The findings were reported in a study, “Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X‐Linked Hypophosphatemia: A Phase 3, Single‐Arm, International Trial,” published in the Journal of Bone and Mineral Research.
XLH is characterized by the excessive production of a hormone called fibroblast growth factor 23 (FGF23). This prevents the kidneys from reabsorbing phosphate and blocks the production of vitamin D, leading to chronic hypophosphatemia (low blood levels of phosphate) and persistent osteomalacia — the abnormal softening of bones, making them more prone to fractures and less able to heal when damaged.
Crysvita, marketed by Ultragenyx Pharmaceutical and Kyowa Kirin, is currently the only targeted therapy approved for the treatment of XLH. The medication is a monoclonal antibody designed to block FGF23, thereby increasing the production of vitamin D and boosting phosphate reabsorption.
A recent label update covering treatment of patients as young as 6 months was based on a Phase 3 study (NCT02526160) in adults with XLH, which showed that treatment with Crysvita improved fracture healing, increased serum phosphorus levels, and reduced patient‐reported stiffness compared to a placebo.
A different Phase 3 trial (NCT02537431) — called UX023‐CL304 and also sponsored by Ultragenyx with support from Kyowa Kirin — assessed the efficacy of Crysvita in easing osteomalacia in 14 adults with XLH, who had not received any treatment for their disease for at least two years before enrolling in the study.
All participants received subcutaneous (under the skin) injections of Crysvita at a dose of 1.0 mg/kg, every four weeks for at least 96 weeks. An initial 48-week treatment period was followed by a extension period of the same duration.
The study’s primary goal was to measure changes from baseline to week 48 in the ratio of osteoid (unmineralized bone) and total bone volume. This was measured in bone biopsies collected at the beginning of the study and after 48 weeks.
Additional goals included measuring changes in the levels of phosphorus in the blood, as well as analyzing several markers of bone turnover (resorption followed by replacement with new bone), healing of fractures or small linear bone cracks called pseudofractures, and treatment safety.
All but one participant completed the first 48 weeks of treatment and 11 underwent biopsies.
Results of this first treatment period showed that the ratio of unmineralized and total bone volume dropped by 54%, indicating that Crysvita reduced osteomalacia and improved bone mineralization. Other measures of osteomalacia also showed improvements: osteoid thickness by 32% and surface area by 26%.
The mean levels of phosphorus in the blood increased during this period, as seen in several markers of bone formation and resorption.
All participants reported at least one treatment‐emergent adverse event. The most common included urticaria, pain, reaction at the injection site, abdominal pain, and asthenia (feeling weak or tired). Most of them were mild or moderate in severity.
“The improvements in osteomalacia coincided with increases in serum phosphorus and biochemical markers of bone remodeling. Such improvements … and healing of osteomalacia provide a physiologic basis for the efficacy of burosumab [Crysvita] to heal fractures and pseudofractures in patients with XLH, and ameliorate symptoms such as pain and stiffness,” the investigators wrote.
“Given its proven efficacy, better safety profile, and sound therapeutic rationale, burosumab represents an appealing therapeutic option for symptomatic adults with XLH,” they added.
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