The Food and Drug Administration (FDA) has approved Crysvita® (burosumab-twza; Ultragenyx) for the treatment of fibroblast growth factor 23 (FGF23)-related hypophosphatemia in tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in patients aged ≥2 years.
Tumor-induced osteomalacia (TIO) is a rare disease characterized by slow-growing tumors that release excess levels of 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.
The approval was based on data from 2 single-arm phase 2 studies (Study 1 and Study 2) that included a total of 27 adults with TIO who received burosumab-twza every 4 weeks. Results from Study 1 showed that 50% of patients (n=7 out of 14) achieved normal phosphate levels with a mean (SD) increase from 1.60 (0.47) mg/dL at baseline to 2.64 (0.76) mg/dL through week 24, which were sustained near or above the lower limit of normal (LLN) through week 144. In Study 2, 69% of patients (n=9 out of 13) achieved normal phosphate levels with a mean (SD) increase from 1.62 (0.49) mg/dL at baseline to 2.63 (0.87) mg/dL through week 24 and were sustained near or above the LLN through week 88.
Additionally, radiographic evaluation of patients in Study 1 showed a reduction in the number of areas of tracer uptake with long-term treatment, suggesting healing of bone lesions related to osteomalacia. In TIO, increased tracer uptake is presumed to be nontraumatic fractures and pseudofractures.
With regard to safety, the most common adverse reactions (>10%) in TIO patients were tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache.
“Treatment for TIO focuses on identifying and removing the tumor that causes the disease. However, when that is not possible, Crysvita can help increase the levels of phosphate in the blood,” said Theresa E. Kehoe, MD, acting director of the Division of General Endocrinology in the FDA’s Center for Drug Evaluation and Research. “As the first FDA-approved therapy to treat this debilitating disease, today’s action is an important step in finding treatment options for patients living with TIO whose tumor cannot be found or removed.”
Crysvita is already indicated for the treatment of X-linked hypophosphatemia in patients aged ≥6 months. The product is available as 10mg/mL, 20mg/mL, and 30mg/mL of burosumab-twza in single-dose vials.
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