US-based Ultragenyx Pharmaceutical has released results from a multiple-dose Phase I/II trial of the investigational anti-FGF23 monoclonal antibody KRN23 (UX023) in adult patients with X-linked hypophosphatemia (XLH).
The trial was carried out by Kyowa Hakko Kirin Pharma for the treatment of XLH, which is an inherited metabolic bone disease characterised by short stature, skeletal deformities, bone pain, fractures, and muscle weakness.
Ultragenyx chief executive officer Emil Kakkis said: "Based on observed improvements in phosphate metabolism, bone remodelling markers, and certain quality of life measures, we are encouraged by the potential for KRN23 to treat the underlying cause of bone disease in both adult and pediatric patients with XLH."
The company completed a multiple-dose Phase I/II trial (INT-001) with up to four escalating doses from 0.05mg/kg to 0.6mg/kg in 28 adult XLH patients.
The trial evaluated the safety and tolerability of subcutaneous injections of KRN23 given once every four weeks.
Efficacy data from the trial show that blocking excess FGF23 increases urinary phosphorus reabsorption, serum phosphorus levels, and 1,25 dihydroxy vitamin D levels.
The company said that repeat doses with KRN23 over four months led to an increase in serum phosphorus in 100% of patients, with about 89% of patients reaching the low end of the normal range.
Peak mean serum phosphorus increased to 3.03 +/- 0.42 mg/dL after the fourth dose, which is about 60% increase from the mean of 1.89 +/- 0.33 mg/dL at baseline.
In the trial comparable increases were observed in mean reabsorption of phosphate from the urine (TmP/GFR) and mean serum 1,25 dihydroxy vitamin D levels.
Increases in bone remodelling markers were also observed, including markers of bone formation and bone resorption.
As well as the four-dose Phase I/II trial (INT-001), a long-term Phase I/II trial (INT-002) was completed to assess KRN23 treatment for an additional 12 doses in 22 of the patients from INT-001.
The company said that administration of KRN23 continued to show a favourable safety profile and sustained improvements in phosphate metabolism and other measures.
Based on the Phase I and Phase I/II trial results to date, Ultragenyx and Kyowa Hakko Kirin (KHK) plan to start a Phase II trial of KRN23 in pediatric patients in 2014 and expect to continue the clinical development of KRN23 in adults with XLH.