Ultragenyx and Kyowa Kirin Report Topline Late-Stage Results of Crysvita for Kids with XLH

Rare Daily Staff

Ultragenyx Pharmaceutical and Kyowa Hakko Kirin reported that a late-stage study of Crysvita met its primary endpoint of showing superiority to conventional therapy of oral phosphate and active vitamin D in improving rickets in children with X-linked hypophosphatemia, a rare and progressive skeletal disorder.

XLH is a genetic condition characterized by renal phosphate wasting caused by excess production of fibroblast growth factor. It affects both children and adults. In children, XLH causes rickets, a softening and distortion of the bones caused by a deficiency of vitamin D. This leads to lower-extremity deformity, delayed growth, and decreased height. Adults with XLH have an increased risk of fractures.

Crysvita is a recombinant fully human monoclonal IgG1 antibody, discovered by Kyowa Hakko Kirin, against the phosphaturic hormone fibroblast growth factor 23. FGF23 is a hormone that reduces serum levels of phosphorus and active vitamin D by regulating phosphate excretion and active vitamin D production by the kidney. Phosphate wasting in XLH is caused by excessive levels and activity of FGF23. Crysvita is designed to bind to and thereby inhibit the biological activity of FGF23 by blocking excess FGF23 in patients. Crysvita is intended to increase phosphate reabsorption from the kidney and increase the production of active vitamin D, which enhances intestinal absorption of phosphate and calcium.

The study met its primary endpoint demonstrating that Crysvita significantly improved rickets compared to conventional therapy, as assessed by three independent blinded pediatric radiologists using the radiographic global impression of change scale. In addition, substantial healing was observed in 72 percent of patients receiving Crysvita compared to 6% of patients receiving conventional therapy.

Treatment with Crysvita showed a significant improvement in mean alkaline phosphatase levels into the normal range after 40 weeks of treatment, compared to conventional therapy. Patients treated with Crysvita also demonstrated a greater numeric but not statistically significant improvement in and in the six-minute walk test, compared to conventional therapy.

The randomized, open-label phase 3 clinical study enrolled 61 patients ages one through 12 in the United States, Europe, Canada, Australia, Japan, and Korea, and compared the efficacy and safety of Crysvita to conventional therapy.

The Crysvita safety profile observed in this study was generally consistent with that seen in other Crysvita pediatric XLH studies. There were no treatment discontinuations and no deaths reported in the study. There were three serious adverse events in the Crysvita arm and one serious adverse event in the conventional therapy arm, none of which were considered treatment-related.

Erik Imel, lead study investigator and associate professor of medicine and pediatrics at Indiana University School of Medicine, said the results of the study demonstrate the value of directing therapy at the mechanism of renal phosphate wasting in XLH.

“While prior conventional therapy fails to improve renal phosphate wasting, Crysvita works to improve serum phosphorus by correcting the renal phosphate wasting,” said Imel. “The differences in mechanism are clearly important to outcomes as demonstrated in this study. By comparing XLH patients treated with Crysvita to patients treated with conventional therapy, we are finally able to demonstrate the magnitude of benefit on parameters of serum phosphorus, bone metabolism, and improvements in the skeleton.”

May 17, 2018
Photo: Erik Imel, lead study investigator and associate professor of medicine and pediatrics at Indiana University School of Medicine