Policy & Regulation
Long-Term Crysvita Treatment Reduces the Burden of Disease in Adults With X-Linked Hypophosphataemia, a Rare Genetic Metabolic Bone Disease
24 September 2021 - - New data has been published highlighting the sustained benefits of treatment with Crysvita (burosumab) in adults with X-linked hypophosphataemia, a rare genetic metabolic bone disease, Japanese pharmaceutical company Kyowa Kirin Co., Ltd. (TSX: 4151) said.

The data show that adults with XLH experience substantial pain, stiffness, fatigue and impairment in physical and ambulatory function.

Treatment with Crysvita was associated with a significant improvement from baseline after 96 weeks.

The data are from a randomised, double-blind, placebo-controlled, phase 3 study with an open-label extension to assess the efficacy and safety of Crysvita in adults with XLH.

The study met its primary endpoint, showing a statistically significant effect in increasing serum phosphorus concentrations at 24 weeks, compared to placebo.

After 24 weeks, all patients were switched to Crysvita treatment and data was collected on metabolic and biochemical markers, patient reported outcomes and measures of mobility up to 96 weeks.

This new publication focuses on the results from the PRO analysis and mobility scores.

At week 96, the study showed statistically significant improvements in PROs, including the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory–Short form (BPI-SF) and Brief Fatigue Inventory, compared to baseline.

Statistically significant improvements in ambulatory function, measured by the six-minute walk test, were also seen at 96 weeks compared to baseline.

Data previously published at 48 weeks also showed improvements in some PROs, including stiffness and pain, as well as fracture healing.

The data were published in the BMJ journal RMD Open, Rheumatic and Musculoskeletal Diseases.

Crysvita is licensed in Europe for the treatment of XLH in children and adolescents aged 1 to 17 years with radiographic evidence of bone disease, and in adults.

X-linked hypophosphataemia is a rare, genetic disease that causes abnormalities in the bones, muscles, and joints. XLH is not life-threatening, but its burden is life-long and progressive, and it may reduce a person's quality of life.

Crysvita (burosumab) was created and developed by Kyowa Kirin and is a recombinant fully human monoclonal IgG1 antibody against the phosphaturic hormone fibroblast growth factor 23 (FGF23). FGF23 is a hormone that reduces serum levels of phosphate by regulating phosphate excretion and active vitamin D production by the kidney.

Phosphate wasting and resulting hypophosphataemia in X-linked hypophosphataemia is caused by excess FGF23. Crysvita is designed to bind to, and thereby inhibit, the biological activity of FGF23.

By blocking excess FGF23 in patients, Crysvita is intended to increase phosphate reabsorption from the kidney and increase the production of active vitamin D, which enhances intestinal absorption of phosphate and calcium.

Crysvita has been available for clinical use since 2018. The first approval came from the European Commission, that granted a conditional marketing authorisation for Crysvita for the treatment of XLH with radiographic evidence of bone disease in children one year of age and older and adolescents with growing skeletons. In 2020, this authorisation was subsequently expanded to include older adolescents and adults.

Crysvita is approved by the US Food and Drug Administration for patients with XLH aged 6 months and older and by Health Canada for patients with XLH aged one year and older.

In 2019, Crysvita received approval from Japan's Ministry of Health, Labour and Welfare for the treatment of FGF23-related hypophosphataemic rickets and osteomalacia. In 2020, Crysvita was reimbursed by National Health Insurance in Japan as a self-injection presentation for the treatment of FGF23-related hypophosphataemic rickets and osteomalacia.

In January 2020, Swissmedic approved Crysvita for the treatment of adults, adolescents and children (one year of age and older) with XLH.

In June 2020, the US Food and Drug Administration approved Crysvita for patients aged two and older with tumour-induced osteomalacia, a rare disease that is characterised by the development of tumours that cause weakened and softened bones.

Kyowa Kirin and Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) have been collaborating in the development and commercialisation of Crysvita globally, based on the collaboration and licence agreement between Kyowa Kirin and Ultragenyx.