, rounded to the nearest 10 mg, up to a maximum dose of 2 mg/kg not to exceed 180mg, administered every 2 weeks.
The FDA approval of Crysvita for XLH was based on the following trials:
Pediatrics with XLH: FDA approval is supported by 64-week data from Study CL201, a randomized, open-label study in 52 patients ages 5 to 12. Data showed that treatment with Crysvita improved rickets, increased serum phosphorus levels, decreased serum alkaline phosphatase activity, and increased growth. The indication is also supported by 40-week data from Study CL205, an open-label study in 13 patients ages 1 to 4. Crysvita improved rickets and lower-limb deformity, increased serum phosphorus levels and decreased serum alkaline phosphatase activity.
Adults with XLH: FDA approval is supported by 24-week data from Study CL303, a randomized, double-blind, placebo-controlled study in 134 adult XLH patients. Crysvita treatment resulted in a higher proportion of patients achieving serum phosphorus levels above the lower limit of normal, and a higher rate of complete healing of active fractures and pseudofractures, compared to placebo. The adult indication is also supported by data from the 48-week, open-label, single-arm bone biopsy study in 14 adult XLH patients, which showed healing of osteomalacia as demonstrated by decreases in osteoid volume/bone volume, osteoid thickness and mineralization lag time.
The FDA approval of Crysvita for TIO was based on data from two single-arm Phase 2 studies, a 144-week study in 14 adult patients conducted by Ultragenyx in the United States and an 88-week study in 13 adult patients conducted by Kyowa Kirin in Japan and South Korea. In both studies, Crysvita was associated with increases in serum phosphorus and serum 1,25-dihydroxyvitamin D levels. Increased phosphate levels led to improvements in osteomalacia. Additionally, whole body bone scans demonstrated reduced tracer uptake with long-term treatment suggesting healing of bone lesions.
Adverse events associated with the use of Crysvita may include, but are not limited to, the following:
- injection site reaction
- pain in extremity
- vitamin D decreased
- back pain
- tooth infection
- restless leg syndrome
- vitamin D decreased
- blood phosphorus increased
Mechanism of Action
Crysvita (burosumab-twza) is a fibroblast growth factor 23 (FGF23) blocking antibody. X-linked hypophosphatemia is caused by excess fibroblast growth factor 23 (FGF23) which suppresses renal tubular phosphate reabsorption and the renal production of 1,25 dihydroxy vitamin D. Burosumab-twza binds to and inhibits the biological activity of FGF23 restoring renal phosphate reabsorption and increasing the serum concentration of 1,25 dihydroxy vitamin D.
For additional information regarding Crysvita or X-linked hypophosphatemia, please visit the Crysvita website.