CRYSVITA

What it is

CRYSVITA is a solution for injection containing burosumab, a recombinant human monoclonal IgG1 antibody for FGF23. The medicine is available in three strengths: 10 mg/mL, 20 mg/mL, and 30 mg/mL solutions for injection in 5 mL vials. Burosumab is administered by subcutaneous injection and should be administered by a healthcare provider.

Approved indications

— Treatment of X-linked hypophosphataemia (XLH) in adults, adolescents and children 1 year of age or older. — Treatment of FGF23-related hypophosphataemia in tumour-induced osteomalacia associated with phosphaturic mesenchymal tumours that cannot be curatively resected or localised in adults, adolescents and children 1 year of age or older.

Dosing overview

Treatment should be initiated and monitored by specialist medical practitioners experienced in the management of patients with metabolic bone disease. Oral phosphate and active Vitamin D analogues should be discontinued 1 week prior to initiation of treatment. Fasting serum phosphate level should be below the reference range for age prior to initiation of treatment.

Key safety warnings

Ectopic mineralisation, manifested by nephrocalcinosis, has been observed in patients with XLH treated with oral phosphate and active Vitamin D analogues; monitoring for signs and symptoms of nephrocalcinosis, such as by renal ultrasonography, is recommended at the start of treatment and every 6 months for the first 12 months of treatment, and annually thereafter. Levels of fasting serum phosphate should be monitored due to the risk of hyperphosphataemia; to decrease the risk for ectopic mineralisation, it is recommended that fasting serum phosphate does not exceed the upper limit of the normal reference range for age. Increases in serum calcium or parathyroid hormone have been reported in patients treated with burosumab; in patients with tertiary hyperparathyroidism, risk factors such as prolonged immobilisation, dehydration, hypervitaminosis D, or renal impairment may increase the risk of moderate to severe hypercalcaemia; serum calcium and parathyroid hormone levels should be monitored before and during burosumab treatment. Administration may result in local injection site reactions; administration should be interrupted in any patient experiencing severe injection site reactions. Burosumab may cause dizziness and, as a result, may influence the ability to drive or operate machinery; patients should be cautioned about operating hazardous machines, including motor vehicles, until they are reasonably certain that burosumab does not affect them adversely.

Contraindications

Hypersensitivity to the active substance or to any of the excipients. Concurrent administration with oral phosphate and/or active Vitamin D analogues. Serum phosphate level within or above the normal range for age at initiation of treatment. Severe renal impairment or end stage renal disease.

PBS listing

CRYSVITA is listed on the PBS in three strengths: 10 mg in 1 mL, 20 mg in 1 mL, and 30 mg in 1 mL solution for injection. Each strength has 2 PBS items with authority required restriction. The ex-manufacturer prices are A$3999.00 for the 10 mg strength, A$7998.00 for the 20 mg strength, and A$11997.00 for the 30 mg strength.

Regulatory history

CRYSVITA was first listed on the ARTG on 2021-09-10 in all three strengths (10 mg/mL, 20 mg/mL, and 30 mg/mL). The TGA approved CRYSVITA on 2021-09-03 for the treatment of X-linked hypophosphataemia (XLH) in adults, adolescents and children 1 year of age or older. The PBAC initially did not recommend the medicine in March 2021 and March 2022. Following a May 2022 PBAC intracycle meeting, the medicine was recommended for listing for treatment of XLH, with high clinical need and strong consumer support noted and incremental cost-effectiveness ratios for paediatric and adult populations found to be acceptable at the proposed price, with an adequate risk sharing arrangement.