Cancer-induced bone softening new drug Crysvita applied

Ultragenyx Pharmaceuticals and partner Kyowa Kirin recently jointly announced that they have submitted a Crysvita (burosumab) Supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for the treatment of FGF23-related hypothyroidism associated with phosphate urinary folioma (tumor-induced osteoma, TIO). Both parties expect to receive a response from the FDA on sBLA acceptance and review of eligibility by February 2020.TIO is caused by typical benign tumors that produce excessive fibroblast growth factor 23 (FGF-23), leading to phosphate consumption in the urine, leading to severe hypophosphate, bone softening, muscle weakness, fatigue, bone pain and fractures. If the cause of the tumor or lesions can be removed, the symptoms will quickly disappear, but there are also cases where it is not possible to remove or the tumor relapses after removal. Current treatments include oral phosphates and/or vitamin D substitutes for patients with tumors or lesions that cannot be operated on. The efficacy of this treatment is often limited because it does not treat the cause of the disease, and its benefits must be balanced with monitoring potential risks such as renal calcium sedation, hypercalcemia, and hyperthyroidism. It is estimated that 500-1,000 people in the United States have TIO, and about half of the cases cannot be operated on.The sBLA packet includes data from two single-arm Phase II studies, one of which was a 144-week study conducted by Ultragenyx in the United States involving 14 adult patients, and the other an 88-week study of 13 adult patients conducted by Concorde in Japan and South Korea. In both studies, Crysvita was associated with elevated levels of serum phosphorus and serum 1,25-hydroxyvixy vitamin D. Increased phosphate levels led to improvements in bone softening, activity and vitality. Bone scans also showed an increase in the number of fractures healed and a decrease in new fractures during Crysvita treatment. During the study period, adverse events usually reflected the patient's underlying disease and there were no serious treatment-related adverse events.Crysvita is a recombinant all-human monoclonal IgG1 antibody, discovered by Concorde Fermentation Kirin, and is the first drug to directly target fibroblast growth factor 23 (FGF-23). FGF23 is a "phosphate urinary" hormone that reduces phosphate and active vitamin D levels in the serum by regulating phosphate excretion and the production of active biotin D in the kidneys. Crysvita has been developed to treat low-blood phosphorus diseases associated with FGF-23, such as X-chain hypophosphate (XLH) and tumor-induced osteoporosis (TIO)/peritiotic syndrome (ENS).Phosphate consumption in FGF-23-related hypophosphate rickets and bone softening is caused by FGF-23 levels and high activity. Crysvita targets binding and inhibits the bioactive activity of FGF-23. By blocking excessive FGF-23 in patients, Crysvita can increase the re-absorption of phosphates by the kidneys, increase the production of active vitamin D, and thus also enhance the absorption of phosphates and calcium in the intestines. Therefore, hypophosphateemia and bone mineralization defects can be improved. (
Bio Valley
)