Study: Recommended Crysvita Starting Dose Too Low to Manage XLH in Children

Study: Recommended Crysvita Starting Dose Too Low to Manage XLH in Children
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The recommended starting dose of Crysvita (burosumab) is too low to effectively manage X-linked hypophosphatemia (XLH) in children with the rare inherited disorder, a Swedish study indicates.

That dose, of 0.4 mg/kg, is insufficient to normalize the phosphate levels in the bodies of children with XLH, according to the study.

Titled “The recommended starting dose of 0.4mg/kg burosumab is insufficient for most children with X-linked hypophosphatemia (XLH) — Results from the first treated patients in Sweden,” the study was published in the journal Bone Reports and presented at the ECTS Congress 2020, recently held online.

In XLH, a protein called fibroblast growth factor 23 (FGF23) is present at higher-than-normal levels. The excess of this protein causes too much phosphate to be excreted in patients’ urine, ultimately resulting in low levels of phosphate in the body. In turn, these low levels of phosphate cause the symptoms characteristic of XLH. Since phosphate is important for proper bone growth, for example, bone abnormalities such as rickets and osteomalacia — the marked softening of bones, leading to bowing in children and fractures in adults — are common in people with XLH.

Crysvita, developed by Kyowa Kirin and Ultragenyx Pharmaceutical, is an antibody that blocks the activity of FGF23, thereby increasing phosphate levels in the body. It is administered by subcutaneous (under-the-skin) injection every two weeks in children and every four weeks in adults. The medication has been approved for the treatment of XLH in the U.S., the European Union, and elsewhere.

An international consensus, published in 2019, recommended a starting dose of 0.4 mg/kg for children with XLH beginning treatment with Crysvita. However, clinical trial data has suggested that a dose of about 1 mg/kg is required to increase body phosphate levels to within a normal range.

Now, researchers from Sweden reported the results of the first five children with XLH who were treated with Crysvita at their center, and who all had overt rickets despite optimized conventional therapy. The treatment was started at a dose of 0.4 mg/kg, and blood and urine tests were conducted regularly. The Crysvita dose was increased if blood phosphate levels were below the normal range on two consecutive tests.

In all five patients, blood phosphate levels did increase following the start of treatment with Crysvita. However, all children continued to have levels below the normal range on the starting dose.

“This finding is consistent with previous dose-finding studies and indicates that the [recommended] dose of 0.4 mg/kg will be insufficient to maintain plasma [blood] phosphorus in the low normal range in most children with XLH,” the researchers concluded.

They noted that starting treatment on a less-than-optimal dose is likely to increase the number of blood draws patients need to undergo for lab tests, and may make it take longer for symptoms to ease.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.

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José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.

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