Burosumab effects persist long-term for children with rare form of rickets
Treatment with the monoclonal antibody burosumab led to normalized serum phosphorus levels and improvements in rickets severity and lower-limb deformity among young children with X-linked hypophosphatemia, according to a speaker.
“X-linked hypophosphatemia is a rare disease in which elevated circulating fibroblast growth factor 23 leads to lifelong hypophosphatemia and causes rickets, skeletal deformities such as bowed legs and short stature in children,” Erik Imel, MD, associate professor of medicine and pediatrics at Indiana University School of Medicine, told Healio. “Burosumab is a monoclonal antibody treatment that targets the excess fibroblast growth factor 23. Burosumab is the only FDA-approved therapy for X-linked hypophosphatemia.”
Imel and colleagues conducted a phase 2, open-label trial with children aged 1 to 4 years who had X-linked hypophosphatemia (XLH) and radiographic evidence of rickets. The study was conducted at three centers in the United States. There were 13 participants, with 12 remaining in the study through week 160.
Participants received a 0.8 mg/kg dose of burosumab-twza (Crysvita, Ultragenyx) every 2 weeks for 64 weeks. The dose could increase to 1.2 mg/kg to keep serum phosphorus at normal levels. An open-label extension period followed for an additional 96 weeks. Researchers recorded serum phosphorus levels, rickets severity score, radiographic global impression of change for lower-limb deformity and serum alkaline phosphatase levels. The findings were reported at the virtual American Society for Bone and Mineral Research Annual Meeting.
Serum phosphorus levels increased from a mean of 2.5 mg/dL at baseline to 3.7 mg/dL after the first week of burosumab. Normal phosphorus levels were maintained through the entire study period. Five participants had a dose increase to 1.2 mg/kg.
Mean rickets severity score improved from 2.9 at baseline to less than 1 at week 64 and was maintained throughout the study (P < .0001). Mean lower limb deformity scores rose above 1 at week 40 and increased again at week 64 and week 112. Mean alkaline phosphatase levels were normal at week 40 and stayed within a normal range through the end of the study.
Two serious adverse events were recorded, with both considered unrelated to the drug. All participants continued to use burosumab through the end of the study period, with no evidence of increasing adverse effects, according to Imel.
“Treating young children with XLH with burosumab was safe and effective at improving rickets,” Imel said. “It is possible that these long-term improvements in rickets and lower-limb deformity may have lifelong benefits and potentially prevent or delay some adult-onset complications of the disease.”
Although the presented study was the longest so far involving children aged 1 to 4 years with XLH, Imel said more research is needed to examine whether burosumab leads to long-term improvements in skeletal deformities and on final adult height.
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Imel E, et al. Three-Year Safety and Efficacy Results of Burosumab for Children Aged 1 to 4 years with X-linked Hypophosphatemia (XLH). Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 11-15, 2020 (virtual meeting).