Ultragenyx Snags EU Orphan Status For XLH Drug KRN23

Biopharmaceutical company Ultragenyx Pharmaceutical announced that it has received Orphan Medicinal Product Designation from the European Commission for its investigational drug KRN23 (or UX023) for the treatment of rare metabolic bone disease, X-linked hypophosphatemia (XLH).

KRN23 is an investigational recombinant fully human monoclonal IgG1 antibody directed against the phosphaturic hormone fibroblast growth factor 23 (FGF23). The antibody is undergoing development as treatment for XLH, a disease characterized by excess FGF23 activity. By binding to FGF23, the drug inhibits excess biological activity of the hormone and thereby restores normal phosphate reabsorption from the kidney. KRN23 also works to increase the production of vitamin D to improve intestinal absorption of phosphate and calcium, addressing the disease’s symptoms. The antibody was originally discovered by Kyowa Hakko Kirin and subsequently licensed to Ultragenyx for co-development and commercialization.

The orphan status designation for KRN23 is supported by results from clinical studies in adult patients with XLH. Sunil Agarwal, CMO of Ultragenyx, said at the time, “By binding and inhibiting FGF23, patients treated with KRN23 demonstrated increases in phosphate levels over the cumulative 16-month treatment period. 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.”

X-Linked Hypophosphatemia is the most common heritable form of rickets inherited as an X-linked dominant trait in both men and women. XLH is a bone disorder characterized by phosphate wasting in the urine resulting in severe hypophosphatemia. The disease causes inadequate mineralization of bone that leads to a range of abnormalities, including bone pain, short stature, gross motor enthesopathy, muscle weakness, and rickets, among others.

“Pediatric patients with XLH can develop significant skeletal deformities and short stature, and adult patients can experience many long-term problems, including severe joint pain and stiffness, muscle weakness, fractures, and an overall decreased quality of life. We believe that, by targeting the underlying mechanism of XLH, KRN23 can help both pediatric and adult patients with this disease.”

Should KRN23 be approved in its orphan indication, Ultragenyx will gain ten years of market exclusivity among other benefits from the orphan designation.