The U.S. Food and Drug Administration (FDA) approved Crysvita to treat both children (age 6 months and older) and adults with XLH beginning in 2018. The treatment was also granted conditional marketing authorization by the European Medicines Agency (EMA) for adults and children (1 year or older) with this disease.
How does Crysvita work?
Ideally, FGF23 helps to maintain normal phosphate levels in the blood by preventing the kidneys from reabsorbing phosphate. The function of FGF23 is regulated by the PHEX gene, situated on the X-chromosome. In XLH, mutations in the PHEX gene cause FGF23 to be overly active, prompting the kidneys to excrete phosphate at excessive levels in the urine. The result is 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.
Crysvita, given by subcutaneous (under the skin) injection, binds to FGF23 and inhibits its action, allowing the kidneys to reabsorb phosphate and increase its levels in the blood. This phosphate can then be deposited in bones, aiding their growth.
Crysvita in clinical trials
A Phase 2 clinical trial (NCT02163577) evaluating the safety and efficacy of Crysvita in children with XLH, ages 5 to 12, was completed in October 2018. The results showed that initial doses of 0.1 mg per kg of Crysvita every two weeks, or 0.2 mg per kg of the treatment every four weeks, and further escalating doses improved the reabsorption of phosphate in the kidneys, improved physical ability, and eased rickets-like symptoms.
A Phase 3 open-label study (NCT02537431) assessed the effect of Crysvita in improving symptoms of osteomalacia (soft and weak bones) in 14 adult XLH patients. This trial, which finished in December 2018, showed that Crysvita was well-tolerated and osteomalacia was significantly reduced. Patients also showed better healing of fractures and a reduction in other skeletal complications.
A Phase 3 double-blinded and randomized clinical trial (NCT02526160) with an open-label extension assessed the safety and efficacy of Crysvita in 134 XLH adults. Results from this study, completed in December 2018, showed that Crysvita treatment increased the reabsorption of phosphate in the kidneys, and promoted full healing of fractures over its 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) of the safety and efficacy of Crysvita in 13 children with XLH, ages 1 to 4, was completed in September 2019. Preliminary results showed that Crysvita had a well-tolerated safety profile, and eased rickets-like symptoms and improved growth in these children.
A Phase 1/2 open-label clinical trial (NCT04188964) to study the safety and efficacy of burosumab in newborns to 1-year-old infants with XLH is expected to start in February 2020, and be completed by April 2024. This study is sponsored by the pharmaceutical company Kyowa Kirin. Study sites are not yet available, but information can be obtained by clicking here.
An investigator-led observational study (NCT04184661) to determine the effect of burosumab and active vitamin D (calcitriol) on human osteoclasts (cells that are required for resorption of bone cells) in 15 patients, ages 2 and older, with hypophosphatemic rickets is expected to open in March 2020 and finish in March 2022. This study will enroll those eligible at its one site in Bron, France.
Children with XLH are usually given an injection of Crysvita at a starting dose of 0.4 mg per kg every two weeks, and adults with the disease are administered the treatment at a dose of 1 mg per kg every four weeks. The dosage is continued until serum phosphate levels are within the normal range, and restarted at half the previous dose should the levels drop below the normal range.
Crysvita should not be taken when using oral phosphate or specific types of vitamin D supplements, or if having kidney problems.
Common side effects 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 have also been reported in adults.
Last updated: Jan. 1, 2020
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