Crysvita (burosumab-twza) - 2 indications

Scroll down for information on each indication:

• the treatment of X-linked hypophosphatemia; approved April 2018
• for the treatment of fibroblast growth factor 23 (FGF23)-related hypophosphatemia in tumor-induced osteomalacia (TIO); approved June of 2020

General Information

Crysvita (burosumab-twza) is a fibroblast growth factor 23 (FGF23) blocking antibody.

Crysvita is specifically indicated for the following:

• the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 1 year of age and older.
• the treatment of FGF23-related hypophosphatemia in 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. Scroll down for the recommended dosing/administration for each condition.

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.  

Side Effects

Adverse events associated with the use of Crysvita may include, but are not limited to, the following:

Pediatrics:

• headache
• injection site reaction
• vomiting
• pyrexia
• pain in extremity
• vitamin D decreased

Adults:

• back pain
• headache
• tooth infection
• restless leg syndrome
• vitamin D decreased
• dizziness
• constipation
• blood phosphorus increased

Indication 1 - X-linked hypophosphatemia

approved April 2018

Dosing/Administration

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.

Clinical Trial Results

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.

Indication 2 - fibroblast growth factor 23 (FGF23)-related hypophosphatemia in tumor-induced osteomalacia (TIO)

approved June of 2020

Dosing/Administration

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.

Clinical Trial Results

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.