The results of a pediatric phase 2 clinical trial of Burosumab ( Crysvita ) for the treatment of X-linked hypophosphatemia ( XLH ) in children aged 5 to 12 years were published by the New England Journal of Medicine ( NEJM ).
The results have demonstrated that Burosumab has improved rickets severity, growth, pain and physical function, and increased serum phosphorus and renal phosphate reabsorption.
Adverse events were consistent with those previously observed for Burosumab for the treatment of XLH in children.
Burosumab is the first treatment to target the underlying pathophysiology of XLH – excess production of fibroblast growth factor 23 ( FGF23 ), a hormone that regulates phosphate excretion and active vitamin D production by the kidney.
In the NEJM article, inhibition of FGF-23 activity with Burosumab, a recombinant human lgG1 monoclonal antibody, was associated with an increase in renal tubular phosphate reabsorption and the correction of hypophosphatemia in children with X-linked hypophosphatemia.
The improvement in phosphate metabolism corresponded to a decrease in the severity of rickets.
The healing of rickets probably contributed to concurrent improvements in growth and physical activity and a reduction in pain.
This study was the natural extension of recent discoveries related to disease mechanisms in XLH, and in particular FGF23’s role as a mediator of renal phosphate metabolism.
The randomized, multicenter, open-label, dose-finding phase 2 study enrolled 52 children aged 5 to 12 years with XLH at nine sites in the United States and European Union ( EU ). Patients were randomized to receive Burosumab subcutaneously either every two or four weeks for 64 weeks.
The primary endpoint was the change in rickets severity as measured by Rickets Severity Score and the Radiographic Global Impression of Change.
Secondary endpoints included changes in: metabolic measures including serum phosphorus, 1,25 dihydroxy vitamin D, and serum alkaline phosphatase; growth; physical ability; patient-reported pain and functional disability; and safety.
X-linked hypophosphatemia is a rare, hereditary, progressive and lifelong skeletal disorder characterized by renal phosphate wasting caused by excess FGF23 production. It affects both children and adults.
In children, X-linked hypophosphatemia causes rickets that leads to lower-extremity deformity, delayed growth and decreased height.
Adults with X-linked hypophosphatemia have an increased risk of fractures. ( Xagena )
Source: Kyowa Hakko Kirin & Ultragenix, 2018