Kyowa Hakko Kirin announced submission of Crysvita (burosumab, KRN23) to the Japanese Ministry of Health, Labor and Welfare (MHLW) for the treatment of FGF-23-related hypophosphatemic rickets and osteomalacia.

The active ingredient of Crysvita is burosumab, a recombinant fully humanized IgG1 monoclonal antibody that binds to and inhibits the activity of fibroblast growth factor 23 (FGF-23). FGF23 reduces serum phosphate and active vitamin D levels by modulating phosphate excretion and production of active biotin D in the kidney. Currently, burosumab has been developed to treat hypophosphatemic diseases associated with FGF-23, such as X-linked hypophosphatemia (XLH), tumor-induced osteomalacia (TIO) and epidermal nevus syndrome (ENS).

Phosphate consumption in FGF-23-associated hypophosphatemic rickets and osteomalacia is caused by excessive levels and activity of FGF-23. Burosumab can target and inhibit the biological activity of FGF-23. By blocking excessive FGF-23 in the patient, burosumab can increase the reabsorption of phosphate by the kidneys and increase the production of active vitamin D, thereby enhancing the absorption of phosphate and calcium in the intestine.

In Japan, burosumab has been granted by MHLW as an Orphan Drug for the treatment of FGF-23-associated hypophosphatemic rickets and osteomalacia. Kyowa Hakko Kirin is expected to receive MHLW’s approval for burosumab in September 2019.

Crysvita was co-developed by Kyowa Hakko Kirin and Ultragenyx. In the European Union and the United States, Crysvita was respectively approved in January 2018 and April 2018 for the treatment of X-linked hypophosphatemia (XLH) in adults and children aged 1 year and older. Previously, Crysvita was granted Orphan Drug designation in the United States and the European Union, and was awarded a Breakthrough Therapy designation in the United States. XLH is the most common cause of childhood hereditary rickets, of which early identification plays a critical role for proper management and monitoring of pediatric patients with disease-related complications.

Crysvita is the world’s first drug to treat XLH, priced at $160,000 per year for children and $200,000 per year for adults. The industry shows a much optimistic attitude to the business prospects of burosumab, whose peak sales are expected to reach $1 billion.