Ultragenyx Announces Positive Results From A Long-Term Phase 1/2 Study Of KRN23 In Adult Patients With X-Linked Hypophosphatemia

Ultragenyx Pharmaceutical Inc.

, a biopharmaceutical company focused on the development of novel products for rare and ultra-rare diseases, today announced the presentation of results from a long-term Phase 1/2 extension study, conducted by Kyowa Hakko Kirin Pharma, Inc., of the investigational fully human anti-FGF23 monoclonal antibody KRN23 (UX023) in adult patients with X-linked hypophosphatemia (XLH). The cumulative 16-month data, combining the four-month dose escalation period data from INT-001 and the 12-month extension data from INT-002, were presented at the American Society of Bone and Mineral Research (ASBMR) Annual Meeting in Houston. "By binding and inhibiting FGF23, patients treated with KRN23 demonstrated increases in phosphate levels over the cumulative 16-month treatment period," said Sunil Agarwal, M.D., Chief Medical Officer of Ultragenyx. "Based on these encouraging results, we plan to continue development in adult XLH patients and are enrolling pediatric XLH patients in our ongoing Phase 2 study." The Phase 1/2 extension study (INT-002) was designed to evaluate long-term safety and efficacy following an initial four-month dose escalation study (INT-001) that was conducted in the US and Canada. During the extension study, 22 adult patients with XLH were evaluated over an additional 12 months. Patients received monthly subcutaneous injections of KRN23 administered at a dose range of 0.1 to 1.0 mg/kg. Data from the INT-001 study were previously presented at the ICE/ENDO joint meeting of The Endocrine Society and The International Congress of Endocrinology in June 2014. Data from the INT-002 study demonstrated that the increases in serum phosphorus levels, urinary phosphorus reabsorption, and 1,25 dihydroxy vitamin D levels observed in the initial INT-001 study were generally sustained during the 12-month extension. All patients continued to demonstrate increases in serum phosphorus levels. Approximately 52.6%-85.7% of subjects in the extension study had serum phosphorus levels that reached the normal range (2.5 to 4.5 mg/dL) at peak time on Day 7 or Day 14 after each dose over this 12-month period. The mean increases in markers of bone remodeling (procollagen type I N propeptide (P1NP) and osteocalcin) observed in INT-001 were also generally sustained. KRN23 was generally safe and well tolerated over the cumulative treatment period. The most common treatment-related adverse events were injection site reaction, arthralgia, diarrhea, restless legs syndrome, injection site erythema, injection site pain, upper abdominal pain, headache, and decreased neutrophil count (the neutrophil changes were not associated with any significant infections). Serious adverse events were reported in three subjects but were all considered unrelated to KRN23. One patient discontinued treatment due to nephrolithiasis and one patient discontinued due to restless legs syndrome. There were no significant changes in parathyroid hormone or renal ultrasound. Serum calcium levels did not change significantly, and mild hypercalcemia was observed intermittently in two subjects. Urinary calcium was not increased, and three subjects had only transient hypercalciuria. No anti-KRN23 antibodies were observed. Ultragenyx and Kyowa Hakko Kirin Co., Ltd. (Tokyo:4151) initiated a Phase 2 study of KRN23 in pediatric patients in the US and EU in June 2014 and expect to continue the clinical development of KRN23 in adults with XLH.