UX023: Phase I/II data

The open-label, dose-escalation, U.S. and Canadian Phase I/II INT-001 trial in 28 adults with XLH showed that once-monthly 0.05-0.6 mg/kg doses of subcutaneous KRN23 increased urinary phosphorus reabsorption, serum phosphorus levels and 1,25 dihydroxy vitamin D levels. KRN23 for 4 months increased serum phosphorus levels in all patients, with about 89% of patients reaching the low end of the normal range. KRN23 increased peak mean serum phosphorus levels to 3.03 mg/dL after the fourth dose from a mean of 1.89 mg/dL at baseline. KRN23 also increased biomarkers of bone formation and bone resorption, including procollagen type I N-propeptide (PINP), osteocalcin, bone alkaline phosphatase and c-terminal telopeptide of type I collage ( CTX-I), compared to baseline. The increase in PINP was significant after all doses (p<0.05) and the increase in osteocalcin was significant after the fourth dose (p<0.05).

Additionally, KRN23 significantly improved scores on the role limitations due to physical health, bodily pain and physical component summary scales of the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) v2 compared to baseline. Furthermore, KRN23 significantly increased scores on the physical functioning and stiffness scales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) compared to baseline. ...