Crysvita (burosumab) is a monoclonal antibody that recognizes a protein called fibroblast growth factor 23 (FGF23). Kyowa Kirin and Ultragenyx developed Crysvita to treat X-linked hypophosphatemia (XLH).

The U.S. Food and Drug Administration approved Crysvita in 2018 to treat XLH patients, 1 year and older, which was then updated the following year to include patients as young as 6 months. The European Medicines Agency also granted Crysvita conditional marketing authorization for the treatment of children (1 year or older) and young adolescents with the disease. The European Commission is reviewing a label update to expand its use into older adolescents and adults.

How does Crysvita work?

In healthy people, FGF23 helps to maintain normal phosphate levels in the blood. The PHEX gene, situated on the X-chromosome, regulates the function of FGF23.

In XLH, mutations in the PHEX gene cause FGF23 to be overly active. This prompts the kidneys to excrete phosphate at excessive levels in the urine. The result is a diminished availability of the mineral in the blood. Since phosphate is essential for proper bone growth and health, low blood levels lead to symptoms that affect the bones, teeth, and muscles.

Doctors administer Crysvita as a subcutaneous (under-the-skin) injection. The medicine binds to FGF23 and inhibits its action. This allows the kidneys to reabsorb phosphate and increase its levels in the blood, which can then be deposited in bones, aiding their growth.

Crysvita in clinical trials

Researchers completed a Phase 2 clinical trial (NCT02163577) evaluating the safety and efficacy of Crysvita in children with XLH, ages 5 to 12, in October 2018. The results showed that initial doses of 0.1 mg of Crysvita per kg of body weight every two weeks, or 0.2 mg/kg every four weeks, and further escalating doses improved the reabsorption of phosphate in the kidneys. It also improved physical ability and eased rickets-like symptoms in patients.

A Phase 3 open-label study (NCT02537431) assessed the effect of Crysvita in improving symptoms of osteomalacia (soft and weak bones) in 14 adult patients with XLH. This trial, which finished in December 2018, showed that patients tolerated Crysvita well. The treatment also significantly reduced osteomalacia in patients, who also showed better healing of fractures and a reduction in other skeletal complications.

A Phase 3 double-blind and randomized trial (NCT02526160) with an open-label extension assessed the safety and efficacy of Crysvita in 134 adult patients with XLH. Results from this study, which was completed in December 2018, showed that Crysvita increased the reabsorption of phosphate in the kidneys, and promoted full healing of fractures over the 24-week treatment period. Greater bone formation and better physical function with diminished pain were also observed.

A Phase 2 open-label clinical trial (NCT02750618) testing the safety and efficacy of Crysvita in 13 children with XLH, ages 1 to 4, concluded in September 2019. Preliminary results showed that Crysvita had a good safety profile, eased rickets-like symptoms, and improved growth in these children.

Ongoing clinical trials

A Phase 1/2 open-label clinical trial (NCT04188964) plans to study the safety and efficacy of Crysvita in children with XLH, from newborn up to 1 year. The trial, sponsored by Kyowa Kirin, is currently recruiting participants in France.

An investigator-led observational study (NCT04184661) seeks to determine the effect of Crysvita and active vitamin D (calcitriol) on human osteoclasts (cells that are necessary for the resorption of bone cells) in 15 patients, 2 years and older, with hypophosphatemic rickets. The study is sponsored by Hospices Civils de Lyon, in France, and is not yet recruiting participants.

Other information

Doctors usually give children with XLH an injection of Crysvita at a starting dose of 0.4 mg per kg of body weight every two weeks. They treat adults with the disease with a dose of 1 mg per kg every four weeks. The patients continue these dosages until serum phosphate levels are within the normal range. If levels drop below normal, they restart treatment at half the previous doses.

Patients should not receive Crysvita when using oral phosphate or specific types of vitamin D supplements, or if they have kidney problems.

Common side effects of Crysvita in children include fever, diarrhea, injection site reaction, toothache, muscle pain, and dizziness. Adults may experience back pain, muscle spasms, restless leg syndrome, dizziness, and constipation. Narrowing of the spaces within the spine and increased pressure on the spinal cord can also occur in adults.

 

Last updated: July 28, 2020

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XLH News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.