Posts by: Margarida Azevedo

One-year treatment with Crysvita (burosumab) led to the normalization of phosphate levels in children with X-linked hypophosphatemia (XLH) and helped improve their growth, a small real-world study shows. The findings provide evidence of Crysvita's effectiveness beyond clinical trials, and show that the therapy has positive effects without major adverse events, the researchers said. The study, "Positive Response to One-Year Treatment With Burosumab in Pediatric Patients With X-Linked Hypophosphatemia," was published in the journal Frontiers in Pediatrics. XLH is caused by mutations in the PHEX gene, situated on the X chromosome, that codes for the PHEX enzyme. These mutations lead to excessive activity of the fibroblast growth factor 23 (FGF23) — crucial for bone strength — which in turn increases the excretion of phosphate from the body and decreases its levels in blood. Phosphate is important for many cellular processes, including the development and growth of bones and teeth. Crysvita is an antibody, or protective protein against FGF23, given by subcutaneous (under-the-skin) injection. Developed by by Ultragenyx Pharmaceutical and Kyowa Kirin, it is intended to increase the reabsorption of phosphate and, as a result, its levels in blood. It was first approved by the U.S. Food and Drug Administration in 2018, with its use later expanded to treat patients 6 months and older. "However, very limited data on pediatric patients with XLH treated with burosumab [Crysvita] are available," the researchers said. Now, a team from Spain addressed this gap in the clinical setting, focusing on five children with XLH, ages 6 to 16, who were on Crysvita for more than a year. The children, identified at three Spanish hospitals, were being treated with phosphate and vitamin D supplements, a classical treatment for XLH. None presented with active radiological lesions of rickets, which are bone abnormalities often found in XLH patients. The treatments were stopped two weeks before the children started receiving Crysvita, given at a dose of 0.8 mg/kg every two weeks, after an initial dose of 0.4 mg/kg. The serum phosphate levels in all of the children reached normal levels following treatment, which was associated with greater renal phosphate reabsorption. One patient had a temporary lowering of phosphate levels, called hypophosphatemia, following the first dose of Crysvita, but it normalized thereafter. Height improved in three of the five children, while in the other two — girls ages 13 and 16, both in puberty — it remained unchanged. Weight and body mass index decreased in most children, especially in those with greater height increases. This effect on weight and body composition was attributed to higher physical activity levels among the children, as reported by the parents. The two patients with greater height increases during treatment were the youngest, at ages 6 and 7, "suggesting the convenience of early administration of burosumab, before puberty," the researchers said. These results also support the idea that growth impairment in XLH is not entirely due to low levels of phosphate and bone lesions and, as such, may persist even after mineral levels are normalized, they said. "The characterization of growth response to burosumab [Crysvita] needs to be investigated in further studies involving greater number of patients and longer follow-ups," the team added. The treatment was well-tolerated. None of the children developed new radiological lesions, increased levels of calcium in the kidneys, or dental problems during the treatment period. No Crysvita-related adverse events were reported, except for mild local pain at the injection site and mild headache following the initial doses, experienced by one patient each. While one patient had elevation of the parathyroid hormone (PTH) at the beginning of treatment, none of the other four developed hyperparathyroidism. PTH levels did increase, but within the normal range. "In summary, this study shows the efficacy and safety of burosumab administered for 1 year in the clinical management and follow-up of pediatric patients with XLH," the researchers said. "Additional studies are necessary to assess the influence of burosumab on the long-term outcome of these patients and to define the criteria for its use."

Posts by: Margarida Azevedo

Margarida Azevedo

XLH Symptoms Significantly Affect Well-being of Patients, Study Finds

Crysvita Normalizes Phosphate Levels, Improves Growth in Children in Real-world Study

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